bluuebunny/crossref_metadata_2025_split huggingface dataset:
Rare heterozygous GDF6 variants in patients with renal anomalies
Authors: Martens Helge , Hennies Imke , Getwan Maike , Christians Anne , Weiss Anna-Carina , Brand Frank , Gjerstad Ann Christin , Christians Arne , Gucev Zoran , Geffers Robert , Seeman Tomáš , Kispert Andreas , Tasic Velibor , Bjerre Anna , Lienkamp Soeren S. , Haffner Dieter , Weber Ruthild G. 
Published: July 2020

AbstractAlthough over 50 genes are known to cause renal malformation if mutated, the underlying genetic basis, most easily identified in syndromic cases, remains unsolved in most patients. In search of novel causative genes, whole-exome sequencing in a patient with renal, i.e., crossed fused renal ectopia, and extrarenal, i.e., skeletal, eye, and ear, malformations yielded a rare heterozygous variant in the GDF6 gene encoding growth differentiation factor 6, a member of the BMP family of ligands. Previously, GDF6 variants were reported to cause pleiotropic defects including skeletal, e.g., vertebral, carpal, tarsal fusions, and ocular, e.g., microphthalmia and coloboma, phenotypes. To assess the role of GDF6 in the pathogenesis of renal malformation, we performed targeted sequencing in 193 further patients identifying rare GDF6 variants in two cases with kidney hypodysplasia and extrarenal manifestations. During development, gdf6 was expressed in the pronephric tubule of Xenopus laevis, and Gdf6 expression was observed in the ureteric tree of the murine kidney by RNA in situ hybridization. CRISPR/Cas9-derived knockout of Gdf6 attenuated migration of murine IMCD3 cells, an effect rescued by expression of wild-type but not mutant GDF6, indicating affected variant function regarding a fundamental developmental process. Knockdown of gdf6 in Xenopus laevis resulted in impaired pronephros development. Altogether, we identified rare heterozygous GDF6 variants in 1.6% of all renal anomaly patients and 5.4% of renal anomaly patients additionally manifesting skeletal, ocular, or auricular abnormalities, adding renal hypodysplasia and fusion to the phenotype spectrum of GDF6 variant carriers and suggesting an involvement of GDF6 in nephrogenesis.
Symmetric neural progenitor divisions require chromatin-mediated homologous recombination DNA repair by Ino80
Authors: Keil Jason M. , Doyle Daniel Z. , Qalieh Adel , Lam Mandy M. , Funk Owen H. , Qalieh Yaman , Shi Lei , Mohan Nitesh , Sorel Alice , Kwan Kenneth Y. 
Published: July 2020

AbstractChromatin regulates spatiotemporal gene expression during neurodevelopment, but it also mediates DNA damage repair essential to proliferating neural progenitor cells (NPCs). Here, we uncover molecularly dissociable roles for nucleosome remodelerIno80in chromatin-mediated transcriptional regulation and genome maintenance in corticogenesis. We find that conditionalIno80deletion from cortical NPCs impairs DNA double-strand break (DSB) repair, triggering p53-dependent apoptosis and microcephaly. Using an in vivo DSB repair pathway assay, we find thatIno80is selectively required for homologous recombination (HR) DNA repair, which is mechanistically distinct fromIno80function in YY1-associated transcription. Unexpectedly, sensitivity to loss ofIno80-mediated HR is dependent on NPC division mode:Ino80deletion leads to unrepaired DNA breaks and apoptosis in symmetric NPC-NPC divisions, but not in asymmetric neurogenic divisions. This division mode dependence is phenocopied following conditional deletion of HR geneBrca2. Thus, distinct modes of NPC division have divergent requirements forIno80-dependent HR DNA repair.
Surface cooling caused by rare but intense near-inertial wave induced mixing in the tropical Atlantic
Authors: Hummels Rebecca , Dengler Marcus , Rath Willi , Foltz Gregory R. , Schütte Florian , Fischer Tim , Brandt Peter 
Published: July 2020

AbstractThe direct response of the tropical mixed layer to near-inertial waves (NIWs) has only rarely been observed. Here, we present upper-ocean turbulence data that provide evidence for a strongly elevated vertical diffusive heat flux across the base of the mixed layer in the presence of a NIW, thereby cooling the mixed layer at a rate of 244 W m−2 over the 20 h of continuous measurements. We investigate the seasonal cycle of strong NIW events and find that despite their local intermittent nature, they occur preferentially during boreal summer, presumably associated with the passage of atmospheric African Easterly Waves. We illustrate the impact of these rare but intense NIW induced mixing events on the mixed layer heat balance, highlight their contribution to the seasonal evolution of sea surface temperature, and discuss their potential impact on biological productivity in the tropical North Atlantic.
A distal regulatory region of a class I human histone deacetylase
Authors: Werbeck Nicolas D. , Shukla Vaibhav Kumar , Kunze Micha B. A. , Yalinca Havva , Pritchard Ruth B. , Siemons Lucas , Mondal Somnath , Greenwood Simon O. R. , Kirkpatrick John , Marson Charles M. , Hansen D. Flemming 
Published: July 2020

