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https://www.readbyqxmd.com/read/28622516/snapshot-phosphoregulation-of-mitosis
#1
Andrew Burgess, Jenny Vuong, Samuel Rogers, Marcos Malumbres, Seán I O'Donoghue
During mitosis, a cell divides its duplicated genome into two identical daughter cells. This process must occur without errors to prevent proliferative diseases (e.g., cancer). A key mechanism controlling mitosis is the precise timing of more than 32,000 phosphorylation and dephosphorylation events by a network of kinases and counterbalancing phosphatases. The identity, magnitude, and temporal regulation of these events have emerged recently, largely from advances in mass spectrometry. Here, we show phosphoevents currently believed to be key regulators of mitosis...
June 15, 2017: Cell
https://www.readbyqxmd.com/read/28622515/a-mechanogenetic-toolkit-for-interrogating-cell-signaling-in-space-and-time
#2
Daeha Seo, Kaden M Southard, Ji-Wook Kim, Hyun Jung Lee, Justin Farlow, Jung-Uk Lee, David B Litt, Thomas Haas, A Paul Alivisatos, Jinwoo Cheon, Zev J Gartner, Young-Wook Jun
No abstract text is available yet for this article.
June 15, 2017: Cell
https://www.readbyqxmd.com/read/28622514/landscape-of-infiltrating-t-cells-in-liver-cancer-revealed-by-single-cell-sequencing
#3
Chunhong Zheng, Liangtao Zheng, Jae-Kwang Yoo, Huahu Guo, Yuanyuan Zhang, Xinyi Guo, Boxi Kang, Ruozhen Hu, Julie Y Huang, Qiming Zhang, Zhouzerui Liu, Minghui Dong, Xueda Hu, Wenjun Ouyang, Jirun Peng, Zemin Zhang
Systematic interrogation of tumor-infiltrating lymphocytes is key to the development of immunotherapies and the prediction of their clinical responses in cancers. Here, we perform deep single-cell RNA sequencing on 5,063 single T cells isolated from peripheral blood, tumor, and adjacent normal tissues from six hepatocellular carcinoma patients. The transcriptional profiles of these individual cells, coupled with assembled T cell receptor (TCR) sequences, enable us to identify 11 T cell subsets based on their molecular and functional properties and delineate their developmental trajectory...
June 15, 2017: Cell
https://www.readbyqxmd.com/read/28622513/comprehensive-and-integrative-genomic-characterization-of-hepatocellular-carcinoma
#4
(no author information available yet)
Liver cancer has the second highest worldwide cancer mortality rate and has limited therapeutic options. We analyzed 363 hepatocellular carcinoma (HCC) cases by whole-exome sequencing and DNA copy number analyses, and we analyzed 196 HCC cases by DNA methylation, RNA, miRNA, and proteomic expression also. DNA sequencing and mutation analysis identified significantly mutated genes, including LZTR1, EEF1A1, SF3B1, and SMARCA4. Significant alterations by mutation or downregulation by hypermethylation in genes likely to result in HCC metabolic reprogramming (ALB, APOB, and CPS1) were observed...
June 15, 2017: Cell
https://www.readbyqxmd.com/read/28622512/structural-basis-of-egg-coat-sperm-recognition-at-fertilization
#5
Isha Raj, Hamed Sadat Al Hosseini, Elisa Dioguardi, Kaoru Nishimura, Ling Han, Alessandra Villa, Daniele de Sanctis, Luca Jovine
Recognition between sperm and the egg surface marks the beginning of life in all sexually reproducing organisms. This fundamental biological event depends on the species-specific interaction between rapidly evolving counterpart molecules on the gametes. We report biochemical, crystallographic, and mutational studies of domain repeats 1-3 of invertebrate egg coat protein VERL and their interaction with cognate sperm protein lysin. VERL repeats fold like the functionally essential N-terminal repeat of mammalian sperm receptor ZP2, whose structure is also described here...
June 15, 2017: Cell
https://www.readbyqxmd.com/read/28622511/metabolic-adaptation-establishes-disease-tolerance-to-sepsis
#6
Sebastian Weis, Ana Rita Carlos, Maria Raquel Moita, Sumnima Singh, Birte Blankenhaus, Silvia Cardoso, Rasmus Larsen, Sofia Rebelo, Sascha Schäuble, Laura Del Barrio, Gilles Mithieux, Fabienne Rajas, Sandro Lindig, Michael Bauer, Miguel P Soares
Sepsis is an often lethal syndrome resulting from maladaptive immune and metabolic responses to infection, compromising host homeostasis. Disease tolerance is a defense strategy against infection that preserves host homeostasis without exerting a direct negative impact on pathogens. Here, we demonstrate that induction of the iron-sequestering ferritin H chain (FTH) in response to polymicrobial infections is critical to establish disease tolerance to sepsis. The protective effect of FTH is exerted via a mechanism that counters iron-driven oxidative inhibition of the liver glucose-6-phosphatase (G6Pase), and in doing so, sustains endogenous glucose production via liver gluconeogenesis...
