bluuebunny/crossref_metadata_2025_split huggingface dataset:
Dynamic symbioses reveal pathways to coral survival through prolonged heatwaves
Authors: Claar Danielle C. , Starko Samuel , Tietjen Kristina L. , Epstein Hannah E. , Cunning Ross , Cobb Kim M. , Baker Andrew C. , Gates Ruth D. , Baum Julia K. 
Published: December 2020

AbstractProspects for coral persistence through increasingly frequent and extended heatwaves seem bleak. Coral recovery from bleaching is only known to occur after temperatures return to normal, and mitigation of local stressors does not appear to augment coral survival. Capitalizing on a natural experiment in the equatorial Pacific, we track individual coral colonies at sites spanning a gradient of local anthropogenic disturbance through a tropical heatwave of unprecedented duration. Unexpectedly, some corals survived the event by recovering from bleaching while still at elevated temperatures. These corals initially had heat-sensitive algal symbiont communities, endured bleaching, and then recovered through proliferation of heat-tolerant symbionts. This pathway to survival only occurred in the absence of strong local stressors. In contrast, corals in highly disturbed areas were already dominated by heat-tolerant symbionts, and despite initially resisting bleaching, these corals had no survival advantage in one species and 3.3 times lower survival in the other. These unanticipated connections between disturbance, coral symbioses and heat stress resilience reveal multiple pathways to coral survival through future prolonged heatwaves.
A machine learning toolkit for genetic engineering attribution to facilitate biosecurity
Authors: Alley Ethan C. , Turpin Miles , Liu Andrew Bo , Kulp-McDowall Taylor , Swett Jacob , Edison Rey , Von Stetina Stephen E. , Church George M. , Esvelt Kevin M. 
Published: December 2020

AbstractThe promise of biotechnology is tempered by its potential for accidental or deliberate misuse. Reliably identifying telltale signatures characteristic to different genetic designers, termed ‘genetic engineering attribution’, would deter misuse, yet is still considered unsolved. Here, we show that recurrent neural networks trained on DNA motifs and basic phenotype data can reach 70% attribution accuracy in distinguishing between over 1,300 labs. To make these models usable in practice, we introduce a framework for weighing predictions against other investigative evidence using calibration, and bring our model to within 1.6% of perfect calibration. Additionally, we demonstrate that simple models can accurately predict both the nation-state-of-origin and ancestor labs, forming the foundation of an integrated attribution toolkit which should promote responsible innovation and international security alike.
Donkey genomes provide new insights into domestication and selection for coat color
Authors: Wang Changfa , Li Haijing , Guo Yu , Huang Jinming , Sun Yan , Min Jiumeng , Wang Jinpeng , Fang Xiaodong , Zhao Zicheng , Wang Shuai , Zhang Yanlin , Liu Qingfeng , Jiang Qiang , Wang Xiuge , Guo Yijun , Yang Chunhong , Wang Yinchao , Tian Fang , Zhuang Guilong , Fan Yanna , Gao Qican , Li Yuhua , Ju Zhihua , Li Jianbin , Li Rongling , Hou Minghai , Yang Guiwen , Liu Guiqin , Liu Wenqiang , Guo Jiao , Pan Shanshan , Fan Guangyi , Zhang Wei , Zhang Ruitao , Yu Jie , Zhang Xinhao , Yin Qi , Ji Chuanliang , Jin Yuanchun , Yue Guidong , Liu Mei , Xu Jiake , Liu Shimin , Jordana Jordi , Noce Antonia , Amills Marcel , Wu Dong Dong , Li Shuaicheng , Zhou Xiangshan , Zhong Jifeng 
Published: December 2020

AbstractCurrent knowledge about the evolutionary history of donkeys is still incomplete due to the lack of archeological and whole-genome diversity data. To fill this gap, we have de novo assembled a chromosome-level reference genome of one male Dezhou donkey and analyzed the genomes of 126 domestic donkeys and seven wild asses. Population genomics analyses indicate that donkeys were domesticated in Africa and conclusively show reduced levels of Y chromosome variability and discordant paternal and maternal histories, possibly reflecting the consequences of reproductive management. We also investigate the genetic basis of coat color. While wild asses show diluted gray pigmentation (Dun phenotype), domestic donkeys display non-diluted black or chestnut coat colors (non-Dun) that were probably established during domestication. Here, we show that the non-Dun phenotype is caused by a 1 bp deletion downstream of the TBX3 gene, which decreases the expression of this gene and its inhibitory effect on pigment deposition.
An epigenetic gene silencing pathway selectively acting on transgenic DNA in the green alga Chlamydomonas
Authors: Neupert Juliane , Gallaher Sean D. , Lu Yinghong , Strenkert Daniela , Segal Na’ama , Barahimipour Rouhollah , Fitz-Gibbon Sorel T. , Schroda Michael , Merchant Sabeeha S. , Bock Ralph 
Published: December 2020

