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Cold Spring Harbor Perspectives in Biology

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https://www.readbyqxmd.com/read/30420555/tailoring-of-proteostasis-networks-with-heat-shock-factors
#1
Jenny Joutsen, Lea Sistonen
Heat shock factors (HSFs) are the main transcriptional regulators of the heat shock response and indispensable for maintaining cellular proteostasis. HSFs mediate their protective functions through diverse genetic programs, which are composed of genes encoding molecular chaperones and other genes crucial for cell survival. The mechanisms that are used to tailor HSF-driven proteostasis networks are not yet completely understood, but they likely comprise from distinct combinations of both genetic and proteomic determinants...
November 12, 2018: Cold Spring Harbor Perspectives in Biology
https://www.readbyqxmd.com/read/30396883/early-events-in-the-endoplasmic-reticulum-unfolded-protein-response
#2
Steffen Preissler, David Ron
The physiological consequences of the unfolded protein response (UPR) are mediated by changes in gene expression. Underlying them are rapid processes involving preexisting components. We review recent insights gained into the regulation of the endoplasmic reticulum (ER) Hsp70 chaperone BiP, whose incorporation into inactive oligomers and reversible AMPylation and de-AMPylation present a first line of response to fluctuating levels of unfolded proteins. BiP activity is tied to the regulation of the UPR transducers by a recently discovered cycle of ER-localized, J-protein-mediated formation of a repressive IRE1-BiP complex, whose working we contrast to an alternative model for UPR regulation that relies on direct recognition of unfolded proteins...
November 5, 2018: Cold Spring Harbor Perspectives in Biology
https://www.readbyqxmd.com/read/30396882/redox-mediated-regulatory-mechanisms-of-endoplasmic-reticulum-homeostasis
#3
Ryo Ushioda, Kazuhiro Nagata
The endoplasmic reticulum (ER) is a dynamic organelle responsible for many cellular functions in eukaryotic cells. Proper redox conditions in the ER are necessary for the functions of many luminal pathways and the maintenance of homeostasis. The redox environment in the ER is oxidative compared with that of the cytosol, and a network of oxidoreductases centering on the protein disulfide isomerase (PDI)-Ero1α hub complex is constructed for efficient electron transfer. Although these oxidizing environments are advantageous for oxidative folding for protein maturation, electron transfer is strictly controlled by Ero1α structurally and spatially...
November 5, 2018: Cold Spring Harbor Perspectives in Biology
https://www.readbyqxmd.com/read/30322887/linking-rna-sequence-structure-and-function-on-massively-parallel-high-throughput-sequencers
#4
Sarah K Denny, William J Greenleaf
SUMMARYHigh-throughput sequencing methods have revolutionized our ability to catalog the diversity of RNAs and RNA-protein interactions that can exist in our cells. However, the relationship between RNA sequence, structure, and function is enormously complex, demonstrating the need for methods that can provide quantitative thermodynamic and kinetic measurements of macromolecular interaction with RNA, at a scale commensurate with the sequence diversity of RNA. Here, we discuss a class of methods that extend the core functionality of DNA sequencers to enable high-throughput measurements of RNA folding and RNA-protein interactions...
October 15, 2018: Cold Spring Harbor Perspectives in Biology
https://www.readbyqxmd.com/read/30181377/what-are-3-utrs-doing
#5
Christine Mayr
SUMMARY3' untranslated regions (3' UTRs) of messenger RNAs (mRNAs) are best known to regulate mRNA-based processes, such as mRNA localization, mRNA stability, and translation. In addition, 3' UTRs can establish 3' UTR-mediated protein-protein interactions (PPIs), and thus can transmit genetic information encoded in 3' UTRs to proteins. This function has been shown to regulate diverse protein features, including protein complex formation or posttranslational modifications, but is also expected to alter protein conformations...
