articles+ search results

BIODIVERSITY, GRASSHOPPER behavior, BIOMES, PHYLOGENY, and SPECIES distribution

Abstract: The open vegetation biomes, within the limits of the Chacoan subregion, occur along a diagonal in eastern South America covering a large range of environmental conditions. In order to contribute to the knowledge on the biodiversity of these open biomes, we analysed the phylogenetic relationships of the grasshopper genus Zoniopoda to the remaining South American Romaleinae, and examined the biogeographical patterns of diversification of the genus. The study is based on morphological and molecular (COI and H3) evidence, including 12 species of Zoniopoda and 17 species of four tribes of South American Romaleinae. We describe a new species of Zoniopoda, and test its taxonomic placement within the group. Results of our phylogenetic analyses recovered Zoniopoda as a monophyletic group with high support values. According to the dispersion–vicariance analysis, the ancestor of Zoniopoda may have been distributed in an area corresponding to the Chacoan and Cerrado provinces. A vicariant event, that could be explained by the uplift of the Brazilian Plateau and the subsidence of the Chaco, is hypothesized to have occurred splitting the ancestral distribution of Zoniopoda, resulting in the independent evolution of the Tarsata group within the Cerrado and the Iheringi group in the Chacoan subregion. This published work has been registered in ZooBank, http://zoobank.org/urn:lsid:zoobank.org:act:FCFB4C5D-1741-46F1-8E25-B37ED2B9D872. [ABSTRACT FROM AUTHOR]

Cross-Sectional Studies, Disease Progression, Humans, Phenotype, Leukoencephalopathies diagnostic imaging, and Leukoencephalopathies genetics

Purpose: Recent reports of individuals with cytoplasmic transfer RNA (tRNA) synthetase-related disorders have identified cases with phenotypic variability from the index presentations. We sought to assess phenotypic variability in individuals with AARS1-related disease.
Methods: A cross-sectional survey was performed on individuals with biallelic variants in AARS1. Clinical data, neuroimaging, and genetic testing results were reviewed. Alanyl tRNA synthetase (AlaRS) activity was measured in available fibroblasts.
Results: We identified 11 affected individuals. Two phenotypic presentations emerged, one with early infantile-onset disease resembling the index cases of AARS1-related epileptic encephalopathy with deficient myelination (n = 7). The second (n = 4) was a later-onset disorder, where disease onset occurred after the first year of life and was characterized on neuroimaging by a progressive posterior predominant leukoencephalopathy evolving to include the frontal white matter. AlaRS activity was significantly reduced in five affected individuals with both early infantile-onset and late-onset phenotypes.
Conclusion: We suggest that variants in AARS1 result in a broader clinical spectrum than previously appreciated. The predominant form results in early infantile-onset disease with epileptic encephalopathy and deficient myelination. However, a subgroup of affected individuals manifests with late-onset disease and similarly rapid progressive clinical decline. Longitudinal imaging and clinical follow-up will be valuable in understanding factors affecting disease progression and outcome.
(© 2021. The Author(s), under exclusive licence to the American College of Medical Genetics and Genomics.)

Adolescent, Autism Spectrum Disorder genetics, Autism Spectrum Disorder pathology, Child, Child, Preschool, Chromosome Deletion, Chromosome Disorders physiopathology, DNA Methylation genetics, Epigenesis, Genetic genetics, Female, Haploinsufficiency genetics, Humans, Intellectual Disability genetics, Intellectual Disability physiopathology, Male, Neurodevelopmental Disorders genetics, Neurodevelopmental Disorders physiopathology, Phenotype, Young Adult, Chromosome Disorders genetics, Chromosomes, Human, Pair 1 genetics, Chromosomes, Human, X genetics, DNA-Binding Proteins genetics, and RNA-Binding Proteins genetics

Deletion 1p36 (del1p36) syndrome is the most common human disorder resulting from a terminal autosomal deletion. This condition is molecularly and clinically heterogeneous. Deletions involving two non-overlapping regions, known as the distal (telomeric) and proximal (centromeric) critical regions, are sufficient to cause the majority of the recurrent clinical features, although with different facial features and dysmorphisms. SPEN encodes a transcriptional repressor commonly deleted in proximal del1p36 syndrome and is located centromeric to the proximal 1p36 critical region. Here, we used clinical data from 34 individuals with truncating variants in SPEN to define a neurodevelopmental disorder presenting with features that overlap considerably with those of proximal del1p36 syndrome. The clinical profile of this disease includes developmental delay/intellectual disability, autism spectrum disorder, anxiety, aggressive behavior, attention deficit disorder, hypotonia, brain and spine anomalies, congenital heart defects, high/narrow palate, facial dysmorphisms, and obesity/increased BMI, especially in females. SPEN also emerges as a relevant gene for del1p36 syndrome by co-expression analyses. Finally, we show that haploinsufficiency of SPEN is associated with a distinctive DNA methylation episignature of the X chromosome in affected females, providing further evidence of a specific contribution of the protein to the epigenetic control of this chromosome, and a paradigm of an X chromosome-specific episignature that classifies syndromic traits. We conclude that SPEN is required for multiple developmental processes and SPEN haploinsufficiency is a major contributor to a disorder associated with deletions centromeric to the previously established 1p36 critical regions.
(Copyright © 2021 American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.)

Adolescent, Animals, Child, Child, Preschool, Drosophila Proteins genetics, Drosophila melanogaster, Female, Genes, Dominant, Genetic Variation, Haploinsufficiency, Humans, Infant, Male, Microscopy, Confocal, Neuroglia metabolism, Neurons metabolism, Protein Binding, Zebrafish, Zebrafish Proteins genetics, Chromosomal Proteins, Non-Histone genetics, Developmental Disabilities genetics, Mutation, Missense, Phenotype, and Tumor Suppressor Proteins genetics

SWI/SNF-related intellectual disability disorders (SSRIDDs) are rare neurodevelopmental disorders characterized by developmental disability, coarse facial features, and fifth digit/nail hypoplasia that are caused by pathogenic variants in genes that encode for members of the SWI/SNF (or BAF) family of chromatin remodeling complexes. We have identified 12 individuals with rare variants (10 loss-of-function, 2 missense) in the BICRA (BRD4 interacting chromatin remodeling complex-associated protein) gene, also known as GLTSCR1, which encodes a subunit of the non-canonical BAF (ncBAF) complex. These individuals exhibited neurodevelopmental phenotypes that include developmental delay, intellectual disability, autism spectrum disorder, and behavioral abnormalities as well as dysmorphic features. Notably, the majority of individuals lack the fifth digit/nail hypoplasia phenotype, a hallmark of most SSRIDDs. To confirm the role of BICRA in the development of these phenotypes, we performed functional characterization of the zebrafish and Drosophila orthologs of BICRA. In zebrafish, a mutation of bicra that mimics one of the loss-of-function variants leads to craniofacial defects possibly akin to the dysmorphic facial features seen in individuals harboring putatively pathogenic BICRA variants. We further show that Bicra physically binds to other non-canonical ncBAF complex members, including the BRD9/7 ortholog, CG7154, and is the defining member of the ncBAF complex in flies. Like other SWI/SNF complex members, loss of Bicra function in flies acts as a dominant enhancer of position effect variegation but in a more context-specific manner. We conclude that haploinsufficiency of BICRA leads to a unique SSRIDD in humans whose phenotypes overlap with those previously reported.
(Copyright © 2020 American Society of Human Genetics. All rights reserved.)

Administration, Oral, Biomarkers analysis, Biopsy, Chenodeoxycholic Acid administration dosage, Chenodeoxycholic Acid therapeutic use, Double-Blind Method, Female, Humans, Liver Function Tests, Male, Middle Aged, Chenodeoxycholic Acid analogs derivatives, and Non-alcoholic Fatty Liver Disease drug therapy

Background: Non-alcoholic steatohepatitis (NASH) is a common type of chronic liver disease that can lead to cirrhosis. Obeticholic acid, a farnesoid X receptor agonist, has been shown to improve the histological features of NASH. Here we report results from a planned interim analysis of an ongoing, phase 3 study of obeticholic acid for NASH.
Methods: In this multicentre, randomised, double-blind, placebo-controlled study, adult patients with definite NASH, non-alcoholic fatty liver disease (NAFLD) activity score of at least 4, and fibrosis stages F2-F3, or F1 with at least one accompanying comorbidity, were randomly assigned using an interactive web response system in a 1:1:1 ratio to receive oral placebo, obeticholic acid 10 mg, or obeticholic acid 25 mg daily. Patients were excluded if cirrhosis, other chronic liver disease, elevated alcohol consumption, or confounding conditions were present. The primary endpoints for the month-18 interim analysis were fibrosis improvement (≥1 stage) with no worsening of NASH, or NASH resolution with no worsening of fibrosis, with the study considered successful if either primary endpoint was met. Primary analyses were done by intention to treat, in patients with fibrosis stage F2-F3 who received at least one dose of treatment and reached, or would have reached, the month 18 visit by the prespecified interim analysis cutoff date. The study also evaluated other histological and biochemical markers of NASH and fibrosis, and safety. This study is ongoing, and registered with ClinicalTrials.gov, NCT02548351, and EudraCT, 20150-025601-6.
Findings: Between Dec 9, 2015, and Oct 26, 2018, 1968 patients with stage F1-F3 fibrosis were enrolled and received at least one dose of study treatment; 931 patients with stage F2-F3 fibrosis were included in the primary analysis (311 in the placebo group, 312 in the obeticholic acid 10 mg group, and 308 in the obeticholic acid 25 mg group). The fibrosis improvement endpoint was achieved by 37 (12%) patients in the placebo group, 55 (18%) in the obeticholic acid 10 mg group (p=0·045), and 71 (23%) in the obeticholic acid 25 mg group (p=0·0002). The NASH resolution endpoint was not met (25 [8%] patients in the placebo group, 35 [11%] in the obeticholic acid 10 mg group [p=0·18], and 36 [12%] in the obeticholic acid 25 mg group [p=0·13]). In the safety population (1968 patients with fibrosis stages F1-F3), the most common adverse event was pruritus (123 [19%] in the placebo group, 183 [28%] in the obeticholic acid 10 mg group, and 336 [51%] in the obeticholic acid 25 mg group); incidence was generally mild to moderate in severity. The overall safety profile was similar to that in previous studies, and incidence of serious adverse events was similar across treatment groups (75 [11%] patients in the placebo group, 72 [11%] in the obeticholic acid 10 mg group, and 93 [14%] in the obeticholic acid 25 mg group).
Interpretation: Obeticholic acid 25 mg significantly improved fibrosis and key components of NASH disease activity among patients with NASH. The results from this planned interim analysis show clinically significant histological improvement that is reasonably likely to predict clinical benefit. This study is ongoing to assess clinical outcomes.
Funding: Intercept Pharmaceuticals.
(Copyright © 2019 Elsevier Ltd. All rights reserved.)

