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https://www.readbyqxmd.com/read/28319733/plasma-cell-and-memory-b-cell-differentiation-from-the-germinal-center
#1
REVIEW
Dan Suan, Christopher Sundling, Robert Brink
Germinal centers (GCs) form in secondary lymphoid tissues in response to antigenic challenge and are the site of somatic hypermutation, generating GC B cells with increasing affinity for the inciting agent that are positively selected over time. However, it is not until GC B cells differentiate into memory B cells and plasma cells and egress from the GC back into the circulation that effective long-lived humoral immunity is conferred upon the host. Here we review what is known about the signals that initiate the transition from a GC B cell into the memory B cell and plasma cell compartments and the downstream transcriptional regulation of these processes...
March 16, 2017: Current Opinion in Immunology
https://www.readbyqxmd.com/read/28319093/human-haematopoietic-stem-cell-lineage-commitment-is-a-continuous-process
#2
Lars Velten, Simon F Haas, Simon Raffel, Sandra Blaszkiewicz, Saiful Islam, Bianca P Hennig, Christoph Hirche, Christoph Lutz, Eike C Buss, Daniel Nowak, Tobias Boch, Wolf-Karsten Hofmann, Anthony D Ho, Wolfgang Huber, Andreas Trumpp, Marieke A G Essers, Lars M Steinmetz
Blood formation is believed to occur through stepwise progression of haematopoietic stem cells (HSCs) following a tree-like hierarchy of oligo-, bi- and unipotent progenitors. However, this model is based on the analysis of predefined flow-sorted cell populations. Here we integrated flow cytometric, transcriptomic and functional data at single-cell resolution to quantitatively map early differentiation of human HSCs towards lineage commitment. During homeostasis, individual HSCs gradually acquire lineage biases along multiple directions without passing through discrete hierarchically organized progenitor populations...
March 20, 2017: Nature Cell Biology
https://www.readbyqxmd.com/read/28318822/genome-wide-analysis-of-rna-polymerase-ii-termination-at-protein-coding-genes
#3
Carlo Baejen, Jessica Andreani, Phillipp Torkler, Sofia Battaglia, Bjoern Schwalb, Michael Lidschreiber, Kerstin C Maier, Andrea Boltendahl, Petra Rus, Stephanie Esslinger, Johannes Söding, Patrick Cramer
At the end of protein-coding genes, RNA polymerase (Pol) II undergoes a concerted transition that involves 3'-processing of the pre-mRNA and transcription termination. Here, we present a genome-wide analysis of the 3'-transition in budding yeast. We find that the 3'-transition globally requires the Pol II elongation factor Spt5 and factors involved in the recognition of the polyadenylation (pA) site and in endonucleolytic RNA cleavage. Pol II release from DNA occurs in a narrow termination window downstream of the pA site and requires the "torpedo" exonuclease Rat1 (XRN2 in human)...
March 6, 2017: Molecular Cell
https://www.readbyqxmd.com/read/28317932/bacterial-secretion-system-skews-the-fate-of-legionella-containing-vacuoles-towards-lc3-associated-phagocytosis
#4
Andree Hubber, Tomoko Kubori, Cevayir Coban, Takeshi Matsuzawa, Michinaga Ogawa, Tsuyoshi Kawabata, Tamotsu Yoshimori, Hiroki Nagai
The evolutionarily conserved processes of endosome-lysosome maturation and macroautophagy are established mechanisms that limit survival of intracellular bacteria. Similarly, another emerging mechanism is LC3-associated phagocytosis (LAP). Here we report that an intracellular vacuolar pathogen, Legionella dumoffii, is specifically targeted by LAP over classical endocytic maturation and macroautophagy pathways. Upon infection, the majority of L. dumoffii resides in ER-like vacuoles and replicate within this niche, which involves inhibition of classical endosomal maturation...
March 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28316013/the-papain-like-protease-of-avian-infectious-bronchitis-virus-has-deubiquitinating-activity
#5
Liping Yu, Xiaorong Zhang, Tianqi Wu, Yuyang Wang, Jie Meng, Qian Liu, Xiaosai Niu, Yantao Wu
Coronavirus papain-like proteases (PLPs) can act as proteases that process virus-encoded large replicase polyproteins and also as deubiquitinating (DUB) enzymes. Like the PLPs of other coronaviruses (CoVs), the avian infectious bronchitis virus (IBV) PLP catalyzes proteolysis of Gly-Gly dipeptide bonds to release mature cleavage products. However, the other functions of the IBV PLP are not well understood. In this study, we found that IBV exhibits strong global DUB activity with significant reductions of the levels of ubiquitin (Ub)-, K48-, and K63-conjugated proteins...