AbstractSilencing of exogenous DNA can make transgene expression very inefficient. Genetic screens in the model alga Chlamydomonas have demonstrated that transgene silencing can be overcome by mutations in unknown gene(s), thus producing algal strains that stably express foreign genes to high levels. Here, we show that the silencing mechanism specifically acts on transgenic DNA. Once a permissive chromatin structure has assembled, transgene expression can persist even in the absence of mutations disrupting the silencing pathway. We have identified the gene conferring the silencing and show it to encode a sirtuin-type histone deacetylase. Loss of gene function does not appreciably affect endogenous gene expression. Our data suggest that transgenic DNA is recognized and then quickly inactivated by the assembly of a repressive chromatin structure composed of deacetylated histones. We propose that this mechanism may have evolved to provide protection from potentially harmful types of environmental DNA.
Reverse C-glycosidase reaction provides C-nucleotide building blocks of xenobiotic nucleic acids
Authors: Pfeiffer Martin , Nidetzky Bernd 
Published: December 2020

AbstractC-Analogues of the canonical N-nucleosides have considerable importance in medicinal chemistry and are promising building blocks of xenobiotic nucleic acids (XNA) in synthetic biology. Although well established for synthesis of N-nucleosides, biocatalytic methods are lacking in C-nucleoside synthetic chemistry. Here, we identify pseudouridine monophosphate C-glycosidase for selective 5-β-C-glycosylation of uracil and derivatives thereof from pentose 5-phosphate (d-ribose, 2-deoxy-d-ribose, d-arabinose, d-xylose) substrates. Substrate requirements of the enzymatic reaction are consistent with a Mannich-like addition between the pyrimidine nucleobase and the iminium intermediate of enzyme (Lys166) and open-chain pentose 5-phosphate. β-Elimination of the lysine and stereoselective ring closure give the product. We demonstrate phosphorylation-glycosylation cascade reactions for efficient, one-pot synthesis of C-nucleoside phosphates (yield: 33 – 94%) from unprotected sugar and nucleobase. We show incorporation of the enzymatically synthesized C-nucleotide triphosphates into nucleic acids by RNA polymerase. Collectively, these findings implement biocatalytic methodology for C-nucleotide synthesis which can facilitate XNA engineering for synthetic biology applications.
SAMMY-seq reveals early alteration of heterochromatin and deregulation of bivalent genes in Hutchinson-Gilford Progeria Syndrome
Authors: Sebestyén Endre , Marullo Fabrizia , Lucini Federica , Petrini Cristiano , Bianchi Andrea , Valsoni Sara , Olivieri Ilaria , Antonelli Laura , Gregoretti Francesco , Oliva Gennaro , Ferrari Francesco , Lanzuolo Chiara 
Published: December 2020

AbstractHutchinson-Gilford progeria syndrome is a genetic disease caused by an aberrant form of Lamin A resulting in chromatin structure disruption, in particular by interfering with lamina associated domains. Early molecular alterations involved in chromatin remodeling have not been identified thus far. Here, we present SAMMY-seq, a high-throughput sequencing-based method for genome-wide characterization of heterochromatin dynamics. Using SAMMY-seq, we detect early stage alterations of heterochromatin structure in progeria primary fibroblasts. These structural changes do not disrupt the distribution of H3K9me3 in early passage cells, thus suggesting that chromatin rearrangements precede H3K9me3 alterations described at later passages. On the other hand, we observe an interplay between changes in chromatin accessibility and Polycomb regulation, with site-specific H3K27me3 variations and transcriptional dysregulation of bivalent genes. We conclude that the correct assembly of lamina associated domains is functionally connected to the Polycomb repression and rapidly lost in early molecular events of progeria pathogenesis.
Myonuclear content regulates cell size with similar scaling properties in mice and humans
Authors: Hansson Kenth-Arne , Eftestøl Einar , Bruusgaard Jo C. , Juvkam Inga , Cramer Alyssa W. , Malthe-Sørenssen Anders , Millay Douglas P. , Gundersen Kristian 
Published: December 2020

