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https://www.readbyqxmd.com/read/28528644/bypassing-negative-epistasis-on-yield-in-tomato-imposed-by-a-domestication-gene
#1
Sebastian Soyk, Zachary H Lemmon, Matan Oved, Josef Fisher, Katie L Liberatore, Soon Ju Park, Anna Goren, Ke Jiang, Alexis Ramos, Esther van der Knaap, Joyce Van Eck, Dani Zamir, Yuval Eshed, Zachary B Lippman
Selection for inflorescence architecture with improved flower production and yield is common to many domesticated crops. However, tomato inflorescences resemble wild ancestors, and breeders avoided excessive branching because of low fertility. We found branched variants carry mutations in two related transcription factors that were selected independently. One founder mutation enlarged the leaf-like organs on fruits and was selected as fruit size increased during domestication. The other mutation eliminated the flower abscission zone, providing "jointless" fruit stems that reduced fruit dropping and facilitated mechanical harvesting...
May 15, 2017: Cell
https://www.readbyqxmd.com/read/28262353/remnants-of-an-ancient-metabolism-without-phosphate
#2
Joshua E Goldford, Hyman Hartman, Temple F Smith, Daniel Segrè
Phosphate is essential for all living systems, serving as a building block of genetic and metabolic machinery. However, it is unclear how phosphate could have assumed these central roles on primordial Earth, given its poor geochemical accessibility. We used systems biology approaches to explore the alternative hypothesis that a protometabolism could have emerged prior to the incorporation of phosphate. Surprisingly, we identified a cryptic phosphate-independent core metabolism producible from simple prebiotic compounds...
March 2, 2017: Cell
https://www.readbyqxmd.com/read/28525760/snapshot-nucleo-cytoskeletal-interactions
#3
Cátia S Janota, Francisco J Calero-Cuenca, Judite Costa, Edgar R Gomes
The nucleus is connected to the cytoskeleton, and these connections are involved in multiple functions such as nuclear positioning, shape and stiffness, cytoskeleton organization, mechanotransduction, gene expression, chromosome positioning, DNA repair, and cell migration.
May 18, 2017: Cell
https://www.readbyqxmd.com/read/28525759/modeling-rett-syndrome-using-talen-edited-mecp2-mutant-cynomolgus-monkeys
#4
Yongchang Chen, Juehua Yu, Yuyu Niu, Dongdong Qin, Hailiang Liu, Gang Li, Yingzhou Hu, Jiaojian Wang, Yi Lu, Yu Kang, Yong Jiang, Kunhua Wu, Siguang Li, Jingkuan Wei, Jing He, Junbang Wang, Xiaojing Liu, Yuping Luo, Chenyang Si, Raoxian Bai, Kunshan Zhang, Jie Liu, Shaoyong Huang, Zhenzhen Chen, Shuang Wang, Xiaoying Chen, Xinhua Bao, Qingping Zhang, Fuxing Li, Rui Geng, Aibin Liang, Dinggang Shen, Tianzi Jiang, Xintian Hu, Yuanye Ma, Weizhi Ji, Yi Eve Sun
Gene-editing technologies have made it feasible to create nonhuman primate models for human genetic disorders. Here, we report detailed genotypes and phenotypes of TALEN-edited MECP2 mutant cynomolgus monkeys serving as a model for a neurodevelopmental disorder, Rett syndrome (RTT), which is caused by loss-of-function mutations in the human MECP2 gene. Male mutant monkeys were embryonic lethal, reiterating that RTT is a disease of females. Through a battery of behavioral analyses, including primate-unique eye-tracking tests, in combination with brain imaging via MRI, we found a series of physiological, behavioral, and structural abnormalities resembling clinical manifestations of RTT...
