bluuebunny/crossref_metadata_2025_split huggingface dataset:
Timed inhibition of CDC7 increases CRISPR-Cas9 mediated templated repair
Authors: Wienert Beeke , Nguyen David N. , Guenther Alexis , Feng Sharon J. , Locke Melissa N. , Wyman Stacia K. , Shin Jiyung , Kazane Katelynn R. , Gregory Georgia L. , Carter Matthew A. M. , Wright Francis , Conklin Bruce R. , Marson Alex , Richardson Chris D. , Corn Jacob E. 
Published: April 2020

AbstractRepair of double strand DNA breaks (DSBs) can result in gene disruption or gene modification via homology directed repair (HDR) from donor DNA. Altering cellular responses to DSBs may rebalance editing outcomes towards HDR and away from other repair outcomes. Here, we utilize a pooled CRISPR screen to define host cell involvement in HDR between a Cas9 DSB and a plasmid double stranded donor DNA (dsDonor). We find that the Fanconi Anemia (FA) pathway is required for dsDonor HDR and that other genes act to repress HDR. Small molecule inhibition of one of these repressors, CDC7, by XL413 and other inhibitors increases the efficiency of HDR by up to 3.5 fold in many contexts, including primary T cells. XL413 stimulates HDR during a reversible slowing of S-phase that is unexplored for Cas9-induced HDR. We anticipate that XL413 and other such rationally developed inhibitors will be useful tools for gene modification.
Endemism patterns are scale dependent
Authors: Daru Barnabas H. , Farooq Harith , Antonelli Alexandre , Faurby Søren 
Published: April 2020

AbstractAreas of endemism are important in biogeography because they capture facets of biodiversity not represented elsewhere. However, the scales at which they are relevant to research and conservation are poorly analysed. Here, we calculate weighted endemism (WE) and phylogenetic endemism (PE) separately for all birds and amphibians across the globe. We show that scale dependence is widespread for both indices and manifests across grain sizes, spatial extents and taxonomic treatments. Variations in taxonomic opinions—whether species are treated by systematic ‘lumping’ or ‘splitting’—can profoundly affect the allocation of WE hotspots. Global patterns of PE can provide insights into complex evolutionary processes but this congruence is lost at the continental to country extents. These findings are explained by environmental heterogeneity at coarser grains, and to a far lesser extent at finer resolutions. Regardless of scale, we find widespread deficits of protection for endemism hotspots. Our study presents a framework for assessing areas for conservation that are robust to assumptions on taxonomy, spatial grain and extent.
Dysregulation of bile acids increases the risk for preterm birth in pregnant women
Authors: You Sangmin , Cui Ai-Min , Hashmi Syed F. , Zhang Xinmu , Nadolny Christina , Chen Yuan , Chen Qiwen , Bush Xin , Hurd Zachary , Ali Winifer , Qin Gang , Deng Ruitang 
Published: April 2020

AbstractPreterm birth (PTB) is the leading cause of perinatal mortality and newborn complications. Bile acids are recognized as signaling molecules regulating a myriad of cellular and metabolic activities but have not been etiologically linked to PTB. In this study, a hospital-based cohort study with 36,755 pregnant women is conducted. We find that serum total bile acid levels directly correlate with the PTB rates regardless of the characteristics of the subjects and etiologies of liver disorders. Consistent with the findings from pregnant women, PTB is successfully reproduced in mice with liver injuries and dysregulated bile acids. More importantly, bile acids dose-dependently induce PTB with minimal hepatotoxicity. Furthermore, restoring bile acid homeostasis by farnesoid X receptor activation markedly reduces PTB and dramatically improves newborn survival rates. The findings thus establish an etiologic link between bile acids and PTB, and open an avenue for developing etiology-based therapies to prevent or delay PTB.
Single-cell transcriptional networks in differentiating preadipocytes suggest drivers associated with tissue heterogeneity
Authors: Ramirez Alfred K. , Dankel Simon N. , Rastegarpanah Bashir , Cai Weikang , Xue Ruidan , Crovella Mark , Tseng Yu-Hua , Kahn C. Ronald , Kasif Simon 
Published: April 2020

