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Cold Spring Harbor Perspectives in Biology

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https://www.readbyqxmd.com/read/28432135/molecular-mechanisms-of-sleep-homeostasis-in-flies-and-mammals
#1
Ravi Allada, Chiara Cirelli, Amita Sehgal
Sleep is homeostatically regulated with sleep pressure accumulating with the increasing duration of prior wakefulness. Yet, a clear understanding of the molecular components of the homeostat, as well as the molecular and cellular processes they sense and control to regulate sleep intensity and duration, remain a mystery. Here, we will discuss the cellular and molecular basis of sleep homeostasis, first focusing on the best homeostatic sleep marker in vertebrates, slow wave activity; second, moving to the molecular genetic analysis of sleep homeostasis in the fruit fly Drosophila; and, finally, discussing more systemic aspects of sleep homeostasis...
April 21, 2017: Cold Spring Harbor Perspectives in Biology
https://www.readbyqxmd.com/read/28432134/tgf-%C3%AE-1-signaling-and-tissue-fibrosis
#2
Kevin K Kim, Dean Sheppard, Harold A Chapman
Activation of TGF-β1 initiates a program of temporary collagen accumulation important to wound repair in many organs. However, the outcome of temporary extracellular matrix strengthening all too frequently morphs into progressive fibrosis, contributing to morbidity and mortality worldwide. To avoid this maladaptive outcome, TGF-β1 signaling is regulated at numerous levels and intimately connected to feedback signals that limit accumulation. Here, we examine the current understanding of the core functions of TGF-β1 in promoting collagen accumulation, parallel pathways that promote physiological repair, and pathological triggers that tip the balance toward progressive fibrosis...
April 21, 2017: Cold Spring Harbor Perspectives in Biology
https://www.readbyqxmd.com/read/28432133/do-memory-cd4-t-cells-keep-their-cell-type-programming-plasticity-versus-fate-commitment-t-cell-heterogeneity-plasticity-and-selection-in-humans
#3
Federica Sallusto, Antonino Cassotta, Daniel Hoces, Mathilde Foglierini, Antonio Lanzavecchia
The wide range of effector and memory T cells is instrumental for immune regulation and tailored mechanisms of protection against pathogens. Here, we will focus on human CD4 T cells and discuss T-cell plasticity and intraclonal diversification in the context of a progressive and selective model of CD4 T-cell differentiation.
April 21, 2017: Cold Spring Harbor Perspectives in Biology
https://www.readbyqxmd.com/read/28432132/do-memory-cd4-t-cells-keep-their-cell-type-programming-plasticity-versus-fate-commitment-epigenome-a-dynamic-vehicle-for-transmitting-and-recording-cytokine-signaling
#4
John L Johnson, Golnaz Vahedi
CD4(+) T cells are critical for the elimination of an immense array of microbial pathogens. Although there are aspects of helper T-cell differentiation that can be modeled as a classic cell-fate commitment, CD4(+) T cells also maintain considerable flexibility in their transcriptional program. Here, we present an overview of chromatin biology during cellular reprogramming and, within this context, envision how the scope of cellular reprogramming may be expanded to further our understanding of the controversy surrounding CD4(+) T lymphocyte plasticity or determinism...
April 21, 2017: Cold Spring Harbor Perspectives in Biology
https://www.readbyqxmd.com/read/28432131/do-the-microbiota-influence-vaccines-and-protective-immunity-to-pathogens-if-so-is-there-potential-for-efficacious-microbiota-based-vaccines
#5
Dan R Littman
The gut-resident constituents of the microbiota protect the mucosa from invasive pathogens through engagement of both innate and adaptive branches of the immune system. They are also likely to provide systemic protection from pathogens, by enhancing host robustness and tolerance to the invasive microbes and by inducing immune responses that prevent their growth. These properties of commensal microbiota, particularly the capacity of some bacteria to induce diverse types of antigen-specific immune responses, raises the prospect that they could be deployed as vaccine vectors to generate effective local and systemic immunity to viral and bacterial pathogens...