September 4, 2018: Cold Spring Harbor Perspectives in Biology
https://www.readbyqxmd.com/read/30385607/drugging-the-rna-world
#6
REVIEW
Matthew D Disney, Brendan G Dwyer, Jessica L Childs-Disney
SUMMARYAlthough we live in the remnants of an RNA world, the world of drug discovery and chemical probes is firmly protein-centric. Developing highly selective small molecules targeting RNA is often considered to be an insurmountable challenge. Our goal is to demystify the design of such compounds. In this review, we describe various approaches to design small molecules that target RNA from sequence and the application of these compounds in RNA biology, with a focus on inhibition of human RNA-protein complexes...
November 1, 2018: Cold Spring Harbor Perspectives in Biology
https://www.readbyqxmd.com/read/30385606/a-career-for-life-scientists-in-management-consulting
#7
REVIEW
Rodney W Zemmel
Compared with life sciences, management consulting is a relatively new field. Nonetheless, leading firms have assumed a central role in the global business economy and command increasing influence as advisors to corporations and organizations in the public and social sectors. Offering robust analysis, independent and expert perspectives, and-in the best cases-valuable creative input, these companies focus on helping clients to improve their performance or more effectively execute their mission.Because the top firms tackle the most complex problems for the most successful organizations in the world, they attract top graduates...
November 1, 2018: Cold Spring Harbor Perspectives in Biology
https://www.readbyqxmd.com/read/30385605/quantifying-single-mrna-translation-kinetics-in-living-cells
#8
REVIEW
Tatsuya Morisaki, Timothy J Stasevich
SUMMARYOne of the last hurdles to quantifying the full central dogma of molecular biology in living cells with single-molecule resolution has been the imaging of single messenger RNA (mRNA) translation. Here we describe how recent advances in protein tagging and imaging technologies are being used to precisely visualize and quantify the synthesis of nascent polypeptide chains from single mRNA in living cells. We focus on recent applications of repeat-epitope tags and describe how they enable quantification of single mRNA ribosomal densities, translation initiation and elongation rates, and translation site mobility and higher-order structure...
November 1, 2018: Cold Spring Harbor Perspectives in Biology
https://www.readbyqxmd.com/read/29844057/riboswitches-and-translation-control
#9
REVIEW
Ronald R Breaker
A growing collection of bacterial riboswitch classes is being discovered that sense central metabolites, coenzymes, and signaling molecules. Included among the various mechanisms of gene regulation exploited by these RNA regulatory elements are several that modulate messenger RNA (mRNA) translation. In this review, the mechanisms of riboswitch-mediated translation control are summarized to highlight both their diversity and potential ancient origins. These mechanisms include ligand-gated presentation or occlusion of ribosome-binding sites, control of alternative splicing of mRNAs, and the regulation of mRNA stability...
November 1, 2018: Cold Spring Harbor Perspectives in Biology
https://www.readbyqxmd.com/read/29254981/is-it-possible-to-develop-cancer-vaccines-to-neoantigens-what-are-the-major-challenges-and-how-can-these-be-overcome-neoantigens-as-vaccine-targets-for-cancer
#10
REVIEW
Haydn T Kissick
Recent work by several groups has undoubtedly shown that we can produce cancer vaccines targeting neoantigens. However, each vaccine is essentially a single-use, patient-specific product, making this approach resource-intensive. For this reason, it is important to ask whether this approach will be any more successful than what has been attempted during the last 30 years using vaccines targeting self-epitopes. Here, we discuss what might be expected from neoantigen vaccines based on our experience in chronic viral infections, and how this new approach may be applied to cancer immunotherapy...