Biodiversity and Conservation of Natural Resources

Female, Genes, Recessive, Humans, Male, Pregnancy, Congenital Abnormalities genetics, Genetic Diseases, Inborn diagnosis, Parents, Prenatal Diagnosis methods, and Whole Exome Sequencing

Objective: Rare genetic disorders resulting in prenatal or neonatal death are genetically heterogeneous, but testing is often limited by the availability of fetal DNA, leaving couples without a potential prenatal test for future pregnancies. We describe our novel strategy of exome sequencing parental DNA samples to diagnose recessive monogenic disorders in an audit of the first 50 couples referred.
Method: Exome sequencing was carried out in a consecutive series of 50 couples who had 1 or more pregnancies affected with a lethal or prenatal-onset disorder. In all cases, there was insufficient DNA for exome sequencing of the affected fetus. Heterozygous rare variants (MAF < 0.001) in the same gene in both parents were selected for analysis. Likely, disease-causing variants were tested in fetal DNA to confirm co-segregation.
Results: Parental exome analysis identified heterozygous pathogenic (or likely pathogenic) variants in 24 different genes in 26/50 couples (52%). Where 2 or more fetuses were affected, a genetic diagnosis was obtained in 18/29 cases (62%). In most cases, the clinical features were typical of the disorder, but in others, they result from a hypomorphic variant or represent the most severe form of a variable phenotypic spectrum.
Conclusion: We conclude that exome sequencing of parental samples is a powerful strategy with high clinical utility for the genetic diagnosis of lethal or prenatal-onset recessive disorders. © 2017 The Authors Prenatal Diagnosis published by John Wiley & Sons Ltd.
(© 2017 The Authors Prenatal Diagnosis published by John Wiley & Sons Ltd.)

Adolescent, Cell Count, Child, Collagen metabolism, Cytokines biosynthesis, Cytokines genetics, Female, Gene Expression Regulation, Humans, Male, Muscle Fibers, Skeletal pathology, RNA, Ribosomal genetics, Real-Time Polymerase Chain Reaction, Ribosomes genetics, Ribosomes pathology, Satellite Cells, Skeletal Muscle pathology, Brain Injuries pathology, Cerebral Palsy pathology, Extracellular Matrix pathology, Muscle, Skeletal pathology, and RNA, Ribosomal biosynthesis

Introduction: Children with cerebral palsy (CP) and acquired brain injury (ABI) commonly develop muscle contractures with advancing age. An underlying growth defect contributing to skeletal muscle contracture formation in CP/ABI has been suggested.
Methods: The biceps muscles of children and adolescents with CP/ABI (n = 20) and typically developing controls (n = 10) were investigated. We used immunohistochemistry, quantitative real-time polymerase chain reaction, and Western blotting to assess gene expression relevant to growth and size homeostasis.
Results: Classical pro-inflammatory cytokines and genes involved in extracellular matrix (ECM) production were elevated in skeletal muscle of children with CP/ABI. Intramuscular collagen content was increased and satellite cell number decreased and this was associated with reduced levels of RNA polymerase I transcription factors, 45s pre-rRNA and 28S rRNA.
Discussion: The present study provides novel data suggesting a role for pro-inflammatory cytokines and reduced ribosomal production in the development/maintenance of muscle contractures, possibly underlying stunted growth and perimysial ECM expansion. Muscle Nerve 58: 277-285, 2018.
(© 2018 Wiley Periodicals, Inc.)

Biomarkers, Tumor metabolism, Breast Neoplasms genetics, Breast Neoplasms metabolism, Cadherins metabolism, Colorectal Neoplasms genetics, Colorectal Neoplasms metabolism, Epithelial-Mesenchymal Transition genetics, Gene Expression Regulation, Neoplastic genetics, Homeodomain Proteins metabolism, Humans, Immunohistochemistry, In Situ Hybridization, Laser Capture Microdissection, Liver Neoplasms secondary, Real-Time Polymerase Chain Reaction, Reverse Transcriptase Polymerase Chain Reaction, Survival Analysis, Transcription Factors metabolism, Zinc Finger E-box-Binding Homeobox 1, Breast Neoplasms physiopathology, Colorectal Neoplasms physiopathology, Epithelial-Mesenchymal Transition physiology, Gene Expression Regulation, Neoplastic physiology, Liver Neoplasms metabolism, MicroRNAs metabolism, and Signal Transduction physiology

The role of the epithelial-mesenchymal transition (EMT) in cancer has been studied extensively in vitro, but involvement of the EMT in tumorigenesis in vivo is largely unknown. We investigated the potential of microRNAs as clinical markers and analyzed participation of the EMT-associated microRNA-200-ZEB-E-cadherin pathway in cancer progression. Expression of the microRNA-200 family was quantified by real-time RT-PCR analysis of fresh-frozen and microdissected formalin-fixed paraffin-embedded primary colorectal tumors, normal colon mucosa, and matched liver metastases. MicroRNA expression was validated by in situ hybridization and after in vitro culture of the malignant cells. To assess EMT as a predictive marker, factors considered relevant in colorectal cancer were investigated in 98 primary breast tumors from a treatment-randomized study. Associations between the studied EMT-markers were found in primary breast tumors and in colorectal liver metastases. MicroRNA-200 expression in epithelial cells was lower in malignant mucosa than in normal mucosa, and was also decreased in metastatic compared to non-metastatic colorectal cancer. Low microRNA-200 expression in colorectal liver metastases was associated with bad prognosis. In breast cancer, low levels of microRNA-200 were related to reduced survival and high expression of microRNA-200 was predictive of benefit from radiotheraphy. MicroRNA-200 was associated with ER positive status, and inversely correlated to HER2 and overactivation of the PI3K/AKT pathway, that was associated with high ZEB1 mRNA expression. Our findings suggest that the stability of microRNAs makes them suitable as clinical markers and that the EMT-related microRNA-200-ZEB-E-cadherin signaling pathway is connected to established clinical characteristics and can give useful prognostic and treatment-predictive information in progressive breast and colorectal cancers.

Animals, Biology, Diet, Female, Nymph growth development, Ovum, Heteroptera growth development, Temperature, and Zea mays

When quinoa, Chenopodium quinoa Willd., is cultivated in South America outside of its Andean origin, the heteropterans Liorhyssus hyalinus (Fabricius) and Nysius simulans Stål may emerge as important pests. Here we studied the development and reproduction of both species at different constant temperatures in the laboratory. Egg and nymphal development were investigated at 18, 22, 26, 30, 34, and 36°C. For both species, egg incubation time significantly decreased as the temperature increased. Nymphs did not successfully develop at 18°C and the total nymphal time significantly decreased as the temperature increased from 22 to 36°C. Based on a linear day-degree (DD) model, the lower developmental threshold (LDT) temperatures for eggs and nymphs were estimated to be 16.0 and 17.9°C for L. hyalinus, and 16.1 and 19.7°C for N. simulans, respectively. Thermal requirements for egg and nymphal development were 68.6 and 114.8 DD for L. hyalinus, and 77.7 and 190.3 DD for N. simulans, respectively. Reproduction and adult longevity were studied at 22, 26, 30, and 34°C. For both species preoviposition time decreased as temperature increased, and the oviposition period was longest at 26°C. The highest fecundity and egg viability were observed at 30°C, whereas longevities were higher at 22-26°C than at 30-34°C. As the lowest tested temperatures were not suitable to both heteropterans and 30°C was found to be the optimal temperature for development and reproduction, peak densities are expected in warm areas and seasons.
(© The Author(s) 2022. Published by Oxford University Press on behalf of Entomological Society of America.)

Adolescent, Adult, Age of Onset, Female, Follow-Up Studies, Growth Hormone-Secreting Pituitary Adenoma genetics, Humans, Male, Pituitary Neoplasms genetics, Prognosis, Prospective Studies, Young Adult, Biomarkers analysis, Genetic Testing methods, Growth Hormone-Secreting Pituitary Adenoma diagnosis, Intracellular Signaling Peptides and Proteins genetics, Mass Screening methods, Mutation, and Pituitary Neoplasms diagnosis

Context: Germline mutations in the aryl hydrocarbon receptor-interacting protein (AIP) gene are responsible for a subset of familial isolated pituitary adenoma (FIPA) cases and sporadic pituitary neuroendocrine tumors (PitNETs).
Objective: To compare prospectively diagnosed AIP mutation-positive (AIPmut) PitNET patients with clinically presenting patients and to compare the clinical characteristics of AIPmut and AIPneg PitNET patients.
Design: 12-year prospective, observational study.
Participants & Setting: We studied probands and family members of FIPA kindreds and sporadic patients with disease onset ≤18 years or macroadenomas with onset ≤30 years (n = 1477). This was a collaborative study conducted at referral centers for pituitary diseases.
Interventions & Outcome: AIP testing and clinical screening for pituitary disease. Comparison of characteristics of prospectively diagnosed (n = 22) vs clinically presenting AIPmut PitNET patients (n = 145), and AIPmut (n = 167) vs AIPneg PitNET patients (n = 1310).
Results: Prospectively diagnosed AIPmut PitNET patients had smaller lesions with less suprasellar extension or cavernous sinus invasion and required fewer treatments with fewer operations and no radiotherapy compared with clinically presenting cases; there were fewer cases with active disease and hypopituitarism at last follow-up. When comparing AIPmut and AIPneg cases, AIPmut patients were more often males, younger, more often had GH excess, pituitary apoplexy, suprasellar extension, and more patients required multimodal therapy, including radiotherapy. AIPmut patients (n = 136) with GH excess were taller than AIPneg counterparts (n = 650).
Conclusions: Prospectively diagnosed AIPmut patients show better outcomes than clinically presenting cases, demonstrating the benefits of genetic and clinical screening. AIP-related pituitary disease has a wide spectrum ranging from aggressively growing lesions to stable or indolent disease course.
(© Endocrine Society 2020.)

Adenoma genetics, Adolescent, Adult, Female, Gene Frequency, Growth Hormone-Secreting Pituitary Adenoma genetics, Humans, Male, Mexico, Mutation, Young Adult, Acromegaly genetics, Gigantism genetics, and Intracellular Signaling Peptides and Proteins genetics

Although aryl hydrocarbon receptor-interacting protein (AIP) mutations are rare in sporadic acromegaly, their prevalence among young patients is nonnegligible. The objectives of this study were to evaluate the frequency of AIP mutations in a cohort of Mexican patients with acromegaly with disease onset before the age of 30 and to search for molecular abnormalities in the AIP gene in teeth obtained from the "Tampico Giant". Peripheral blood DNA from 71 patients with acromegaly (51 females) with disease onset <30 years was analysed (median age of disease onset of 23 years) and correlated with clinical, biochemical and imaging characteristics. Sequencing was also carried out in DNA extracted from teeth of the Tampico Giant. Five patients (7 %) harboured heterozygous, germline mutations of the AIP gene. In two of them (a 9-year-old girl with gigantism and a young man with symptoms of GH excess since age 14) the c.910C>T (p.Arg304Ter), well-known truncating mutation was identified; in one of these two cases and her identical twin sister, the mutation proved to be a de novo event, since neither of their parents were found to be carriers. In the remaining three patients, new mutations were identified: a frameshift mutation (c.976_977insC, p.Gly326AfsTer), an in-frame deletion (c.872_877del, p.Val291_Leu292del) and a nonsense mutation (c.868A > T, p.Lys290Ter), which are predicted to be pathogenic based on in silico analysis. Patients with AIP mutations tended to have an earlier onset of acromegaly and harboured larger and more invasive tumours. A previously described genetic variant of unknown significance (c.869C > T, p.Ala299Val) was identified in DNA from the Tampico Giant. The prevalence of AIP mutations in young Mexican patients with acromegaly is similar to that of European cohorts. Our results support the need for genetic evaluation of patients with early onset acromegaly.