AbstractHistone deacetylases (HDACs) are key enzymes in epigenetics and important drug targets in cancer biology. Whilst it has been established that HDACs regulate many cellular processes, far less is known about the regulation of these enzymes themselves. Here, we show that HDAC8 is allosterically regulated by shifts in populations between exchanging states. An inactive state is identified, which is stabilised by a range of mutations and resembles a sparsely-populated state in equilibrium with active HDAC8. Computational models show that the inactive and active states differ by small changes in a regulatory region that extends up to 28 Å from the active site. The regulatory allosteric region identified here in HDAC8 corresponds to regions in other class I HDACs known to bind regulators, thus suggesting a general mechanism. The presented results pave the way for the development of allosteric HDAC inhibitors and regulators to improve the therapy for several disease states.
A nanoscale metal organic frameworks-based vaccine synergises with PD-1 blockade to potentiate anti-tumour immunity
Authors: Li Xia , Wang Xiupeng , Ito Atsuo , Tsuji Noriko M. 
Published: July 2020

AbstractCheckpoint blockade therapy has provided noteworthy benefits in multiple cancers in recent years; however, its clinical benefits remain confined to 10–40% of patients with extremely high costs. Here, we design an ultrafast, low-temperature, and universal self-assembly route to integrate immunology-associated large molecules into metal-organic-framework (MOF)-gated mesoporous silica (MS) as cancer vaccines. Core MS nanoparticles, acting as an intrinsic immunopotentiator, provide the niche, void, and space to accommodate antigens, soluble immunopotentiators, and so on, whereas the MOF gatekeeper protects the interiors from robust and off-target release. A combination of MOF-gated MS cancer vaccines with systemic programmed cell death 1 (PD-1) blockade therapy generates synergistic effects that potentiate antitumour immunity and reduce the effective dose of an anti-PD-1 antibody to as low as 1/10 of that for PD-1 blockade monotherapy in E.G7-OVA tumour-bearing mice, with eliciting the robust adaptive OVA-specific CD8+ T-cell responses, reversing the immunosuppressive pathway and inducing durable tumour suppression.
Testing and controlling for horizontal pleiotropy with probabilistic Mendelian randomization in transcriptome-wide association studies
Authors: Yuan Zhongshang , Zhu Huanhuan , Zeng Ping , Yang Sheng , Sun Shiquan , Yang Can , Liu Jin , Zhou Xiang 
Published: July 2020

AbstractIntegrating results from genome-wide association studies (GWASs) and gene expression studies through transcriptome-wide association study (TWAS) has the potential to shed light on the causal molecular mechanisms underlying disease etiology. Here, we present a probabilistic Mendelian randomization (MR) method, PMR-Egger, for TWAS applications. PMR-Egger relies on a MR likelihood framework that unifies many existing TWAS and MR methods, accommodates multiple correlated instruments, tests the causal effect of gene on trait in the presence of horizontal pleiotropy, and is scalable to hundreds of thousands of individuals. In simulations, PMR-Egger provides calibrated type I error control for causal effect testing in the presence of horizontal pleiotropic effects, is reasonably robust under various types of model misspecifications, is more powerful than existing TWAS/MR approaches, and can directly test for horizontal pleiotropy. We illustrate the benefits of PMR-Egger in applications to 39 diseases and complex traits obtained from three GWASs including the UK Biobank.
Designer patterned functional fibers via direct imprinting in thermal drawing
Authors: Wang Zhe , Wu Tingting , Wang Zhixun , Zhang Ting , Chen Mengxiao , Zhang Jing , Liu Lin , Qi Miao , Zhang Qichong , Yang Jiao , Liu Wei , Chen Haisheng , Luo Yu , Wei Lei 
Published: July 2020

