bluuebunny/crossref_metadata_2025_split huggingface dataset:
Lake Sediments From Littoral and Profundal Zones are Heterogeneous but Equivalent Sources of Methane Produced by Distinct Methanogenic Communities—A Case Study From Lake Remoray
Authors: Tardy Vincent , Etienne David , Millet Laurent , Lyautey Emilie 
Published: November 2022

AbstractLake ecosystems contribute significantly to atmospheric methane and are likely to become even bigger methane emitters with the global spread of hypoxia/anoxia in freshwater ecosystems. Here we characterized the spatial heterogeneity of methane production potential, methane concentration, archeal and bacterial communities across Lake Remoray sediment during the summer period when hypoxic conditions settle in the deepest part of the water column. It was hypothesized that methane concentration and production would be higher in the deeper part of the lake, our results showed that some littoral areas exhibited similar or higher values than the deepest area. The full 16S rRNA gene sequencing dataset counted 41 OTUs affiliated with methanogenic species in abundances that depended more on sampling‐site location than on the water depth gradient. The methanogenic co‐occurrence network revealed the existence of five distinct sub‐communities, suggesting the presence of different methanogenic niches across Lake Remoray. The variation in abundance of the two larger methanogenic sub‐communities was significantly related to methanogenesis potential and sediment methane concentration across‐lake but further studies investigating their real activities would provide additional insights. In a globally changing environment (temperature, eutrophication, …) a better understanding of the functional specificities and characteristics of the potential of methane cycle actors would allow us to better predict their future implications for greenhouse gas production and mitigation.
The circadian transcription factor ARNTL2 is regulated by weight-loss interventions in human white adipose tissue and inhibits adipogenesis
Authors: Mandl Markus , Viertler Hans P. , Zopoglou Maria , Mitterberger-Vogt Maria C. , Gasser Juliane , Hatzmann Florian M. , Rauchenwald Tina , Zwierzina Marit E. , Mattesich Monika , Weiss Alexander K. H. , Mottes Lorenza , Brucker Camille , Waldegger Petra , Pierer Gerhard , Zwerschke Werner 
Published: November 2022

AbstractMisalignment of physiological circadian rhythms promotes obesity which is characterized by white adipose tissue (WAT) expansion. Differentiation of Adipose stem/progenitor cells (ASCs) contributes to WAT increase but the importance of the cellular clock in this process is incompletely understood. In the present study, we reveal the role of the circadian transcription factor Aryl hydrocarbon receptor nuclear translocator-like 2 (ARNTL2) in human ASCs, isolated from subcutaneous (s)WAT samples of patients undergoing routine elective plastic abdominal surgery. We show that circadian synchronization by serum-shock or stimulation with adipogenic stimuli leads to a different expression pattern of ARNTL2 relative to its well-studied paralogue ARNTL1. We demonstrate that ARNTL2 mRNA is downregulated in ASCs upon weight-loss (WL) whereas ARNTL2 protein is rapidly induced in the course of adipogenic differentiation and highly abundant in adipocytes. ARNTL2 protein is maintained in ASCs cooperatively by mechanistic Target of Rapamycin (mTOR) and Mitogen-activated Protein Kinase (MAPK) signalling pathways while ARNTL2 functions as an inhibitor on both circuits, leading to a feedback mechanism. Consistently, ectopic overexpression of ARNTL2 repressed adipogenesis by facilitating the degradation of ARNTL1, inhibition of Kruppel-Like Factor 15 (KLF15) gene expression and down-regulation of the MAPK-CCAAT/enhancer-binding protein β (C/EBPβ) axis. Western blot analysis of sWAT samples from normal-weight, obese and WL donors revealed that ARNTL2 protein was solely elevated by WL compared to ARNTL1 which underscores unique functions of both transcription factors. In conclusion, our study reveals ARNTL2 to be a WL-regulated inhibitor of adipogenesis which might provide opportunities to develop strategies to ameliorate obesity.
Three-dimensional imaging of ferroaxial domains using circularly polarized second harmonic generation microscopy
Authors: Yokota Hiroko , Hayashida Takeshi , Kitahara Dan , Kimura Tsuyoshi 
Published: November 2022

AbstractThe spontaneous symmetry breakdown of matter is one of the most important concepts in materials physics and leads to a phase transition into an ordered phase and domain formation in its consequence. The so-called ‘ferroaxial order’ characterized by a rotational structural distortion with an axial vector symmetry has gained growing interest as a new class of ordered state. However, the observation of ferroaxial domain states, that is, clockwise and counterclockwise rotational states, is not straightforward and has been little investigated. Here, we propose that the circular intensity difference in second harmonic generation (CID-SHG) offers an experimental technique to investigate ferroaxial order and its domain states through the transition process of higher-order multipoles such as magnetic-dipole and electric-quadrupole. By using CID-SHG microscopy, we successfully visualize three-dimensional images of ferroaxial domain structures in NiTiO3. Our results indicate that CID-SHG is a sensitive probe of ferroaxial order and opens possibilities for the use of ferroaxial materials in nonlinear optical manipulations.
Pesticide risk constraints to achieving Sustainable Development Goals in China based on national modeling
Authors: Zhang Ziqi , Yan Xiaoman , Jones Kevin C. , Jiao Cong , Sun Cheng , Liu Yong , Zhu Ying , Zhang Qianqian , Zhai Limei , Shen Zhenyao , Chen Lei 
Published: November 2022