March 18, 2017: Archives of Virology
https://www.readbyqxmd.com/read/28315697/the-role-of-the-tor-pathway-in-mediating-the-link-between-nutrition-and-longevity
#6
REVIEW
Oleh Lushchak, Olha Strilbytska, Veronika Piskovatska, Kenneth B Storey, Alexander Koliada, Alexander Vaiserman
The target of rapamycin (TOR) pathway integrates signals from extracellular and intracellular agents, such as growth factors, nutrients, mediators of energy balance, oxygen availability and other environmental cues. It allows the regulation of multiple cellular processes including protein and lipid synthesis, ribosome biogenesis, autophagy and metabolic processes. Being conserved across different phyla, TOR regulates longevity of various organisms in response to dietary conditions. In this review we described the main components of the TOR pathway and its upstream effectors and downstream processes in relation to aging...
March 15, 2017: Mechanisms of Ageing and Development
https://www.readbyqxmd.com/read/28315470/the-nitric-oxide-synthase-2-pathway-is-targeted-by-both-pro-and-anti-inflammatory-treatments-in-the-immature-human-intestine
#7
Emanuela Ferretti, Eric Tremblay, Marie-Pier Thibault, David Grynspan, Karolina M Burghardt, Marcos Bettolli, Corentin Babakissa, Emile Levy, Jean-François Beaulieu
BACKGROUND AND AIM: NO synthase 2 (NOS2) was recently identified as one the most overexpressed genes in intestinal samples of premature infants with necrotizing enterocolitis (NEC). NOS2 is widely implicated in the processes of epithelial cell injury/apoptosis and host immune defense but its specific role in inflammation of the immature human intestinal mucosa remains unclear. Interestingly, factors that prevent NEC such as epidermal growth factor (EGF) attenuate the inflammatory response in the mid-gestation human small intestine using serum-free organ culture while drugs that are associated with NEC occurrence such as the non-steroidal anti-inflammatory drug, indomethacin (INDO), exert multiple detrimental effects on the immature human intestine...
March 14, 2017: Nitric Oxide: Biology and Chemistry
https://www.readbyqxmd.com/read/28315409/in-vivo-tau-pet-imaging-in-dementia-pathophysiology-radiotracer-quantification-and-a-systematic-review-of-clinical-findings
#8
REVIEW
Benjamin Hall, Elijah Mak, Simon Cervenka, Franklin I Aigbirhio, James B Rowe, John T O'Brien
In addition to the deposition of β-amyloid plaques, neurofibrillary tangles composed of aggregated hyperphosphorylated tau are one of the pathological hallmarks of Alzheimer's disease and other neurodegenerative disorders. Until now, our understanding about the natural history and topography of tau deposition has only been based on post-mortem and cerebrospinal fluid studies, and evidence continues to implicate tau as a central driver of downstream neurodegenerative processes and cognitive decline. Recently, it has become possible to assess the regional distribution and severity of tau burden in vivo with the development of novel radiotracers for positron emission tomography (PET) imaging...
March 14, 2017: Ageing Research Reviews
https://www.readbyqxmd.com/read/28303334/an-insect-inspired-model-for-visual-binding-ii-functional-analysis-and-visual-attention
#9
Brandon D Northcutt, Charles M Higgins
We have developed a neural network model capable of performing visual binding inspired by neuronal circuitry in the optic glomeruli of flies: a brain area that lies just downstream of the optic lobes where early visual processing is performed. This visual binding model is able to detect objects in dynamic image sequences and bind together their respective characteristic visual features-such as color, motion, and orientation-by taking advantage of their common temporal fluctuations. Visual binding is represented in the form of an inhibitory weight matrix which learns over time which features originate from a given visual object...
March 16, 2017: Biological Cybernetics
https://www.readbyqxmd.com/read/28303333/an-insect-inspired-model-for-visual-binding-i-learning-objects-and-their-characteristics
#10
Brandon D Northcutt, Jonathan P Dyhr, Charles M Higgins
Visual binding is the process of associating the responses of visual interneurons in different visual submodalities all of which are responding to the same object in the visual field. Recently identified neuropils in the insect brain termed optic glomeruli reside just downstream of the optic lobes and have an internal organization that could support visual binding. Working from anatomical similarities between optic and olfactory glomeruli, we have developed a model of visual binding based on common temporal fluctuations among signals of independent visual submodalities...