Adenoma epidemiology, Adrenal Gland Neoplasms epidemiology, Adult, Cohort Studies, Female, Genetic Association Studies, Genetic Testing, Humans, Male, Middle Aged, Paraganglioma epidemiology, Pheochromocytoma epidemiology, Pituitary Neoplasms epidemiology, Young Adult, Adenoma genetics, Adrenal Gland Neoplasms genetics, Genetic Heterogeneity, Genetic Predisposition to Disease, Paraganglioma genetics, Pheochromocytoma genetics, and Pituitary Neoplasms genetics

Context: Pituitary adenomas and pheochromocytomas/paragangliomas (pheo/PGL) can occur in the same patient or in the same family. Coexistence of the two diseases could be due to either a common pathogenic mechanism or a coincidence.
Objective: The objective of the investigation was to study the possible coexistence of pituitary adenoma and pheo/PGL.
Design: Thirty-nine cases of sporadic or familial pheo/PGL and pituitary adenomas were investigated. Known pheo/PGL genes (SDHA-D, SDHAF2, RET, VHL, TMEM127, MAX, FH) and pituitary adenoma genes (MEN1, AIP, CDKN1B) were sequenced using next generation or Sanger sequencing. Loss of heterozygosity study and pathological studies were performed on the available tumor samples.
Setting: The study was conducted at university hospitals.
Patients: Thirty-nine patients with sporadic of familial pituitary adenoma and pheo/PGL participated in the study.
Outcome: Outcomes included genetic screening and clinical characteristics.
Results: Eleven germline mutations (five SDHB, one SDHC, one SDHD, two VHL, and two MEN1) and four variants of unknown significance (two SDHA, one SDHB, and one SDHAF2) were identified in the studied genes in our patient cohort. Tumor tissue analysis identified LOH at the SDHB locus in three pituitary adenomas and loss of heterozygosity at the MEN1 locus in two pheochromocytomas. All the pituitary adenomas of patients affected by SDHX alterations have a unique histological feature not previously described in this context.
Conclusions: Mutations in the genes known to cause pheo/PGL can rarely be associated with pituitary adenomas, whereas mutation in a gene predisposing to pituitary adenomas (MEN1) can be associated with pheo/PGL. Our findings suggest that genetic testing should be considered in all patients or families with the constellation of pheo/PGL and a pituitary adenoma.

Androstadienes therapeutic use, Antineoplastic Agents, Hormonal pharmacology, Aromatase Inhibitors therapeutic use, Biomarkers, Tumor genetics, Breast pathology, Breast Neoplasms genetics, Breast Neoplasms pathology, Cell Line, Tumor, Cell Proliferation drug effects, Cell Survival drug effects, Enzyme Activators pharmacology, ErbB Receptors antagonists inhibitors, Erlotinib Hydrochloride, Estrogen Receptor alpha antagonists inhibitors, Estrogen Receptor alpha genetics, Female, Gene Expression Regulation, Neoplastic, Genetic Association Studies, Genetic Variation, Humans, Letrozole, MCF-7 Cells, Nitriles therapeutic use, Protein Kinase Inhibitors pharmacology, Quinazolines pharmacology, RNA Interference, RNA, Small Interfering, Tamoxifen pharmacology, Tamoxifen therapeutic use, Toremifene pharmacology, Toremifene therapeutic use, Triazoles therapeutic use, Breast Neoplasms drug therapy, Drug Resistance, Neoplasm genetics, Estrogen Receptor alpha metabolism, Indazoles pharmacology, and Proto-Oncogene Proteins c-vav genetics

Introduction: Endocrine therapies targeting cell proliferation and survival mediated by estrogen receptor α (ERα) are among the most effective systemic treatments for ERα-positive breast cancer. However, most tumors initially responsive to these therapies acquire resistance through mechanisms that involve ERα transcriptional regulatory plasticity. Herein we identify VAV3 as a critical component in this process.
Methods: A cell-based chemical compound screen was carried out to identify therapeutic strategies against resistance to endocrine therapy. Binding to ERα was evaluated by molecular docking analyses, an agonist fluoligand assay and short hairpin (sh)RNA-mediated protein depletion. Microarray analyses were performed to identify altered gene expression. Western blot analysis of signaling and proliferation markers, and shRNA-mediated protein depletion in viability and clonogenic assays, were performed to delineate the role of VAV3. Genetic variation in VAV3 was assessed for association with the response to tamoxifen. Immunohistochemical analyses of VAV3 were carried out to determine its association with therapeutic response and different tumor markers. An analysis of gene expression association with drug sensitivity was carried out to identify a potential therapeutic approach based on differential VAV3 expression.
Results: The compound YC-1 was found to comparatively reduce the viability of cell models of acquired resistance. This effect was probably not due to activation of its canonical target (soluble guanylyl cyclase), but instead was likely a result of binding to ERα. VAV3 was selectively reduced upon exposure to YC-1 or ERα depletion, and, accordingly, VAV3 depletion comparatively reduced the viability of cell models of acquired resistance. In the clinical scenario, germline variation in VAV3 was associated with the response to tamoxifen in Japanese breast cancer patients (rs10494071 combined P value = 8.4 × 10-4). The allele association combined with gene expression analyses indicated that low VAV3 expression predicts better clinical outcome. Conversely, high nuclear VAV3 expression in tumor cells was associated with poorer endocrine therapy response. Based on VAV3 expression levels and the response to erlotinib in cancer cell lines, targeting EGFR signaling may be a promising therapeutic strategy.
Conclusions: This study proposes VAV3 as a biomarker and a rationale for its use as a signaling target to prevent and/or overcome resistance to endocrine therapy in breast cancer.

DIAGNOSIS of diabetes, KIDNEY disease diagnosis, LIVER, GENETIC polymorphisms, GENETICS, GENETIC mutation, and ANATOMY

Diabet. Med. 30, 114-117 (2013) Abstract Aims Hepatocyte nuclear factor 1β ( HNF1B) mutations cause a syndrome of renal cysts and diabetes, with whole gene deletions accounting for approximately 50% of cases. The severity of the renal phenotype is variable, from enlarged cystic kidneys incompatible with life to normal renal development and function. We investigated the prevalence of HNF1B deletions in patients with diabetes but no known renal disease. Methods We tested 461 patients with familial diabetes diagnosed before 45 years, including 258 probands who met clinical criteria for maturity-onset diabetes of the young (two generations affected and at least one family member diagnosed under 25 years). A fluorescent polymerase chain reaction assay was used to analyse two intragenic polymorphic HNF1B markers and identify heterozygous patients who therefore did not have whole gene deletions. Those patients homozygous for both markers were then tested for an HNF1B deletion using multiplex ligation-dependent probe amplification. Results Heterozygous HNF1B intragenic polymorphisms were identified in 337/461 subjects. Multiplex ligation-dependent probe amplification analysis showed an HNF1B gene deletion in three of the remaining 124 probands, all of whom met the criteria for maturity-onset diabetes of the young. Testing of their relatives identified three additional deletion carriers and ultrasound scanning showed renal developmental abnormalities in three of these six patients. Conclusions We estimate that HNF1B mutations account for < 1% of cases of maturity-onset diabetes of the young. Although HNF1B mutations are a rare cause of diabetes in the absence of known renal disease, a genetic diagnosis of renal cysts and diabetes syndrome is important as it raises the possibility of subclinical renal disease and the 50% risk of renal cysts and diabetes syndrome in the patient's offspring. [ABSTRACT FROM AUTHOR]

Aged, Female, Genome, Human, Genome-Wide Association Study, Hemochromatosis complications, Hemochromatosis pathology, Hemochromatosis Protein, Homozygote, Humans, Iron metabolism, Male, Middle Aged, Polymorphism, Single Nucleotide, Risk Factors, Hemochromatosis genetics, Histocompatibility Antigens Class I genetics, Liver Cirrhosis genetics, Membrane Proteins genetics, and Subtilisins genetics

Genome-wide association studies (GWAS) have revealed genetic determinants of iron metabolism, but correlation of these with clinical phenotypes is pending. Homozygosity for HFE C282Y is the predominant genetic risk factor for hereditary hemochromatosis (HH) and may cause liver cirrhosis. However, this genotype has a low penetrance. Thus, detection of yet unknown genetic markers that identify patients at risk of developing severe liver disease is necessary for better prevention. Genetic loci associated with iron metabolism (TF, TMPRSS6, PCSK7, TFR2 and Chr2p14) in recent GWAS and liver fibrosis (PNPLA3) in recent meta-analysis were analyzed for association with either liver cirrhosis or advanced fibrosis in 148 German HFE C282Y homozygotes. Replication of associations was sought in additional 499 Austrian/Swiss and 112 HFE C282Y homozygotes from Sweden. Only variant rs236918 in the PCSK7 gene (proprotein convertase subtilisin/kexin type 7) was associated with cirrhosis or advanced fibrosis (P = 1.02 × 10(-5)) in the German cohort with genotypic odds ratios of 3.56 (95% CI 1.29-9.77) for CG heterozygotes and 5.38 (95% CI 2.39-12.10) for C allele carriers. Association between rs236918 and cirrhosis was confirmed in Austrian/Swiss HFE C282Y homozygotes (P = 0.014; ORallelic = 1.82 (95% CI 1.12-2.95) but not in Swedish patients. Post hoc combined analyses of German/Swiss/Austrian patients with available liver histology (N = 244, P = 0.00014, ORallelic = 2.84) and of males only (N = 431, P = 2.17 × 10(-5), ORallelic = 2.54) were consistent with the premier finding. Association between rs236918 and cirrhosis was not confirmed in alcoholic cirrhotics, suggesting specificity of this genetic risk factor for HH. PCSK7 variant rs236918 is a risk factor for cirrhosis in HH patients homozygous for the HFE C282Y mutation.
(© The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

In Arabidopsis thaliana, seven cyclin-dependent kinase (CDK) inhibitors have been identified, designated interactors of CDKs or Kip-related proteins (KRPs). Here, the function of KRP6 was investigated during cell cycle progression in roots infected by plant-parasitic root-knot nematodes. Contrary to expectations, analysis of Meloidogyne incognita-induced galls of KRP6-overexpressing lines revealed a role for this particular KRP as an activator of the mitotic cell cycle. In accordance, KRP6-overexpressing suspension cultures displayed accelerated entry into mitosis, but delayed mitotic progression. Likewise, phenotypic analysis of cultured cells and nematode-induced giant cells revealed a failure in mitotic exit, with the appearance of multinucleated cells as a consequence. Strong KRP6 expression upon nematode infection and the phenotypic resemblance between KRP6 overexpression cell cultures and root-knot morphology point toward the involvement of KRP6 in the multinucleate and acytokinetic state of giant cells. Along these lines, the parasite might have evolved to manipulate plant KRP6 transcription to the benefit of gall establishment.
(© 2014 American Society of Plant Biologists. All rights reserved.)