AbstractWhite adipose tissue plays an important role in physiological homeostasis and metabolic disease. Different fat depots have distinct metabolic and inflammatory profiles and are differentially associated with disease risk. It is unclear whether these differences are intrinsic to the pre-differentiated stage. Using single-cell RNA sequencing, a unique network methodology and a data integration technique, we predict metabolic phenotypes in differentiating cells. Single-cell RNA-seq profiles of human preadipocytes during adipogenesis in vitro identifies at least two distinct classes of subcutaneous white adipocytes. These differences in gene expression are separate from the process of browning and beiging. Using a systems biology approach, we identify a new network of zinc-finger proteins that are expressed in one class of preadipocytes and is potentially involved in regulating adipogenesis. Our findings gain a deeper understanding of both the heterogeneity of white adipocytes and their link to normal metabolism and disease.
A drug-inducible sex-separation technique for insects
Authors: Kandul Nikolay P. , Liu Junru , Hsu Alexander D. , Hay Bruce A. , Akbari Omar S. 
Published: April 2020

AbstractHere, we describe a drug-inducible genetic system for insect sex-separation that demonstrates proof-of-principle for positive sex selection inD. melanogaster. The system exploits the toxicity of commonly used broad-spectrum antibiotics geneticin and puromycin to kill the non-rescued sex. Sex-specific rescue is achieved by inserting sex-specific introns into the coding sequences of antibiotic-resistance genes. When raised on geneticin-supplemented food, the sex-sorter line establishes 100% positive selection for female progeny, while the food supplemented with puromycin positively selects 100% male progeny. Since the described system exploits conserved sex-specific splicing mechanisms and reagents, it has the potential to be adaptable to other insect species of medical and agricultural importance.
Contributions of recycled wastewater to clean water and sanitation Sustainable Development Goals
Authors: Tortajada Cecilia 
Published: April 2020

AbstractWater resources are essential for every development activity, not only in terms of available quantity but also in terms of quality. Population growth and urbanisation are increasing the number of users and uses of water, making water resources scarcer and more polluted. Changes in rainfall patterns threaten to worsen these effects in many areas. Water scarcity, due to physical lack or pollution, has become one of the most pressing issues globally, a matter of human, economic and environmental insecurity. Wastewater, whose value had not been appreciated until recently, is increasingly recognised as a potential ‘new’ source of clean water for potable and non-potable uses, resulting in social, environmental and economic benefits. This paper discusses the potential of recycled wastewater (also known as reused water) to become a significant source of safe water for drinking purposes and improved sanitation in support of the Sustainable Development Goals.
Effects of a Sudden Drop in Salinity on Scapharca subcrenata Antioxidant Defenses and Metabolism Determined Using LC-MS Non-targeted Metabolomics
Authors: Zhang Mo , Li Li , Liu Ying , Gao Xiaolong 
Published: April 2020

AbstractIn this experiment, the effects of a sudden drop in salinity on the antioxidant defense system and related gene expression of the ark shell Scapharca subcrenata were examined. The sudden drop in seawater salinity after a rainstorm was simulated, and subsequently differentially expressed metabolic markers were identified by LC-MS non-targeted metabolomics. When the salinity dropped to 14‰ (S14), the total anti-oxidant content, activity of Na+/K+-ATPase, superoxide dismutase (SOD), and catalase (CAT), content of malondialdehyde, and expression levels of Mn-SOD, CAT, and C-type lectin of S. subcrenata were significantly higher than in groups with salinity of 22‰ (S22) or 30‰ (S30) (P < 0.05). The activity of glutathione peroxidase (GPx), the content of reduced glutathione, and the expression levels of GPx were not significantly different between S14 and S22, but the values in each group were significantly higher than those in S30 (P < 0.05). Using the metabolomics technique, 361, 271, and 264 metabolites with significant differences were identified from S22 vs. S14, S30 vs. S14, and S30 vs. S22, respectively. The drop in salinity was accompanied by up-regulation of phosphatidylcholine (PC) (20:4 (5Z, 8Z, 11Z, 14Z)/P-18: 1 (11Z)), PC (16:0/22: 6 (4Z, 7Z, 10Z, 13Z, 16Z, 19Z)), phosphatidylethanolamine (PE) (18:4 (6Z, 9Z, 12Z, 15Z)/24:1 (15Z)), phosphatidylinositol (PI) (20:1 (11Z)/0:0), phalluside-1, C16 sphinganine, and LacCer (d18:0/14:0) and by significant down-regulation of PI-Cer (d18:1/14:0) and PE (14:0/16:1(9Z). The results of this study illustrate how these nine metabolites can be used as metabolic markers for the response of S. subcrenata to a sudden drop in salinity. They also provide the theoretical groundwork for selection of bottom areas with salinity that is optimal for release and proliferation of S. subcrenata, which is needed to restore the declining populations of this species.
Multiaxial Lenticular Stress-Strain Relationship of Native Myocardium is Preserved by Infarct-Induced Natural Heart Regeneration in Neonatal Mice
Authors: Wang Hanjay , Bennett-Kennett Ross , Paulsen Michael J. , Hironaka Camille E. , Thakore Akshara D. , Farry Justin M. , Eskandari Anahita , Lucian Haley J. , Shin Hye Sook , Wu Matthew A. , Imbrie-Moore Annabel M. , Steele Amanda N. , Stapleton Lyndsay M. , Zhu Yuanjia , Dauskardt Reinhold H. , Woo Y. Joseph 
Published: April 2020

