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https://www.readbyqxmd.com/read/28689640/distinct-ventral-pallidal-neural-populations-mediate-separate-symptoms-of-depression
#1
Daniel Knowland, Varoth Lilascharoen, Christopher Pham Pacia, Sora Shin, Eric Hou-Jen Wang, Byung Kook Lim
Major depressive disorder (MDD) patients display a common but often variable set of symptoms making successful, sustained treatment difficult to achieve. Separate depressive symptoms may be encoded by differential changes in distinct circuits in the brain, yet how discrete circuits underlie behavioral subsets of depression and how they adapt in response to stress has not been addressed. We identify two discrete circuits of parvalbumin-positive (PV) neurons in the ventral pallidum (VP) projecting to either the lateral habenula or ventral tegmental area contributing to depression...
July 5, 2017: Cell
https://www.readbyqxmd.com/read/28689641/life-long-genetic-and-functional-access-to-neural-circuits-using-self-inactivating-rabies-virus
#2
Ernesto Ciabatti, Ana González-Rueda, Letizia Mariotti, Fabio Morgese, Marco Tripodi
Neural networks are emerging as the fundamental computational unit of the brain and it is becoming progressively clearer that network dysfunction is at the core of a number of psychiatric and neurodegenerative disorders. Yet, our ability to target specific networks for functional or genetic manipulations remains limited. Monosynaptically restricted rabies virus facilitates the anatomical investigation of neural circuits. However, the inherent cytotoxicity of the rabies largely prevents its implementation in long-term functional studies and the genetic manipulation of neural networks...
July 1, 2017: Cell
https://www.readbyqxmd.com/read/28709005/retraction-notice-to-vulnerability-of-glioblastoma-cells-to-catastrophic-vacuolization-and-death-induced-by-a-small-molecule
#3
Satish Srinivas Kitambi, Enrique M Toledo, Dmitry Usoskin, Shimei Wee, Aditya Harisankar, Richard Svensson, Kristmundur Sigmundsson, Christina Kalderén, Mia Niklasson, Soumi Kundu, Sergi Aranda, Bengt Westermark, Lene Uhrbom, Michael Andäng, Peter Damberg, Sven Nelander, Ernest Arenas, Per Artursson, Julian Walfridsson, Karin Forsberg Nilsson, Lars G J Hammarström, Patrik Ernfors
No abstract text is available yet for this article.
July 13, 2017: Cell
https://www.readbyqxmd.com/read/28709004/mapping-the-neural-substrates-of-behavior
#4
Alice A Robie, Jonathan Hirokawa, Austin W Edwards, Lowell A Umayam, Allen Lee, Mary L Phillips, Gwyneth M Card, Wyatt Korff, Gerald M Rubin, Julie H Simpson, Michael B Reiser, Kristin Branson
Assigning behavioral functions to neural structures has long been a central goal in neuroscience and is a necessary first step toward a circuit-level understanding of how the brain generates behavior. Here, we map the neural substrates of locomotion and social behaviors for Drosophila melanogaster using automated machine-vision and machine-learning techniques. From videos of 400,000 flies, we quantified the behavioral effects of activating 2,204 genetically targeted populations of neurons. We combined a novel quantification of anatomy with our behavioral analysis to create brain-behavior correlation maps, which are shared as browsable web pages and interactive software...
July 13, 2017: Cell
https://www.readbyqxmd.com/read/28709003/3d-chromatin-structures-of-mature-gametes-and-structural-reprogramming-during-mammalian-embryogenesis
#5
Yuwen Ke, Yanan Xu, Xuepeng Chen, Songjie Feng, Zhenbo Liu, Yaoyu Sun, Xuelong Yao, Fangzhen Li, Wei Zhu, Lei Gao, Haojie Chen, Zhenhai Du, Wei Xie, Xiaocui Xu, Xingxu Huang, Jiang Liu
High-order chromatin structure plays important roles in gene expression regulation. Knowledge of the dynamics of 3D chromatin structures during mammalian embryo development remains limited. We report the 3D chromatin architecture of mouse gametes and early embryos using an optimized Hi-C method with low-cell samples. We find that mature oocytes at the metaphase II stage do not have topologically associated domains (TADs). In sperm, extra-long-range interactions (>4 Mb) and interchromosomal interactions occur frequently...