Animals, Antioxidants metabolism, Apoptosis drug effects, Body Weight drug effects, Carbon Tetrachloride antagonists inhibitors, Carcinogens toxicity, Cell Division drug effects, Diet, Diethylnitrosamine toxicity, Iron administration dosage, Iron metabolism, Kupffer Cells drug effects, Kupffer Cells pathology, Liver metabolism, Liver pathology, Liver Neoplasms, Experimental chemically induced, Liver Neoplasms, Experimental pathology, Male, Necrosis, Organ Size drug effects, Rats, Rats, Wistar, Ubiquinone metabolism, Vitamin E metabolism, Carbon Tetrachloride toxicity, Iron pharmacology, Liver drug effects, and Liver Neoplasms, Experimental prevention control

Background/aims: The aim of this study was to investigate if feeding with carbonyl iron would facilitate the development of preneoplastic lesions initiated by diethylnitrosamine (DEN) and promoted by CCl4-induced liver cirrhosis.
Methods: Male Wistar rats were fed a diet with 1.25%-2.5% carbonyl iron for 23 weeks and received intragastric injections of CCl4 (1.0 or 2.0 ml/kg per week) for 13 weeks, followed by one i.p. injection of DEN (200 mg/kg), after which CCl4 was administered for 8 additional weeks. Animals were killed 48 h after the first CCl4 injection to evaluate liver necrosis, 8 weeks later to evaluate fibrosis, and 9 weeks after DEN to determine formation of glutathione S-transferase 7,7 (GST-7,7) positive foci.
Results: Treatment with iron counteracted the increased serum alanine aminotransferase levels and liver necrosis following CCl4 administration. Hepatic levels of reduced Q9 and alpha-tocopherol were elevated in rats treated with CCl4 and decreased in rats treated with iron compared to the controls. Fibrogenesis was not altered by iron treatment. Nine weeks after DEN initiation, the number and volume density of GST-7,7-positive foci in rats treated with CCl4 were significantly increased as compared with controls, but co-treatment with iron inhibited this increase. Apoptotic index was increased in iron-loaded livers, and labelling index (the fraction of S-phase hepatocytes) was decreased by co-treatment with iron in livers exposed to CCl4.
Conclusion: Carbonyl iron depleted hepatic levels of antioxidants, it decreased CCl4-induced necrosis and cell proliferation, it enhanced apoptosis and did not facilitate fibrogenesis. These effects together may explain the suppression of CCl4-induced promotion after DEN initiation exerted by carbonyl iron in the present study.

Computational Biology, Cyclin-Dependent Kinases metabolism, Cyclins metabolism, DNA Replication, Luciferases metabolism, Mitosis, Models, Biological, Multiprotein Complexes metabolism, Protein Binding, Protein Interaction Mapping, Reproducibility of Results, Arabidopsis cytology, Arabidopsis metabolism, Arabidopsis Proteins metabolism, Cell Cycle, and Cell Cycle Proteins metabolism

Cell proliferation is the main driving force for plant growth. Although genome sequence analysis revealed a high number of cell cycle genes in plants, little is known about the molecular complexes steering cell division. In a targeted proteomics approach, we mapped the core complex machinery at the heart of the Arabidopsis thaliana cell cycle control. Besides a central regulatory network of core complexes, we distinguished a peripheral network that links the core machinery to up- and downstream pathways. Over 100 new candidate cell cycle proteins were predicted and an in-depth biological interpretation demonstrated the hypothesis-generating power of the interaction data. The data set provided a comprehensive view on heterodimeric cyclin-dependent kinase (CDK)-cyclin complexes in plants. For the first time, inhibitory proteins of plant-specific B-type CDKs were discovered and the anaphase-promoting complex was characterized and extended. Important conclusions were that mitotic A- and B-type cyclins form complexes with the plant-specific B-type CDKs and not with CDKA;1, and that D-type cyclins and S-phase-specific A-type cyclins seem to be associated exclusively with CDKA;1. Furthermore, we could show that plants have evolved a combinatorial toolkit consisting of at least 92 different CDK-cyclin complex variants, which strongly underscores the functional diversification among the large family of cyclins and reflects the pivotal role of cell cycle regulation in the developmental plasticity of plants.

Antibodies, Monoclonal immunology, Antibody Affinity immunology, Carrier Proteins genetics, Gene Expression, Humans, Immunoglobulin Variable Region immunology, Immunoglobulin Variable Region isolation purification, Immunoglobulin kappa-Chains genetics, Recombinant Fusion Proteins genetics, Recombinant Fusion Proteins immunology, Recombinant Fusion Proteins isolation purification, Substrate Specificity genetics, Substrate Specificity immunology, Antibodies, Monoclonal genetics, Antibody Affinity genetics, Gene Library, Immunoglobulin Variable Region genetics, Peptides immunology, and Plant Proteins immunology

The application of recombinant antibodies in plant biology research is limited because plant researchers have minimal access to high-quality phage display libraries. Therefore, we constructed a library of 1.3 x 10(10) clones displaying human single-chain variable fragments (scFvs) that is available to the academic community. The scFvs selected from the library against a diverse set of plant proteins showed moderate to high antigen-binding affinity together with high specificity. Moreover, to optimize an scFv as immunodetection agent, two expression systems that allow efficient production and purification of bivalent scFv-Fc and scFv-CkappaZIP fusion proteins were integrated. We are convinced that this antibody platform will further stimulate applications of recombinant antibodies such as the diagnostic detection or immunomodulation of specific antigens in plants.

Adenoma genetics, Adenoma pathology, Adolescent, Adult, Aged, Aged, 80 and over, Child, Child, Preschool, Female, Genetic Testing, Germ-Line Mutation, Growth Hormone-Secreting Pituitary Adenoma genetics, Growth Hormone-Secreting Pituitary Adenoma pathology, Humans, Longitudinal Studies, Male, Middle Aged, Mutation, Pituitary Neoplasms genetics, Pituitary Neoplasms pathology, Prospective Studies, Young Adult, Adenoma diagnosis, Growth Hormone-Secreting Pituitary Adenoma diagnosis, Intracellular Signaling Peptides and Proteins genetics, and Pituitary Neoplasms diagnosis

Context: Familial isolated pituitary adenoma (FIPA) due to aryl hydrocarbon receptor interacting protein (AIP) gene mutations is an autosomal dominant disease with incomplete penetrance. Clinical screening of apparently unaffected AIP mutation (AIPmut) carriers could identify previously unrecognized disease.
Objective: To determine the AIP mutational status of FIPA and young pituitary adenoma patients, analyzing their clinical characteristics, and to perform clinical screening of apparently unaffected AIPmut carrier family members.
Design: This was an observational, longitudinal study conducted over 7 years.
Setting: International collaborative study conducted at referral centers for pituitary diseases.
Participants: FIPA families (n 216) and sporadic young-onset (30 y) pituitary adenoma patients (n 404) participated in the study.
Interventions: We performed genetic screening of patients for AIPmuts, clinical assessment of their family members, and genetic screening for somatic GNAS1 mutations and the germline FGFR4 p.G388R variant.
Main Outcome Measure(s): We assessed clinical disease in mutation carriers, comparison of characteristics of AIPmut positive and negative patients, results of GNAS1, and FGFR4 analysis.
Results: Thirty-seven FIPA families and 34 sporadic patients had AIPmuts. Patients with truncating AIPmuts had a younger age at disease onset and diagnosis, compared with patients with nontruncating AIPmuts. Somatic GNAS1 mutations were absent in tumors from AIPmut-positive patients, and the studied FGFR4 variant did not modify the disease behavior or penetrance in AIPmut-positive individuals. A total of 164 AIPmut-positive unaffected family members were identified; pituitary disease was detected in 18 of those who underwent clinical screening.
Conclusions: A quarter of the AIPmut carriers screened were diagnosed with pituitary disease, justifying this screening and suggesting a variable clinical course for AIPmut-positive pituitary adenomas.

Adult, Alternative Splicing genetics, Amino Acid Sequence, Animals, Cell Line, Cyclic AMP metabolism, Cyclic AMP-Dependent Protein Kinases metabolism, Family, Female, Gene Expression Regulation, Neoplastic, Humans, Intracellular Signaling Peptides and Proteins chemistry, Intracellular Signaling Peptides and Proteins metabolism, Male, Middle Aged, Molecular Sequence Data, Mutant Proteins genetics, Mutant Proteins metabolism, Mutation, Missense genetics, Pedigree, Pituitary Neoplasms enzymology, Promoter Regions, Genetic genetics, RNA Splice Sites genetics, RNA, Messenger genetics, RNA, Messenger metabolism, Rats, Signal Transduction, Intracellular Signaling Peptides and Proteins genetics, Mutation genetics, and Pituitary Neoplasms genetics

Familial isolated pituitary adenoma (FIPA) is an autosomal dominant condition with variable genetic background and incomplete penetrance. Germline mutations of the aryl hydrocarbon receptor interacting protein (AIP) gene have been reported in 15-40% of FIPA patients. Limited data are available on the functional consequences of the mutations or regarding the regulation of the AIP gene. We describe a large cohort of FIPA families and characterize missense and silent mutations using minigene constructs, luciferase and beta-galactosidase assays, as well as in silico predictions. Patients with AIP mutations had a lower mean age at diagnosis (23.6+/-11.2 years) than AIP mutation-negative patients (40.4+/-14.5 years). A promoter mutation showed reduced in vitro activity corresponding to lower mRNA expression in patient samples. Stimulation of the protein kinase A-pathway positively regulates the AIP promoter. Silent mutations led to abnormal splicing resulting in truncated protein or reduced AIP expression. A two-hybrid assay of protein-protein interaction of all missense variants showed variable disruption of AIP-phosphodiesterase-4A5 binding. In summary, exonic, promoter, splice-site, and large deletion mutations in AIP are implicated in 31% of families in our FIPA cohort. Functional characterization of AIP changes is important to identify the functional impact of gene sequence variants.

Adult, Antineoplastic Agents, Hormonal therapeutic use, Biomarkers, Tumor metabolism, Breast Neoplasms drug therapy, Female, Humans, Lymphatic Metastasis, Middle Aged, Neoplastic Stem Cells pathology, Prognosis, Randomized Controlled Trials as Topic, Retrospective Studies, Survival Rate, Adaptor Proteins, Vesicular Transport metabolism, Breast Neoplasms metabolism, Breast Neoplasms pathology, Neoplastic Stem Cells metabolism, Progranulins metabolism, and Tamoxifen therapeutic use

Background: The growth factor progranulin has been implicated in numerous biological processes such as wound healing, inflammation and progressive tumorigenesis. Both progranulin and its receptor sortilin are known to be highly expressed in subgroups of breast cancer and have been associated with various clinical properties including tamoxifen resistance. Recent data further suggest that progranulin, via its receptor sortilin, drives breast cancer stem cell propagation in vitro and increases metastasis formation in an in vivo breast cancer xenograft model. In this retrospective biomarker analysis, we aimed to determine whether tumor co-expression of progranulin and sortilin has prognostic and treatment predictive values for breast cancer patients.
Methods: We explored how co-expression of progranulin and sortilin was associated with established clinical markers by analyzing a tissue microarray including 560 randomized premenopausal breast cancer patients receiving either 2 years of tamoxifen treatment or no adjuvant treatment, with a median follow-up time of 28 years. Breast cancer-specific survival was analyzed using Kaplan-Meier and Cox Proportional Hazards regression models to assess the prognostic and predictive value of progranulin and sortilin in relation to known clinical markers.
Results: Co-expression of progranulin and sortilin was observed in 20% of the breast cancer samples. In untreated patients, prognostic considerations could be detailed separately from treatment prediction and the high progranulin and sortilin expressing subgroup was significantly associated with breast cancer-specific death in multivariable analyses (HR=2.188, CI: 1.317-3.637, p=0.003) along with tumor size, high tumor grade and lymph node positivity. When comparing the untreated patients with tamoxifen treated patients in the ERα positive subgroup, co-expression of progranulin and sortilin was not linked to tamoxifen resistance.
Conclusion: Data suggest that co-expression of progranulin and its receptor sortilin is a novel prognostic biomarker combination identifying a highly malignant subgroup of breast cancer. Importantly, this subpopulation could potentially be targeted with anti-sortilin based therapies.