AbstractNeonatal mice exhibit natural heart regeneration after myocardial infarction (MI) on postnatal day 1 (P1), but this ability is lost by postnatal day 7 (P7). Cardiac biomechanics intricately affect long-term heart function, but whether regenerated cardiac muscle is biomechanically similar to native myocardium remains unknown. We hypothesized that neonatal heart regeneration preserves native left ventricular (LV) biomechanical properties after MI. C57BL/6J mice underwent sham surgery or left anterior descending coronary artery ligation at age P1 or P7. Echocardiography performed 4 weeks post-MI showed that P1 MI and sham mice (n = 22, each) had similar LV wall thickness, diameter, and ejection fraction (59.6% vs 60.7%, p = 0.6514). Compared to P7 shams (n = 20), P7 MI mice (n = 20) had significant LV wall thinning, chamber enlargement, and depressed ejection fraction (32.6% vs 61.8%, p < 0.0001). Afterward, the LV was explanted and pressurized ex vivo, and the multiaxial lenticular stress-strain relationship was tracked. While LV tissue modulus for P1 MI and sham mice were similar (341.9 kPa vs 363.4 kPa, p = 0.6140), the modulus for P7 MI mice was significantly greater than that for P7 shams (691.6 kPa vs 429.2 kPa, p = 0.0194). We conclude that, in neonatal mice, regenerated LV muscle has similar biomechanical properties as native LV myocardium.
A new non-invasive index for prognosis evaluation in patients with aortic stenosis
Authors: Sim Hui Wen , Ngiam Nicholas Jinghao , Zhong Liang , Tan Benjamin Yong-Qiang , Low Lyndon Y , Djohan Andie Hartanto , Boey Elaine , Kong William Kok Fai , Tan Ru San , Poh Kian Keong 
Published: April 2020

AbstractThe global left ventricular (LV) contractility index,dσ*/dtmaxmeasures the maximal rate of change in pressure-normalized LV wall stress. We aim to describe the trend ofdσ*/dtmaxin differing severity of aortic stenosis (AS) with preserved left ventricular ejection fraction (LVEF) and the association ofdσ*/dtmaxwith clinical outcomes in moderate AS and severe AS. We retrospectively studied a total of 1738 patients with AS (550 mild AS, 738 moderate AS, 450 severe AS) and preserved LVEF ≥ 50% diagnosed from 1stJanuary 2001 to 31stDecember 2015.dσ*/dtmaxworsened with increasing severity of AS despite preserved LVEF (mild AS: 3.69 ± 1.28 s−1, moderate AS: 3.17 ± 1.09 s−1, severe AS: 2.58 ± 0.83 s−1,p < 0.001). Lowdσ*/dtmax < 2.8 s−1was independently associated with a higher composite outcome of aortic valve replacement, congestive cardiac failure admissions and all-cause mortality (adjusted hazard ratio 1.48, 95% CI: 1.25–1.77,p < 0.001). In conclusion,dσ*/dtmaxdeclined with worsening AS despite preserved LVEF. Lowdσ*/dtmax < 2.8 s−1was independently associated with adverse clinical outcomes in moderate AS and severe AS with preserved LVEF.
Discovery of Ternary Silicon Titanium Nitride with Spinel-Type Structure
Authors: Bhat Shrikant , Lale Abhijeet , Bernard Samuel , Zhang Wei , Ishikawa Ryo , Haseen Shariq , Kroll Peter , Wiehl Leonore , Farla Robert , Katsura Tomoo , Ikuhara Yuichi , Riedel Ralf 
Published: April 2020

