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Cell Reports

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https://www.readbyqxmd.com/read/28445737/rapid-automatic-motor-encoding-of-competing-reach-options
#1
Jason P Gallivan, Brandie M Stewart, Lee A Baugh, Daniel M Wolpert, J Randall Flanagan
No abstract text is available yet for this article.
April 25, 2017: Cell Reports
https://www.readbyqxmd.com/read/28445736/systematic-epigenomic-analysis-reveals-chromatin-states-associated-with-melanoma-progression
#2
Petko Fiziev, Kadir C Akdemir, John P Miller, Emily Z Keung, Neha S Samant, Sneha Sharma, Christopher A Natale, Christopher J Terranova, Mayinuer Maitituoheti, Samirkumar B Amin, Emmanuel Martinez-Ledesma, Mayura Dhamdhere, Jacob B Axelrad, Amiksha Shah, Christine S Cheng, Harshad Mahadeshwar, Sahil Seth, Michelle C Barton, Alexei Protopopov, Kenneth Y Tsai, Michael A Davies, Benjamin A Garcia, Ido Amit, Lynda Chin, Jason Ernst, Kunal Rai
The extent and nature of epigenomic changes associated with melanoma progression is poorly understood. Through systematic epigenomic profiling of 35 epigenetic modifications and transcriptomic analysis, we define chromatin state changes associated with melanomagenesis by using a cell phenotypic model of non-tumorigenic and tumorigenic states. Computation of specific chromatin state transitions showed loss of histone acetylations and H3K4me2/3 on regulatory regions proximal to specific cancer-regulatory genes in important melanoma-driving cell signaling pathways...
April 25, 2017: Cell Reports
https://www.readbyqxmd.com/read/28445735/a-design-principle-for-an-autonomous-post-translational-pattern-formation
#3
Shuhei S Sugai, Koji L Ode, Hiroki R Ueda
Previous autonomous pattern-formation models often assumed complex molecular and cellular networks. This theoretical study, however, shows that a system composed of one substrate with multisite phosphorylation and a pair of kinase and phosphatase can generate autonomous spatial information, including complex stripe patterns. All (de-)phosphorylation reactions are described with a generic Michaelis-Menten scheme, and all species freely diffuse without pre-existing gradients. Computational simulation upon >23,000,000 randomly generated parameter sets revealed the design motifs of cyclic reaction and enzyme sequestration by slow-diffusing substrates...
April 25, 2017: Cell Reports
https://www.readbyqxmd.com/read/28445734/opposing-actions-of-fgf8a-on-notch-signaling-distinguish-two-muller-glial-cell-populations-that-contribute-to-retina-growth-and-regeneration
#4
Jin Wan, Daniel Goldman
The teleost retina grows throughout life and exhibits a robust regenerative response following injury. Critical to both these events are Muller glia (or, Muller glial cells; MGs), which produce progenitors for retinal growth and repair. We report that Fgf8a may be an MG niche factor that acts through Notch signaling to regulate spontaneous and injury-dependent MG proliferation. Remarkably, forced Fgf8a expression inhibits Notch signaling and stimulates MG proliferation in young tissue but increases Notch signaling and suppresses MG proliferation in older tissue...
April 25, 2017: Cell Reports
https://www.readbyqxmd.com/read/28445733/nf-%C3%AE%C2%BAb-immunity-in-the-brain-determines-fly-lifespan-in-healthy-aging-and-age-related-neurodegeneration
#5
Ilias Kounatidis, Stanislava Chtarbanova, Yang Cao, Margaret Hayne, Dhruv Jayanth, Barry Ganetzky, Petros Ligoxygakis
During aging, innate immunity progresses to a chronically active state. However, what distinguishes those that "age well" from those developing age-related neurological conditions is unclear. We used Drosophila to explore the cost of immunity in the aging brain. We show that mutations in intracellular negative regulators of the IMD/NF-κB pathway predisposed flies to toxic levels of antimicrobial peptides, resulting in early locomotor defects, extensive neurodegeneration, and reduced lifespan. These phenotypes were rescued when immunity was suppressed in glia...
April 25, 2017: Cell Reports
https://www.readbyqxmd.com/read/28445732/the-hect-family-ubiquitin-ligase-eel-1-regulates-neuronal-function-and-development
#6
Karla J Opperman, Ben Mulcahy, Andrew C Giles, Monica G Risley, Rayna L Birnbaum, Erik D Tulgren, Ken Dawson-Scully, Mei Zhen, Brock Grill
Genetic changes in the HECT ubiquitin ligase HUWE1 are associated with intellectual disability, but it remains unknown whether HUWE1 functions in post-mitotic neurons to affect circuit function. Using genetics, pharmacology, and electrophysiology, we show that EEL-1, the HUWE1 ortholog in C. elegans, preferentially regulates GABAergic presynaptic transmission. Decreasing or increasing EEL-1 function alters GABAergic transmission and the excitatory/inhibitory (E/I) balance in the worm motor circuit, which leads to impaired locomotion and increased sensitivity to electroshock...