MALONDIALDEHYDE, PEROXIDATION, CRYOBIOLOGY, and ALCOHOLS (Chemical class)

Abstract: Malondialdehyde (MDA) is a widely used marker of oxidative lipid injury whose concentration varies in response to biotic and abiotic stress. Commonly, MDA is quantified as a strong light-absorbing and fluorescing adduct following reaction with thiobarbituric acid (TBA). However, plant tissues in particular contain many compounds that potentially interfere with this reaction and whose concentrations also vary according to the tissue type and stress conditions. As part of our studies into the stress responses of plant tissues, we were interested in developing a rapid, accurate, and robust protocol for MDA analysis using reverse-phased HPLC to avoid these problems with reaction specificity. We demonstrate that a partitioning step into n-butanol during sample preparation is essential and that gradient HPLC analysis is necessary to prevent sample carryover between injections. Furthermore, the starting composition of the mobile phase must be sufficiently hydrophobic to allow direct injection of the n-butanol extracts without peak splitting, tailing, and other artifacts. To minimize analysis times, we used a short, so-called “Rocket” HPLC column and high flow rates. The optimized HPLC separation has a turnaround time of 2.5min per sample. Butanolic extracts of MDA(TBA)2 were stable for at least 48h, and recoveries were linear between 0.38 and 7.5pmol MDA added. Importantly, this procedure proved to be compatible with existing extraction procedures for l-ascorbate and glutathione analysis in different plant species, allowing multiple “stress metabolite” analyses to be carried out on a single tissue extract. [Copyright &y& Elsevier]

TAMARISKS, ASSASSIN bugs, LIFE history theory, PREDATORY animals, BODY size, and NATURAL history

The harpactorine assassin bug, Zelus tetracanthus (Stål) (Hemiptera: Reduviidae), is an insect predator frequently found in surveys of saltcedar (Tamarix spp.) in Oklahoma. Previous studies in a laboratory showed it could prey on Diorhabda carinulata (Desbrochers) (Coleoptera: Chrysomelidae), a recently introduced biological control agent for Tamarix. An F2 cohort of Z. tetracanthus was reared from egg to adult to measure stage-specific development rates and describe immature stages at 22 ± 1.0°C and 16:8 light:dark hours. The mean times for development of the five instars were 6.96 ± 0.13, 5.18 ± 0.13, 6.94 ± 0.29, 10.92 ± 0.43, and 17.93 ± 0.76 days, respectively. Several anatomical characters to distinguish instars, including body size, body color, and select morphological characters were described. Data from museum collections of Z. tetracanthus suggested the insect has a univoltine life cycle. The development data contrast with a previous description of Z. socius (= Z. tetracanthus) and illustrate the need to further study the variable morphology, natural history, and genetic makeup of the species. [ABSTRACT FROM AUTHOR]

MELIACEAE, HOST plants, HEMIPTERA, STINKBUGS, and INSECT antifeedants

Currently, the invasive brown marmorated stink bug, Halyomorpha halys (Stål) (Hemiptera: Pentatomidae), is considered an agricultural and nuisance pest in Georgia. The invasive chinaberry tree, Melia azedarach L. (Meliaceae), commonly grows in dense thickets along roadsides, and in woodlands adjacent to agricultural crops across the southeastern USA. Thus, the objective of this study was to determine the potential of M. azedarach to serve as a host plant of H. halys by examining mortality and feeding of first and second instars on M. azedarach leaves vs. carrot (i.e., a control diet), and documenting presence of H. halys on M. azedarach in woodlands at 2 locations in Georgia where this stink bug has become established. Over all sampling dates and locations, the number of H. halys in chinaberry was very low (0.1 per tree), and only 3 late instars and 1 adult were observed feeding on M. azedarach at 1 field site late in the season. Percentage feeding by second instars of H. halys was lower for individuals given M. azedarach leaves vs. those provided with carrot, most likely indicating that compounds in M. azedarach have an antifeeding effect. In fact, mortality for second instars on M. azedarach leaves was very high, and thus we conclude that M. azedarach is an unsuitable host plant for H. halys. [ABSTRACT FROM AUTHOR]

STIMULANTS, LEAFHOPPERS, RICE diseases & pests, BIOLOGICAL assay, and METHANOL

A crude rice extract caused a higher probing response than did the control in the green rice leafhopper, Nephotettix nigropictus. Bioassay-guided separation led to the isolation of four active compounds, isoscoparin 2"-O-glucoside, isoscoparin 2"-O-(6"'-(E)-feruloyl)glucoside, isoscoparin 2"-O-(6"'-(E)-p-coumaroyl)glucoside, and isovitexin 2"-O-(6"'- (E)-feruloyl)glucoside from ODS 40% methanol in water faction. Each of the compounds, or any combination without one of the four compounds, caused weaker probing responses than the crude rice extract. The activity was recovered only when all the compounds were combined. [ABSTRACT FROM AUTHOR]

Adolescent, Adult, Aged, Child, Child, Preschool, Female, Follow-Up Studies, Humans, Infant, International Agencies, Male, Mental Disorders etiology, Middle Aged, Monocarboxylic Acid Transporters genetics, Muscular Diseases etiology, Mutation, Neurodevelopmental Disorders etiology, Prognosis, Retrospective Studies, Survival Rate, Symporters genetics, Young Adult, Biomarkers analysis, Mental Disorders pathology, Monocarboxylic Acid Transporters deficiency, Muscular Diseases pathology, Neurodevelopmental Disorders pathology, and Symporters deficiency

Background: Disordered thyroid hormone transport, due to mutations in the SLC16A2 gene encoding monocarboxylate transporter 8 (MCT8), is characterised by intellectual and motor disability resulting from cerebral hypothyroidism and chronic peripheral thyrotoxicosis. We sought to systematically assess the phenotypic characteristics and natural history of patients with MCT8 deficiency.
Methods: We did an international, multicentre, cohort study, analysing retrospective data from Jan 1, 2003, to Dec 31, 2019, from patients with MCT8 deficiency followed up in 47 hospitals in 22 countries globally. The key inclusion criterion was genetically confirmed MCT8 deficiency. There were no exclusion criteria. Our primary objective was to analyse the overall survival of patients with MCT8 deficiency and document causes of death. We also compared survival between patients who did or did not attain full head control by age 1·5 years and between patients who were or were not underweight by age 1-3 years (defined as a bodyweight-for-age Z score <-2 SDs or <5th percentile according to WHO definition). Other objectives were to assess neurocognitive function and outcomes, and clinical parameters including anthropometric characteristics, biochemical markers, and neuroimaging findings.
Findings: Between Oct 14, 2014, and Jan 17, 2020, we enrolled 151 patients with 73 different MCT8 (SLC16A2) mutations. Median age at diagnosis was 24·0 months (IQR 12·0-60·0, range 0·0-744·0). 32 (21%) of 151 patients died; the main causes of mortality in these patients were pulmonary infection (six [19%]) and sudden death (six [19%]). Median overall survival was 35·0 years (95% CI 8·3-61·7). Individuals who did not attain head control by age 1·5 years had an increased risk of death compared with patients who did attain head control (hazard ratio [HR] 3·46, 95% CI 1·76-8·34; log-rank test p=0·0041). Patients who were underweight during age 1-3 years had an increased risk for death compared with patients who were of normal bodyweight at this age (HR 4·71, 95% CI 1·26-17·58, p=0·021). The few motor and cognitive abilities of patients did not improve with age, as evidenced by the absence of significant correlations between biological age and scores on the Gross Motor Function Measure-88 and Bayley Scales of Infant Development III. Tri-iodothyronine concentrations were above the age-specific upper limit in 96 (95%) of 101 patients and free thyroxine concentrations were below the age-specific lower limit in 94 (89%) of 106 patients. 59 (71%) of 83 patients were underweight. 25 (53%) of 47 patients had elevated systolic blood pressure above the 90th percentile, 34 (76%) of 45 patients had premature atrial contractions, and 20 (31%) of 64 had resting tachycardia. The most consistent MRI finding was a global delay in myelination, which occurred in 13 (100%) of 13 patients.
Interpretation: Our description of characteristics of MCT8 deficiency in a large patient cohort reveals poor survival with a high prevalence of treatable underlying risk factors, and provides knowledge that might inform clinical management and future evaluation of therapies.
Funding: Netherlands Organisation for Health Research and Development, and the Sherman Foundation.
(Copyright © 2020 Elsevier Ltd. All rights reserved.)

Adolescent, Adult, Aged, Amylases blood, Biopsy, Diabetes Mellitus, Type 2 complications, Diabetes Mellitus, Type 2 drug therapy, Dose-Response Relationship, Drug, Double-Blind Method, Female, Glucagon-Like Peptides adverse effects, Humans, Injections, Subcutaneous, Lipase blood, Liver pathology, Liver Cirrhosis drug therapy, Liver Cirrhosis etiology, Liver Cirrhosis pathology, Male, Middle Aged, Non-alcoholic Fatty Liver Disease blood, Non-alcoholic Fatty Liver Disease complications, Non-alcoholic Fatty Liver Disease pathology, Young Adult, Glucagon-Like Peptides administration dosage, and Non-alcoholic Fatty Liver Disease drug therapy

Background: Nonalcoholic steatohepatitis (NASH) is a common disease that is associated with increased morbidity and mortality, but treatment options are limited. The efficacy and safety of the glucagon-like peptide-1 receptor agonist semaglutide in patients with NASH is not known.
Methods: We conducted a 72-week, double-blind phase 2 trial involving patients with biopsy-confirmed NASH and liver fibrosis of stage F1, F2, or F3. Patients were randomly assigned, in a 3:3:3:1:1:1 ratio, to receive once-daily subcutaneous semaglutide at a dose of 0.1, 0.2, or 0.4 mg or corresponding placebo. The primary end point was resolution of NASH with no worsening of fibrosis. The confirmatory secondary end point was an improvement of at least one fibrosis stage with no worsening of NASH. The analyses of these end points were performed only in patients with stage F2 or F3 fibrosis; other analyses were performed in all the patients.
Results: In total, 320 patients (of whom 230 had stage F2 or F3 fibrosis) were randomly assigned to receive semaglutide at a dose of 0.1 mg (80 patients), 0.2 mg (78 patients), or 0.4 mg (82 patients) or to receive placebo (80 patients). The percentage of patients in whom NASH resolution was achieved with no worsening of fibrosis was 40% in the 0.1-mg group, 36% in the 0.2-mg group, 59% in the 0.4-mg group, and 17% in the placebo group (P<0.001 for semaglutide 0.4 mg vs. placebo). An improvement in fibrosis stage occurred in 43% of the patients in the 0.4-mg group and in 33% of the patients in the placebo group (P = 0.48). The mean percent weight loss was 13% in the 0.4-mg group and 1% in the placebo group. The incidence of nausea, constipation, and vomiting was higher in the 0.4-mg group than in the placebo group (nausea, 42% vs. 11%; constipation, 22% vs. 12%; and vomiting, 15% vs. 2%). Malignant neoplasms were reported in 3 patients who received semaglutide (1%) and in no patients who received placebo. Overall, neoplasms (benign, malignant, or unspecified) were reported in 15% of the patients in the semaglutide groups and in 8% in the placebo group; no pattern of occurrence in specific organs was observed.
Conclusions: This phase 2 trial involving patients with NASH showed that treatment with semaglutide resulted in a significantly higher percentage of patients with NASH resolution than placebo. However, the trial did not show a significant between-group difference in the percentage of patients with an improvement in fibrosis stage. (Funded by Novo Nordisk; ClinicalTrials.gov number, NCT02970942.).
(Copyright © 2020 Massachusetts Medical Society.)

