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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.
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.
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.
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.
1 online resource ()
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
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.
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.
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.
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.
1 online resource (various pagings) : illustrations (some color).
  • Preface
  • 1. Single molecule biophysics
  • 1.1. Introduction
  • 1.2. A brief history of single molecule study
  • 1.3. Single molecule methods
  • 1.4. Single molecule data analysis
  • 1.5. Brief overview of thermodynamics and statistical mechanics
  • 1.6. Future outlook
  • 1.7. Conclusion
  • 2. The total internal reflection fluorescence microscope
  • 2.1. Introduction
  • 2.2. Design considerations
  • 2.3. Microscope frame and associated parts
  • 2.4. Microscope objectives
  • 2.5. Detection path and camera
  • 2.6. Excitation path
  • 2.7. Computer, computer software, and other computing hardware
  • 2.8. Experimental protocol for slide preparation
  • 2.9. Specifications of the TIRF microscope
  • 2.10. Objective-type TIRFM
  • 2.11. Multichannel detection and FRET
  • 2.12. Circular dichroism spectroscopy and microscope enclosure
  • 2.13. Acknowledgments
  • 3. Poisson process approach to statistical mechanics
  • 3.1. Introduction
  • 3.2. Diffusion
  • 3.3. Inter-conversion of the states of molecules
  • 3.4. Photon statistics from lasers
  • 3.5. Statistics of fluorescent centers on a surface
  • 3.6. Location of stars in the sky
  • 3.7. Quantifying the heterogeneity of the locations of cosmic ray sources
  • 3.8. Conclusion
  • 3.9. Acknowledgments
  • Appendices.
  • A. Building a total internal reflection fluorescence microscope: parts, vendors, and costs
  • B. The Poisson process.
This is an overview of single molecule physics, the study of both equilibrium and non-equilibrium properties at the single molecule level. It begins with an introduction to this fascinating science and includes a chapter on how to build the most popular instrument for single molecule biophysics, the total internal reflection fluorescence (TIRF) microscope. It concludes with the Poisson process approach to statistical mechanics, explaining how to relate the process to diverse areas and see how data analysis and error bars are integral parts of science.
(source: Nielsen Book Data)9781681740522 20160704
1 online resource (Article No. e0149337 ) : digital, PDF file.
The multi-layered cell envelope structure of Gram-negative bacteria represents significant physical and chemical barriers for short-tailed phages to inject phage DNA into the host cytoplasm. Here we show that a DNA-injection protein of bacteriophage Sf6, gp12, forms a 465-kDa, decameric assembly <i>in vitro</i>. The electron microscopic structure of the gp12 assembly shows a ~150-Å, mushroom-like architecture consisting of a crown domain and a tube-like domain, which embraces a 25-Å-wide channel that could precisely accommodate dsDNA. The constricted channel suggests that gp12 mediates rapid, uni-directional injection of phage DNA into host cells by providing a molecular conduit for DNA translocation. The assembly exhibits a 10-fold symmetry, which may be a common feature among DNA-injection proteins of P22-like phages and may suggest a symmetry mismatch with respect to the 6-fold symmetric phage tail. As a result, the gp12 monomer is highly flexible in solution, supporting a mechanism for translocation of the protein through the conduit of the phage tail toward the host cell envelope, where it assembles into a DNA-injection device.
1 online resource (1 streaming video file (38 min.) : color, sound).
  • Contents: Trichoplax and the origin of animal complexity
  • Complex patterns usually evolve from more basic patterns
  • Introducing the placozoan Trichoplax
  • Metazoan
  • Definition
  • The Biology of Placozoa
  • Trichoplax adhaerens: Grell clone
  • Comparing Placozoa with other Metazoa
  • Parallel evolution: diploblasts & triploblasts
  • The new Placula hypothesis
  • Hox-like genes.
1 online resource (1 streaming video file (18 min.) : color, sound).
  • Contents: Neutral Lipid Trafficking
  • Bronchopulmonary Dysplasia (BPD) as failed cell-cell interactions
  • PPARγ prevention of BPD
  • de Duve Hypothesis
  • Preventive Medicine
  • PTHrP, Glucocorticoid and βAdrenergic Receptor gene duplications
  • Oxygen effects on cell-cell interactions
  • Phylogeny of lung, kidney, heart
  • Skin-lung homology
  • Lung-kidney homology
  • Lung-brain homology
  • Predictive Model.
1 online resource (1 streaming video file (12 min.) : color, sound).