AbstractMuscle fibers are the largest cells in the body, and one of its few syncytia. Individual cell sizes are variable and adaptable, but what governs cell size has been unclear. We find that muscle fibers are DNA scarce compared to other cells, and that the nuclear number (N) adheres to the relationship N = aVb where V is the cytoplasmic volume. N invariably scales sublinearly to V (b < 1), making larger cells even more DNA scarce. N scales linearly to cell surface in adult humans, in adult and developing mice, and in mice with genetically reduced N, but in the latter the relationship eventually fails when they reach adulthood with extremely large myonuclear domains. Another exception is denervation-atrophy where nuclei are not eliminated. In conclusion, scaling exponents are remarkably similar across species, developmental stages and experimental conditions, suggesting an underlying scaling law where DNA-content functions as a limiter of muscle cell size.
A dual-labeling probe to track functional mitochondria–lysosome interactions in live cells
Authors: Chen Qixin , Fang Hongbao , Shao Xintian , Tian Zhiqi , Geng Shanshan , Zhang Yuming , Fan Huaxun , Xiang Pan , Zhang Jie , Tian Xiaohe , Zhang Kai , He Weijiang , Guo Zijian , Diao Jiajie 
Published: December 2020

AbstractMitochondria–lysosome interactions are essential for maintaining intracellular homeostasis. Although various fluorescent probes have been developed to visualize such interactions, they remain unable to label mitochondria and lysosomes simultaneously and dynamically track their interaction. Here, we introduce a cell-permeable, biocompatible, viscosity-responsive, small organic molecular probe, Coupa, to monitor the interaction of mitochondria and lysosomes in living cells. Through a functional fluorescence conversion, Coupa can simultaneously label mitochondria with blue fluorescence and lysosomes with red fluorescence, and the correlation between the red–blue fluorescence intensity indicates the progress of mitochondria–lysosome interplay during mitophagy. Moreover, because its fluorescence is sensitive to viscosity, Coupa allowed us to precisely localize sites of mitochondria–lysosome contact and reveal increases in local viscosity on mitochondria associated with mitochondria–lysosome contact. Thus, our probe represents an attractive tool for the localization and dynamic tracking of functional mitochondria–lysosome interactions in living cells.
Pontin arginine methylation by CARM1 is crucial for epigenetic regulation of autophagy
Authors: Yu Young Suk , Shin Hijai R. , Kim Dongha , Baek Seon Ah , Choi Seon Ah , Ahn Hyejin , Shamim Amen , Kim Jeonghwan , Kim Ik Soo , Kim Kyeong Kyu , Won Kyoung-Jae , Baek Sung Hee 
Published: December 2020

AbstractAutophagy is a catabolic process through which cytoplasmic components are degraded and recycled in response to various stresses including starvation. Recently, transcriptional and epigenetic regulations of autophagy have emerged as essential mechanisms for maintaining homeostasis. Here, we identify that coactivator-associated arginine methyltransferase 1 (CARM1) methylates Pontin chromatin-remodeling factor under glucose starvation, and methylated Pontin binds Forkhead Box O 3a (FOXO3a). Genome-wide analyses and biochemical studies reveal that methylated Pontin functions as a platform for recruiting Tip60 histone acetyltransferase with increased H4 acetylation and subsequent activation of autophagy genes regulated by FOXO3a. Surprisingly, CARM1-Pontin-FOXO3a signaling axis can work in the distal regions and activate autophagy genes through enhancer activation. Together, our findings provide a signaling axis of CARM1-Pontin-FOXO3a and further expand the role of CARM1 in nuclear regulation of autophagy.
Cloning of wheat keto-acyl thiolase 2B reveals a role of jasmonic acid in grain weight determination
Authors: Chen Yun , Yan Yan , Wu Tian-Tian , Zhang Guo-Liang , Yin Huanran , Chen Wei , Wang Shuangshuang , Chang Fang , Gou Jin-Ying 
Published: December 2020

