bluuebunny/crossref_metadata_2025_split huggingface dataset:
Temporal regulation of prenatal embryonic development by paternal imprinted loci
Authors: Li Qing , Li Yuanyuan , Yin Qi , Huang Shuo , Wang Kai , Zhuo Liangchai , Li Wei , Chang Boran , Li Jinsong 
Published: July 2019

ABSTRACTH19andGtl2are paternal imprinted genes that are pivotal for prenatal embryonic development. Meanwhile, mouse nongrowing oocytes and sperm- or oocyte-originated haploid embryonic stem cells (haESCs) carrying bothH19andIG-DMR (differentially DNA-methylated region) deletions (DKO) that partially mimic paternal imprinting ofH19-Igf2andDlk1-Dio3can be employed as sperm replacement to efficiently support full-term embryonic development. However, howH19-DMR andIG-DMR act together to regulate embryonic development is still largely unknown. Here, using androgenetic haESC (AG-haESC)-mediated semi-cloned (SC) technology, we showed that paternalH19-DMR andIG-DMR are not essential for pre-implantation development of SC embryos generated through injection of AG-haESCs into oocytes.H19-DMR plays critical roles before 12.5 days of gestation whileIG-DMR is essential for late-gestation of SC embryos. Interestingly, we found that combined deletions ofH19andH19-DMR can further improve the efficiency of normal development of SC embryos at mid-gestation compared to DKO SC embryos. Transcriptome and histology analyses revealed thatH19andH19-DMR combined deletions rescue the placental defects. Furthermore, we showed thatH19,H19-DMR andIG-DMR deletions (TKO) give rise to better prenatal and postnatal embryonic development of SC embryos compared to DKO. Together, our results indicate the temporal regulation of paternal imprinted loci during embryonic development.
Exploring the Complexity of Protein-Level Dosage Compensation that Fine-Tunes Stoichiometry of Multiprotein Complexes
Authors: Ishikawa Koji , Ishihara Akari , Moriya Hisao 
Published: July 2019

AbstractProper control of gene expression levels upon various perturbations is a fundamental aspect of cellular robustness. Protein-level dosage compensation is one mechanism buffering perturbations to stoichiometry of multiprotein complexes through accelerated proteolysis of unassembled subunits. Although N-terminal acetylation- and ubiquitin-mediated proteasomal degradation by the Ac/N-end rule pathway enables selective compensation of excess subunits, it is unclear how dominant this pathway contributes to stoichiometry control. Here we report that dosage compensation depends only partially on the Ac/N-end rule pathway. Our analysis of genetic interactions between 18 subunits and 10 quality control factors in budding yeast demonstrated that multiple E3 ubiquitin ligases and N-acetyltransferases are involved in dosage compensation. We find that N-acetyltransferases-mediated compensation is not simply predictable from N-terminal sequence despite their sequence specificity for N-acetylation. We also find that the compensation of Pop3 and Bet4 is due in large part to a minor N-acetyltransferase NatD. Furthermore, canonical NatD substrates histone H2A/H4 were compensated even in its absence, suggesting N-acetylation-independent compensation. Our study reveals the complexity and robustness of the stoichiometry control system.
Genome-wide analysis reveals genetic diversity, linkage disequilibrium, and selection for milk traits in Chinese buffalo breeds
Authors: Lu Xing-Rong , Duan An-Qin , Liang Sha-Sha , Ma Xiao-Ya , Liang Xian-Wei , Deng Ting-Xian 
Published: July 2019