July 13, 2017: Cell
https://www.readbyqxmd.com/read/28709002/exosome-rna-unshielding-couples-stromal-activation-to-pattern-recognition-receptor-signaling-in-cancer
#6
Barzin Y Nabet, Yu Qiu, Jacob E Shabason, Tony J Wu, Taewon Yoon, Brian C Kim, Joseph L Benci, Angela M DeMichele, Julia Tchou, Joseph Marcotrigiano, Andy J Minn
Interactions between stromal fibroblasts and cancer cells generate signals for cancer progression, therapy resistance, and inflammatory responses. Although endogenous RNAs acting as damage-associated molecular patterns (DAMPs) for pattern recognition receptors (PRRs) may represent one such signal, these RNAs must remain unrecognized under non-pathological conditions. We show that triggering of stromal NOTCH-MYC by breast cancer cells results in a POL3-driven increase in RN7SL1, an endogenous RNA normally shielded by RNA binding proteins SRP9/14...
July 13, 2017: Cell
https://www.readbyqxmd.com/read/28709001/ciliary-hedgehog-signaling-restricts-injury-induced-adipogenesis
#7
Daniel Kopinke, Elle C Roberson, Jeremy F Reiter
Injured skeletal muscle regenerates, but with age or in muscular dystrophies, muscle is replaced by fat. Upon injury, muscle-resident fibro/adipogenic progenitors (FAPs) proliferated and gave rise to adipocytes. These FAPs dynamically produced primary cilia, structures that transduce intercellular cues such as Hedgehog (Hh) signals. Genetically removing cilia from FAPs inhibited intramuscular adipogenesis, both after injury and in a mouse model of Duchenne muscular dystrophy. Blocking FAP ciliation also enhanced myofiber regeneration after injury and reduced myofiber size decline in the muscular dystrophy model...
July 13, 2017: Cell
https://www.readbyqxmd.com/read/28709000/regulatory-expansion-in-mammals-of-multivalent-hnrnp-assemblies-that-globally-control-alternative-splicing
#8
Serge Gueroussov, Robert J Weatheritt, Dave O'Hanlon, Zhen-Yuan Lin, Ashrut Narula, Anne-Claude Gingras, Benjamin J Blencowe
Alternative splicing (AS) patterns have diverged rapidly during vertebrate evolution, yet the functions of most species- and lineage-specific splicing events are not known. We observe that mammalian-specific AS events are enriched in transcript sequences encoding intrinsically disordered regions (IDRs) of proteins, in particular those containing glycine/tyrosine repeats that mediate formation of higher-order protein assemblies implicated in gene regulation and human disease. These evolutionary changes impact nearly all members of the hnRNP A and D families of RNA binding proteins...
July 13, 2017: Cell
https://www.readbyqxmd.com/read/28708999/splicing-activation-by-rbfox-requires-self-aggregation-through-its-tyrosine-rich-domain
#9
Yi Ying, Xiao-Jun Wang, Celine K Vuong, Chia-Ho Lin, Andrey Damianov, Douglas L Black
Proteins of the Rbfox family act with a complex of proteins called the Large Assembly of Splicing Regulators (LASR). We find that Rbfox interacts with LASR via its C-terminal domain (CTD), and this domain is essential for its splicing activity. In addition to LASR recruitment, a low-complexity (LC) sequence within the CTD contains repeated tyrosines that mediate higher-order assembly of Rbfox/LASR and are required for splicing activation by Rbfox. This sequence spontaneously aggregates in solution to form fibrous structures and hydrogels, suggesting an assembly similar to the insoluble cellular inclusions formed by FUS and other proteins in neurologic disease...