AbstractHere we report on the discovery of a ternary silicon titanium nitride with the general composition (Si1−x,Tix)3N4with x = 0 < x < 1 and spinel-type crystal structure. The novel nitride is formed from an amorphous silicon titanium nitride (SiTiN) precursor under high-pressure/high-temperature conditions in a large volume high-pressure device. Under the conditions of 15–20 GPa and 1800–2000 °C, spinel-type γ-Si3N4and rock salt-type c-TiN are formed. In addition, crystals of the discovered nano-sized ternary phase (Si1−x,Tix)3N4embedded in γ-Si3N4are identified. The ternary compound is formed due to kinetically-controlled synthesis conditions and is analyzed to exhibit the spinel-type structure with ca. 8 atom% of Ti. The Ti atoms occur in both Ti3+and Ti4+oxidation states and are located on the Si sites. The ternary nano-crystals have to be described as (Si,Ti)3N4with N-vacancies resulting in the general composition (Si4+1−xTi4+x-δTi3+δ)3N4-δ.
Genetic diversity and ecology of coronaviruses hosted by cave-dwelling bats in Gabon
Authors: Maganga Gael Darren , Pinto Anaïs , Mombo Illich Manfred , Madjitobaye Mankomra , Mbeang Beyeme Antoine Mitte , Boundenga Larson , Ar Gouilh Meriadeg , N’Dilimabaka Nadine , Drexler Jan Felix , Drosten Christian , Leroy Eric Maurice 
Published: April 2020

AbstractLittle research on coronaviruses has been conducted on wild animals in Africa. Here, we screened a wide range of wild animals collected in six provinces and five caves of Gabon between 2009 and 2015. We collected a total of 1867 animal samples (cave-dwelling bats, rodents, non-human primates and other wild animals). We explored the diversity of CoVs and determined the factors driving the infection of CoVs in wild animals. Based on a nested reverse transcription-polymerase chain reaction, only bats, belonging to the Hipposideros gigas (4/156), Hipposideros cf. ruber (13/262) and Miniopterus inflatus (1/249) species, were found infected with CoVs. We identified alphacoronaviruses in H. gigas and H. cf. ruber and betacoronaviruses in H. gigas. All Alphacoronavirus sequences grouped with Human coronavirus 229E (HCoV-229E). Ecological analyses revealed that CoV infection was significantly found in July and October in H. gigas and in October and November in H. cf ruber. The prevalence in the Faucon cave was significantly higher. Our findings suggest that insectivorous bats harbor potentially zoonotic CoVs; highlight a probable seasonality of the infection in cave-dwelling bats from the North-East of Gabon and pointed to an association between the disturbance of the bats’ habitat by human activities and CoV infection.
Fully automated rapid quantification of Hepatitis C Virus RNA in human plasma and serum by integrated on-chip RT-qPCR and capillary electrophoresis
Authors: Chan Samuel D. H. , Toyoda Hidenori , Sanjeeviraman Jayashree , Souppe Aurelie , Iwamoto Mari , Wu Warren , Eto Daisuke , Tada Toshifumi , Kumada Takashi , Zhang Jian-Ping 
Published: April 2020

AbstractThe quantification of hepatitis C virus (HCV) is essential for the management of chronic hepatitis C therapy. We have developed a fully automated microfluidic RT-qPCR system for rapid quantitative detection of HCV RNA in human EDTA-plasma and serum, and the performance of the method was assessed. The platform for the assay, µTASWako g1 Fully Automated Genetic Analyzer, performs automated sample preparation and RNA extraction, followed by amplification and detection on an integrated RT-qPCR-CE (capillary electrophoresis (CE)) microfluidic chip. The total assay time from sample input to data output is less than 120 minutes. The HCV assay has a linear quantitative range of 15 to 107 IU/mL, with a limit of detection (LOD) of 10.65 IU/mL in EDTA-plasma and 12.43 IU/mL in serum. The assay has a reproducibility of SD ≤ 0.16 log10 IU/mL and an accuracy of ≤ 0.22 log10 IU/mL difference when compared to the assigned values. The main HCV genotypes 1 to 6 are detected with an accuracy of ± 0.3 log10 IU/mL. The assay is specific for HCV RNA and is free of interference from non-HCV pathogens, elevated levels of anti-viral and anti-bacterial drugs, and common endogenous interferents. In the linear quantitative range, the assay is highly correlated with the Roche cobas AmpliPrep/cobas TaqMan HCV Test, version 2.0 (r2 = 0.949). As the assay is highly sensitive, accurate and specific, and provides reliable quantification of HCV in plasma and serum, it can potentially be applicable for monitoring the therapy and management of HCV infection.
Intervention-induced changes in neural connectivity during motor preparation may affect cortical activity at motor execution
Authors: Wilkins Kevin B. , Dewald Julius P. A. , Yao Jun 
Published: April 2020