AbstractGrain weight (GW) is one of the component traits of wheat yield. Existing reports have shown that multiple phytohormones are involved in the regulation of GW in different crops. However, the potential role of jasmonic acid (JA) remains unclear. Here, we report that triticale grain weight 1 (tgw1) mutant, with marked reductions in both GW and JA content, is caused by a premature stop mutation in keto-acyl thiolase 2B (KAT-2B) involved in β-oxidation during JA synthesis. KAT-2B overexpression increases GW in wild type and boosts yield. Additionally, KAT-2B compliments the grain defect in tgw1 and rescues the lethal phenotype of the Arabidopsis kat2 mutant in a sucrose-free medium. Despite the suppression of JA synthesis in tgw1 mutant, ABA synthesis is upregulated, which is accompanied by enhanced expression of SAG3 and reduction of chlorophyll content in leaves. Together, these results demonstrate a role of the JA synthetic gene KAT-2B in controlling GW and its potential application value for wheat improvement.
The bacterial multidrug resistance regulator BmrR distorts promoter DNA to activate transcription
Authors: Fang Chengli , Li Linyu , Zhao Yihan , Wu Xiaoxian , Philips Steven J. , You Linlin , Zhong Mingkang , Shi Xiaojin , O’Halloran Thomas V. , Li Qunyi , Zhang Yu 
Published: December 2020

AbstractThe MerR-family proteins represent a unique family of bacteria transcription factors (TFs), which activate transcription in a manner distinct from canonical ones. Here, we report a cryo-EM structure of a B. subtilis transcription activation complex comprising B. subtilis six-subunit (2αββ‘ωε) RNA Polymerase (RNAP) core enzyme, σA, a promoter DNA, and the ligand-bound B. subtilis BmrR, a prototype of MerR-family TFs. The structure reveals that RNAP and BmrR recognize the upstream promoter DNA from opposite faces and induce four significant kinks from the −35 element to the −10 element of the promoter DNA in a cooperative manner, which restores otherwise inactive promoter activity by shortening the length of promoter non-optimal −35/−10 spacer. Our structure supports a DNA-distortion and RNAP-non-contact paradigm of transcriptional activation by MerR TFs.
Optogenetic stimulation of the liver-projecting melanocortinergic pathway promotes hepatic glucose production
Authors: Kwon Eunjin , Joung Hye-Young , Liu Shun-Mei , Chua Streamson C. , Schwartz Gary J. , Jo Young-Hwan 
Published: December 2020

AbstractThe central melanocortin system plays a fundamental role in the control of feeding and body weight. Proopiomelanocortin (POMC) neurons in the arcuate nucleus of the hypothalamus (ARC) also regulate overall glucose homeostasis via insulin-dependent and -independent pathways. Here, we report that a subset of ARC POMC neurons innervate the liver via preganglionic parasympathetic acetylcholine (ACh) neurons in the dorsal motor nucleus of the vagus (DMV). Optogenetic stimulation of this liver-projecting melanocortinergic pathway elevates blood glucose levels that is associated with increased expression of hepatic gluconeogenic enzymes in female and male mice. Pharmacological blockade and knockdown of the melanocortin-4 receptor gene in the DMV abolish this stimulation-induced effect. Activation of melanocortin-4 receptors inhibits DMV cholinergic neurons and optogenetic inhibition of liver-projecting parasympathetic cholinergic fibers increases blood glucose levels. This elevated blood glucose is not due to altered pancreatic hormone release. Interestingly, insulin-induced hypoglycemia increases ARC POMC neuron activity. Hence, this liver-projecting melanocortinergic circuit that we identified may play a critical role in the counterregulatory response to hypoglycemia.
A computational model for classification of BRCA2 variants using mouse embryonic stem cell-based functional assays
Authors: Biswas Kajal , Lipton Gary B. , Stauffer Stacey , Sullivan Teresa , Cleveland Linda , Southon Eileen , Reid Susan , Magidson Valentin , Iversen Edwin S. , Sharan Shyam K. 
Published: December 2020

