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https://www.readbyqxmd.com/read/28089356/insertions-and-deletions-target-lineage-defining-genes-in-human-cancers
#1
Marcin Imielinski, Guangwu Guo, Matthew Meyerson
Certain cell types function as factories, secreting large quantities of one or more proteins that are central to the physiology of the respective organ. Examples include surfactant proteins in lung alveoli, albumin in liver parenchyma, and lipase in the stomach lining. Whole-genome sequencing analysis of lung adenocarcinomas revealed noncoding somatic mutational hotspots near VMP1/MIR21 and indel hotspots in surfactant protein genes (SFTPA1, SFTPB, and SFTPC). Extrapolation to other solid cancers demonstrated highly recurrent and tumor-type-specific indel hotspots targeting the noncoding regions of highly expressed genes defining certain secretory cellular lineages: albumin (ALB) in liver carcinoma, gastric lipase (LIPF) in stomach carcinoma, and thyroglobulin (TG) in thyroid carcinoma...
January 11, 2017: Cell
https://www.readbyqxmd.com/read/28086100/the-interfaces-of-genetic-conflict-are-hot-spots-for-innovation
#2
Joshua Carter, Connor Hoffman, Blake Wiedenheft
RNA-guided Cas9 endonucleases protect bacteria from viral infection and have been creatively repurposed as programmable molecular scalpels for surgical manipulation of DNA. Now, two papers in Cell (Pawluk et al. and Rauch et al.) identify viral proteins that suppress Cas9 and may function like molecular sheaths for the Cas9 scalpel.
January 12, 2017: Cell
https://www.readbyqxmd.com/read/28086099/gaba-signaling-stimulates-%C3%AE-cell-regeneration-in-diabetic-mice
#3
Gordon C Weir, Susan Bonner-Weir
GABA and the antimalarial drug artemether, which acts on GABAergic pathways, can drive pancreatic cells with an α-cell phenotype toward a β-cell-like phenotype. As reported in two papers (Ben-Othman et al. and Li et al.), these drugs can stimulate the production of sufficient numbers of new β-like cells to reverse severe diabetes in mice.
January 12, 2017: Cell
https://www.readbyqxmd.com/read/28086098/30-years-of-nf-%C3%AE%C2%BAb-a-blossoming-of-relevance-to-human-pathobiology
#4
REVIEW
Qian Zhang, Michael J Lenardo, David Baltimore
NF-κB was discovered 30 years ago as a rapidly inducible transcription factor. Since that time, it has been found to have a broad role in gene induction in diverse cellular responses, particularly throughout the immune system. Here, we summarize elaborate regulatory pathways involving this transcription factor and use recent discoveries in human genetic diseases to place specific proteins within their relevant medical and biological contexts.
January 12, 2017: Cell
https://www.readbyqxmd.com/read/28086097/snapshot-class-2-crispr-cas-systems
#5
Kira S Makarova, Feng Zhang, Eugene V Koonin
Class 2 CRISPR-Cas systems are characterized by effector modules consisting of single, large, multidomain proteins that appear to have been derived from mobile genetic elements. Some Class 2 effector proteins, such as Cas9 and Cas12a (Cpf1), have been successfully repurposed for genome engineering.
January 12, 2017: Cell
https://www.readbyqxmd.com/read/28086096/the-c-%C3%A2-elegans-taste-receptor-homolog-lite-1-is-a-photoreceptor
#6
Jianke Gong, Yiyuan Yuan, Alex Ward, Lijun Kang, Bi Zhang, Zhiping Wu, Junmin Peng, Zhaoyang Feng, Jianfeng Liu, X Z Shawn Xu
No abstract text is available yet for this article.
January 12, 2017: Cell
https://www.readbyqxmd.com/read/28086095/integrated-control-of-predatory-hunting-by-the-central-nucleus-of-the-amygdala
#7
Wenfei Han, Luis A Tellez, Miguel J Rangel, Simone C Motta, Xiaobing Zhang, Isaac O Perez, Newton S Canteras, Sara J Shammah-Lagnado, Anthony N van den Pol, Ivan E de Araujo
Superior predatory skills led to the evolutionary triumph of jawed vertebrates. However, the mechanisms by which the vertebrate brain controls predation remain largely unknown. Here, we reveal a critical role for the central nucleus of the amygdala in predatory hunting. Both optogenetic and chemogenetic stimulation of central amygdala of mice elicited predatory-like attacks upon both insect and artificial prey. Coordinated control of cervical and mandibular musculatures, which is necessary for accurately positioning lethal bites on prey, was mediated by a central amygdala projection to the reticular formation in the brainstem...
