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Book
8 p. : digital, PDF file.
<i>Escherichia coli</i> plays an important role as a member of the gut microbiota; however, pathogenic strains also exist, including various diarrheagenic <i>E. coli</i> pathotypes and extraintestinal pathogenic <i>E. coli</i> that cause illness outside of the GI-tract. <i>E. coli</i> have traditionally been serotyped using antisera against the ca. 186 O-antigens and 53 H-flagellar antigens. Phenotypic methods, including bacteriophage typing and O- and H- serotyping for differentiating and characterizing <i>E. coli</i> have been used for many years; however, these methods are generally time consuming and not always accurate. Advances in next generation sequencing technologies have made it possible to develop genetic-based subtyping and molecular serotyping methods for <i>E. coli</i>, which are more discriminatory compared to phenotypic typing methods. Furthermore, whole genome sequencing (WGS) of <i>E. coli</i> is replacing established subtyping methods such as pulsedfield gel electrophoresis, providing a major advancement in the ability to investigate food-borne disease outbreaks and for trace-back to sources. Furthermore, a variety of sequence analysis tools and bioinformatic pipelines are being developed to analyze the vast amount of data generated by WGS and to obtain specific information such as O- and H-group determination and the presence of virulence genes and other genetic markers.
Video
1 online resource (1 streaming video file (24 min.) : color, sound).
  • Contents: Uniformitarianism, Lamarckism and Darwin's theory
  • Mendel’s work and the science of genetics
  • The modern synthesis: a mechanistic basis for variation and heredity
  • Molecular biology: the age of biological information
  • Rethinking gradual progressive evolution
  • Evolutionary biology in the age of genomics
  • Eugenics, the dark chapter of evolutionary biology
  • Group-level selection and evolution of morality.
Video
1 online resource (1 streaming video file (36 min.) : color, sound).
  • Contents: Cardiac aging in human and animal models
  • Molecular mechanisms for cardiac aging
  • Recent advances on potential interventions for cardiac aging
  • Future perspectives of cardiac aging interventions.
Video
1 online resource (1 streaming video file (16 min.) : color, sound).
  • Contents: Niche construction: definitions and examples
  • The endomembrane system
  • Advent of cholesterol depended on oxygen
  • Ecosystems and the process of death
  • Internal niche construction
  • The swim-bladder, the lung and PTHrP
  • Niche construction and epigenetics interactions
  • Gaia hypothesis.
Book
10 p. : digital, PDF file.
Similar to ruminants, swine have been shown to be a reservoir for Shiga toxin-producing Escherichia coli (STEC), and pork products have been linked with outbreaks associated with STEC O157 and O111:H-. STEC strains, isolated in a previous study from fecal samples of late-finisher pigs, belonged to a total of 56 serotypes, including O15:H27, O91:H14, and other serogroups previously associated with human illness. The isolates were tested by polymerase chain reaction (PCR) and a high-throughput real-time PCR system to determine the Shiga toxin (Stx) subtype and virulence-associated and putative virulence-associated genes they carried. Select STEC strains were further analyzed using a Minimal Signature E. coli Array Strip. As expected, stx<sub>2e</sub> (81%) was the most common Stx variant, followed by stx<sub>1a</sub> (14%), stx<sub>2d</sub> (3%), and stx<sub>1c</sub> (1%). The STEC serogroups that carried stx<sub>2d</sub> were O15:H27, O159:H16 and O159:H-. Similar to stx<sub>2a</sub> and stx<sub>2c</sub>, the stx<sub>2d</sub> variant is associated with development of hemorrhagic colitis and hemolytic uremic syndrome, and reports on the presence of this variant in STEC strains isolated from swine are lacking. Moreover, the genes encoding heat stable toxin (estIa) and enteroaggregative E. coli heat stable enterotoxin-1 (astA) were commonly found in 50 and 44% of isolates, respectively. The hemolysin genes, hlyA and ehxA, were both detected in 7% of the swine STEC strains. Although the eae gene was not found, other genes involved in host cell adhesion, including lpfA<sub>O113</sub> and paa were detected in more than 50% of swine STEC strains, and a number of strains also carried iha, lpfA<sub>O26</sub>, lpfA<sub>O157</sub>, fedA, orfA, and orfB. Furthermore, the present work provides new insights on the distribution of virulence factors among swine STEC strains and shows that swine may carry Stx1a-, Stx2e-, or Stx2d-producing E. coli with virulence gene profiles associated with human infections.