AbstractEffective interventions have demonstrated the ability to improve motor function by reengaging ipsilesional resources, which appears to be critical and feasible for hand function recovery even in individuals with severe chronic stroke. However, previous studies focus on changes in brain activity related to motor execution. How changes in motor preparation may facilitate these changes at motor execution is still unclear. To address this question, 8 individuals with severe chronic hemiparetic stroke participated in a device-assisted intervention for seven weeks. We then quantified changes in both coupling between regions during motor preparation and changes in topographical cortical activity at motor execution for both hand opening in isolation and together with the shoulder using high-density EEG. We hypothesized that intervention-induced changes in cortico-cortico interactions during motor preparation would lead to changes in activity at motor execution specifically towards an increased reliance on the ipsilesional hemisphere. In agreement with this hypothesis, we found that, following the intervention, individuals displayed a reduction in coupling from ipsilesional M1 to contralesional M1 within gamma frequencies during motor preparation for hand opening. This was followed by a reduction in activity in the contralesional primary sensorimotor cortex during motor execution. Similarly, during lifting and opening, a shift to negative coupling within ipsilesional M1 from gamma to beta frequencies was accompanied by an increase in ipsilesional primary sensorimotor cortex activity following the intervention. Together, these results show that intervention-induced changes in coupling within or between motor regions during motor preparation may affect cortical activity at execution.
Determination of Residential Soil Gas Radon Risk Indices Over the Lithological Units of a Southwestern Nigeria University
Authors: Esan Deborah Tolulope , Sridhar Mynepalli Kameswara Chandra , Obed Rachel , Ajiboye Yinka , Afolabi Olusegun , Olubodun Babakayode , Oni Olatunde Michael 
Published: April 2020

AbstractRadiation dose from natural sources is mainly from exposure to radon in the environment. Radon has its origin from uranium-bearing bedrocks and overburden. In the present study, assessment of the level of radon over the three lithological units upon which the residential areas of ObafemiAwolowo University Campus, Ile-Ife (OAU) was situated was carried out. Soil gas radon concentration measurement was carried out at a constant depth of 0.80 m across the three lithologies (granite gneiss, grey gneiss and mica schist) using a RAD7 electronic radon detector. A total of 138 in-situ soil gas radon measurements were carried out. Obtained experimental data were analysed and summarised using descriptive and inferential statistics with statistical significance set at p < 0.05. A radon potential map was also developed using existing permeability data of the soils in the area. Soil radon concentration varied across the different lithologies ranging from 0.04 kBq/m3 – 190 kBq/m3 with a mean value of 14 kBq/m3. The mean value of Rn-222 concentration obtained in the three lithologies are 3.5 ± 5.9, 11.5 ± 25.8 and 28.4 ± 37.4 kBq/m3 for granite gneiss, grey gneiss and mica schist respectively. There is a statistically significant difference (p < 0.001) in the mean concentration of radon-222 measured on the three lithologies. The granite gneiss and grey gneiss lithologies have been designated into low radon index, while mica schist lithology has been designated as medium radon index. 34% of the sampled areas exhibit high radon risk based on Swedish risk criteria, thereby warranting protective actions.
Rab27a plays a dual role in metastatic propensity of pancreatic cancer
Authors: Kren Nancy , Michaud Daniel , Bagchi Sukriti , Greene Kevin , Pylayeva-Gupta Yuliya 
Published: April 2020

AbstractPancreatic cancer is an aggressive malignancy, often diagnosed at metastatic stages. Several studies have implicated systemic factors, such as extracellular vesicle release and myeloid cell expansion, in the establishment of pre-metastatic niches in cancer. The Rab27a GTPase is overexpressed in advanced cancers, can regulate vesicle trafficking, and has been previously linked to non-cell autonomous control of tumor growth and metastasis, however, the role of Rab27a itself in the metastatic propensity of pancreatic cancer is not well understood. Here, we have established a model to study how Rab27a directs formation of the pre-metastatic niche. Loss of Rab27a in pancreatic cancer cells did not decrease tumor growth in vivo, but resulted in altered systemic myeloid cell expansion, both in the primary tumors and at the distant organ sites. In metastasis assays, loss of Rab27a expression in tumor cells injected into circulation compromised efficient outgrowth of metastatic lesions. However, Rab27a knockdown cells had an unexpected advantage at initial steps of metastatic seeding, suggesting that Rab27a may alter cell-autonomous invasive properties of the tumor cells. Gene expression analysis of gene expression revealed that downregulation of Rab27a increased expression of genes involved in epithelial-to-mesenchymal transition pathways, consistent with our findings that primary tumors arising from Rab27a knockdown cells were more invasive. Overall, these data reveal that Rab27a can play divergent roles in regulating pro-metastatic propensity of pancreatic cancer cells: by generating pro-metastatic environment at the distant organ sites, and by suppressing invasive properties of the cancer cells.