March 16, 2017: Biological Cybernetics
https://www.readbyqxmd.com/read/28303325/use-of-pervaporation-process-for-the-recovery-of-aroma-compounds-produced-by-p-fermentans-in-sugarcane-molasses
#11
Suzan Cristina Rossi, Adriane Bianchi Pedroni Medeiros, Thiago André Weschenfelder, Agnes de Paula Scheer, Carlos Ricardo Soccol
Natural fruity aroma was produced during submerged fermentation by Pichia fermentans using sugarcane molasses as a cultivation broth. The aroma compounds were recovered from the fermentation by a pervaporation process using a polydimethylsiloxane membrane (Pervap 4060-Sulzer). Isoamyl acetate, a characteristic compound associated with fruity aromas, was the major compound produced. The pervaporation module was fed at three different temperatures to test the best conditions to recover the natural fruity aroma...
March 17, 2017: Bioprocess and Biosystems Engineering
https://www.readbyqxmd.com/read/28303271/a-computational-method-for-analyzing-the-biomechanics-of-heart-murmurs
#12
Chi Zhu, Jung-Hee Seo, Hani Bakhshaee, Rajat Mittal
A computational framework consisting of a one-way coupled hemodynamic-acoustic method and a wave-decomposition based post-processing approach is developed to investigate the biomechanics of arterial bruits. This framework is then applied to studying the effect of the shear wave on the generation and propagation of bruits from a modeled stenosed artery. The blood flow in the artery is solved by an immersed boundary method (IBM) based incompressible flow solver. The sound generation and propagation in the blood volume is modeled by the linearized perturbed compressible equations, while the sound propagation through the surrounding tissue is modeled by the linear elastic wave equation...
March 17, 2017: Journal of Biomechanical Engineering
https://www.readbyqxmd.com/read/28303264/the-strange-case-of-cdk4-6-inhibitors-mechanisms-resistance-and-combination-strategies
#13
Erik S Knudsen, Agnieszka K Witkiewicz
CDK4/6 inhibitors have emerged as a powerful class of agents with clinical activity in a number of malignancies. Targeting the cell cycle represents a core attack on a defining feature of cancer. However, the mechanisms through which selective CDK4/6 targeted agents act has few parallels in the current pharmaceutical armamentarium against cancer. Notably, CDK4/6 inhibitors act downstream of most mitogenic signaling cascades, which have implications both related to clinical efficacy and resistance. Core knowledge of cell cycle processes has provided insights into mechanisms of intrinsic resistance to CDK4/6 inhibitors; however, the basis of acquired resistance versus durable response is only beginning to emerge...
January 2017: Trends in Cancer
https://www.readbyqxmd.com/read/28302906/distinct-focal-adhesion-protein-modules-control-different-aspects-of-mechanotransduction
#14
Ben Stutchbury, Paul Atherton, Ricky Tsang, De-Yao Wang, Christoph Ballestrem
Focal adhesions (FAs) are macromolecular complexes that regulate cell adhesion and mechanotransduction. Using fluorescence recovery after photobleaching (FRAP) and fluorescence loss after photoactivation (FLAP), we found that the mobility of core FA proteins correlates with protein function. Structural proteins such as tensin, talin and vinculin are significantly less mobile in FAs than signaling proteins such as FAK and paxillin. The mobilities of the structural proteins are directly influenced by substrate stiffness, suggesting they are involved in sensing the rigidity of the extracellular environment...
March 16, 2017: Journal of Cell Science
https://www.readbyqxmd.com/read/28302722/amyloid-%C3%AE-oligomers-transiently-inhibit-amp-activated-kinase-and-cause-metabolic-defects-in-hippocampal-neurons
#15
Gisele S Seixas da Silva, Helen M Melo, Mychael V Lourenco, Natalia de M Lyra E Silva, Marcelo B de Carvalho, Soniza Alves-Leon, Jorge M de Souza, William L Klein, Wagner S da-Silva, Sergio T Ferreira, Fernanda G De Felice
AMP-activated kinase (AMPK) is a key player in energy sensing and metabolic reprogramming under cellular energy restriction. Several studies have linked impaired AMPK function to peripheral metabolic diseases such as diabetes. However, the impact of neurological disorders, such as Alzheimer disease (AD), on AMPK function and downstream effects of altered AMPK activity on neuronal metabolism have been investigated only recently. Here, we report the impact of A β oligomers (AβOs), synaptotoxins that accumulate in AD brains, on neuronal AMPK activity...