Video
1 online resource (1 streaming video file (52 min.) : color, sound).
  • Contents: Application of new diagnostic techniques in clinical medicine, mainly in molecular cytogenetics of neoplasia
  • Relevant chromosomal abnormalities that impact the diagnosis and prognosis of patients with acute lymphoblastic leukemia and acute myeloblastic leukemia.
Book
25 p. : digital, PDF file.
Microbial-mat communities in the effluent channels of Octopus and Mushroom Springs within the Lower Geyser Basin at Yellowstone National Park have been studied for nearly 50 years. The emphasis has mostly focused on the chlorophototrophic bacterial organisms of the phyla <i>Cyanobacteria</i> and <i>Chloroflexi</i>. In contrast, the diversity and metabolic functions of the heterotrophic community in the microoxic/anoxic region of the mat are not well understood. In this study we analyzed the orange-colored undermat of the microbial community of Mushroom Spring using metagenomic and rRNA-amplicon (iTag) analyses. Our analyses disclosed a highly diverse community exhibiting a high degree of unevenness, strongly dominated by a single taxon, the filamentous anoxygenic phototroph, <i>Roseiflexus</i> spp. The second most abundant organisms belonged to the <i>Thermotogae</i>, which have been hypothesized to be a major source of H-2 from fermentation that could enable photomixotrophic metabolism by <i>Chloroflexus</i> and <i>Roseiflexus</i> spp. Other abundant organisms include two members of the <i>Armatimonadetes</i> (OP10); <i>Thermocrinis</i> sp.; and phototrophic and heterotrophic members of the <i>Chloroflexi</i>. Further, an <i>Atribacteria</i> (OP9/JS1) member; a sulfate-reducing <i>Therrnodesulfovibrio</i> sp.; a <i>Planctomycetes</i> member; a member of the EM3 group tentatively affiliated with the <i>Thermotogae</i>, as well as a putative member of the <i>Arrninicenantes</i> (OP8) represented ≥ 1% of the reads. <i>Archaea</i> were not abundant in the iTag analysis, and no metagenomic bin representing an archaeon was identified. A high microdiversity of 16S rRNA gene sequences was identified for the dominant taxon, <i>Roseiflexus</i> spp. Previous studies demonstrated that highly similar <i>Synechococcus</i> variants in the upper layer of the mats represent ecological species populations with specific ecological adaptations. In conclusion, this study suggests that similar putative ecotypes specifically adapted to different niches occur within the undermat community, particularly for <i>Roseiflexus</i> spp.
Video
1 online resource (1 streaming video file (11 min.) : color, sound).
  • Contents: History of descriptive physiology
  • Systems biology
  • The biota expansion
  • Downward causation vs. cell-cell signaling
  • Holism vs. Reductionism: philosophical views about nature
  • Molecular changes mediating evolution
  • Cell communication as mechanism of novelty
  • From phylogeny-ontogeny to homeostasis & repair
  • Homeostasis as the mechanism for evolution
  • Explicate/Implicate order.
Video
1 online resource (1 streaming video file (15 min.) : color, sound).
  • Contents: Tissue interactions during morphogenesis
  • Automaturation due to mechanotransduction
  • PTHrP is stretch-regulated
  • Dissociation of endoderm from mesoderm and fibrosis
  • Co-culture of endoderm and mesoderm lead to homeostasis
  • Neutral Lipid Trafficking.