April 21, 2017: Cold Spring Harbor Perspectives in Biology
https://www.readbyqxmd.com/read/28432130/do-the-microbiota-influence-vaccines-and-protective-immunity-to-pathogens-engaging-our-endogenous-adjuvants
#6
Nicholas Collins, Yasmine Belkaid
The reliance of the immune system on constitutive microbial stimulation support the idea that both responsiveness to vaccines and vaccine design need to be considered in the context of host-microbiota interactions. Manipulation of microbe function or composition via diet alteration or microbiota engraftment may soon become a viable approach to control immunity and, as such, vaccine responses. Learning from our endogenous original adjuvants could be critical in overcoming the enormous hurdle of vaccine design against the numerous pathogens that cause chronic infection...
April 21, 2017: Cold Spring Harbor Perspectives in Biology
https://www.readbyqxmd.com/read/28432129/do-memory-cd4-t-cells-keep-their-cell-type-programming-plasticity-versus-fate-commitment-complexities-of-interpretation-due-to-the-heterogeneity-of-memory-cd4-t-cells-including-t-follicular-helper-cells
#7
Shane Crotty
Plasticity is the ability of a cell type to convert to another cell type. There are multiple effector CD4 T-cell subtypes, including TH1, TH2, TH17, TH1*, CD4 CTL, TH9, and TFH cells. It is commonly thought that a CD4 T cell can readily show full plasticity-full conversion from one differentiated cell-and this propensity to plasticity is possessed by memory CD4 T cells. However, there remains no direct demonstration of in vivo-generated resting memory CD4 T-cell conversion to a different subtype on secondary antigen challenge in vivo in an intact animal at the single-cell level...
April 21, 2017: Cold Spring Harbor Perspectives in Biology
https://www.readbyqxmd.com/read/28432128/do-the-microbiota-influence-vaccines-and-protective-immunity-to-pathogens-issues-of-sovereignty-federalism-and-points-testing-in-the-prokaryotic-and-eukaryotic-spaces-of-the-host-microbial-superorganism
#8
Andrew J Macpherson
In contrast to live attenuated vaccines, which are designed to induce immunity through a time-limited bloom in systemic tissues, the microbiota is a persistent feature of body surfaces, especially the intestine. The immune responses to the microbiota are idiosyncratic depending on the niche intimacy of different taxa and generally adapt the host to avoid overgrowth and maintain mutualism rather than to eliminate the organisms of that taxon. Both the microbiota and the host have so much molecular cross talk controlling each other, that the prokaryotic and the eukaryotic spaces of the host-microbial superorganism are federal rather than sovereign...
April 21, 2017: Cold Spring Harbor Perspectives in Biology
https://www.readbyqxmd.com/read/28389444/bone-morphogenetic-protein-based-therapeutic-approaches
#9
Jonathan W Lowery, Vicki Rosen
Bone morphogenetic proteins (BMPs) constitute the largest subdivision of the transforming growth factor (TGF)-β family of ligands and exert most of their effects through the canonical effectors Smad1, 5, and 8. Appropriate regulation of BMP signaling is critical for the development and homeostasis of numerous human organ systems. Aberrations in BMP pathways or their regulation are increasingly associated with diverse human pathologies, and there is an urgent and growing need to develop effective approaches to modulate BMP signaling in the clinic...
April 7, 2017: Cold Spring Harbor Perspectives in Biology
https://www.readbyqxmd.com/read/28348039/what-is-the-predictive-value-of-animal-models-for-vaccine-efficacy-in-humans-reevaluating-the-potential-of-mouse-models-for-the-human-immune-system
#10
Stephen C Jameson, David Masopust
Much of what we understand about immunology, including the response to vaccines, come from studies in mice because they provide many practical advantages compared with research in higher mammals and humans. Nevertheless, modalities for preventing or treating disease do not always translate from mouse to humans, which has led to increasing scrutiny of the continued merits of mouse research. Here, we summarize the pros and cons of current laboratory mouse models for immunology research and discuss whether overreliance on nonphysiological, ultra-hygienic animal husbandry approaches has limited the ultimate translation potential of mouse-derived data to humans...