January 12, 2017: Cell
https://www.readbyqxmd.com/read/28086094/in-search-of-scientific-inspiration
#8
(no author information available yet)
In the ever-expanding sea of scientific advances, how do you find inspiration for your own study? Cell editor Jiaying Tan talked with Mark Lemmon and Joseph (Yossi) Schlessinger about the importance of fueling your research creativity with the conceptual excitement and technical advance from the broad scientific field. An excerpt of the conversation appears below.
January 12, 2017: Cell
https://www.readbyqxmd.com/read/28086093/dynamic-remodeling-of-membrane-composition-drives-cell-cycle-through-primary-cilia-excision
#9
Siew Cheng Phua, Shuhei Chiba, Masako Suzuki, Emily Su, Elle C Roberson, Ganesh V Pusapati, Mitsutoshi Setou, Rajat Rohatgi, Jeremy F Reiter, Koji Ikegami, Takanari Inoue
The life cycle of a primary cilium begins in quiescence and ends prior to mitosis. In quiescent cells, the primary cilium insulates itself from contiguous dynamic membrane processes on the cell surface to function as a stable signaling apparatus. Here, we demonstrate that basal restriction of ciliary structure dynamics is established by the cilia-enriched phosphoinositide 5-phosphatase, Inpp5e. Growth induction displaces ciliary Inpp5e and accumulates phosphatidylinositol 4,5-bisphosphate in distal cilia. This change triggers otherwise-forbidden actin polymerization in primary cilia, which excises cilia tips in a process we call cilia decapitation...
January 12, 2017: Cell
https://www.readbyqxmd.com/read/28086092/nuclear-localization-of-mitochondrial-tca-cycle-enzymes-as-a-critical-step-in-mammalian-zygotic-genome-activation
#10
Raghavendra Nagaraj, Mark S Sharpley, Fangtao Chi, Daniel Braas, Yonggang Zhou, Rachel Kim, Amander T Clark, Utpal Banerjee
Transcriptional control requires epigenetic changes directed by mitochondrial tricarboxylic acid (TCA) cycle metabolites. In the mouse embryo, global epigenetic changes occur during zygotic genome activation (ZGA) at the 2-cell stage. Pyruvate is essential for development beyond this stage, which is at odds with the low activity of mitochondria in this period. We now show that a number of enzymatically active mitochondrial enzymes associated with the TCA cycle are essential for epigenetic remodeling and are transiently and partially localized to the nucleus...
January 12, 2017: Cell
https://www.readbyqxmd.com/read/28086091/species-independent-attraction-to-biofilms-through-electrical-signaling
#11
Jacqueline Humphries, Liyang Xiong, Jintao Liu, Arthur Prindle, Fang Yuan, Heidi A Arjes, Lev Tsimring, Gürol M Süel
Bacteria residing within biofilm communities can coordinate their behavior through cell-to-cell signaling. However, it remains unclear if these signals can also influence the behavior of distant cells that are not part of the community. Using a microfluidic approach, we find that potassium ion channel-mediated electrical signaling generated by a Bacillus subtilis biofilm can attract distant cells. Integration of experiments and mathematical modeling indicates that extracellular potassium emitted from the biofilm alters the membrane potential of distant cells, thereby directing their motility...
January 12, 2017: Cell
https://www.readbyqxmd.com/read/28086090/a-periplasmic-polymer-curves-vibrio-cholerae-and-promotes-pathogenesis
#12
Thomas M Bartlett, Benjamin P Bratton, Amit Duvshani, Amanda Miguel, Ying Sheng, Nicholas R Martin, Jeffrey P Nguyen, Alexandre Persat, Samantha M Desmarais, Michael S VanNieuwenhze, Kerwyn Casey Huang, Jun Zhu, Joshua W Shaevitz, Zemer Gitai
Pathogenic Vibrio cholerae remains a major human health concern. V. cholerae has a characteristic curved rod morphology, with a longer outer face and a shorter inner face. The mechanism and function of this curvature were previously unknown. Here, we identify and characterize CrvA, the first curvature determinant in V. cholerae. CrvA self-assembles into filaments at the inner face of cell curvature. Unlike traditional cytoskeletons, CrvA localizes to the periplasm and thus can be considered a periskeletal element...
January 12, 2017: Cell
https://www.readbyqxmd.com/read/28086089/blood-on-the-tracks-two-pathways-for-predation
#13
Robert R Rozeske, Cyril Herry
Accurate predatory behavior requires coordination between pursuit activity and prey consumption, yet the underlying neuronal circuits are unknown. A novel study published in this issue of Cell identifies two coordinated circuits emanating from the central amygdala that control the efficiency of prey capture and the ability to deliver fatal bites to prey.