Video
1 online resource (1 streaming video file (33 min.) : color, sound).
  • Contents: Evolution of endothermy
  • PTHrP, Glucocorticoid and β-Adrenergic Receptor gene duplications
  • Hypoxia integrates respiratory and endocrine systems
  • Selection pressure for integrated physiology: lung, kidney, heart
  • Ontogeny-phylogeny of lung cell evolution
  • Swim bladder-lung functional homology
  • PTHrP is stretch-regulated
  • Chemiosmosis-homeostasis and the origins of life
  • Vertical integration of the effect of cholesterol on homeostasis
  • Cell-cell interactions and adaptation to oxygen
  • Endothermy as exaptation of oxygen adaptation
  • Physiologic homology based on cell-cell interactions.
Video
1 online resource (1 streaming video file (5 min.) : color, sound).
  • Contents: Basis for predictive medicine
  • Utility in rational drug design & improving medical practices
  • Bioethics based on physiologic principles
  • A universal database for the natural sciences
  • The ideal human living environment.
Video
1 online resource (1 streaming video file (41 min.) : color, sound).
  • Contents: Overview of lens anatomy and function
  • Lens macrostructure/microanatomy and lens transparency
  • Molecular mechanisms of the vertebrate lens development
  • Factors contributing to normal lens physiology
  • The role of proteins integral to lenticular transparency
  • Genetics of lens abnormalities
  • The importance of precision diagnoses in congenital lens abnormality cases
  • Next generation sequencing technologies in the diagnosis of lens abnormalities.
Video
1 online resource (1 streaming video file (26 min.) : color, sound).
  • Contents: The origin of life
  • Major transitions and size increase
  • Formation of cells
  • Molecules in the cellular environment
  • Complex cells
  • Conflict mediation
  • Multi level selection
  • Multicellularity
  • Origin of societies.
Book
1 online resource ()
  • Front Cover; Molecular Basis of Nutrition and Aging; Copyright Page; Contents; List of Contributors; Introduction to the Molecular Basis of Nutrition and Aging; Series Preface; Acknowledgments; I. Introductory Aspects on Aging and Nutrition; 1 Molecular and Cellular Basis of Aging; Introduction; Biological Principles of Aging; Occurrence, Accumulation, and Consequences of Molecular Damage; Homeodynamics and the Homeodynamic Space; Nutrition and Food for Aging Interventions; Nutritional Hormetins; Conclusions; Summary Points; References.
  • 2 Unraveling Stochastic Aging Processes in Mouse Liver: Dissecting Biological from Chronological AgeIntroduction; Pathological Parameters are only Partially Associated with Chronological Age; Intraorgan Specific Biological Phenotypes; Tissue-Specific Biological Phenotypes; Gene Expression Profiles Related to Pathological Aging Parameters; Gene Expression Profiles Correlating with Pathological Parameters are Largely Specific to the Pathological Parameters; Future Perspectives; Conclusion; References; 3 Nutrigenomics and Nutrigenetics: The Basis of Molecular Nutrition; Introduction.
  • Nutrigenetics of Omega-3 PUFA in CVDNutrigenetics of Omega-3 PUHA in Cancer; DNA Damage and Nutrients; Cellular Senescence and Nutrients; Epigenetics and Nutrients; Summary Points; References; 4 Diet and Longevity Phenotype; Introduction; Main Text; Nutrient Components and Aging Process; Crucial Role of Fatty Acid Component; Genomic Studies and Importance of Palmitoleic Acid; The Central Position of Energy Sensor Systems; The Involvement of Sympathetic System; Epigenetic Linkage of Aging and Nutrition; Summary; References; 5 Nutrition in the Elderly: General Aspects; Introduction.