June 15, 2017: Cell
https://www.readbyqxmd.com/read/28622510/microbial-genetic-composition-tunes-host-longevity
#7
Bing Han, Priya Sivaramakrishnan, Chih-Chun J Lin, Isaiah A A Neve, Jingquan He, Li Wei Rachel Tay, Jessica N Sowa, Antons Sizovs, Guangwei Du, Jin Wang, Christophe Herman, Meng C Wang
Homeostasis of the gut microbiota critically influences host health and aging. Developing genetically engineered probiotics holds great promise as a new therapeutic paradigm to promote healthy aging. Here, through screening 3,983 Escherichia coli mutants, we discovered that 29 bacterial genes, when deleted, increase longevity in the host Caenorhabditis elegans. A dozen of these bacterial mutants also protect the host from age-related progression of tumor growth and amyloid-beta accumulation. Mechanistically, we discovered that five bacterial mutants promote longevity through increased secretion of the polysaccharide colanic acid (CA), which regulates mitochondrial dynamics and unfolded protein response (UPR(mt)) in the host...
June 15, 2017: Cell
https://www.readbyqxmd.com/read/28622509/antibacterial-nucleoside-analog-inhibitor-of-bacterial-rna-polymerase
#8
Sonia I Maffioli, Yu Zhang, David Degen, Thomas Carzaniga, Giancarlo Del Gatto, Stefania Serina, Paolo Monciardini, Carlo Mazzetti, Paola Guglierame, Gianpaolo Candiani, Alina Iulia Chiriac, Giuseppe Facchetti, Petra Kaltofen, Hans-Georg Sahl, Gianni Dehò, Stefano Donadio, Richard H Ebright
Drug-resistant bacterial pathogens pose an urgent public-health crisis. Here, we report the discovery, from microbial-extract screening, of a nucleoside-analog inhibitor that inhibits bacterial RNA polymerase (RNAP) and exhibits antibacterial activity against drug-resistant bacterial pathogens: pseudouridimycin (PUM). PUM is a natural product comprising a formamidinylated, N-hydroxylated Gly-Gln dipeptide conjugated to 6'-amino-pseudouridine. PUM potently and selectively inhibits bacterial RNAP in vitro, inhibits bacterial growth in culture, and clears infection in a mouse model of Streptococcus pyogenes peritonitis...
June 15, 2017: Cell
https://www.readbyqxmd.com/read/28622508/saf-a-regulates-interphase-chromosome-structure-through-oligomerization-with-chromatin-associated-rnas
#9
Ryu-Suke Nozawa, Lora Boteva, Dinesh C Soares, Catherine Naughton, Alison R Dun, Adam Buckle, Bernard Ramsahoye, Peter C Bruton, Rebecca S Saleeb, Maria Arnedo, Bill Hill, Rory R Duncan, Sutherland K Maciver, Nick Gilbert
Higher eukaryotic chromosomes are organized into topologically constrained functional domains; however, the molecular mechanisms required to sustain these complex interphase chromatin structures are unknown. A stable matrix underpinning nuclear organization was hypothesized, but the idea was abandoned as more dynamic models of chromatin behavior became prevalent. Here, we report that scaffold attachment factor A (SAF-A), originally identified as a structural nuclear protein, interacts with chromatin-associated RNAs (caRNAs) via its RGG domain to regulate human interphase chromatin structures in a transcription-dependent manner...
June 15, 2017: Cell
https://www.readbyqxmd.com/read/28622507/independent-and-stochastic-action-of-dna-polymerases-in-the-replisome
#10
James E Graham, Kenneth J Marians, Stephen C Kowalczykowski
It has been assumed that DNA synthesis by the leading- and lagging-strand polymerases in the replisome must be coordinated to avoid the formation of significant gaps in the nascent strands. Using real-time single-molecule analysis, we establish that leading- and lagging-strand DNA polymerases function independently within a single replisome. Although average rates of DNA synthesis on leading and lagging strands are similar, individual trajectories of both DNA polymerases display stochastically switchable rates of synthesis interspersed with distinct pauses...