March 27, 2017: Cold Spring Harbor Perspectives in Biology
https://www.readbyqxmd.com/read/28348038/bone-morphogenetic-proteins-in-vascular-homeostasis-and-disease
#11
Marie-José Goumans, An Zwijsen, Peter Ten Dijke, Sabine Bailly
It is well established that control of vascular morphogenesis and homeostasis is regulated by vascular endothelial growth factor (VEGF), fibroblast growth factor (FGF), Delta-like 4 (Dll4), angiopoietin, and ephrin signaling. It has become clear that signaling by bone morphogenetic proteins (BMPs), which have a long history of studies in bone and early heart development, are also essential for regulating vascular function. Indeed, mutations that cause deregulated BMP signaling are linked to two human vascular diseases, hereditary hemorrhagic telangiectasia and pulmonary arterial hypertension...
March 27, 2017: Cold Spring Harbor Perspectives in Biology
https://www.readbyqxmd.com/read/28348037/what-is-the-predictive-value-of-animal-models-for-vaccine-efficacy-in-humans-consideration-of-strategies-to-improve-the-value-of-animal-models
#12
Ramin Sedaghat Herati, E John Wherry
Animal models are an essential feature of the vaccine design toolkit. Although animal models have been invaluable in delineating the mechanisms of immune function, their precision in predicting how well specific vaccines work in humans is often suboptimal. There are, of course, many obvious species differences that may limit animal models from predicting all details of how a vaccine works in humans. However, careful consideration of which animal models may have limitations should also allow more accurate interpretations of animal model data and more accurate predictions of what is to be expected in clinical trials...
March 27, 2017: Cold Spring Harbor Perspectives in Biology
https://www.readbyqxmd.com/read/28348036/tgf-%C3%AE-signaling-in-control-of-cardiovascular-function
#13
Marie-José Goumans, Peter Ten Dijke
Genetic studies in animals and humans indicate that gene mutations that functionally perturb transforming growth factor β (TGF-β) signaling are linked to specific hereditary vascular syndromes, including Osler-Rendu-Weber disease or hereditary hemorrhagic telangiectasia and Marfan syndrome. Disturbed TGF-β signaling can also cause nonhereditary disorders like atherosclerosis and cardiac fibrosis. Accordingly, cell culture studies using endothelial cells or smooth muscle cells (SMCs), cultured alone or together in two- or three-dimensional cell culture assays, on plastic or embedded in matrix, have shown that TGF-β has a pivotal effect on endothelial and SMC proliferation, differentiation, migration, tube formation, and sprouting...
March 27, 2017: Cold Spring Harbor Perspectives in Biology
https://www.readbyqxmd.com/read/28348035/what-is-the-predictive-value-of-animal-models-for-vaccine-efficacy-in-humans-the-importance-of-bridging-studies-and-species-independent-correlates-of-protection
#14
Hana Golding, Surender Khurana, Marina Zaitseva
Animal models have played a pivotal role in all stages of vaccine development. Their predictive value for vaccine effectiveness depends on the pathogen, the robustness of the animal challenge model, and the correlates of protection (if known). This article will cover key questions regarding bridging animal studies to efficacy trials in humans. Examples include human papillomavirus (HPV) vaccine in which animal protection after vaccination with heterologous prototype virus-like particles (VLPs) predicted successful efficacy trials in humans, and a recent approval of anthrax vaccine in accordance with the "Animal Rule...
March 27, 2017: Cold Spring Harbor Perspectives in Biology
https://www.readbyqxmd.com/read/28348034/what-is-the-predictive-value-of-animal-models-for-vaccine-efficacy-in-humans-rigorous-simian-immunodeficiency-virus-vaccine-trials-can-be-instructive
#15
Mauricio A Martins, David I Watkins
Simian immunodeficiency virus (SIV) challenge of rhesus macaques provides an invaluable tool to evaluate the clinical prospects of HIV-1 vaccine concepts. However, as with any animal model of human disease, it is crucial to understand the advantages and limitations of this system to maximize the translational value of SIV vaccine studies. Here, we discuss the importance of assessing the efficacy of vaccine prototypes using stringent SIV challenge regimens that mimic HIV-1 transmission and pathogenesis. We also review some of the cautionary tales of HIV-1 vaccine research because they provide general lessons for the preclinical assessment of vaccine candidates...