NILAPARVATA lugens, SINGLE nucleotide polymorphisms, LOCUS (Genetics), GENOTYPES, INSECT pests, and RICE

Rice is the most important staple food crop, and it feeds more than half of the world population. Brown planthopper (BPH) is a major insect pest of rice that causes 20–80% yield loss through direct and indirect damage. The identification and use of BPH resistance genes can efficiently manage BPH. A molecular marker-based genetic analysis of BPH resistance was carried out using 101 BC1F5 mapping population derived from a cross between a BPH-resistant indica variety Khazar and an elite BPH-susceptible line Huang–Huan–Zhan. The genetic analysis indicated the existence of Mendelian segregation for BPH resistance. A total of 702 high-quality polymorphic single nucleotide polymorphism (SNP) markers, genotypic data, and precisely estimated BPH scores were used for molecular mapping, which resulted in the identification of the BPH38(t) locus on the long arm of chromosome 1 between SNP markers 693,369 and id 10,112,165 of 496.2 kb in size with LOD of 20.53 and phenotypic variation explained of 35.91%. A total of 71 candidate genes were predicted in the detected locus. Among these candidate genes, LOC_Os01g37260 was found to belong to the FBXL class of F-box protein possessing the LRR domain, which is reported to be involved in biotic stress resistance. Furthermore, background analysis and phenotypic selection resulted in the identification of introgression lines (ILs) possessing at least 90% recurrent parent genome recovery and showing superior performance for several agro-morphological traits. The BPH resistance locus and ILs identified in the present study will be useful in marker-assisted BPH resistance breeding programs. [ABSTRACT FROM AUTHOR]

Anti-Bacterial Agents pharmacology, Bacterial Proteins metabolism, Carbapenem-Resistant Enterobacteriaceae drug effects, Enterobacter cloacae drug effects, Enterobacter cloacae genetics, Enterobacter cloacae isolation purification, Enterobacteriaceae Infections drug therapy, Enterobacteriaceae Infections microbiology, Escherichia coli drug effects, Escherichia coli genetics, Escherichia coli isolation purification, Humans, Interspersed Repetitive Sequences genetics, Klebsiella pneumoniae drug effects, Klebsiella pneumoniae genetics, Klebsiella pneumoniae isolation purification, Meropenem pharmacology, Microbial Sensitivity Tests, Molecular Epidemiology, Netherlands epidemiology, beta-Lactamases metabolism, Bacterial Proteins genetics, Carbapenem-Resistant Enterobacteriaceae genetics, Carbapenem-Resistant Enterobacteriaceae isolation purification, Enterobacteriaceae Infections epidemiology, and beta-Lactamases genetics

Objectives: Carbapenem resistance mediated by mobile genetic elements has emerged worldwide and has become a major public health threat. To gain insight into the molecular epidemiology of carbapenem resistance in The Netherlands, Dutch medical microbiology laboratories are requested to submit suspected carbapenemase-producing Enterobacterales (CPE) to the National Institute for Public Health and the Environment as part of a national surveillance system.
Methods: Meropenem MICs and species identification were confirmed by E-test and MALDI-TOF and carbapenemase production was assessed by the Carbapenem Inactivation Method. Of all submitted CPE, one species/carbapenemase gene combination per person per year was subjected to next-generation sequencing (NGS).
Results: In total, 1838 unique isolates were received between 2014 and 2018, of which 892 were unique CPE isolates with NGS data available. The predominant CPE species were Klebsiella pneumoniae (n = 388, 43%), Escherichia coli (n = 264, 30%) and Enterobacter cloacae complex (n = 116, 13%). Various carbapenemase alleles of the same carbapenemase gene resulted in different susceptibilities to meropenem and this effect varied between species. Analyses of NGS data showed variation of prevalence of carbapenemase alleles over time with bla OXA-48 being predominant (38%, 336/892), followed by bla NDM-1 (16%, 145/892). For the first time in the Netherlands, bla OXA-181 , bla OXA-232 and bla VIM-4 were detected. The genetic background of K. pneumoniae and E. coli isolates was highly diverse.
Conclusions: The CPE population in the Netherlands is diverse, suggesting multiple introductions. The predominant carbapenemase alleles are bla OXA-48 and bla NDM-1 . There was a clear association between species, carbapenemase allele and susceptibility to meropenem.
(Copyright © 2020 National Institute for Public Health and the Environment, Bilthoven, The Netherlands. Published by Elsevier Ltd.. All rights reserved.)

HYMENOPTERA, CURCULIONIDAE, HOMOPTERA, PEST control, INSECT collection & preservation, BEETLES, and HEMIPTERA

The knowledge of the entomological fauna in productive systems is important for the agroecological management since beneficial insects are a key resource for pest management in horticultural systems. Scientific information on the biodiversity present in a given area is essential as well as the ecological function and/or feeding habits of the insects. In Alto Valle de Río Negro and Neuquén, horticultural production systems can be described as highly dependent on chemical inputs for pest management and fertilization. The aim of this study is to carry out an inventory of the biodiversity of some families of Hemiptera, Coleoptera (Curculionidae) and Hymenoptera present in peri-urban and rural farms located in Neuquén and Río Negro, respectively. Insects were collected through pitfall and sweeping net on tomato and pepper crops and the surrounding non-cultivated areas. Idiosystatus Berg (Auchenorrhyncha) was cited for the first time from Argentina. Species cited for the first time from Neuquén: Hemiptera: Auchenorrhyncha: Acanalonia chloris (Berg), Syncharina punctatissima (Signoret), Amplicephalus dubius Linnavuori, Exitianus obscurinervis (Stål), Agalliana ensigera Oman and Bergallia signata (Stål); Hemiptera: Heteroptera: Harmostes (Harmostes) prolixus Stål and Atrachelus (Atrachelus) cinereus (Fabricius); Coleoptera: Curculionidae: Hypurus bertrandi (Perris), Naupactus leucoloma Boheman, Otiorhynchus rugosostriatus (Goeze) and Sitona discoideus Gyllenhal and Hymenoptera: Xylocopa (Neoxylocopa) augusti Lepeletier and Pseudagapostemon (Neagapostemon) singularis Jörgensen. Species cited for the first time from Río Negro: Hemiptera: Auchenorrhyncha: Amplicephalus dubius Linnavuori, Amplicephalus marginellanus Linnavuori, Circulifer tenellus (Baker) and Xerophloea viridis (Fabricius); Hemiptera: Heteroptera: Tupiocoris cucurbitaceus (Spinola), Atrachelus (Atrachelus) cinereus (Fabricius), Dichelops furcatus (Fabricius) and Harmostes (Harmostes) prolixus Stål; Coleptera: Curculionidae: Naupactus xanthographus (Germar) and Hymenoptera: Diadasia pereyrae (Holmberg) and Dialictus autranellus (Vachal). [ABSTRACT FROM AUTHOR]

Anti-Bacterial Agents pharmacology, Geography, Medical, History, 21st Century, Humans, Microbial Sensitivity Tests, Multilocus Sequence Typing, Netherlands epidemiology, Phylogeny, Pilot Projects, Pseudomonas Infections history, Pseudomonas aeruginosa classification, Pseudomonas aeruginosa drug effects, Pseudomonas aeruginosa isolation purification, Public Health Surveillance, beta-Lactam Resistance, beta-Lactamases biosynthesis, Disease Outbreaks, Pseudomonas Infections epidemiology, Pseudomonas Infections microbiology, Pseudomonas aeruginosa genetics, and beta-Lactamases genetics

Verona Integron-encoded Metallo-beta-lactamase (VIM) is the most frequently-encountered carbapenemase in the healthcare-related pathogen Pseudomonas aeruginosa. In the Netherlands, a low-endemic country for antibiotic-resistant bacteria, no national surveillance data on the prevalence of carbapenemase-producing P. aeruginosa (CPPA) was available. Therefore, in 2016, a national surveillance pilot study was initiated to investigate the occurrence, molecular epidemiology, genetic characterization, and resistomes of CPPA among P. aeruginosa isolates submitted by medical microbiology laboratories (MMLs) throughout the country. From 1221 isolates included in the study, 124 (10%) produced carbapenemase (CIM-positive); of these, the majority (95, 77%) were positive for the bla VIM gene using PCR. Sequencing was performed on 112 CIM-positive and 56 CIM-negative isolates (n = 168), and genetic clustering revealed that 75/168 (45%) isolates were highly similar. This genetic cluster, designated Group 1, comprised isolates that belonged to high-risk sequence type ST111/serotype O12, had similar resistomes, and all but two carried the bla VIM-2 allele on an identical class 1 integron. Additionally, Group 1 isolates originated from around the country (i.e. seven provinces) and from multiple MMLs. In conclusion, the Netherlands had experienced a nationwide, inter-institutional, clonal outbreak of VIM-2-producing P. aeruginosa for at least three years, which this pilot study was crucial in identifying. A structured, national surveillance program is strongly advised to monitor the spread of Group 1 CPPA, to identify emerging clones/carbapenemase genes, and to detect transmission in and especially between hospitals in order to control current and future outbreaks.
(© 2021. The Author(s).)

STINKBUGS, OLIVE fly, OLIVE, FRUIT development, BROWN marmorated stink bug, INTRODUCED organisms, and LEAFHOPPERS

Olives, Olea europaea L. (Oleaceae), are an emerging commercial crop in Florida; however, potential arthropod threats during olive tree establishment and fruit development remain uncharacterized. Two potential pests that may threaten olive fruit production directly are native and invasive pentatomid stink bugs, which are important pest species of many crops in the southeast, and the invasive olive fruit fly, Bactrocera oleae (Gmelin) (Diptera: Tephritidae),which is not known to be established in Florida. Monitoring for stink bugs during fruit maturation was done using dual funnel tube traps baited with stink bug lures. Yellow sticky card traps baited with food and pheromone lures were used to monitor for the olive fruit fly. Both trap types were placed in tree canopies in 4 North Central Florida olive groves during the anticipated fruit development period for 2 growing seasons. Whereas neither of the invasive species targeted (Halyomorpha halys Stål [Hemiptera: Pentatomidae] or B. oleae) were detected, several other potential pests were identified including brown stink bugs (Euschistus spp.; Hemiptera: Pentatomidae), glassy winged sharpshooters, Homalodisca vitripennis Germar (Hemiptera: Cicadellidae), and grasshoppers. No fruit damage attributable to arthropod pests was detected although fruit production was very low with limited samples. These results contribute to awareness of potential pests that may jeopardize olive fruit production and aid in the future studies to develop effective monitoring activities for Florida growers. [ABSTRACT FROM AUTHOR]

HEMIPTERA, HOST plants, RICE diseases & pests, ECHINOCHLOA, and REPRODUCTION

Obtaining eggs of Oebalus insularis Stal., for the multiplication of Telenomus podisi Ashmead depends on the quality of the food provided by diverse host plants. Therefore, the biological and reproductive performance of O. insularis on Oryza sativa L. and Echinochloa colona (L.) was determined at 28±2°C, 80 ± 5% of relative humidity and 12 hours photophase. The duration of the period of nymph eclosion until the emergence of the adult of O. insularis varied between 20,9 and 21,2 days, for O. sativa and E. colona, respectively. The longevity of the female and male of O. insularis was statistically similar on both host plants. The female longevity was higher than that shown by the male, varying between 15 and 12 days, respectively. The O. insularis female fed with E. colona presented a high number of eggs per batch, total number of eggs per female and the eclosion rate of nymphs was higher. The biological and reproductive parameters of this insect confirmed their adaptation to the alternative host E. colona, optimizing the production of eggs subjected to T. podisi parasitism. [ABSTRACT FROM AUTHOR]

LANTANA camara, ORNAMENTAL plants, BIOSAFETY, QUARANTINE, ECOSYSTEM dynamics, NATURALIZATION, and WEEDS

The article presents a research focused on analyzing the status of ornamental plant lantana camara that grows in the urban areas and also discusses its implication on the biosafety and quarantine of the region. Various topics discussed in the research includes natural enemies of lantana, natural ecosystem of Botswana and impact of naturalization on weed removal.