May 18, 2017: Cell
https://www.readbyqxmd.com/read/28525758/targeted-degradation-of-ctcf-decouples-local-insulation-of-chromosome-domains-from-genomic-compartmentalization
#5
Elphège P Nora, Anton Goloborodko, Anne-Laure Valton, Johan H Gibcus, Alec Uebersohn, Nezar Abdennur, Job Dekker, Leonid A Mirny, Benoit G Bruneau
The molecular mechanisms underlying folding of mammalian chromosomes remain poorly understood. The transcription factor CTCF is a candidate regulator of chromosomal structure. Using the auxin-inducible degron system in mouse embryonic stem cells, we show that CTCF is absolutely and dose-dependently required for looping between CTCF target sites and insulation of topologically associating domains (TADs). Restoring CTCF reinstates proper architecture on altered chromosomes, indicating a powerful instructive function for CTCF in chromatin folding...
May 18, 2017: Cell
https://www.readbyqxmd.com/read/28525757/widespread-influence-of-3-end-structures-on-mammalian-mrna-processing-and-stability
#6
Xuebing Wu, David P Bartel
The physiological relevance of structures within mammalian mRNAs has been elusive, as these mRNAs are less folded in cells than in vitro and have predicted secondary structures no more stable than those of random sequences. Here, we investigate the possibility that mRNA structures facilitate the 3'-end processing of thousands of human mRNAs by juxtaposing poly(A) signals (PASs) and cleavage sites that are otherwise too far apart. We find that RNA structures are predicted to be more prevalent within these extended 3'-end regions than within PAS-upstream regions and indeed are substantially more folded within cells, as determined by intracellular probing...
May 18, 2017: Cell
https://www.readbyqxmd.com/read/28525756/immunization-elicited-broadly-protective-antibody-reveals-ebolavirus-fusion-loop-as-a-site-of-vulnerability
#7
Xuelian Zhao, Katie A Howell, Shihua He, Jennifer M Brannan, Anna Z Wec, Edgar Davidson, Hannah L Turner, Chi-I Chiang, Lin Lei, J Maximilian Fels, Hong Vu, Sergey Shulenin, Ashley N Turonis, Ana I Kuehne, Guodong Liu, Mi Ta, Yimeng Wang, Christopher Sundling, Yongli Xiao, Jennifer S Spence, Benjamin J Doranz, Frederick W Holtsberg, Andrew B Ward, Kartik Chandran, John M Dye, Xiangguo Qiu, Yuxing Li, M Javad Aman
While neutralizing antibodies are highly effective against ebolavirus infections, current experimental ebolavirus vaccines primarily elicit species-specific antibody responses. Here, we describe an immunization-elicited macaque antibody (CA45) that clamps the internal fusion loop with the N terminus of the ebolavirus glycoproteins (GPs) and potently neutralizes Ebola, Sudan, Bundibugyo, and Reston viruses. CA45, alone or in combination with an antibody that blocks receptor binding, provided full protection against all pathogenic ebolaviruses in mice, guinea pigs, and ferrets...
May 18, 2017: Cell
https://www.readbyqxmd.com/read/28525755/antibodies-from-a-human-survivor-define-sites-of-vulnerability-for-broad-protection-against-ebolaviruses
#8
Anna Z Wec, Andrew S Herbert, Charles D Murin, Elisabeth K Nyakatura, Dafna M Abelson, J Maximilian Fels, Shihua He, Rebekah M James, Marc-Antoine de La Vega, Wenjun Zhu, Russell R Bakken, Eileen Goodwin, Hannah L Turner, Rohit K Jangra, Larry Zeitlin, Xiangguo Qiu, Jonathan R Lai, Laura M Walker, Andrew B Ward, John M Dye, Kartik Chandran, Zachary A Bornholdt
Experimental monoclonal antibody (mAb) therapies have shown promise for treatment of lethal Ebola virus (EBOV) infections, but their species-specific recognition of the viral glycoprotein (GP) has limited their use against other divergent ebolaviruses associated with human disease. Here, we mined the human immune response to natural EBOV infection and identified mAbs with exceptionally potent pan-ebolavirus neutralizing activity and protective efficacy against three virulent ebolaviruses. These mAbs recognize an inter-protomer epitope in the GP fusion loop, a critical and conserved element of the viral membrane fusion machinery, and neutralize viral entry by targeting a proteolytically primed, fusion-competent GP intermediate (GPCL) generated in host cell endosomes...