April 25, 2017: Cell Reports
https://www.readbyqxmd.com/read/28445731/hair-follicle-terminal-differentiation-is-orchestrated-by-distinct-early-and-late-matrix-progenitors
#7
Arlee L Mesler, Natalia A Veniaminova, Madison V Lull, Sunny Y Wong
During development and regeneration, matrix progenitors undergo terminal differentiation to form the concentric layers of the hair follicle. These differentiation events are thought to require signals from the mesenchymal dermal papilla (DP); however, it remains unclear how DP-progenitor cell interactions govern specific cell fate decisions. Here, we show that the hair follicle differentiated layers are specified asynchronously, with early matrix progenitors initiating differentiation before surrounding the DP...
April 25, 2017: Cell Reports
https://www.readbyqxmd.com/read/28445730/ripk3-mediates-necroptosis-during-embryonic-development-and-postnatal-inflammation-in-fadd-deficient-mice
#8
Qun Zhao, XianJun Yu, HaiWei Zhang, YongBo Liu, XiXi Zhang, XiaoXia Wu, Qun Xie, Ming Li, Hao Ying, Haibing Zhang
RIPK3 mediates cell death and regulates inflammatory responses. Although genetic studies have suggested that RIPK3-MLKL-mediated necroptosis leads to embryonic lethality in Fadd or Caspase-8-deficient mice, the exact mechanisms are not fully understood. Here, we generated Ripk3 mutant mice by altering the RIPK3 kinase domain (Ripk3(Δ/Δ) mice), thus abolishing its kinase activity. Ripk3(Δ/Δ) cells were resistant to necroptosis stimulation in vitro, and Ripk3(Δ/Δ) mice were protected from necroptotic diseases...
April 25, 2017: Cell Reports
https://www.readbyqxmd.com/read/28445729/caspase-10-negatively-regulates-caspase-8-mediated-cell-death-switching-the-response-to-cd95l-in-favor-of-nf-%C3%AE%C2%BAb-activation-and-cell-survival
#9
Sebastian Horn, Michelle A Hughes, Ramon Schilling, Carsten Sticht, Tencho Tenev, Michaela Ploesser, Pascal Meier, Martin R Sprick, Marion MacFarlane, Martin Leverkus
Formation of the death-inducing signaling complex (DISC) initiates extrinsic apoptosis. Caspase-8 and its regulator cFLIP control death signaling by binding to death-receptor-bound FADD. By elucidating the function of the caspase-8 homolog, caspase-10, we discover that caspase-10 negatively regulates caspase-8-mediated cell death. Significantly, we reveal that caspase-10 reduces DISC association and activation of caspase-8. Furthermore, we extend our co-operative/hierarchical binding model of caspase-8/cFLIP and show that caspase-10 does not compete with caspase-8 for binding to FADD...
April 25, 2017: Cell Reports
https://www.readbyqxmd.com/read/28445728/blocking-surgically-induced-lysyl-oxidase-activity-reduces-the-risk-of-lung-metastases
#10
Chen Rachman-Tzemah, Shelly Zaffryar-Eilot, Moran Grossman, Dario Ribero, Michael Timaner, Joni M Mäki, Johanna Myllyharju, Francesco Bertolini, Dov Hershkovitz, Irit Sagi, Peleg Hasson, Yuval Shaked
Surgery remains the most successful curative treatment for cancer. However, some patients with early-stage disease who undergo surgery eventually succumb to distant metastasis. Here, we show that in response to surgery, the lungs become more vulnerable to metastasis due to extracellular matrix remodeling. Mice that undergo surgery or that are preconditioned with plasma from donor mice that underwent surgery succumb to lung metastases earlier than controls. Increased lysyl oxidase (LOX) activity and expression, fibrillary collagen crosslinking, and focal adhesion signaling contribute to this effect, with the hypoxic surgical site serving as the source of LOX...
April 25, 2017: Cell Reports
https://www.readbyqxmd.com/read/28445727/environmental-enrichment-induces-pericyte-and-iga-dependent-wound-repair-and-lifespan-extension-in-a-colon-tumor-model
#11
Benjamin D Bice, Megan R Stephens, Stephanie J Georges, Ashlee R Venancio, Peter C Bermant, Annika V Warncke, Kajsa E Affolter, Julio R Hidalgo, Melinda L Angus-Hill
Environmental enrichment (EE) replicates mind-body therapy by providing complex housing to laboratory animals to improve their activity levels, behavior, and social interactions. Using a Tcf4(Het/+)Apc(Min/+)-mediated model of colon tumorigenesis, we found that EE vastly improved the survival of tumor-bearing animals, with differential effect on tumor load in male compared to female animals. Analysis of Tcf4(Het/+)Apc(Min/+) males showed drastically reduced expression of circulating inflammatory cytokines and induced nuclear hormone receptor (NHR) signaling, both of which are common in the wound repair process...