The work's aims were to identify both harmful and helpful insect species for safflower crop and to study their distribution along time in relation to plant phenological state. The insect species identified as harmful were: Uroleucon jaceae L., Capitophorus elaeagni, Frankliniella occidentalis P., Dichelops furcatus (F.), Athaumasthus haematicus (Stál), Nezara viridula (L.), Nysius simulans Stál, Edessa meditabunda (F.), Piezodorus guildinii (W.), Helicoverpa zea B., Epicauta adspersa K., Spodoptera frugiperda (J. E. Smith), Chauliognathus scriptus (Germ.), Pantomorus auripes H. and Rachiplusia nu (G.). Regarding aphids, their highest density was observed at the beginning of November, when crop was in the state of branching, with invasion mainly of the upper third of plants: leaves, young shoots and flower heads. Among all harmful true bugs found in the crop, red bug - Athaumastus haematicus (Stál)- comprised the highest proportion and was detected before aphids attacks, when stem elongation of plants was just beginning. As for beneficial species, the six insects detected in sufflower crop were Hippodamia convergens G., Eriopis connexa G., Harmonia axyridis (P.), Nabis sp., Ophion sp. and Apis melifera L., besides various spider species. The coccinellids- Hippodamia convergens; Eriopis connexa and Harmonia axydiris performed as the main natural control agents at crop. KE [ABSTRACT FROM AUTHOR]

MIRIDAE, EGGS as food, PREDATORY animals, TEMPERATURE effect, and MEDITERRANEAN flour moth

Three Neotropical predators Campyloneuropsis infumatus (Carvalho), Engytatus varians (Distant) and Macrolophus basicornis (Stål) (Hemiptera: Miridae) are considered in Brazil as potential biological control agents of Tuta absoluta Meyrick (Lepidoptera: Gelechiidae) and other tomato pests. This study evaluated the effect of five constant temperatures (16, 20, 24, 28 and 32°C, all ±1°C) on the reproduction, population growth and longevity of these predatory mirids. Adults freshly emerged from nymphs reared at each temperature, were separated in couples and kept in 1.7 l glass pots with tobacco plant seedlings (Nicotiana tabacum L., cv. TNN) as oviposition substrate and ad libitum Ephestia kuehniella (Zeller) (Lepidoptera: Pyralidae) eggs as food. The shortest pre-oviposition and the longest oviposition periods were observed at 24°C and 28°C in all three mirid species. At 24°C all three species showed the highest daily and total fecundities. The population growth parameters represented by the intrinsic rate of increase (rm) and the finite rate of increase (λ) were highest at 24°C and 28°C, and the net reproductive rate (R0) was highest at 24°C for all three species. Longevities of both males and females were longest at 24°C and 28°C in all three mirids. The size of tibia and adult weight in the three species were greatest at 20°C and 28°C, respectively. Differences in values for all above variables were small and often statistically non-significant for the three mirid species at the same temperature. Also, not a single significant difference was found for any of the growth parameters at each of the temperatures, including rm. The results indicate that temperatures in the range from 24-28°C are best for reproduction and population growth of C. infumatus, E. varians and M. basicornis. The factitious prey E. kuehniella is an excellent food source and tobacco plants provide a good rearing substrate for these mirids. The obtained results may assist in developing a mass rearing method for C. infumatus, E. varians and M. basicornis, in determining optimal timing and frequency of mirid releases in the crop, and in determining whether they are active at the temperature spectrum observed during tomato production in the field or greenhouse. [ABSTRACT FROM AUTHOR]

HEMIPTERA and STINKBUGS

The Neotropical genus Lincus Stål, 1867 is frequently associated with the transmission of diseases to palms and coconut trees (Elaeis guineensis and Cocos nucifera) in commercial plantations in South America. Here we update the geographical distribution of 15 species of Lincus collected in E. guineensis and C. nucifera in the Neotropics. The geographical range of five species is expanded with new countries recorded for L. malevolus and L. styliger, and detailed geographic information is given for the first time for L. lobuliger and L. securiger. [ABSTRACT FROM AUTHOR]

LYASES, PLANTHOPPERS, RICE, GENES, and XANTHOMONAS

A pre-infestation of the white-backed planthopper (WBPH), Sogatella furcifera Horváth, conferred resistance to bacterial blight caused by Xanthomonas oryzae pv. oryzae ( Xoo) in rice ( Oryza sativa L.) under both laboratory and field conditions. The infestation of another planthopper species, the brown planthopper (BPH) Nilaparvata lugens Stål, did not significantly reduce the incidence of bacterial blight symptoms. A large-scale screening using a rice DNA microarray and quantitative RT-PCR revealed that WBPH infestation caused the upregulation of more defence-related genes than did BPH infestation. Hydroperoxide lyase 2 ( OsHPL2), an enzyme for producing C6 volatiles, was upregulated by WBPH infestation, but not by BPH infestation. One C6 volatile, ( E)-2-hexenal, accumulated in rice after WBPH infestation, but not after BPH infestation. A direct application of ( E)-2-hexenal to a liquid culture of Xoo inhibited the growth of the bacterium. Furthermore, a vapour treatment of rice plants with ( E)-2-hexenal induced resistance to bacterial blight. OsHPL2-overexpressing transgenic rice plants exhibited increased resistance to bacterial blight. Based on these data, we conclude that OsHPL2 and its derived ( E)-2-hexenal play some role in WBPH-induced resistance in rice. [ABSTRACT FROM AUTHOR]

STINKBUGS, BROWN marmorated stink bug, CYTOCHROME oxidase, GENETIC variation, and HEMIPTERA

The arrival, establishment and pest status of Halyomorpha halys in Europe and non-native countries in Asia have been well-documented, with thorough characterisation of the genetic diversity and occurrence of cytochrome oxidase I (COI) haplotypes in Switzerland, France, Hungary, Italy and Greece. However, a number of gaps exist in terms of the characterisation of the haplotype diversity and occurrence of H. halys along the invasion front that covers eastern Europe, western and central Asia. To contribute towards filling this gap, the COI haplotype diversity and distribution were investigated for H. halys collected in Serbia, Ukraine, Russia, Georgia and Kazakhstan. A total of 646 specimens were analysed and five haplotypes were found (H1, H3, H8, H33 and H80). Haplotype H1 was present in all five countries investigated and was the only haplotype detected amongst > 500 specimens collected from Ukraine, Russia and Georgia. H1 (82%) was the dominant haplotype found in Kazakhstan, alongside H3 (18%). In contrast to the low or no diversity observed in these four countries, Serbia had higher haplotype diversity and was represented by five haplotypes. Although H3 was dominant (47%) in Serbia, H1 was also prevalent (40%); the remaining haplotypes (H8, H33 and H80) were minor contributors (1-11%) to the haplotype composition. The results are discussed in context with other known populations in neighbouring countries and patterns of haplotype diversity indicate the movement of successful invasive populations in Europe to generate secondary invasions along the eastern front of the invasion in Eurasia. Possible scenarios regarding the spread of particular haplotypes in these regions are discussed, along with suggestions for future research to fill existing gaps. [ABSTRACT FROM AUTHOR]

PLANT chemical defenses, VIGNA, and COREIDAE

The effects of secondary metabolites in different Vigna species on the development of Clavigralla tomentosicollis were investigated in an artificial seed system using different fractions of crude pod extracts, while the orientation response of this pod-bug to volatile extracts was studied using a dual-choice olfactometer. Feeding on the neutral fraction extracts, in contrast to the basic and acidic fractions, resulted in significantly higher mortalities, longer total developmental time, and lower growth index of the insects in comparison with controls. All volatile extracts elicited an avoidance reaction by C. tomentosicollis, except the volatile from the susceptible genotype IT84S-2246 which generally attracted as many insects as controls. Extracts from wild Vigna species showed higher activity than those from their cultivated relatives. The present study which has established that most secondary metabolites in cowpea pods were localized in the neutral fraction of the crude extract, could facilitate experiments on the separation and characterization of the toxic factors involved. [ABSTRACT FROM AUTHOR]

STINKBUGS, BROWN marmorated stink bug, HYMENOPTERA, OVIPARITY, BIOLOGICAL pest control agents, GREENBUG, and HOSTS of parasitoids

• We tested the physiological host ranges of an introduced biocontrol agent (T. basalis) and native parasitoid (T. oenone). • T. basalis attacks and develops in all nine pentatomid taxa we tested. • The native T. oenone attacks and develops in seven out of eight pentatomid species we tested. • Parasitism efficiencies were high for all treatments (>60%). Retrospective host range testing is essential for understanding the physiological host range of introduced biological control agents (BCAs) and updating forecasts of non-target risks. It is especially important to conduct this work if there was no host range testing prior to release of the agent. Trissolcus basalis Wollaston was released in New Zealand in 1949 against green vegetable bug (Nezara viridula [L.]), but host range testing was never undertaken, and subsequent work in the 1960s was only of a qualitative nature and remains incomplete. The host-parasitoid complex between New Zealand pentatomids, T. basalis , and the native pentatomid parasitoid Trissolcus oenone Dodd, is therefore poorly understood. We conducted no-choice oviposition tests between the two resident Trissolcus species and all available New Zealand pentatomid species to characterise the physiological (=fundamental) host ranges of these parasitoids. We present the results of the first retrospective host-specificity study on T. basalis in New Zealand. Our results show T. basalis attacks and develops in all nine pentatomid taxa we exposed it to (including the endemic alpine species Hypsithocus hudsonae Bergroth), while T. oenone attacks and develops in seven out of eight pentatomid species we tested it against (and its capacity to attack H. hudsonae remains unknown). Parasitism efficiencies for all treatments exceeded 60%, while development times were similar for both parasitoids regardless of host. We discuss the importance of physiological host range testing for understanding potential non-target effects. Trissolcus japonicus Ashmead (Hymenoptera: Scelionidae) was recently approved for release in New Zealand against brown marmorated stink bug Halyomorpha halys Stål (Hemiptera: Pentatomidae), subject to its potential establishment, and we examine our results in the context of potential competition between introduced parasitoids for non-target species. [ABSTRACT FROM AUTHOR]