AbstractWater buffalo holds the tremendous potential of milk and meat that widespread throughout central and southern China. However, characterization of the population genetics of Chinese buffalo is poorly understood. Using Axiom®buffalo genotyping array, we performed the genetic diversity, linkage disequilibrium (LD) pattern and signature of selection in the 176 Chinese buffaloes from thirteen breeds. A total of 35,547 SNPs passed quality control and were used for further analyses. Population genetic analysis revealed a clear separation between the swamp and river types. Ten Chinese indigenous breeds clustered into the swamp group, Murrah and Nili-Ravi breeds were the river group, and the crossbred breed was closer to the river group. Genetic diversity analysis showed that the swamp group had a lower average expected heterozygosities compared to the river group. LD decay distance was much shorter in the swamp group compared with the river group withvalue of approximately 50 Kb. Analysis of runs of homozygosity indicated that extensive remote and recent inbreeding activity was respectively found within swamp and river groups. Moreover, a total of 12 genomic regions under selection were detected between river and swamp groups. Further, 12 QTL regions were found associated with buffalo milk production traits. Some candidate genes within these QTLs were predicted to be involved in the cell structure and function, suggesting that these genes might play vital roles in the buffalo milk performance. Our data contribute to our understanding of the characterization of population genetics in Chinese buffaloes, which in turn may be utilized in buffalo breeding programs.Author SummaryIdentifying the causal genes or markers associated with important economic traits in livestock is critical to increasing the production level on the species. However, current understanding of the genetic basis for milk production traits in buffalo is limited. Here, we confirmed the divergent evolution, distinct population structure, and LD extent among Chinese buffalo breeds. We also identified 12 QTL regions associated with milk production traits in buffaloes using the selective sweeps and haplotype analysis. Further, a total of 7 genes involved in the cell structure and function were predicted within the identified QTLs. These findings suggested that these genes can serve as the candidate genes associated with buffalo milk production, which hold a vital role in the milk trait improvement of dairy buffalo industry.
The Impact of a Wireless Audio System on Communication in Robotic-Assisted Laparoscopic Surgery: A Prospective Controlled Trial
Authors: Tsafrir Ziv , Janosek-Albright Kirsten , Aoun Joelle , Diaz-Insua Mireya , Abd-El-Barr Abd-El-Rahman , Schiff Lauren , Talukdar Shobhana , Menon Mani , Munkarah Adnan , Theoharis Evan , Eisenstein David 
Published: July 2019

AbstractBackgroundRobotic surgery presents a challenge to effective teamwork and communication in the operating theatre (OR). Our objective was to evaluate the effect of using a wireless audio headset device on communication, efficiency and patient outcome in robotic surgery.Methods and findingsA prospective controlled trial of team members participating in gynecologic and urologic robotic procedures between January and March 2015. In the first phase, all surgeries were performed without headsets (control), followed by the intervention phase where all team members used the wireless headsets. Noise levels were measured during both phases. After each case, all team members evaluated the quality of communication, performance, teamwork and mental load using a validated 14-point questionnaire graded on a 1-10 scale. Higher overall scores indicated better communication and efficiency. Clinical and surgical data of all patients in the study were retrieved, analyzed and correlated with the survey results.The study included 137 procedures, yielding 843 questionnaires with an overall response rate of 89% (843/943). Self-reported communication quality was better in cases where headsets were used (113.0 ± 1.6 vs. 101.4 ± 1.6; p < .001). Use of headsets reduced the percentage of time with a noise level above 70 dB at the console (8.2% ± 0.6 vs. 5.3% ± 0.6, p < .001), but had no significant effect on length of surgery nor postoperative complications.ConclusionsThe use of wireless headset devices improved quality of communication between team members and reduced the peak noise level in the robotic OR.
An updated analysis of opioids increasing the risk of fractures
Authors: Yue Qiaoning , Ma Yue , Teng Yirong , Zhu Yun , Liu Hao , Xu Shuanglan , Liu Jie , Liu Jianping , Teng Zhaowei , Zhang Xiguang 
Published: July 2019

AbstractObjectiveTo assess the relationship between opioid therapy for chronic noncancer pain and fracture risk by a meta-analysis of cohort studies and case-control studies.MethodsThe included cohort studies and case-control studies were identified by searching the PubMed and EMBASE databases from their inception until May 24, 2019. The outcome of interest was a fracture. This information was independently screened by two authors. When the heterogeneity among studies was significant, a random effects model was used to determine the overall combined risk estimate.ResultsIn total, 12 cohort studies and 6 case-control studies were included. We used the Newcastle-Ottawa Scale (NOS) to evaluate the quality of the included literature, and 14 of the studies were considered high-quality studies. The overall relative risk of opioid therapy and fractures was 1.78 (95% confidence interval (CI) 1.53 - 2.07). Subgroup analyses revealed sources of heterogeneity, sensitivity analysis was stable, and no publication bias was observed.ConclusionsThe meta-analysis showed that the use of opioids significantly increased the risk of fracture.
Augmented base pairing networks encode RNA-small molecule binding preferences
Authors: Oliver Carlos , Mallet Vincent , Sarrazin Gendron Roman , Reinharz Vladimir , Hamilton William L. , Moitessier Nicolas , Waldispühl Jérôme 
Published: July 2019