AbstractCreating micro/nanostructures on fibers is beneficial for extending the application range of fiber-based devices. To achieve this using thermal fiber drawing is particularly important for the mass production of longitudinally uniform fibers up to tens of kilometers. However, the current thermal fiber drawing technique can only fabricate one-directional micro/nano-grooves longitudinally due to structure elongation and polymer reflow. Here, we develop a direct imprinting thermal drawing (DITD) technique to achieve arbitrarily designed surface patterns on entire fiber surfaces with high resolution in all directions. Such a thermal imprinting process is simulated and confirmed experimentally. Key process parameters are further examined, showing a process feature size as small as tens of nanometers. Furthermore, nanopatterns are fabricated on fibers as plasmonic metasurfaces, and double-sided patterned fibers are produced to construct self-powered wearable touch sensing fabric, revealing the bright future of the DITD technology in multifunctional fiber-based devices, wearable electronics, and smart textiles.
European polygenic risk score for prediction of breast cancer shows similar performance in Asian women
Authors: Ho Weang-Kee , Tan Min-Min , Mavaddat Nasim , Tai Mei-Chee , Mariapun Shivaani , Li Jingmei , Ho Peh-Joo , Dennis Joe , Tyrer Jonathan P. , Bolla Manjeet K. , Michailidou Kyriaki , Wang Qin , Kang Daehee , Choi Ji-Yeob , Jamaris Suniza , Shu Xiao-Ou , Yoon Sook-Yee , Park Sue K. , Kim Sung-Won , Shen Chen-Yang , Yu Jyh-Cherng , Tan Ern Yu , Chan Patrick Mun Yew , Muir Kenneth , Lophatananon Artitaya , Wu Anna H. , Stram Daniel O. , Matsuo Keitaro , Ito Hidemi , Chan Ching Wan , Ngeow Joanne , Yong Wei Sean , Lim Swee Ho , Lim Geok Hoon , Kwong Ava , Chan Tsun L. , Tan Su Ming , Seah Jaime , John Esther M. , Kurian Allison W. , Koh Woon-Puay , Khor Chiea Chuen , Iwasaki Motoki , Yamaji Taiki , Tan Kiak Mien Veronique , Tan Kiat Tee Benita , Spinelli John J. , Aronson Kristan J. , Hasan Siti Norhidayu , Rahmat Kartini , Vijayananthan Anushya , Sim Xueling , Pharoah Paul D. P. , Zheng Wei , Dunning Alison M. , Simard Jacques , van Dam Rob Martinus , Yip Cheng-Har , Taib Nur Aishah Mohd , Hartman Mikael , Easton Douglas F. , Teo Soo-Hwang , Antoniou Antonis C. 
Published: July 2020

AbstractPolygenic risk scores (PRS) have been shown to predict breast cancer risk in European women, but their utility in Asian women is unclear. Here we evaluate the best performing PRSs for European-ancestry women using data from 17,262 breast cancer cases and 17,695 controls of Asian ancestry from 13 case-control studies, and 10,255 Chinese women from a prospective cohort (413 incident breast cancers). Compared to women in the middle quintile of the risk distribution, women in the highest 1% of PRS distribution have a ~2.7-fold risk and women in the lowest 1% of PRS distribution has ~0.4-fold risk of developing breast cancer. There is no evidence of heterogeneity in PRS performance in Chinese, Malay and Indian women. A PRS developed for European-ancestry women is also predictive of breast cancer risk in Asian women and can help in developing risk-stratified screening programmes in Asia.
Assessing the response of micro-eukaryotic diversity to the Great Acceleration using lake sedimentary DNA
Authors: Keck François , Millet Laurent , Debroas Didier , Etienne David , Galop Didier , Rius Damien , Domaizon Isabelle 
Published: July 2020

AbstractLong-term time series have provided evidence that anthropogenic pressures can threaten lakes. Yet it remains unclear how and the extent to which lake biodiversity has changed during the Anthropocene, in particular for microbes. Here, we used DNA preserved in sediments to compare modern micro-eukaryotic communities with those from the end of the 19th century, i.e., before acceleration of the human imprint on ecosystems. Our results obtained for 48 lakes indicate drastic changes in the composition of microbial communities, coupled with a homogenization of their diversity between lakes. Remote high elevation lakes were globally less impacted than lowland lakes affected by local human activity. All functional groups (micro-algae, parasites, saprotrophs and consumers) underwent significant changes in diversity. However, we show that the effects of anthropogenic changes have benefited in particular phototrophic and mixotrophic species, which is consistent with the hypothesis of a global increase of primary productivity in lakes.
A joint role for forced and internally-driven variability in the decadal modulation of global warming
Authors: Liguori Giovanni , McGregor Shayne , Arblaster Julie M. , Singh Martin S. , Meehl Gerald A. 
Published: July 2020