April 25, 2017: Cell Reports
https://www.readbyqxmd.com/read/28445726/sirtuin-1-activation-controls-tumor-growth-by-impeding-th17-differentiation-via-stat3-deacetylation
#12
Emeric Limagne, Marion Thibaudin, Romain Euvrard, Hélène Berger, Pauline Chalons, Frédérique Végan, Etienne Humblin, Romain Boidot, Cédric Rébé, Valentin Derangère, Sylvain Ladoire, Lionel Apetoh, Dominique Delmas, François Ghiringhelli
Sirtuin-1 deacetylates proteins and has emerged as a critical regulator of different cellular processes, particularly inflammation. Basal SIRT1 activity was previously found to limit Th9 and enhance Th17 differentiation in mice, but the effect of pharmacological SIRT1 activation on T cell differentiation and antitumor responses remains unclear. Here, we find that SIRT1 pharmacological agonists selectively impede mouse and human Th17 cell differentiation. SIRT1 activation induces STAT3 deacetylation, thus reducing its ability to translocate into the nucleus, bind to Rorc promoter, and induce its transcription...
April 25, 2017: Cell Reports
https://www.readbyqxmd.com/read/28445725/nlrp6-protects-il10-mice-from-colitis-by-limiting-colonization-of-akkermansia-muciniphila
#13
Sergey S Seregin, Natasha Golovchenko, Bryan Schaf, Jiachen Chen, Nicholas A Pudlo, Jonathan Mitchell, Nielson T Baxter, Lili Zhao, Patrick D Schloss, Eric C Martens, Kathryn A Eaton, Grace Y Chen
Dysfunction in host immune responses and pathologic alterations in the gut microbiota, referred to as dysbiosis, can both contribute to the development of inflammatory bowel disease (IBD). However, it remains unclear how specific changes in host immunity or the microbiota cause disease. We previously demonstrated that the loss of the innate immune receptor NLRP6 in mice resulted in impaired production of interleukin-18 (IL-18) and increased susceptibility to epithelial-induced injury. Here, we show that NLRP6 is important for suppressing the development of spontaneous colitis in the Il10(-/-) mice model of IBD and that NLRP6 deficiency results in the enrichment of Akkermansia muciniphila...
April 25, 2017: Cell Reports
https://www.readbyqxmd.com/read/28445724/quantification-of-the-impact-of-the-hiv-1-glycan-shield-on-antibody-elicitation
#14
Tongqing Zhou, Nicole A Doria-Rose, Cheng Cheng, Guillaume B E Stewart-Jones, Gwo-Yu Chuang, Michael Chambers, Aliaksandr Druz, Hui Geng, Krisha McKee, Young Do Kwon, Sijy O'Dell, Mallika Sastry, Stephen D Schmidt, Kai Xu, Lei Chen, Rita E Chen, Mark K Louder, Marie Pancera, Timothy G Wanninger, Baoshan Zhang, Anqi Zheng, S Katie Farney, Kathryn E Foulds, Ivelin S Georgiev, M Gordon Joyce, Thomas Lemmin, Sandeep Narpala, Reda Rawi, Cinque Soto, John-Paul Todd, Chen-Hsiang Shen, Yaroslav Tsybovsky, Yongping Yang, Peng Zhao, Barton F Haynes, Leonidas Stamatatos, Michael Tiemeyer, Lance Wells, Diana G Scorpio, Lawrence Shapiro, Adrian B McDermott, John R Mascola, Peter D Kwong
While the HIV-1-glycan shield is known to shelter Env from the humoral immune response, its quantitative impact on antibody elicitation has been unclear. Here, we use targeted deglycosylation to measure the impact of the glycan shield on elicitation of antibodies against the CD4 supersite. We engineered diverse Env trimers with select glycans removed proximal to the CD4 supersite, characterized their structures and glycosylation, and immunized guinea pigs and rhesus macaques. Immunizations yielded little neutralization against wild-type viruses but potent CD4-supersite neutralization (titers 1: >1,000,000 against four-glycan-deleted autologous viruses with over 90% breadth against four-glycan-deleted heterologous strains exhibiting tier 2 neutralization character)...