AbstractMotivationThe binding of small molecules to RNAs is an important mechanism which can stabilize 3D structures or activate key molecular functions. To date, computational and experimental efforts toward small molecule binding prediction have primarily focused on protein targets. Considering that a very large portion of the genome is transcribed into non-coding RNAs but only few regions are translated into proteins, successful annotations of RNA elements targeted by small-molecule would likely uncover a vast repertoire of biological pathways and possibly lead to new therapeutic avenues.ResultsOur work is a first attempt at bringing machine learning approaches to the problem of RNA drug discovery. RNAmigos takes advantage of the unique structural properties of RNA to predict small molecule ligands for unseen binding sites. A key feature of our model is an efficient representation of binding sites as augmented base pairing networks (ABPNs) aimed at encoding important structural patterns. We subject our ligand predictions to two virtual screen settings and show that we are able to rank the known ligand on average in the 73rd percentile, showing a significant improvement over several baselines. Furthermore, we observe that graphs which are augmented with non-Watson Crick (a.k.a non-canonical) base pairs are the only representation which is able to retrieve a significant signal, suggesting that non-canonical interactions are an necessary source of binding specificity in RNAs. We also find that an auxiliary graph representation task significantly boosts performance by providing efficient structural embeddings to the low data setting of ligand prediction. RNAmigos shows that RNA binding data contains structural patterns with potential for drug discovery, and provides methodological insights which can be applied to other structure-function learning tasks.AvailabilityCode and data is freely available at http://csb.cs.mcgill.ca/RNAmigos.Contactjerome@cs.mcgill.ca
Performance assessment of total RNA sequencing of human biofluids and extracellular vesicles
Authors: Everaert Celine , Helsmoortel Hetty , Decock Anneleen , Hulstaert Eva , Van Paemel Ruben , Verniers Kimberly , Nuytens Justine , Anckaert Jasper , Nijs Nele , Tulkens Joeri , Dhondt Bert , Hendrix An , Mestdagh Pieter , Vandesompele Jo 
Published: July 2019

AbstractRNA profiling has emerged as a powerful tool to investigate the biomarker potential of human biofluids. However, despite enormous interest in extracellular nucleic acids, RNA sequencing methods to quantify the total RNA content outside cells are rare. Here, we evaluate the performance of the SMARTer Stranded Total RNA-Seq method in human platelet-rich plasma, platelet-free plasma, urine, conditioned medium, and extracellular vesicles (EVs) from these biofluids. We found the method to be accurate, precise, compatible with low-input volumes and able to quantify a few thousand genes. We picked up distinct classes of RNA molecules, including mRNA, lncRNA, circRNA, miscRNA and pseudogenes. Notably, the read distribution and gene content drastically differ among biofluids. In conclusion, we are the first to show that the SMARTer method can be used for unbiased unraveling of the complete transcriptome of a wide range of biofluids and their extracellular vesicles.
Detection and quantification of single mRNA dynamics with the Riboglow fluorescent RNA tag
Authors: Braselmann Esther , Stasevich Timothy J. , Lyon Kenneth , Batey Robert T. , Palmer Amy E. 
Published: July 2019

AbstractLabeling and tracking biomolecules with fluorescent probes on the single molecule level enables quantitative insights into their dynamics in living cells. We previously developed Riboglow, a platform to label RNAs in live mammalian cells, consisting of a short RNA tag and a small organic probe that increases fluorescence upon binding RNA. Here, we demonstrate that Riboglow is capable of detecting and tracking single RNA molecules. We benchmark RNA tracking by comparing results with the established MS2 RNA tagging system. To demonstrate versatility of Riboglow, we assay translation on the single molecule level, where the translated mRNA is tagged with Riboglow and the nascent polypeptide is labeled with a fluorescent antibody. The growing effort to investigate RNA biology on the single molecule level requires sophisticated and diverse fluorescent probes for multiplexed, multi-color labeling of biomolecules of interest, and we present Riboglow as a new member in this toolbox.
Multiple Measures Reveal The Value of Both Race And Geographic Ancestry For Self-Identification
Authors: Damotte Vincent , Zhao Chao , Lin Chris , Williams Eric , Louzoun Yoram , Madbouly Abeer , Kotlarz Rochelle , McDaniel Marisa , Norman Paul J. , Lizee Antoine , Myres Natalie M. , Ball Catherine A. , Chahine Kenneth G. , Byrnes Jake , Wang Yong , Maiers Martin , Hollenbach Jill A. 
Published: July 2019