AbstractDespite the observed monotonic increase in greenhouse-gas concentrations, global mean temperature displays important decadal fluctuations typically attributed to both external forcing and internal variability. Here, we provide a robust quantification of the relative contributions of anthropogenic, natural, and internally-driven decadal variability of global mean sea surface temperature (GMSST) by using a unique dataset consisting of 30-member large initial-condition ensembles with five Earth System Models (ESM-LE). We present evidence that a large fraction (~29–53%) of the simulated decadal-scale variance in individual timeseries of GMSST over 1950–2010 is externally forced and largely linked to the representation of volcanic aerosols. Comparison with the future (2010–2070) period suggests that external forcing provides a source of additional decadal-scale variability in the historical period. Given the unpredictable nature of future volcanic aerosol forcing, it is suggested that a large portion of decadal GMSST variability might not be predictable.
Oxygen induced promotion of electrochemical reduction of CO2 via co-electrolysis
Authors: He Ming , Li Chunsong , Zhang Haochen , Chang Xiaoxia , Chen Jingguang G. , Goddard William A. , Cheng Mu-jeng , Xu Bingjun , Lu Qi 
Published: July 2020

AbstractHarnessing renewable electricity to drive the electrochemical reduction of CO2 is being intensely studied for sustainable fuel production and as a means for energy storage. Copper is the only monometallic electrocatalyst capable of converting CO2 to value-added products, e.g., hydrocarbons and oxygenates, but suffers from poor selectivity and mediocre activity. Multiple oxidative treatments have shown improvements in the performance of copper catalysts. However, the fundamental underpinning for such enhancement remains controversial. Here, we combine reactivity, in-situ surface-enhanced Raman spectroscopy, and computational investigations to demonstrate that the presence of surface hydroxyl species by co-electrolysis of CO2 with low concentrations of O2 can dramatically enhance the activity of copper catalyzed CO2 electroreduction. Our results indicate that co-electrolysis of CO2 with an oxidant is a promising strategy to introduce catalytically active species in electrocatalysis.
T-square resistivity without Umklapp scattering in dilute metallic Bi2O2Se
Authors: Wang Jialu , Wu Jing , Wang Tao , Xu Zhuokai , Wu Jifeng , Hu Wanghua , Ren Zhi , Liu Shi , Behnia Kamran , Lin Xiao 
Published: July 2020

AbstractFermi liquids (FLs) display a quadratic temperature (T) dependent resistivity. This can be caused by electron-electron (e-e) scattering in presence of inter-band or Umklapp scattering. However, dilute metallic SrTiO3 was found to display T2 resistivity in absence of either of the two mechanisms. The presence of soft phonons as possible scattering centers raised the suspicion that T2 resistivity is not due to e-e scattering. Here, we present the case of Bi2O2Se, a layered semiconductor with hard phonons, which becomes a dilute metal with a small single-component Fermi surface upon doping. It displays T2 resistivity well below the degeneracy temperature in absence of Umklapp and inter-band scattering. We observe a universal scaling between the T2 resistivity prefactor (A) and the Fermi energy (EF), an extension of the Kadowaki-Woods plot to dilute metals. Our results imply the absence of a satisfactory understanding of the ubiquity of e-e T2 resistivity in FLs.
Protein-responsive protein release of supramolecular/polymer hydrogel composite integrating enzyme activation systems
Authors: Shigemitsu Hajime , Kubota Ryou , Nakamura Keisuke , Matsuzaki Tomonobu , Minami Saori , Aoyama Takuma , Urayama Kenji , Hamachi Itaru 
Published: July 2020

AbstractNon-enzymatic proteins including antibodies function as biomarkers and are used as biopharmaceuticals in several diseases. Protein-responsive soft materials capable of the controlled release of drugs and proteins have potential for use in next-generation diagnosis and therapies. Here, we describe a supramolecular/agarose hydrogel composite that can release a protein in response to a non-enzymatic protein. A non-enzymatic protein-responsive system is developed by hybridization of an enzyme-sensitive supramolecular hydrogel with a protein-triggered enzyme activation set. In situ imaging shows that the supramolecular/agarose hydrogel composite consists of orthogonal domains of supramolecular fibers and agarose, which play distinct roles in protein entrapment and mechanical stiffness, respectively. Integrating the enzyme activation set with the composite allows for controlled release of the embedded RNase in response to an antibody. Such composite hydrogels would be promising as a matrix embedded in a body, which can autonomously release biopharmaceuticals by sensing biomarker proteins.
Catalytic nanosponges of acidic aluminosilicates for plastic degradation and CO2 to fuel conversion
Authors: Maity Ayan , Chaudhari Sachin , Titman Jeremy J. , Polshettiwar Vivek 
Published: July 2020