July 13, 2017: Cell
https://www.readbyqxmd.com/read/28708998/profiling-ssb-nascent-chain-interactions-reveals-principles-of-hsp70-assisted-folding
#10
Kristina Döring, Nabeel Ahmed, Trine Riemer, Harsha Garadi Suresh, Yevhen Vainshtein, Markus Habich, Jan Riemer, Matthias P Mayer, Edward P O'Brien, Günter Kramer, Bernd Bukau
The yeast Hsp70 chaperone Ssb interacts with ribosomes and nascent polypeptides to assist protein folding. To reveal its working principle, we determined the nascent chain-binding pattern of Ssb at near-residue resolution by in vivo selective ribosome profiling. Ssb associates broadly with cytosolic, nuclear, and hitherto unknown substrate classes of mitochondrial and endoplasmic reticulum (ER) nascent proteins, supporting its general chaperone function. Ssb engages most substrates by multiple binding-release cycles to a degenerate sequence enriched in positively charged and aromatic amino acids...
July 13, 2017: Cell
https://www.readbyqxmd.com/read/28708997/vaccine-mediated-protection-against-zika-virus-induced-congenital-disease
#11
Justin M Richner, Brett W Jagger, Chao Shan, Camila R Fontes, Kimberly A Dowd, Bin Cao, Sunny Himansu, Elizabeth A Caine, Bruno T D Nunes, Daniele B A Medeiros, Antonio E Muruato, Bryant M Foreman, Huanle Luo, Tian Wang, Alan D Barrett, Scott C Weaver, Pedro F C Vasconcelos, Shannan L Rossi, Giuseppe Ciaramella, Indira U Mysorekar, Theodore C Pierson, Pei-Yong Shi, Michael S Diamond
The emergence of Zika virus (ZIKV) and its association with congenital malformations has prompted the rapid development of vaccines. Although efficacy with multiple viral vaccine platforms has been established in animals, no study has addressed protection during pregnancy. We tested in mice two vaccine platforms, a lipid nanoparticle-encapsulated modified mRNA vaccine encoding ZIKV prM and E genes and a live-attenuated ZIKV strain encoding an NS1 protein without glycosylation, for their ability to protect against transmission to the fetus...
July 13, 2017: Cell
https://www.readbyqxmd.com/read/28708996/functional-profiling-of-a-plasmodium-genome-reveals-an-abundance-of-essential-genes
#12
Ellen Bushell, Ana Rita Gomes, Theo Sanderson, Burcu Anar, Gareth Girling, Colin Herd, Tom Metcalf, Katarzyna Modrzynska, Frank Schwach, Rowena E Martin, Michael W Mather, Geoffrey I McFadden, Leopold Parts, Gavin G Rutledge, Akhil B Vaidya, Kai Wengelnik, Julian C Rayner, Oliver Billker
The genomes of malaria parasites contain many genes of unknown function. To assist drug development through the identification of essential genes and pathways, we have measured competitive growth rates in mice of 2,578 barcoded Plasmodium berghei knockout mutants, representing >50% of the genome, and created a phenotype database. At a single stage of its complex life cycle, P. berghei requires two-thirds of genes for optimal growth, the highest proportion reported from any organism and a probable consequence of functional optimization necessitated by genomic reductions during the evolution of parasitism...
July 13, 2017: Cell
https://www.readbyqxmd.com/read/28708995/evolution-of-the-human-nervous-system-function-structure-and-development
#13
REVIEW
André M M Sousa, Kyle A Meyer, Gabriel Santpere, Forrest O Gulden, Nenad Sestan
The nervous system-in particular, the brain and its cognitive abilities-is among humans' most distinctive and impressive attributes. How the nervous system has changed in the human lineage and how it differs from that of closely related primates is not well understood. Here, we consider recent comparative analyses of extant species that are uncovering new evidence for evolutionary changes in the size and the number of neurons in the human nervous system, as well as the cellular and molecular reorganization of its neural circuits...
July 13, 2017: Cell
https://www.readbyqxmd.com/read/28708994/unshielding-exosomal-rna-unleashes-tumor-growth-and-metastasis
#14
Irina Matei, Han Sang Kim, David Lyden
Reciprocal interactions between tumor cells and their microenvironment drive cancer progression and therapy resistance. In this issue, Nabet et al. demonstrate that dynamic feedback between tumor and stroma subverts normal inflammatory responses by triggering the release of exosomes containing unshielded RNAs that activate pattern recognition receptors, thereby promoting tumor growth and metastasis.