BIODIVERSITY, VERTEBRATES, HABITATS, GLACIATION, and PLIOCENE Epoch

It is now rare to find a semi-aquatic organism group with which to vigorously test whether their diversification model and distribution pattern are closely related to the Cenozoic temperature variation. This hypothesis is explored for water striders of the genera Aquarius Schellenberg, Gerris Fabricius and Limnoporus Stål, which comprise a monophyletic clade with primarily Holarctic distribution. We sample almost 90% of the currently recognized Aquarius, Gerris and Limnoporus species. Five DNA fragments from 62 species are used to reconstruct a phylogram. Divergence time is estimated using Bayesian relaxed-clock method and three fossil calibrations. We investigate diversification dynamics, biogeography and ancestral state reconstruction by using maximum-likelihood, Bayesian and parsimony approaches. Our results showed that the crown of the three genera originated and underwent an initial diversification in Asia at 72 Ma (HPD: 59-86 Ma) in the Late Cretaceous, subsequently expanding into other regions via dispersal. The Bering Land Bridge was the major migration route between Eurasia and North America but was interrupted before the early Oligocene (34 Ma). Ancestors most likely used lentic habitats, and a minimum of two independent shifts to lotic habitats occurred in the initial diversification. Cenozoic temperature variation regulated the evolutionary history of Holarctic water striders of the genera Aquarius, Gerris and Limnoporus. Temperature warming during Stage I (52-66 Ma) was associated with the disappearance of shallow lentic habitats; this phenomenon forced certain lentic lineages to colonize new lotic habitats and promoted the diversification of lineages. Temperature cooling during Stage II (after 34 Ma) was associated with the fragmentation of water habitats of the 'mixed-mesophytic' belt, resulting in the extinction of historical taxa and influencing close lineages that shaped the present disjunct Eurasian-North American distribution. [ABSTRACT FROM AUTHOR]

HEMIPTERA, ORYZA, PARASITOIDS, RICE, PLANTING, STINKBUGS, and PARASITES

The rice stem bug, Tibraca limbativentris Stal. (Hemiptera: Pentatomidae) is one of the most important pests of rice crops, especially irrigated crops. Plant defence strategies against these bugs may involve the emission of chemical compounds, which are released following herbivore attacks, directly or indirectly harming pest performance. The aim of this study was to evaluate the influence of constitutive and herbivory-induced volatiles from rice plants (Oryza sativa L.) on the behavioural responses of T. limbativentris adults and egg parasitoids Trissolcus basalis (Wollaston) and Telenomus podisi (Ashmead) (Hymenoptera, Platygastridae). Plant volatiles were collected from undamaged plants of the rice cultivar IRGA 424 and from plants that suffered herbivory by five males or five females of T. limbativentris. Air-entrainment extracts were analysed by GC–flame ionization detector and GC–MS, and insect responses evaluated in a ‘Y’ olfactometer. T. limbativentris feeding damaged on rice plants induced the release of 16 volatiles compounds in a higher amounts compared to undamaged plants The main compounds induced were (E)-2-hexenal, (E)-2-octen-1-ol, methyl salicylate and α-muurolene. Female bugs were significantly attracted to air-entrainment extracts containing volatiles from undamaged plants compared with air-entrainment extracts containing volatiles emitted from plants damaged by T. limbativentris, whereas males showed no preference. Telenomus podisi females were significantly attracted to volatiles from air-entrainment extracts of plants damaged by females, whereas T. basalis showed no preference. These results suggest that rice plants may be emitting defence compounds, which could be avoided by T. limbativentris females and also acted indirectly by attracting natural enemies. [ABSTRACT FROM AUTHOR]

BIOLOGICAL weed control, BIOLOGICAL pest control agents, CHRYSOMELIDAE, BEETLES, HYMENOPTERA, and EUCALYPTUS

The solitary larval endoparasitoid Eadya daenerys Ridenbaugh (Hymenoptera: Braconidae) is a proposed biocontrol agent of Paropsis charybdis Stål (Coleoptera: Chrysomelidae, Chrysomelinae), a pest of eucalypts in New Zealand. Eadya daenerys oviposition behaviour was examined in two assay types during host range testing, with the aim of improving ecological host range prediction. No‐choice sequential and two‐choice behavioural observations were undertaken against nine closely related species of New Zealand non‐target beetle larvae, including a native beetle, introduced weed biocontrol agents, and invasive paropsine beetles. No behavioural measure was significantly different between no‐choice and two‐choice tests. In sequential no‐choice assays the order of first presentation (target–non‐target) had no significant effect on the median number of attacks or the attack rate while on the plant. Beetle species was the most important factor. Parasitoids expressed significantly lower on‐plant attack rates against non‐targets compared to target P. charybdis larvae. The median number of attacks was always higher towards target larvae than towards non‐target larvae, except for the phylogenetically closest related non‐target Trachymela sloanei (Blackburn) (Coleoptera: Chrysomelidae, Chrysomelinae). Most non‐target larvae were disregarded upon contact, which suggests that the infrequent attack behaviour observed by two individual E. daenerys against Allocharis nr. tarsalis larvae in two‐choice tests and the frass of Chrysolina abchasica (Weise) was probably abnormal host selection behaviour. Results indicate that E. daenerys is unlikely to attack non‐target species apart from Eucalyptus‐feeding invasive paropsines (Chrysomelinae). Non‐lethal negative impacts upon less preferred non‐target larvae are possible if E. daenerys does attack them in the field; however, this is likely to be rare. [ABSTRACT FROM AUTHOR]

PLANTING and RICE

Monthly plantings of the rice variety Bouake 189 were made under lowland irrigated conditions, to obtain information on the phenological and seasonal occurrence of pests and diseases on the West African Rice Development Association (WARDA) research farm near Bouake, Cote d'Ivoire. Regular sampling of insect pests and observations on rice yellow mottle virus (RYMV) disease infection throughout the year provided information on the occurrence of RYMV and potential insect vectors. RYMV incidence and grain yields varied depending on planting date, and for a given planting date, varied from one year to another. There was no evidence that RYMV incidence increases in successive seasons under continuous cropping. There was no significant correlation between RYMV incidence and either rainfall or wind speed. Leaf feeding damage by the beetle vector of RYMV, Trichispa sericea Guerin-Meneville (Coleoptera: Chrysomelidae), and percentage RYMV infected plants were severe in the July and August plantings in 1993, but whereas T. sericea was not observed thereafter, RYMV spread continued. The white leafhoppers Cofana spectra (Distant) and C. unimaculata (Signoret) (Hemiptera: Cicadellidae), the green leafhoppers Nephotettix spp. (Hemiptera: Cicadellidae), the spittle bug Locris rubra F. (Hemiptera: Cercopidae), the diopsids Diopsis longicornis Macquart and D. apicalis Dalman (Diptera: Diopsidae), and the grasshopper Oxy hyla Stal (Orthoptera: Acridadae) were the most abundant of the insect pests and had distinct population peaks within a year. However, population abundances were not correlated with RYMV incidence. The variability of RYMV in time and space and the potential role of weeds as alternative hosts for RYMV are discussed. [ABSTRACT FROM AUTHOR]

BROWN marmorated stink bug, AGRICULTURAL ecology, POPULATION dynamics, PHYSIOLOGICAL control systems, and PARASITISM

Understanding native natural enemy impacts on the invasive brown marmorated stink bug, Halyomorpha halys (Stål), offers insight into the population dynamics of this invasive pest and the potential for biological control. This two-year study offers a broad-scale assessment of mortality factors affecting sentinel and naturally laid H. halys eggs in agroecosystems in the pest’s invaded range in eastern North America. Predation and parasitism rates varied among states and crops, but overall were low. Average maximum levels of biological control were estimated to be about 19% and 20% in 2013 and 2014, respectively. Of the eggs destroyed by natural enemies, chewing predation was the most prevalent. Parasitism by native parasitoids was very low, with adult parasitoids emerging from <1% of eggs averaged across crops, locations, and years; an additional 2.8% of eggs contained partially developed parasitoids. Lower percentages of sentinel H. halys hatched in organically versus conventionally managed crops, and in most cases had higher percentages of predation. Parasitism of sentinel and naturally laid eggs of the native stink bugs Euschistus servus (Say) and Chinavia hilare (Say) averaged 49.3% (±8.6 SE) and 0.6% (±0.3), respectively, across locations and years. Telenomus podisi (Ashmead) was the most common parasitoid parasitizing E. servus and H. halys eggs, but rarely did >1 individual parasitoid emerge from a H. halys egg mass. Parasitism of H. halys eggs by a complex of parasitoids is an important population regulation factor in its native Asian range, but this study found that parasitoids native to eastern US agroecosystems do not provide that service in this introduced region. The greatest potential for biological control of H. halys may be via classical biological control by the Asian parasitoid Trissolcus japonicus (Ashmead), which has recently been detected in both the eastern and western US. [ABSTRACT FROM AUTHOR]

RHODNIUS, CONENOSES, CLASSIFICATION of insects, and SPECIES diversity

Tribe Rhodniini includes Rhodnius Stål and Psammolestes Bergroth. Enzymatic and molecular evidence suggest the tribe is monophyletic. Most species are wild, living in palms and bird nests. Traditionally both genera were considered related; nevertheless, molecular studies don't support the Rhodnius monophyly. The goal was to phylogenetically analyze morphometric variation in wing architecture in support of Rhodniini taxonomy and systematics. We photographed 524 wings of five representatives of Rhodniini: Psammolestes arthuri (Pinto) (n = 89), Rhodnius pictipes Stål (n = 21), R. robustus Larrousse (n = 24), R. prolixus Stål (n = 16), and R. neivai Lent (n = 22). As outgroups we studied four representatives of Triatomini: Eratyrus mucronatus Stål (n = 15), Panstrongylus rufotuberculatus (Champion) (n = 45), P. geniculatus (Latreille) (n = 183), and Triatoma maculata (Erichson) (n = 109). Landmark coordinate (x, y) configurations were registered and aligned by Generalized Procrustes Analysis. Covariance Analyses were implemented with proportions of re-classified groups and MANOVA. Then, wing shape variables (confidence intervals from relative warps) and centroid size were cladistically analysed. Statistical analyses of variance found not significant differences in wing isometric size (Kruskal-Wallis) among P. arthuri-R. neivai-R. pictipes; R. robustus-R. prolixus-T. maculata and between P. rufotuberculatus-P. geniculatus. The a posteriori re-classification was perfect in E. mucrunatus 100% and R. pictipes, followed by T. maculata 96%, R. neivai 95%, P arthuri 93.2%; R. prolixus 87.5%, P. geniculatus 87.4%, P. rufotuberculatus 84.4%, and R. robustus 76%. Cladistic analyses under parsimony selected two most parsimonious trees (L=4.461 IC=0.973 and IR=0.979), where the strict consensus showed a monophyletic group with Panstrongylus (rufotuberculatus + geniculatus) and Triatoma + Rhodniini (Rhodinus + Psammolestes), but internally it shows the paraphyly of Rhodnius regarding Psammolestes. The congruence between these results and previous molecular analyses in Rhodniini, reveal the phylogenetic information of our morphometric characters as support to systematic studies, allowing the combination of geometric morphometrics and phylogenetic methods for the first time in this group. [ABSTRACT FROM AUTHOR]