March 27, 2017: Cold Spring Harbor Perspectives in Biology
https://www.readbyqxmd.com/read/28348033/minimal-cells-real-and-imagined
#16
John I Glass, Chuck Merryman, Kim S Wise, Clyde A Hutchison, Hamilton O Smith
A minimal cell is one whose genome only encodes the minimal set of genes necessary for the cell to survive. Scientific reductionism postulates the best way to learn the first principles of cellular biology would be to use a minimal cell in which the functions of all genes and components are understood. The genes in a minimal cell are, by definition, essential. In 2016, synthesis of a genome comprised of only the set of essential and quasi-essential genes encoded by the bacterium Mycoplasma mycoides created a near-minimal bacterial cell...
March 27, 2017: Cold Spring Harbor Perspectives in Biology
https://www.readbyqxmd.com/read/28320756/do-memory-b-cells-form-secondary-germinal-centers-it-depends
#17
Kathryn A Pape, Marc K Jenkins
The memory B-cell pool in an immune individual is more heterogeneous than previously recognized. The different types of memory B cells likely play distinct roles in tuning the secondary immune response because they differ in their potential to generate plasmablasts, which secrete antibodies, or germinal center (GC) cells, which generate new and higher affinity memory cells. We propose that the production of plasmablasts or GC cells by a memory B cell is controlled by its state of differentiation and the amount and affinity of antigen-specific antibodies present in the individual in which it resides...
March 20, 2017: Cold Spring Harbor Perspectives in Biology
https://www.readbyqxmd.com/read/28320755/ciliary-mechanisms-of-cyst-formation-in-polycystic-kidney-disease
#18
Ming Ma, Anna-Rachel Gallagher, Stefan Somlo
Autosomal-dominant polycystic kidney disease (ADPKD) is a disease of defective tissue homeostasis resulting in active remodeling of nephrons and bile ducts to form fluid-filled sacs called cysts. The causal genes PKD1 and PKD2 encode transmembrane proteins polycystin 1 (PC1) and polycystin 2 (PC2), respectively. Together, the polycystins localize to the solitary primary cilium that protrudes from the apical surface of most kidney tubule cells and is thought to function as a privileged compartment that the cell uses for signal integration of sensory inputs...
March 20, 2017: Cold Spring Harbor Perspectives in Biology
https://www.readbyqxmd.com/read/28320754/do-memory-b-cells-form-secondary-germinal-center-cells-yes-and-no
#19
Mark J Shlomchik
Memory is the defining feature of the adaptive immune system. Humoral immune memory is largely though not exclusively generated in the germinal center (GC), which spawns long-lived plasma cells that support ongoing serum antibody titers as well as "memory B cells" (MBCs) that persist in the immune host at expanded frequencies. Upon reencounter with antigen, these MBCs are reactivated and potentially can contribute to protection by further expansion, rapid differentiation to antibody-forming cells, and/or reseeding of a new round of GCs along with somatic V region mutation and selection...
March 20, 2017: Cold Spring Harbor Perspectives in Biology
https://www.readbyqxmd.com/read/28320753/do-memory-b-cells-form-secondary-germinal-centers-impact-of-antibody-class-and-quality-of-memory-t-cell-help-at-recall
#20
Louise J McHeyzer-Williams, Chad Dufaud, Michael G McHeyzer-Williams
Antigen recall can clearly induce a germinal center (GC) reaction. What has become an issue for debate are the origins of the antigen-specific B cells that form memory-response GCs (mGCs). Using antigen labeling and adoptive transfer, memory B cells expressing different antibody class can give rise to mGCs with differing efficiency. Here, we will argue that the range of class-specific memory responses reported across multiple systems represents the spectrum of memory B-cell fate and function. While the formulation of recall immunogen and location of mGCs have an important role, we propose that effective cognate regulation is the key variable influencing recall outcome...
March 20, 2017: Cold Spring Harbor Perspectives in Biology
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