June 15, 2017: Cell
https://www.readbyqxmd.com/read/28622506/dynamic-rna-modifications-in-gene-expression-regulation
#11
REVIEW
Ian A Roundtree, Molly E Evans, Tao Pan, Chuan He
Over 100 types of chemical modifications have been identified in cellular RNAs. While the 5' cap modification and the poly(A) tail of eukaryotic mRNA play key roles in regulation, internal modifications are gaining attention for their roles in mRNA metabolism. The most abundant internal mRNA modification is N(6)-methyladenosine (m(6)A), and identification of proteins that install, recognize, and remove this and other marks have revealed roles for mRNA modification in nearly every aspect of the mRNA life cycle, as well as in various cellular, developmental, and disease processes...
June 15, 2017: Cell
https://www.readbyqxmd.com/read/28622505/an-expanded-view-of-complex-traits-from-polygenic-to-omnigenic
#12
REVIEW
Evan A Boyle, Yang I Li, Jonathan K Pritchard
A central goal of genetics is to understand the links between genetic variation and disease. Intuitively, one might expect disease-causing variants to cluster into key pathways that drive disease etiology. But for complex traits, association signals tend to be spread across most of the genome-including near many genes without an obvious connection to disease. We propose that gene regulatory networks are sufficiently interconnected such that all genes expressed in disease-relevant cells are liable to affect the functions of core disease-related genes and that most heritability can be explained by effects on genes outside core pathways...
June 15, 2017: Cell
https://www.readbyqxmd.com/read/28622504/sex-at-atomic-resolution
#13
Jae Yeon Hwang, Jean-Ju Chung
Interspecies fertilization is rare, partly due to species separation enforced at the molecular level. In this issue, Raj et al. now reveal the crystal structures of mollusk egg coat protein, VERL, complexed with cognate sperm protein lysin. Given that VERL is structurally similar to mammalian ZP2, the mechanism elucidating species-specific gamete recognition likely exists in mammals.
June 15, 2017: Cell
https://www.readbyqxmd.com/read/28622503/damed-in-trem-2-steps
#14
Sandro Da Mesquita, Jonathan Kipnis
The role of microglia in neurodegenerative diseases has been controversial. In this issue, Keren-Shaul et al. identify a unique population of disease-associated microglia (DAM) that develop in two steps and may help to restrict damage in Alzheimer and related diseases.
June 15, 2017: Cell
https://www.readbyqxmd.com/read/28622502/just-a-spoonful-of-sugar-helps-the-tolerance-go-up
#15
Alexander V Chervonsky
Survival of deleterious infections depends significantly on how much stress the affected organism can tolerate. In this issue, Weis et al. find that mice can survive sepsis by maintaining normoglycemia through ferritin's capacity to inactivate Fe(2+) ions that otherwise induce free radicals impacting gluconeogenesis in the liver.
June 15, 2017: Cell
https://www.readbyqxmd.com/read/28622501/microbiome-and-longevity-gut-microbes-send-signals-to-host-mitochondria
#16
Jan Gruber, Brian K Kennedy
The microbiome has emerged as a major determinant of the functioning of host organisms, affecting both health and disease. Here, Han et al. use the workhorse of aging research, C. elegans, to identify specific mechanisms by which gut bacteria influence mitochondrial dynamics and aging, a first step toward analogous manipulations to modulate human aging.
June 15, 2017: Cell
https://www.readbyqxmd.com/read/28622500/getting-surprising-answers-to-unasked-questions
#17
Ueli Schibler
No abstract text is available yet for this article.
June 15, 2017: Cell
https://www.readbyqxmd.com/read/28622499/the-measure-of-a-man
#18
Neil Savage
Moving beyond simple fitness tracking, wearable devices may soon offer opportunities for monitoring health and bring vast amounts of new data to the study of human diseases.
June 15, 2017: Cell
https://www.readbyqxmd.com/read/28622498/sorting-out-complex-thoughts-and-messy-emotions
#19
Stephen Matheson
No abstract text is available yet for this article.
June 15, 2017: Cell
https://www.readbyqxmd.com/read/28602353/visuomotor-coupling-shapes-the-functional-development-of-mouse-visual-cortex
#20
Alexander Attinger, Bo Wang, Georg B Keller
The emergence of sensory-guided behavior depends on sensorimotor coupling during development. How sensorimotor experience shapes neural processing is unclear. Here, we show that the coupling between motor output and visual feedback is necessary for the functional development of visual processing in layer 2/3 (L2/3) of primary visual cortex (V1) of the mouse. Using a virtual reality system, we reared mice in conditions of normal or random visuomotor coupling. We recorded the activity of identified excitatory and inhibitory L2/3 neurons in response to transient visuomotor mismatches in both groups of mice...
June 15, 2017: Cell
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