AbstractSequencing-based genetic tests to identify individuals at increased risk of hereditary breast and ovarian cancers have resulted in the identification of more than 40,000 sequence variants of BRCA1 and BRCA2. A majority of these variants are considered to be variants of uncertain significance (VUS) because their impact on disease risk remains unknown, largely due to lack of sufficient familial linkage and epidemiological data. Several assays have been developed to examine the effect of VUS on protein function, which can be used to assess their impact on cancer susceptibility. In this study, we report the functional characterization of 88 BRCA2 variants, including several previously uncharacterized variants, using a well-established mouse embryonic stem cell (mESC)-based assay. We have examined their ability to rescue the lethality of Brca2 null mESC as well as sensitivity to six DNA damaging agents including ionizing radiation and a PARP inhibitor. We have also examined the impact of BRCA2 variants on splicing. In addition, we have developed a computational model to determine the probability of impact on function of the variants that can be used for risk assessment. In contrast to the previous VarCall models that are based on a single functional assay, we have developed a new platform to analyze the data from multiple functional assays separately and in combination. We have validated our VarCall models using 12 known pathogenic and 10 neutral variants and demonstrated their usefulness in determining the pathogenicity of BRCA2 variants that are listed as VUS or as variants with conflicting functional interpretation.
A behavioural dataset for studying individual differences in language skills
Authors: Hintz Florian , Dijkhuis Marjolijn , van ‘t Hoff Vera , McQueen James M. , Meyer Antje S. 
Published: December 2020

AbstractThis resource contains data from 112 Dutch adults (18–29 years of age) who completed the Individual Differences in Language Skills test battery that included 33 behavioural tests assessing language skills and domain-general cognitive skills likely involved in language tasks. The battery included tests measuring linguistic experience (e.g. vocabulary size, prescriptive grammar knowledge), general cognitive skills (e.g. working memory, non-verbal intelligence) and linguistic processing skills (word production/comprehension, sentence production/comprehension). Testing was done in a lab-based setting resulting in high quality data due to tight monitoring of the experimental protocol and to the use of software and hardware that were optimized for behavioural testing. Each participant completed the battery twice (i.e., two test days of four hours each). We provide the raw data from all tests on both days as well as pre-processed data that were used to calculate various reliability measures (including internal consistency and test-retest reliability). We encourage other researchers to use this resource for conducting exploratory and/or targeted analyses of individual differences in language and general cognitive skills.
Expanded dataset of mechanical properties and observed phases of multi-principal element alloys
Authors: Borg Christopher K. H. , Frey Carolina , Moh Jasper , Pollock Tresa M. , Gorsse Stéphane , Miracle Daniel B. , Senkov Oleg N. , Meredig Bryce , Saal James E. 
Published: December 2020

AbstractThis data article presents a compilation of mechanical properties of 630 multi-principal element alloys (MPEAs). Built upon recently published MPEA databases, this article includes updated records from previous reviews (with minor error corrections) along with new data from articles that were published since 2019. The extracted properties include reported composition, processing method, microstructure, density, hardness, yield strength, ultimate tensile strength (or maximum compression strength), elongation (or maximum compression strain), and Young’s modulus. Additionally, descriptors (e.g. grain size) not included in previous reviews were also extracted for articles that reported them. The database is hosted and continually updated on an open data platform, Citrination. To promote interpretation, some data are graphically presented.
3-D ocean particle tracking modeling reveals extensive vertical movement and downstream interdependence of closed areas in the northwest Atlantic
Authors: Wang S. , Kenchington E. L. , Wang Z. , Yashayaev I. , Davies A. J. 
Published: December 2020

AbstractNovel 3-D passive particle tracking experiments were performed in the northwest Atlantic to elucidate connectivity among areas closed to protect vulnerable marine ecosystems. We examined (1) the degree of vertical movement of particles released at different depths and locations; (2) the location of potential source populations for the deep-sea taxa protected by the closures; and (3) the degree of functional connectivity. A long-term oceanographic dataset (EN4) was queried to characterize the temperature and salinity regimes in each of the closed areas as a basis for interpreting recently published climate change projections. Using the Parcels Lagrangian particle tracking framework and the BNAM hydrodynamic model, we found enhanced connectivity over previously developed 2-D models and unexpected, current-driven, strong (to a maximum of about 1340 m) downward displacement at depth (450, 1000 and 2250 m), with weaker upward displacement except for the release depth of 2250 m which showed upward movement of 955 m with a drift duration of 3 months. The current velocities create down-stream interdependence among closed areas and allow redundancy to develop in some of the areas of the network, with some of the larger areas also showing retention. Source populations for sponges in the upstream closure are likely in adjacent waters of the Canadian continental shelf. Collectively this information can be used to inform management decisions related to the size and placement of these closed areas, and vertical velocity surfaces have potential for use in species distribution modeling of benthic species and habitats.