AbstractThe synthesis of solid acids with strong zeolite-like acidity and textural properties like amorphous aluminosilicates (ASAs) is still a challenge. In this work, we report the synthesis of amorphous “acidic aluminosilicates (AAS)”, which possesses Brønsted acidic sites like in zeolites and textural properties like ASAs. AAS catalyzes different reactions (styrene oxide ring-opening, vesidryl synthesis, Friedel−Crafts alkylation, jasminaldehyde synthesis, m-xylene isomerization, and cumene cracking) with better performance than state-of-the-art zeolites and amorphous aluminosilicates. Notably, AAS efficiently converts a range of waste plastics to hydrocarbons at significantly lower temperatures. A Cu-Zn-Al/AAS hybrid shows excellent performance for CO2 to fuel conversion with 79% selectivity for dimethyl ether. Conventional and DNP-enhanced solid-state NMR provides a molecular-level understanding of the distinctive Brønsted acidic sites of these materials. Due to their unique combination of strong acidity and accessibility, AAS will be a potential alternative to zeolites.
Anchoring the Late Devonian mass extinction in absolute time by integrating climatic controls and radio-isotopic dating
Authors: Da Silva Anne-Christine , Sinnesael Matthias , Claeys Philippe , Davies Joshua H. F. L. , de Winter Niels J. , Percival L. M. E. , Schaltegger Urs , De Vleeschouwer David 
Published: July 2020

AbstractThe Devonian Frasnian–Famennian (F–F) boundary marks one of the five main extinction intervals of the Phanerozoic Aeon. This time was characterized by two pulses of oceanic anoxia, named the Lower and Upper Kellwasser events, during which massive marine biodiversity losses occurred. This paper presents high-resolution magnetic susceptibility, X-ray fluorescence elemental geochemistry and carbon isotope datasets obtained from the Steinbruch Schmidt F–F boundary section (Germany). These records lead to an astronomical time calibration of the environmental changes associated with the two ocean anoxia pulses. Cyclostratigraphic interpretation indicates deposition of the black argillaceous Lower and Upper Kellwasser horizons over ~ 90 and ~ 110 kyr, respectively; approximately equivalent to the duration of one short eccentricity cycle. This study confirms that the succession of events within the Upper Kellwasser event is paced by obliquity, under a low-eccentricity orbit. Hence, astronomical insolation forcing likely contributed to the expansion of ocean anoxia and other environmental perturbations associated with these two crises. The new floating chronology established for the Steinbruch Schmidt section is anchored in numerical time by means of a radio-isotopic date, obtained from a bentonite layer interbedded between the two Kellwasser horizons. After anchoring, this time scale gives a high-precision age of 371.870 ± 0.108 Ma for the F–F boundary.
Methyl-donor supplementation prevents intestinal colonization by Adherent-Invasive E. coli in a mouse model of Crohn’s disease
Authors: Gimier Elodie , Chervy Mélissa , Agus Allison , Sivignon Adeline , Billard Elisabeth , Privat Maud , Viala Sandrine , Minet-Quinard Régine , Buisson Anthony , Vazeille Emilie , Barnich Nicolas , Denizot Jérémy 
Published: July 2020

AbstractDeficiencies in methyl-donor molecules (folate, B12 vitamin), DNA methylation alteration and high prevalence of Adherent-Invasive Escherichia coli (AIEC) are frequently observed in Crohn’s disease (CD) patients. AIEC bacteria adhere to the enterocytes through abnormally expressed carcinoembryonic antigen-related cell adhesion molecule 6 (CEACAM6) glycoprotein on host cells. This work aims at studying the relationship between methyl-donor molecules and AIEC-induced intestinal inflammatory response. CEABAC10 mice, a mouse model of CD, were fed a control or Methyl-donor Supplemented diet (MS diet). CEACAM6 promoter was hypermethylated in intestinal epithelial cells from mice fed an MS diet, which was associated with a significant decrease in CEACAM6 expression. Transcriptomic analysis revealed increased expression of anti-microbial peptides, increase in HSP70 gene family expression and a decreased expression of inflammatory marker Calprotectin upon MS diet, associated to a lower ability of AIEC bacteria to colonize gut mucosa. We observed in a cohort of CD patients that serum folate concentration was inversely correlated to Crohn’s disease endoscopic index of severity and to fecal inflammatory markers. This study demonstrates that methyl-donor supplementation through the diet induces a specific intestinal micro-environment limiting pathobiont colonization of the gut. Clinicians may wish to consider methyl-donor supplementation for methyl-donor deficient CD patients.