April 25, 2017: Cell Reports
https://www.readbyqxmd.com/read/28445723/mosquitoes-transmit-unique-west-nile-virus-populations-during-each-feeding-episode
#15
Nathan D Grubaugh, Joseph R Fauver, Claudia Rückert, James Weger-Lucarelli, Selene Garcia-Luna, Reyes A Murrieta, Alex Gendernalik, Darci R Smith, Doug E Brackney, Gregory D Ebel
Arthropod-borne viruses (arboviruses), such as Zika virus, chikungunya virus, and West Nile virus (WNV), pose continuous threats to emerge and cause large epidemics. Often, these events are associated with novel virus variants optimized for local transmission that first arise as minorities within a host. Thus, the conditions that regulate the frequency of intrahost variants are important determinants of emergence. Here, we describe the dynamics of WNV genetic diversity during its transmission cycle. By temporally sampling saliva from individual mosquitoes, we demonstrate that virus populations expectorated by mosquitoes are highly diverse and unique to each feeding episode...
April 25, 2017: Cell Reports
https://www.readbyqxmd.com/read/28445722/genomic-analyses-reveal-the-influence-of-geographic-origin-migration-and-hybridization-on-modern-dog-breed-development
#16
Heidi G Parker, Dayna L Dreger, Maud Rimbault, Brian W Davis, Alexandra B Mullen, Gretchen Carpintero-Ramirez, Elaine A Ostrander
There are nearly 400 modern domestic dog breeds with a unique histories and genetic profiles. To track the genetic signatures of breed development, we have assembled the most diverse dataset of dog breeds, reflecting their extensive phenotypic variation and heritage. Combining genetic distance, migration, and genome-wide haplotype sharing analyses, we uncover geographic patterns of development and independent origins of common traits. Our analyses reveal the hybrid history of breeds and elucidate the effects of immigration, revealing for the first time a suggestion of New World dog within some modern breeds...
April 25, 2017: Cell Reports
https://www.readbyqxmd.com/read/28445721/nacho-mediates-nicotinic-acetylcholine-receptor-function-throughout-the-brain
#17
Jose A Matta, Shenyan Gu, Weston B Davini, Brian Lord, Edward R Siuda, Anthony W Harrington, David S Bredt
Neuronal nicotinic acetylcholine receptors (nAChRs) participate in diverse aspects of brain function and mediate behavioral and addictive properties of nicotine. Neuronal nAChRs derive from combinations of α and β subunits, whose assembly is tightly regulated. NACHO was recently identified as a chaperone for α7-type nAChRs. Here, we find NACHO mediates assembly of all major classes of presynaptic and postsynaptic nAChR tested. NACHO acts at early intracellular stages of nAChR subunit assembly and then synergizes with RIC-3 for receptor surface expression...
April 25, 2017: Cell Reports
https://www.readbyqxmd.com/read/28445720/hsp90-is-essential-under-heat-stress-in-the-bacterium-shewanella-oneidensis
#18
Flora Ambre Honoré, Vincent Méjean, Olivier Genest
The Hsp90 chaperone is essential in eukaryotes and activates a large array of client proteins. In contrast, its role is still elusive in bacteria, and only a few Hsp90 bacterial clients are known. Here, we found that Hsp90 is essential in the model bacterium Shewanella oneidensis under heat stress. A genetic screen for Hsp90 client proteins identified TilS, an essential protein involved in tRNA maturation. Overexpression of TilS rescued the growth defect of the hsp90 deletion strain under heat stress. In vivo, the activity and the amount of TilS were significantly reduced in the absence of Hsp90 at high temperature...
April 25, 2017: Cell Reports
https://www.readbyqxmd.com/read/28445719/kat-independent-gene-regulation-by-tip60-promotes-esc-self-renewal-but-not-pluripotency
#19
Diwash Acharya, Sarah J Hainer, Yeonsoo Yoon, Feng Wang, Ingolf Bach, Jaime A Rivera-Pérez, Thomas G Fazzio
Although histone-modifying enzymes are generally assumed to function in a manner dependent on their enzymatic activities, this assumption remains untested for many factors. Here, we show that the Tip60 (Kat5) lysine acetyltransferase (KAT), which is essential for embryonic stem cell (ESC) self-renewal and pre-implantation development, performs these functions independently of its KAT activity. Unlike ESCs depleted of Tip60, KAT-deficient ESCs exhibited minimal alterations in gene expression, chromatin accessibility at Tip60 binding sites, and self-renewal, thus demonstrating a critical KAT-independent role of Tip60 in ESC maintenance...
April 25, 2017: Cell Reports
https://www.readbyqxmd.com/read/28445718/the-hiv-1-glycan-shield-strategically-placed-kinks-in-the-armor-improve-antigen-design
#20
Christina Beatrice Karsten, Galit Alter
Dense glycosylation on the HIV-1 envelope glycoprotein hampers the induction of broadly neutralizing antibodies against HIV-1. Zhou et al. remove key glycans to unmask sites of vulnerability and enable the induction of neutralizing antibodies.
April 25, 2017: Cell Reports
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