March 16, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28302566/mechanisms-of-sphingosine-1-phosphate-receptor-signalling-in-cancer
#16
REVIEW
Sathya Narayanan Patmanathan, Wei Wang, Lee Fah Yap, Deron R Herr, Ian C Paterson
S1P is a small bioactive lipid which exerts its effects following binding to a family of five G protein-coupled receptors, known as S1P1-5. Following receptor activation, multiple signalling cascades are activated, allowing S1P to regulate a range of cellular processes, such as proliferation, apoptosis, migration and angiogenesis. There is strong evidence implicating the involvement of S1P receptors (S1PRs) in cancer progression and the oncogenic effects of S1P can result from alterations in the expression of one or more of the S1PRs and/or the enzymes that regulate the levels of S1P...
March 14, 2017: Cellular Signalling
https://www.readbyqxmd.com/read/28302504/mitochondrial-nudix-hydrolases-a-metabolic-link-between-nad-catabolism-gtp-and-mitochondrial-dynamics
#17
Aaron Long, Nina Klimova, Tibor Kristian
NAD(+) catabolism and mitochondrial dynamics are important parts of normal mitochondrial function and are both reported to be disrupted in aging, neurodegenerative diseases, and acute brain injury. While both processes have been extensively studied there has been little reported on how the mechanisms of these two processes are linked. This review focuses on how downstream NAD(+) catabolism via NUDIX hydrolases affects mitochondrial dynamics under pathologic conditions. Additionally, several potential targets in mitochondrial dysfunction and fragmentation are discussed, including the roles of mitochondrial poly(ADP-ribose) polymerase 1(mtPARP1), AMPK, AMP, and intra-mitochondrial GTP metabolism...
March 14, 2017: Neurochemistry International
https://www.readbyqxmd.com/read/28302467/recent-advances-in-enzyme-extraction-strategies-a-comprehensive-review
#18
REVIEW
Shamraja S Nadar, Rohini G Pawar, Virendra K Rathod
The increasing interest of industrial enzymes demands for development of new downstream strategies for maximizing enzyme recovery. The significant efforts have been focused on the development of newly adapted technologies to purify enzymes in catalytically active form. Recently, an aqueous two phase system (ATPS) is emerged as powerful tools for efficient extraction and purification of enzymes due to their versatility, lower cost, process integration capability and easy scale-up. The present review gives an overview of effect of parameters such as tie line length, pH, neutral salts, properties of polymer and salt involved in traditional polymer/polymer and polymer/salt ATPS for enzyme recovery...
March 13, 2017: International Journal of Biological Macromolecules
https://www.readbyqxmd.com/read/28301357/the-effect-of-microporous-polysaccharide-hemospheres-on-wound-healing-and-scarring-in-wild-type-and-db-db-mice
#19
Kyle J Miller, Wei Cao, Mohamed M Ibrahim, Howard Levinson
BACKGROUND: Hemostasis, the initial phase of wound healing, sets the stage for tissue repair. Microporous polysaccharide hemosphere powder (MPH) is an FDA-approved hemostatic agent that may impact the wound-healing process. OBJECTIVE: This study examined the role of MPH in murine wild-type and diabetic (db/db) wound-healing models and a foreign body response scarring model. METHODS: The powder was topically applied to excisional wounds in wild-type C57BL/6 mice and db/db mice...
April 2017: Advances in Skin & Wound Care
https://www.readbyqxmd.com/read/28300844/il-27-triggers-il-10-production-in-th17-cells-via-a-c-maf-ror%C3%AE-t-blimp-1-signal-to-promote-the-progression-of-endometriosis
#20
Kai-Kai Chang, Li-Bing Liu, Li-Ping Jin, Bing Zhang, Jie Mei, Hui Li, Chun-Yan Wei, Wen-Jie Zhou, Xiao-Yong Zhu, Jun Shao, Da-Jin Li, Ming-Qing Li
Endometriosis is an estrogen-dependent inflammatory disease. The anti-inflammatory cytokine IL-10 is also increased in endometriosis. IL-10 production by Th17 cells is critical for limiting autoimmunity and inflammatory responses. However, the mechanism of inducing IL-10-producing Th17 cells is still largely unknown. The present study investigated the differentiation mechanism and role of IL-10-producing Th17 cells in endometriosis. Here, we report that IL-10(+)Th17 cells are significantly increased in the peritoneal fluid of women with endometriosis, along with an elevation of IL-27, IL-6 and TGF-β...
March 16, 2017: Cell Death & Disease
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