  • Malnutrition in the Elderly: Definition and General AspectsCauses of Malnutrition in the Elderly; Malnutrition: Possible Correction With Supplements in the Elderly; Nutrient-Sensing Pathways; Nutrient-Gene Interaction in the Elderly (Nutrigenomic Approach); Conclusions and Perspectives; Summary Points; Acknowledgments; References; 6 Nutrition in the Hospitalized Elderly; Introduction; Pathogenesis of Malnutrition in Hospitalized Elderly; The Interaction Between Aging, Health Status, Hospital Environment, and Nutritional Status; Why Are Hospitalized Older Adults Nutritionally Vulnerable?
  • Age-Related ChangesAnorexia of Aging; Changes in the Body Composition; Taste, Smell, and Mastication Dysfunction; Gastrointestinal Changes; Medical Causes; Use of Multiple Medications; Functional and Psychosocial Factors; Hospital Environment-Related Risks; Clinical Consequences of Malnutrition in Hospital; Malnutrition Screening and Assessment in Hospitalized Elderly; Malnutrition Screening as a Part from Comprehensive Geriatric Assessment (CGA); Comprehensive Nutritional Assessment; Nutritional History; Physical and Clinical Assessment; Anthropometry; The Biochemical Investigations.
Book
Article No. e0153700 : digital, PDF file.
Recently, catalytic peptides were introduced that mimicked protease activities and showed promising selectivity of products even in organic solvents where protease cannot perform well. However, their catalytic efficiency was extremely low compared to natural enzyme counterparts presumably due to the lack of stable tertiary fold. We hypothesized that assembling these peptides along with simple hydrophobic pockets, mimicking enzyme active sites, could enhance the catalytic activity. Here we fused the sequence of catalytic peptide CP4, capable of protease and esterase-like activities, into a short amyloidogenic peptide fragment of Aβ. When the fused CP4-Aβ construct assembled into antiparallel β- sheets and amyloid fibrils, a 4.0-fold increase in the hydrolysis rate of p-nitrophenyl acetate (p-NPA) compared to neat CP4 peptide was observed. Furthermore, the enhanced catalytic activity of CP4-Aβ assembly could be explained both by pre-organization of a catalytically competent Ser-His-acid triad and hydrophobic stabilization of a bound substrate between the triad and p-NPA, indicating that a design strategy for self-assembled peptides is important to accomplish the desired functionality.
Book
1 online resource (vi, 300 p.) : ill. (some col.). Digital: text file; PDF.
  • Forward.- Past.- mTOR inhibitors: a little bit of history.- Present.- The mTOR pathway .- The evolving role of mTOR inhibitors in renal cell carcinoma.- The role of mTOR inhibitors in breast cancer.- The role of mTOR inhibitors in neuroendocrine tumors.- New indications of mTOR inhibitors in rare tumors.- The role of mTOR inhibitors in the treatment of hematological malignancies.- The clinical pharmacology and toxicity profile of rapalogs.- Resistance to mTOR inhibitors.- Rational combinations of mTOR inhibitors as anticancer strategies.- Future.- Predictive biomarkers of response to mTOR inhibitors.- The potential future indication of rapamycin analogs for the treatment of other solid tumors.- mTOR inhibition beyond rapalogs.- mTOR, aging and cancer: the missing link?.- New study design for mTOR inhibitors and other biological agents.- Future directions for the development of mTOR inhibitors.
  • (source: Nielsen Book Data)9782817804910 20160619
This book describes the challenges involved in developing mTOR inhibitors for cancer treatment, starting with an in-depth examination of their molecular mechanism of action, with emphasis on the class side-effects, efficacy and mechanisms of resistance, as well as on promising novel directions for their development, including novel compounds and rational combinations with other anti-neoplastic drugs. Over the last 10 years, inhibitors of mTOR have emerged as a major class of anticancer drugs. Two rapamycin analogs are currently approved for the treatment of renal cell carcinoma, and it is estimated that a variety of other tumor types could benefit from mTOR inhibition, with numerous clinical trials (including pivotal registration trials) already underway. Second-generation small-molecule inhibitors of the pathway have also shown promise in terms of their superior tolerability and efficacy and are undergoing extensive clinical evaluation, with an estimated 30+ compounds currently under evaluation.