AbstractThere is long-standing tension regarding whether and how to use race or geographic ancestry in biomedical research. We examined multiple self-reported measures of race and ancestry from a cohort of over 100,000 U.S. residents alongside genetic data. We found that these measures are often non-overlapping, and that no single self-reported measure alone provides a better fit to genetic ancestry than a combination including both race and geographic ancestry. We also found that patterns of reporting for race and ancestry appear to be influenced by participation in direct-to-consumer genetic ancestry testing. Our results demonstrate that there is a place for the language of both race and geographic ancestry as we seek to empower individuals to fully describe their family history in research and medicine.One Sentence SummarySelf-identification in the United States according to both racial and geographic terms best reflects genetic ancestry in individuals.
Two distinct actin filament populations have effects on mitochondria, with differences in stimuli and assembly factors
Authors: Fung Tak Shun , Ji Wei-Ke , Higgs Henry N. , Chakrabarti Rajarshi 
Published: July 2019

AbstractRecent studies show that mitochondria and actin filaments work together in two contexts: 1) increased cytoplasmic calcium induces cytoplasmic actin polymerization that stimulates mitochondrial fission, and 2) mitochondrial depolarization causes actin assembly around mitochondria, with roles in mitophagy. It is unclear whether these two processes utilize similar actin assembly mechanisms. Here, we show that these are distinct actin assembly mechanisms in the acute phase after treatment (<10 min). Calcium-induced actin assembly is INF2-dependent and Arp2/3 complex-independent, whereas depolarization-induced actin assembly is Arp2/3 complex-dependent and INF2-independent. The two types of actin polymerization are morphologically distinct, with calcium-induced filaments throughout the cytosol and depolarization-induced filaments as “clouds” around depolarized mitochondria. We have previously shown that calcium-induced actin stimulates increases in both mitochondrial calcium and recruitment of the dynamin GTPase Drp1. In contrast, depolarization-induced actin is temporally-associated with extensive mitochondrial dynamics that do not result in mitochondrial fission, but in circularization of the inner mitochondrial membrane (IMM). These dynamics are dependent upon the protease Oma1 and independent of Drp1. Actin cloud inhibition causes increased IMM circularization, suggesting that actin clouds limit these dynamics.Summary statementMitochondrial depolarization induces Arp2/3 complex-dependent actin clouds that restrain mitochondrial shape changes induced by Oma1 on the inner mitochondrial membrane. A distinct actin network stimulates mitochondrial fission in response to calcium.
Collapse and rescue of evolutionary food webs under global warming
Authors: Yacine Youssef , Allhoff Korinna T. , Weinbach Avril , Loeuille Nicolas 
Published: July 2019

AbstractGlobal warming is severely impacting ecosystems and threatening ecosystem services as well as human well-being. While some species face extinction risk, several studies suggest the possibility that fast evolution may allow species to adapt and survive in spite of environmental changes.We assess how such evolutionary rescue extends to multitrophic communities and whether evolution systematically preserves biodiversity under global warming.More precisely, we expose simulated trophic networks of co-evolving consumers to warming under different evolutionary scenarios, which allows us to assess the effect of evolution on diversity maintenance. We also investigate how the evolution of body mass and feeding preference affects coexistence within a simplified consumer-resource module.Our simulations predict that the long-term diversity loss triggered by warming is considerably higher in scenarios where evolution is slowed down or switched off completely, indicating that eco-evolutionary feedback indeed helps to preserve biodiversity. However, even with fast evolution, food webs still experience vast disruptions in their structure and functioning. Reversing warming may thus not be sufficient to restore previous structures.Our findings highlight how the interaction between evolutionary rescue and changes in trophic structures constrains ecosystem responses to warming with important implications for conservation and management policies.
Investigating the influence of spore maturation and sporulation conditions on MalS expression during Bacillus subtilis spore germination
Authors: Swarge Bhagyashree , Nafid Chahida , Vischer Norbert , Brul Stanley 
Published: July 2019