January 12, 2017: Cell
https://www.readbyqxmd.com/read/28086088/staying-in-touch-while-on-the-go
#14
Kerwyn Casey Huang
While chemical forms of cell-to-cell communication are well recognized to coordinate bacterial populations, electrical signaling has been relatively ignored. Humphries et al. show that Bacillus subtilis biofilms utilize potassium production to attract far away, motile cells of even phylogenetically distant species by altering their membrane potential.
January 12, 2017: Cell
https://www.readbyqxmd.com/read/28086087/rna-binding-to-cbp-stimulates-histone-acetylation-and-transcription
#15
Daniel A Bose, Greg Donahue, Danny Reinberg, Ramin Shiekhattar, Roberto Bonasio, Shelley L Berger
CBP/p300 are transcription co-activators whose binding is a signature of enhancers, cis-regulatory elements that control patterns of gene expression in multicellular organisms. Active enhancers produce bi-directional enhancer RNAs (eRNAs) and display CBP/p300-dependent histone acetylation. Here, we demonstrate that CBP binds directly to RNAs in vivo and in vitro. RNAs bound to CBP in vivo include a large number of eRNAs. Using steady-state histone acetyltransferase (HAT) assays, we show that an RNA binding region in the HAT domain of CBP-a regulatory motif unique to CBP/p300-allows RNA to stimulate CBP's HAT activity...
January 12, 2017: Cell
https://www.readbyqxmd.com/read/28086086/vesicles-spread-susceptibility-to-phages
#16
Gal Ofir, Rotem Sorek
Extracellular membrane vesicles from bacteria are now shown to transfer phage receptors from susceptible to resistant cells, thus making them transiently sensitive to phage infection (Tzipilevich et al.).
January 12, 2017: Cell
https://www.readbyqxmd.com/read/28086085/two-distant-catalytic-sites-are-responsible-for-c2c2-rnase-activities
#17
Liang Liu, Xueyan Li, Jiuyu Wang, Min Wang, Peng Chen, Maolu Yin, Jiazhi Li, Gang Sheng, Yanli Wang
C2c2, the effector of type VI CRISPR-Cas systems, has two RNase activities-one for cutting its RNA target and the other for processing the CRISPR RNA (crRNA). Here, we report the structures of Leptotrichia shahii C2c2 in its crRNA-free and crRNA-bound states. While C2c2 has a bilobed structure reminiscent of all other Class 2 effectors, it also exhibits different structural characteristics. It contains the REC lobe with a Helical-1 domain and the NUC lobe with two HEPN domains. The two RNase catalytic pockets responsible for cleaving pre-crRNA and target RNA are independently located on Helical-1 and HEPN domains, respectively...
January 12, 2017: Cell
https://www.readbyqxmd.com/read/28086084/structures-of-the-human-hcn1-hyperpolarization-activated-channel
#18
Chia-Hsueh Lee, Roderick MacKinnon
Hyperpolarization-activated cyclic nucleotide-gated (HCN) channels underlie the control of rhythmic activity in cardiac and neuronal pacemaker cells. In HCN, the polarity of voltage dependence is uniquely reversed. Intracellular cyclic adenosine monophosphate (cAMP) levels tune the voltage response, enabling sympathetic nerve stimulation to increase the heart rate. We present cryo-electron microscopy structures of the human HCN channel in the absence and presence of cAMP at 3.5 Å resolution. HCN channels contain a K(+) channel selectivity filter-forming sequence from which the amino acids create a unique structure that explains Na(+) and K(+) permeability...
January 12, 2017: Cell
https://www.readbyqxmd.com/read/28086083/shining-a-light-on-phase-separation-in-the-cell
#19
Giulia Paci, Edward A Lemke
Phase separation of proteins is recognized as an important aspect of cellular organization and disease mechanisms. Shin et al. introduce a novel optogenetic tool, which enables different phase-space regimes inside living cells to be assessed and the transition paths between them to be studied with unprecedented spatiotemporal control.
January 12, 2017: Cell
https://www.readbyqxmd.com/read/28086082/structure-of-a-pancreatic-atp-sensitive-potassium-channel
#20
Ningning Li, Jing-Xiang Wu, Dian Ding, Jiaxuan Cheng, Ning Gao, Lei Chen
ATP-sensitive potassium channels (KATP) couple intracellular ATP levels with membrane excitability. These channels play crucial roles in many essential physiological processes and have been implicated extensively in a spectrum of metabolic diseases and disorders. To gain insight into the mechanism of KATP, we elucidated the structure of a hetero-octameric pancreatic KATP channel in complex with a non-competitive inhibitor glibenclamide by single-particle cryoelectron microscopy to 5.6-Å resolution. The structure shows that four SUR1 regulatory subunits locate peripherally and dock onto the central Kir6...
January 12, 2017: Cell
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