(source: Nielsen Book Data)9782817804910 20160619
Video
1 online resource (1 streaming video file (47 min.) : color, sound).
  • Contents: The Origin of Life
  • Physics entrained
  • Multiple theories over the ages
  • Character and origination of organic molecules linking to self organization
  • Necessity of cells
  • Theoretical pathways to the origination of life
  • Exploration of what actually constitutes life
  • Emphasizes the paramount aspects of cognition, communication, and cellular collaboration towards problem solving in evolution.
Video
1 online resource (1 streaming video file (29 min.) : color, sound).
  • Contents: Events leading up to eukaryotic cell formation
  • Evolutionary conflicts
  • Mediation of conflicts
  • Surface-to-volume constraints
  • Endosymbiosis
  • Mechanisms of metabolic homeostasis
  • The major features of eukaryotes.
Book
1 online resource (592 p.) : ill. (some col.).
"The Pacific Symposium on Biocomputing (PSB) 2016 is an international, multidisciplinary conference for the presentation and discussion of current research in the theory and application of computational methods in problems of biological significance. Presentations are rigorously peer reviewed and are published in an archival proceedings volume. PSB 2016 will be held on January 4 – 8, 2016 in Kohala Coast, Hawaii. Tutorials and workshops will be offered prior to the start of the conference. PSB 2016 will bring together top researchers from the US, the Asian Pacific nations, and around the world to exchange research results and address open issues in all aspects of computational biology. It is a forum for the presentation of work in databases, algorithms, interfaces, visualization, modeling, and other computational methods, as applied to biological problems, with emphasis on applications in data-rich areas of molecular biology. The PSB has been designed to be responsive to the need for critical mass in sub-disciplines within biocomputing. For that reason, it is the only meeting whose sessions are defined dynamically each year in response to specific proposals. PSB sessions are organized by leaders of research in biocomputing's "hot topics." In this way, the meeting provides an early forum for serious examination of emerging methods and approaches in this rapidly changing field."-- Provided by publisher.
Book
1 online resource (p. 3108-3116 ) : digital, PDF file.
The processive cycle of the bacterial cellulose synthase (Bcs) includes the addition of a single glucose moiety to the end of a growing cellulose chain followed by the translocation of the nascent chain across the plasma membrane. The mechanism of this translocation and its precise location within the processive cycle are not well understood. In particular, the molecular details of how a polymer (cellulose) whose basic structural unit is a dimer (cellobiose) can be constructed by adding one monomer (glucose) at a time are yet to be elucidated. Here, we have utilized molecular dynamics simulations and free energy calculations to the shed light on these questions. We find that translocation forward by one glucose unit is quite favorable energetically, giving a free energy stabilization of greater than 10 kcal mol-1. In addition, there is only a small barrier to translocation, implying that translocation is not rate limiting within the Bcs processive cycle (given experimental rates for cellulose synthesis in vitro). Perhaps most significantly, our results also indicate that steric constraints at the transmembrane tunnel entrance regulate the dimeric structure of cellulose. Namely, when a glucose molecule is added to the cellulose chain in the same orientation as the acceptor glucose, the terminal glucose freely rotates upon forward motion, thus suggesting a regulatory mechanism for the dimeric structure of cellulose. We characterize both the conserved and non-conserved enzyme-polysaccharide interactions that drive translocation, and find that 20 of the 25 residues that strongly interact with the translocating cellulose chain in the simulations are well conserved, mostly with polar or aromatic side chains. Our results also allow for a dynamical analysis of the role of the so-called 'finger helix' in cellulose translocation that has been observed structurally. Taken together, these findings aid in the elucidation of the translocation steps of the Bcs processive cycle and may be widely relevant to polysaccharide synthesizing or degrading enzymes that couple catalysis with chain translocation.