AbstractSpore forming bacteria of the orders Bacillales and Clostridiales play a major role in food spoilage and food-borne diseases. The spores remain in a dormant state for extended periods due to their highly resistant features. When environmental conditions become favourable, they can germinate as the germinant receptors located on the spore’s inner membrane get activated via germinant binding. This leads to the formation of vegetative cells via germination and subsequent outgrowth. The present study focuses on the synthesis of protein MalS during B. subtilis spore germination by investigating the dynamics of the fluorescence level of a MalS-GFP fusion protein using time-lapse fluorescence microscopy. Our results show an initial increase within the first 15 minutes of germination, followed by a drop and stabilization of the fluorescence throughout the spore ripening period. Western blot analyses, however, indicate no increase in the levels of the MalS-GFP fusion protein during the first 15 minutes after the addition of the germinants. Thus the instantaneous increase in fluorescence of MalS-GFP may likely due to a change in the physical environment as the spore germination is triggered. Our findings also show that the different sporulation conditions and the maturation time of spores affect the expression of MalS-GFP and the germination behaviour of the spores.
Normalization by Valence and Motivational Intensity in the Sensorimotor Cortices (PMd, rM1, and cS1)
Authors: Yao Zhao , Hessburg John P , Francis Joseph Thachil 
Published: July 2019

AbstractOur brain’s ability to represent vast amounts of information, such as continuous ranges of reward spanning orders of magnitude, with limited dynamic range neurons, may be possible due to normalization. Recently our group and others have shown that the sensorimotor cortices are sensitive to reward value. Here we ask if psychological affect causes normalization of the sensorimotor cortices by modulating valence and motivational intensity. We had two non-human primate (NHP) subjects (one male bonnet macaque and one female rhesus macaque) make visually cued grip-force movements while simultaneously cueing the level of possible reward if successful, or timeout punishment, if unsuccessful. We recorded simultaneously from 96 electrodes in each the following: caudal somatosensory, rostral motor, and dorsal premotor cortices (cS1, rM1, PMd). We utilized several normalization models for valence and motivational intensity in all three regions. We found three types of divisive normalized relationships between neural activity and the representation of valence and motivation, linear, sigmodal, and hyperbolic. The hyperbolic relationships resemble receptive fields in psychological affect space, where a unit is susceptible to a small range of the valence/motivational space. We found that these cortical regions have both strong valence and motivational intensity representations.
The MRL/MpJ Mouse Strain Is Not Protected From Muscle Atrophy And Weakness After Rotator Cuff Tear
Authors: Talarek Jeffrey R , Piacentini Alex N , Konja Alexis C , Wada Susumu , Swanson Jacob B , Nussenzweig Samuel C , Dines Joshua S , Rodeo Scott A , Mendias Christopher L 
Published: July 2019

AbstractChronic rotator cuff tears are a common source of shoulder pain and disability. Patients with rotator cuff tears often have substantial weakness, fibrosis, and fat accumulation which limit successful surgical repair and postoperative rehabilitation. The Murphy Roths Large (MRL) strain of mice have demonstrated superior healing and protection against pathological changes in several disease and injury conditions. We tested the hypothesis that, compared to the commonly used C57Bl/6 (B6) strain, MRL mice would have less muscle fiber atrophy and fat accumulation, and be protected against the loss in force production that occurs after cuff tear. Adult male mice B6 and MRL mice were subjected to a rotator cuff tear, and changes in muscle fiber contractility and histology were measured. RNA sequencing, and shotgun metabolomics and lipidomics were also performed. Muscles were harvested one month after tear. B6 and MRL mice had a 40% reduction in relative muscle force production after rotator cuff tear. RNA sequencing identified an increase in fibrosis-associated genes and a reduction in mitochondrial metabolism genes. Markers of glycolytic metabolism increased in B6 mice, while MRL mice appeared to increase amino acid metabolism after tear. There was an accumulation of lipid after injury, although there was a divergent response between B6 and MRL mice in the types of lipid species that accrued. There were strain-specific differences between the transcriptome, metabolome, and lipidome of B6 and MRL mice, but these differences did not protect MRL mice from weakness and pathological changes after rotator cuff tear.