May 18, 2017: Cell
https://www.readbyqxmd.com/read/28525754/regulated-intron-removal-integrates-motivational-state-and-experience
#9
Jason Gill, Younshim Park, J P McGinnis, Consuelo Perez-Sanchez, Marco Blanchette, Kausik Si
Myriad experiences produce transient memory, yet, contingent on the internal state of the organism and the saliency of the experience, only some memories persist over time. How experience and internal state influence the duration of memory at the molecular level remains unknown. A self-assembled aggregated state of Drosophila Orb2A protein is required specifically for long-lasting memory. We report that in the adult fly brain the mRNA encoding Orb2A protein exists in an unspliced non-protein-coding form. The convergence of experience and internal drive transiently increases the spliced protein-coding Orb2A mRNA...
May 18, 2017: Cell
https://www.readbyqxmd.com/read/28525753/the-u6-snrna-m-6-a-methyltransferase-mettl16-regulates-sam-synthetase-intron-retention
#10
Kathryn E Pendleton, Beibei Chen, Kuanqing Liu, Olga V Hunter, Yang Xie, Benjamin P Tu, Nicholas K Conrad
Maintenance of proper levels of the methyl donor S-adenosylmethionine (SAM) is critical for a wide variety of biological processes. We demonstrate that the N(6)-adenosine methyltransferase METTL16 regulates expression of human MAT2A, which encodes the SAM synthetase expressed in most cells. Upon SAM depletion by methionine starvation, cells induce MAT2A expression by enhanced splicing of a retained intron. Induction requires METTL16 and its methylation substrate, a vertebrate conserved hairpin (hp1) in the MAT2A 3' UTR...
May 18, 2017: Cell
https://www.readbyqxmd.com/read/28525752/the-logic-of-the-26s-proteasome
#11
REVIEW
Galen Andrew Collins, Alfred L Goldberg
The ubiquitin proteasome pathway is responsible for most of the protein degradation in mammalian cells. Rates of degradation by this pathway have generally been assumed to be determined by rates of ubiquitylation. However, recent studies indicate that proteasome function is also tightly regulated and determines whether a ubiquitylated protein is destroyed or deubiquitylated and survives longer. This article reviews recent advances in our understanding of the proteasome's multistep ATP-dependent mechanism, its biochemical and structural features that ensure efficient proteolysis and ubiquitin recycling while preventing nonselective proteolysis, and the regulation of proteasome activity by interacting proteins and subunit modifications, especially phosphorylation...
May 18, 2017: Cell
https://www.readbyqxmd.com/read/28525751/lamina-associated-domains-links-with-chromosome-architecture-heterochromatin-and-gene-repression
#12
REVIEW
Bas van Steensel, Andrew S Belmont
In metazoan cell nuclei, hundreds of large chromatin domains are in close contact with the nuclear lamina. Such lamina-associated domains (LADs) are thought to help organize chromosomes inside the nucleus and have been associated with gene repression. Here, we discuss the properties of LADs, the molecular mechanisms that determine their association with the nuclear lamina, their dynamic links with other nuclear compartments, and their proposed roles in gene regulation.
May 18, 2017: Cell
https://www.readbyqxmd.com/read/28525750/lung-cancer-a-wily-genetic-opponent
#13
Peggy P Hsu, Alice T Shaw
In two companion reports, the TRACERx consortium investigates tumor heterogeneity and evolution in early-stage non-small cell lung cancer. The studies highlight the prognostic value of copy-number heterogeneity assessment in tumor biopsies and circulating tumor DNA detection in plasma and suggest that tracking the evolution of lung cancers might aid clinical practice.
May 18, 2017: Cell
https://www.readbyqxmd.com/read/28525749/how-does-familiarity-breed-contempt
#14
Kevin Mann, Thomas R Clandinin
Classifying sensory experiences as either novel or familiar represents a fundamental challenge to neural processing. In this issue of Cell, Hattori et al. describe a circuit mechanism by which a novel stimulus that initially interests a fruit fly turns into a familiar one.