  • Contents: Ontogeny, the "short history" of the organism
  • Embryogenesis, blastula to gastrula
  • Molecular signaling and morphogenesis
  • Alternating extrinsic/intrinsic selection pressure
  • Swim Bladder-Lung homology
  • Continuum from ontogeny to phylogeny, homeostasis, repair
  • PTHrP necessary for alveolarization
  • PTHrP, Glucocorticoid and βAdrenergic Receptor gene duplications
  • Evolution of Endothermy.
online resource (xi, 395 pages) : illustrations (some color)
  • Time-lapse fluorescence microscopy of budding yeast cells / Arun Kumar and Manuel Mendoza
  • Real-time visualization and quantification of contractile ring proteins in single living cells / Reshma Davidson ... [et al.]
  • Fluorescence recovery after photo-bleaching (FRAP) and fluorescence loss in photo-bleaching (FLIP) experiments to study protein dynamics during budding yeast cell division / Alessio Bolognesi ... [et al.]
  • High-speed super-resolution imaging of live fission yeast cells / Caroline Laplante ... [et al.]
  • Monitoring chitin deposition during septum assembly in budding yeast / Irene Arcones and Cesar Roncero
  • Imaging septum formation by fluorescence microscopy / Juan Carlos Ribas and Juan Carlos G. Cortés
  • Visualization of cytokinesis events in budding yeast by transmission electron microscopy / Franz Meitinger and Gislene Pereira
  • Visualization of fission yeast cells by transmission electron microscopy / Matthias Sipiczki
  • Characterization of septin ultrastructure in budding yeast using electron tomography / Aurélie Bertin and Eva Nogales
  • Isolation of cytokinetic actomyosin rings from Saccharomyces cerevisiae and Schizosaccharomyces pombe / Junqi Huang ... [et al.]
  • Measurements of myosin-II motor activity during cytokinesis in fission yeast / Qing Tang, Luther W. Pollard, and Matthew Lord
  • In vitro biochemical characterization of cytokinesis actin-binding proteins / Dennis Zimmermann ... [et al.]
  • Characterization of cytokinetic F-BARs and other membrane-binding proteins / Nathan A. McDonald and Kathleen L. Gould
  • Analysis of three-dimensional structures of exocyst components / Johannes Lesigang and Gang Dong
  • Analysis of Rho-GTPase activity during budding yeast cytokinesis / Masayuki Onishi and John R. Pringle
  • Detection of phosphorylation status of cytokinetic components / Franz Meitinger, Saravanan Palani, and Gislene Pereira
  • Studying protein-protein interactions in budding yeast using co-immunoprecipitation / Magdalena Foltman and Alberto Sanchez-Diaz
  • Conditional budding yeast mutants with temperature-sensitive and auxin-inducible degrons for screening of suppressor genes / Asli Devrekanli and Masato T. Kanemaki
  • Synchronization of the budding yeast Saccharomyces cerevisiae / Magdalena Foltman, Iago Molist, and Alberto Sanchez-Diaz
  • Fission yeast cell cycle synchronization methods / Marta Tormos-Pérez, Livia Pérez-Hidalgo, and Sergio Moreno
  • Review of fluorescent proteins for use in yeast / Maja Bialecka-Fornal, Tatyana Makushok, and Susanne M. Rafelski
  • Visualization and image analysis of yeast cells / Steve Bagley
  • Toolbox for protein structure prediction / Daniel Barry Roche and Liam James McGuffin
  • From structure to function : a comprehensive compendium of tools to unveil protein domains and understand their role in cytokinesis / Sergio A. Rincon and Anne Paoletti.
Medical Library (Lane)
1 online resource (Page 54 ) : digital, PDF file.