November 1, 2018: Cold Spring Harbor Perspectives in Biology
https://www.readbyqxmd.com/read/29254980/is-it-possible-to-develop-cancer-vaccines-to-neoantigens-what-are-the-major-challenges-and-how-can-these-be-overcome-neoantigens-nothing-new-in-spite-of-the-name
#11
REVIEW
Olivera J Finn, Hans-Georg Rammensee
The term "neoantigen," as applied to molecules newly expressed on tumor cells, has a long history. The groundbreaking discovery of a cancer causing virus in chickens by Rous over 100 years ago, followed by discoveries of other tumor-causing viruses in animals, suggested a viral etiology of human cancers. The search for other oncogenic viruses in the 1960s and 1970s resulted in the discoveries of Epstein-Barr virus (EBV), hepatitis B virus (HBV), and human papilloma virus (HPV), and continues until the present time...
November 1, 2018: Cold Spring Harbor Perspectives in Biology
https://www.readbyqxmd.com/read/29254974/is-it-possible-to-develop-cancer-vaccines-to-neoantigens-what-are-the-major-challenges-and-how-can-these-be-overcome-targeting-the-right-antigens-in-the-right-patients
#12
REVIEW
Stephen P Schoenberger
Recent advances in genomic sequencing and bioinformatics have empowered a revolution in immuno-oncology that has led to numerous unambiguous demonstrations of spontaneous and therapy-induced T-cell responses in patients against a subset of immunogenic tumor-specific somatic mutations known as neoantigens. These findings raise the exciting possibility that patients could be therapeutically treated with personalized vaccines against the mutations expressed by their own tumor. A central challenge for the broader clinical application of this approach will be to define the best antigens to target, to determine the subset of patients most likely to derive significant clinical benefit, and, finally, to discover both the best method of vaccine delivery and the optimal time in the disease course to do so...
November 1, 2018: Cold Spring Harbor Perspectives in Biology
https://www.readbyqxmd.com/read/28963110/development-diversity-and-function-of-dendritic-cells-in-mouse-and-human
#13
REVIEW
David A Anderson, Kenneth M Murphy, Carlos G Briseño
The study of murine dendritic cell (DC) development has been integral to the identification of specialized DC subsets that have unique requirements for their form and function. Advances in the field have also provided a framework for the identification of human DC counterparts, which appear to have conserved mechanisms of development and function. Multiple transcription factors are expressed in unique combinations that direct the development of classical DCs (cDCs), which include two major subsets known as cDC1s and cDC2s, and plasmacytoid DCs (pDCs)...
November 1, 2018: Cold Spring Harbor Perspectives in Biology
https://www.readbyqxmd.com/read/28963109/the-interferon-ifn-class-of-cytokines-and-the-ifn-regulatory-factor-irf-transcription-factor-family
#14
REVIEW
Hideo Negishi, Tadatsugu Taniguchi, Hideyuki Yanai
Interferons (IFNs) are a broad class of cytokines elicited on challenge to the host defense and are essential for mobilizing immune responses to pathogens. Divided into three classes, type I, type II, and type III, all IFNs share in common the ability to evoke antiviral activities initiated by the interaction with their cognate receptors. The nine-member IFN regulatory factor (IRF) family, first discovered in the context of transcriptional regulation of type I IFN genes following viral infection, are pivotal for the regulation of the IFN responses...
November 1, 2018: Cold Spring Harbor Perspectives in Biology
https://www.readbyqxmd.com/read/28893859/adherens-junctions-and-desmosomes-coordinate-mechanics-and-signaling-to-orchestrate-tissue-morphogenesis-and-function-an-evolutionary-perspective
#15
REVIEW
Matthias Rübsam, Joshua A Broussard, Sara A Wickström, Oxana Nekrasova, Kathleen J Green, Carien M Niessen
Cadherin-based adherens junctions (AJs) and desmosomes are crucial to couple intercellular adhesion to the actin or intermediate filament cytoskeletons, respectively. As such, these intercellular junctions are essential to provide not only integrity to epithelia and other tissues but also the mechanical machinery necessary to execute complex morphogenetic and homeostatic intercellular rearrangements. Moreover, these spatially defined junctions serve as signaling hubs that integrate mechanical and chemical pathways to coordinate tissue architecture with behavior...