July 13, 2017: Cell
https://www.readbyqxmd.com/read/28708993/il-4r%C3%AE-inhibitor-for-atopic-disease
#15
Howard Y Chang, Kari C Nadeau
Dupilumab is a fully human IgG4 monoclonal antibody directed against the IL-4Rα subunit of IL-4 and IL-13 receptors. It blocks the signaling pathways of IL-4 and IL-13, key cytokines that drive type 2 inflammatory response. In March 2017, dupilumab was approved for use in the treatment of atopic dermatitis (eczema). To view this Bench to Bedside, open or download the PDF.
July 13, 2017: Cell
https://www.readbyqxmd.com/read/28708992/biology-gone-wild
#16
Diana Crow
To study how genes, cells, or organisms operate in natural environments, researchers often need to leave the bench and venture into the field. Here are a few approaches that field biologists use in designing and conducting semi-wild experiments and the many challenges they face.
July 13, 2017: Cell
https://www.readbyqxmd.com/read/28708991/tiny-answers-to-big-questions
#17
April Pawluk
No abstract text is available yet for this article.
July 13, 2017: Cell
https://www.readbyqxmd.com/read/28669536/development-of-a-novel-lead-that-targets-m-%C3%A2-tuberculosis-polyketide-synthase-13
#18
Anup Aggarwal, Maloy K Parai, Nishant Shetty, Deeann Wallis, Lisa Woolhiser, Courtney Hastings, Noton K Dutta, Stacy Galaviz, Ramesh C Dhakal, Rupesh Shrestha, Shoko Wakabayashi, Chris Walpole, David Matthews, David Floyd, Paul Scullion, Jennifer Riley, Ola Epemolu, Suzanne Norval, Thomas Snavely, Gregory T Robertson, Eric J Rubin, Thomas R Ioerger, Frik A Sirgel, Ruben van der Merwe, Paul D van Helden, Peter Keller, Erik C Böttger, Petros C Karakousis, Anne J Lenaerts, James C Sacchettini
Widespread resistance to first-line TB drugs is a major problem that will likely only be resolved through the development of new drugs with novel mechanisms of action. We have used structure-guided methods to develop a lead molecule that targets the thioesterase activity of polyketide synthase Pks13, an essential enzyme that forms mycolic acids, required for the cell wall of Mycobacterium tuberculosis. Our lead, TAM16, is a benzofuran class inhibitor of Pks13 with highly potent in vitro bactericidal activity against drug-susceptible and drug-resistant clinical isolates of M...
July 13, 2017: Cell
https://www.readbyqxmd.com/read/28666128/terra-rna-antagonizes-atrx-and-protects-telomeres
#19
Hsueh-Ping Chu, Catherine Cifuentes-Rojas, Barry Kesner, Eric Aeby, Hun-Goo Lee, Chunyao Wei, Hyun Jung Oh, Myriam Boukhali, Wilhelm Haas, Jeannie T Lee
Through an integration of genomic and proteomic approaches to advance understanding of long noncoding RNAs, we investigate the function of the telomeric transcript, TERRA. By identifying thousands of TERRA target sites in the mouse genome, we demonstrate that TERRA can bind both in cis to telomeres and in trans to genic targets. We then define a large network of interacting proteins, including epigenetic factors, telomeric proteins, and the RNA helicase, ATRX. TERRA and ATRX share hundreds of target genes and are functionally antagonistic at these loci: whereas TERRA activates, ATRX represses gene expression...
June 29, 2017: Cell
https://www.readbyqxmd.com/read/28666127/approaching-terra-firma-genomic-functions-of-telomeric-noncoding-rna
#20
Caitlin M Roake, Steven E Artandi
Functions of the telomeric repeat-containing RNA (TERRA), the long noncoding RNA (lncRNA) transcribed from telomeres, have eluded researchers. In this issue of Cell, Graf el al. and Chu et al. uncover new regulatory roles for TERRA at the telomere and at distant genomic sites.
June 29, 2017: Cell
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