May 18, 2017: Cell
https://www.readbyqxmd.com/read/28525748/ebolavirus-s-foibles
#15
Seiya Yamayoshi, Yoshihiro Kawaoka
Ebola virus disease poses a global health threat. Here, two studies by Wec et al. and Zhao et al. identified vulnerability in an internal fusion loop of an ebolavirus glycoprotein. Monoclonal antibodies elicited from immunization and isolated from a human survivor that recognized epitopes in this area neutralized all five ebolaviruses, guiding the development of a pan-ebolavirus immunotherapy.
May 18, 2017: Cell
https://www.readbyqxmd.com/read/28525747/big-questions-in-microbiology
#16
(no author information available yet)
No abstract text is available yet for this article.
May 18, 2017: Cell
https://www.readbyqxmd.com/read/28525746/silicon-valley-meets-biomedical-research-in-the-chan-zuckerberg-initiative
#17
Diana Crow
The Chan Zuckerberg Initiative, the philanthropy launched by Facebook CEO Mark Zuckerberg and his wife Priscilla Chan, drew attention with its stated goal of helping to "cure, manage, or treat all diseases" by the end of the century. They intend to do it through funding basic research and addressing gaps in biomedical technology.
May 18, 2017: Cell
https://www.readbyqxmd.com/read/28502772/representations-of-novelty-and-familiarity-in-a-mushroom-body-compartment
#18
Daisuke Hattori, Yoshinori Aso, Kurtis J Swartz, Gerald M Rubin, L F Abbott, Richard Axel
Animals exhibit a behavioral response to novel sensory stimuli about which they have no prior knowledge. We have examined the neural and behavioral correlates of novelty and familiarity in the olfactory system of Drosophila. Novel odors elicit strong activity in output neurons (MBONs) of the α'3 compartment of the mushroom body that is rapidly suppressed upon repeated exposure to the same odor. This transition in neural activity upon familiarization requires odor-evoked activity in the dopaminergic neuron innervating this compartment...
May 18, 2017: Cell
https://www.readbyqxmd.com/read/28502771/metabolic-phenotypes-of-response-to-vaccination-in-humans
#19
Shuzhao Li, Nicole L Sullivan, Nadine Rouphael, Tianwei Yu, Sophia Banton, Mohan S Maddur, Megan McCausland, Christopher Chiu, Jennifer Canniff, Sheri Dubey, Ken Liu, ViLinh Tran, Thomas Hagan, Sai Duraisingham, Andreas Wieland, Aneesh K Mehta, Jennifer A Whitaker, Shankar Subramaniam, Dean P Jones, Alessandro Sette, Kalpit Vora, Adriana Weinberg, Mark J Mulligan, Helder I Nakaya, Myron Levin, Rafi Ahmed, Bali Pulendran
Herpes zoster (shingles) causes significant morbidity in immune compromised hosts and older adults. Whereas a vaccine is available for prevention of shingles, its efficacy declines with age. To help to understand the mechanisms driving vaccinal responses, we constructed a multiscale, multifactorial response network (MMRN) of immunity in healthy young and older adults immunized with the live attenuated shingles vaccine Zostavax. Vaccination induces robust antigen-specific antibody, plasmablasts, and CD4(+) T cells yet limited CD8(+) T cell and antiviral responses...
May 18, 2017: Cell
https://www.readbyqxmd.com/read/28502770/an-atomic-structure-of-the-human-spliceosome
#20
Xiaofeng Zhang, Chuangye Yan, Jing Hang, Lorenzo I Finci, Jianlin Lei, Yigong Shi
Mechanistic understanding of pre-mRNA splicing requires detailed structural information on various states of the spliceosome. Here we report the cryo electron microscopy (cryo-EM) structure of the human spliceosome just before exon ligation (the C(∗) complex) at an average resolution of 3.76 Å. The splicing factor Prp17 stabilizes the active site conformation. The step II factor Slu7 adopts an extended conformation, binds Prp8 and Cwc22, and is poised for selection of the 3'-splice site. Remarkably, the intron lariat traverses through a positively charged central channel of RBM22; this unusual organization suggests mechanisms of intron recruitment, confinement, and release...
May 18, 2017: Cell
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