November 1, 2018: Cold Spring Harbor Perspectives in Biology
https://www.readbyqxmd.com/read/28847900/making-connections-guidance-cues-and-receptors-at-nonneural-cell-cell-junctions
#16
REVIEW
Ian V Beamish, Lindsay Hinck, Timothy E Kennedy
The field of axon guidance was revolutionized over the past three decades by the identification of highly conserved families of guidance cues and receptors. These proteins are essential for normal neural development and function, directing cell and axon migration, neuron-glial interactions, and synapse formation and plasticity. Many of these genes are also expressed outside the nervous system in which they influence cell migration, adhesion and proliferation. Because the nervous system develops from neural epithelium, it is perhaps not surprising that these guidance cues have significant nonneural roles in governing the specialized junctional connections between cells in polarized epithelia...
November 1, 2018: Cold Spring Harbor Perspectives in Biology
https://www.readbyqxmd.com/read/30275277/at-the-crossroads-of-science-and-society-careers-in-science-policy
#17
REVIEW
Amy P Patterson, Mary E Groesch, Allan C Shipp, Christopher J Viggiani
Science policy offers a challenging and rewarding career path for scientists interested in the social, ethical, and legal implications of their field. This topic encompasses a broad spectrum of activities all in support of advancing the scientific enterprise. Science policy spans various sectors, and policy careers are found in many different organizations, including the federal government, scientific societies, and professional organizations. Although their specific duties may vary greatly, science policy professionals generally apply their scientific training to ensure that the scientific enterprise advances in a responsible and ethical manner and to solve challenges with broad scientific and societal implications...
October 1, 2018: Cold Spring Harbor Perspectives in Biology
https://www.readbyqxmd.com/read/30275276/the-story-of-rna-folding-as-told-in-epochs
#18
REVIEW
Daniel Herschlag, Steve Bonilla, Namita Bisaria
SUMMARYThe past decades have witnessed tremendous developments in our understanding of RNA biology. At the core of these advances have been studies aimed at discerning RNA structure and at understanding the forces that influence the RNA folding process. It is easy to take the present state of understanding for granted, but there is much to be learned by considering the path to our current understanding, which has been tortuous, with the birth and death of models, the adaptation of experimental tools originally developed for characterization of protein structure and catalysis, and the development of novel tools for probing RNA...
October 1, 2018: Cold Spring Harbor Perspectives in Biology
https://www.readbyqxmd.com/read/30275275/technique-development-for-probing-rna-structure-in-vivo-and-genome-wide
#19
REVIEW
Philip C Bevilacqua, Sarah M Assmann
SUMMARYHow organisms perceive and respond to their surroundings is one of the great questions in biology. It is clear that RNA plays key roles in sensing. Cellular and environmental cues that RNA responds to include temperature, ions, metabolites, and biopolymers. Recent advances in next-generation sequencing and in vivo chemical probing have provided unprecedented insights into RNA folding in vivo and genome-wide. Patterns of chemical reactivity have implicated control of gene expression by RNA and aided prediction of RNA structure...
October 1, 2018: Cold Spring Harbor Perspectives in Biology
https://www.readbyqxmd.com/read/29735640/translation-termination-and-ribosome-recycling-in-eukaryotes
#20
REVIEW
Christopher U T Hellen
Termination of mRNA translation occurs when a stop codon enters the A site of the ribosome, and in eukaryotes is mediated by release factors eRF1 and eRF3, which form a ternary eRF1/eRF3-guanosine triphosphate (GTP) complex. eRF1 recognizes the stop codon, and after hydrolysis of GTP by eRF3, mediates release of the nascent peptide. The post-termination complex is then disassembled, enabling its constituents to participate in further rounds of translation. Ribosome recycling involves splitting of the 80S ribosome by the ATP-binding cassette protein ABCE1 to release the 60S subunit...
October 1, 2018: Cold Spring Harbor Perspectives in Biology
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