Background: The established methods for detecting prostate cancer (CaP) are based on tests using PSA (blood), PCA3 (urine), and AMACR (tissue) as biomarkers in patient samples. The demonstration of ERG oncoprotein overexpression due to gene fusion in CaP has thus provided ERG as an additional biomarker. Based on this, we hypothesized that ERG protein quantification methods can be of use in the diagnosis of prostate cancer. Methods: Therefore, an antibody-free assay for ERG3 protein detection was developed based on PRISM (high-pressure high-resolution separations with intelligent selection and multiplexing)-SRM (selected reaction monitoring) mass spectrometry. We utilized TMPRSS2-ERG positive VCaP and TMPRSS2-ERG negative LNCaP cells to simulate three different sample types (cells, tissue, and post-DRE urine sediment). Results: Recombinant ERG3 protein spiked into LNCaP cell lysates could be detected at levels as low as 20 pg by PRISM-SRM analysis. The sensitivity of the PRISM-SRM assay was around approximately 10,000 VCaP cells in a mixed cell population model of VCaP and LNCaP cells. Interestingly, ERG protein could be detected in as few as 600 VCaP cells spiked into female urine. The sensitivity of the in-house enzyme-linked immunosorbent assay (ELISA) was similar to the PRISM-SRM assay, with detection of 30 pg of purified recombinant ERG3 protein and 10,000 VCaP cells. On the other hand, qRT-PCR exhibited a higher sensitivity, as TMPRSS2-ERG transcripts were detected in as few as 100 VCaP cells, in comparison to NanoString methodologies which detected ERG from 10,000 cells. Conclusions: Based on this data, we propose that the detection of both ERG transcriptional products with RNA-based assays, as well as protein products of ERG using PRISM-SRM assays, may be of clinical value in developing diagnostics and prognostics assays for prostate cancer given their sensitivity, specificity, and reproducibility.
1 online resource (1 streaming video file (40 min.) : color, sound).
  • Contents: Patterns of genetic variation in Europe and the Neolithic
  • Ancient DNA and anatomically modern humans (Challenges & Potential)
  • The Neolithic transition in Europe (Scandinavia, Iberia and Eastern Europe).
1 online resource (p.117-123 ) : digital, PDF file.
In this study, the interaction of nanomaterials with biomolecules, cells, and organisms is an enormously vital area of current research, with applications in nanoenabled diagnostics, imaging agents, therapeutics, and contaminant removal technologies. Yet the potential for adverse biological and environmental impacts of nanomaterial exposure is considerable and needs to be addressed to ensure sustainable development of nanomaterials. In this Outlook four research needs for the next decade are outlined: (i) measurement of the chemical nature of nanomaterials in dynamic, complex aqueous environments; (ii) real-time measurements of nanomaterial-biological interactions with chemical specificity; (iii) delineation of molecular modes of action for nanomaterial effects on living systems as functions of nanomaterial properties; and (iv) an integrated systems approach that includes computation and simulation across orders of magnitude in time and space.
online resource (xii, 252 pages) : illustrations (some color)
  • Library construction for mutation identification by whole-genome sequencing / Harold E. Smith
  • Fundamentals of comparative genome analysis in caenorhabditis nematodes / Eric S. Haag and Cristel G. Thomas
  • Genetic methods for cellular manipulations in C. elegans / Menachem Katz
  • Fusion PCR method for expressing genetic tools in C. elegans / Yifat Eliezer and Alon Zaslaver
  • Transposon-assisted genetic engineering with Mos1- mediated single-copy insertion (MosSCI) / Christian Frøkjær-Jensen
  • Creating genome modifications in C. elegans using the CRISPR/Cas9 system / John A. Calarco and Ari E. Friedland
  • Observing and quantifying fluorescent reporters / Michael Hendricks
  • Microbial rhodopsin optogenetic tools : application for analyses of synaptic transmission and of neuronal network activity in behavior / Caspar Glock, Jatin Nagpal, and Alexander Gottschalk
  • Simultaneous optogenetic stimulation of individual pharyngeal neurons and monitoring of feeding behavior in intact C. elegans / Nicholas F. Trojanowski and Christopher Fang-Yen
  • High-pressure freeze and freeze substitution electron microscopy in C. elegans / Laura Manning and Janet Richmond
  • Electron tomography methods for C. elegans / David H. Hall and William J. Rice
  • Microfluidic devices for behavioral analysis, microscopy, and neuronal imaging in Caenorhabditis elegans / Ross C. Lagoy and Dirk R. Albrecht
  • Tracking single C. elegans using a USB microscope on a motorized stage / Eviatar I. Yemini and André E. X. Brown
  • Imaging system for C. elegans behavior / Matthew A. Churgin and Christopher Fang-Yen
  • Method for obtaining large populations of synchronized Caenorhabditis elegans dauer larvae / Maria C. Ow and Sarah E. Hall
  • Sampling and isolation of C. elegans from the natural habitat / Nausicaa Poullet and Christian Braendle
  • Primer on prototyping / Dylan Lynch and David Biron
  • Primer on quantitative modeling / Iulia Neagu and Erel Levine.
Medical Library (Lane)