AbstractPesticides applied worldwide to meet food demand is recognized as a key threat to the Sustainable Development Goals (SDGs) set by the United Nations. Studies on pesticide risks employ different ingredients, methods or specific environments, which makes it difficult to quantify the scale of the problem. Furthermore, the complex influences and hotspots of long-term pesticide usage remain unclear. Herein, we present a national-scale study of four typical pesticides in China, the world’s largest pesticide user. The spatiotemporal changes in legacy and risk of pesticides over 30 years were analyzed using a modified fugacity model approach coupled with comprehensive ingredient database. Pesticide risk in mainland China might last until 2075 due to the previous legacy, although the usage has declined since 2014. The use of target pesticides was estimated as 2.38 × 105 tonnes in 2017, and about 6.59 × 103 tonnes discharged into the ocean from major basins. Risk areas expanded from 47% in 1991 to 79% in 2017, with 30% at high risk. Of the risk areas, 31% were highly populated while 3% had high biodiversity. 7% of mainland China suffered from both limited water resource and high pesticide risk. It is shown that the improper substitution with lower toxicity pesticides would make the proportion of high-risk regions unexpectedly increased from 18% to 44% due to the longer half-lives of the alternatives. Pesticides pose risks to environmental and human health, and the tailored assessment tool will be vital in contributing towards future pesticide management and meeting sustainability targets in China.
AAA+ protease-adaptor structures reveal altered conformations and ring specialization
Authors: Kim Sora , Fei Xue , Sauer Robert T. , Baker Tania A. 
Published: November 2022

AbstractClpAP, a two-ring AAA+ protease, degrades N-end-rule proteins bound by the ClpS adaptor. Here we present high-resolution cryo-EM structures of Escherichia coli ClpAPS complexes, showing how ClpA pore loops interact with the ClpS N-terminal extension (NTE), which is normally intrinsically disordered. In two classes, the NTE is bound by a spiral of pore-1 and pore-2 loops in a manner similar to substrate-polypeptide binding by many AAA+ unfoldases. Kinetic studies reveal that pore-2 loops of the ClpA D1 ring catalyze the protein remodeling required for substrate delivery by ClpS. In a third class, D2 pore-1 loops are rotated, tucked away from the channel and do not bind the NTE, demonstrating asymmetry in engagement by the D1 and D2 rings. These studies show additional structures and functions for key AAA+ elements. Pore-loop tucking may be used broadly by AAA+ unfoldases, for example, during enzyme pausing/unloading.
Reversible conduction failure in acute inflammatory demyelinating polyneuropathy
Authors: Kim Sooyoung , Lee Eun Kyoung , Sohn Eunhee 
Published: November 2022

AbstractReversible conduction failure (RCF) has been documented in acute motor axonal neuropathy (AMAN) and is considered a sign of nodopathy. Several reports of RCF in acute inflammatory demyelinating polyneuropathy (AIDP) have suggested that it could be a manifestation of nodopathy. We conducted this study to determine the frequency of RCF in AMAN and AIDP and to compare the clinical features between the two groups with or without RCF. RCF was observed in 38.9% and 18.5% patients in the AMAN and AIDP groups in our study, respectively. AIDP patients with anti-ganglioside antibodies represented 29.4% of the cohort. The clinical features of AIDP with RCF were more similar to those of AMAN with RCF than to those of typical AIDP. However, there were no significant differences in the frequency of anti-ganglioside antibody status between the groups. AIDP with RCF may be a manifestation of nodopathy. The current dichotomous electrodiagnostic criteria, classifying demyelinating and axonal neuropathy, are insufficient to define nodopathy. Further studies are required to revise the electrodiagnostic criteria for Guillain–Barré syndrome.
Butyrate reduces cellular magnesium absorption independently of metabolic regulation in Caco-2 human colon cells
Authors: Gommers Lisanne M. M. , Leermakers Pieter A. , van der Wijst Jenny , Roig Sara R. , Adella Anastasia , van de Wal Melissa A. E. , Bindels René J. M. , de Baaij Jeroen H. F. , Hoenderop Joost G. J. 
Published: November 2022

AbstractDigestion of dietary fibers by gut bacteria has been shown to stimulate intestinal mineral absorption [e.g., calcium (Ca2+) and magnesium (Mg2+)]. Although it has been suggested that local pH and short-chain fatty acid (SCFA) concentrations determine divalent cation absorption, the exact molecular mechanisms are still unknown. Therefore, this study aimed to determine the effects of SCFAs on intestinal Mg2+ absorption. We show that the butyrate concentration in the colon negatively correlates with serum Mg2+ levels in wildtype mice. Moreover, Na-butyrate significantly inhibited Mg2+ uptake in Caco-2 cells, while Ca2+ uptake was unaffected. Although Na-butyrate significantly lowered total ATP production rate, and resulted in increased phosphorylation of AMP-activated protein kinase (AMPK), inhibition of Mg2+ uptake by butyrate preceded these consequences. Importantly, electrophysiological examinations demonstrated that intracellular butyrate directly reduced the activity of the heteromeric Mg2+ channel complex, transient receptor potential melastatin (TRPM)6/7. Blocking cellular butyrate uptake prevented its inhibitory effect on Mg2+ uptake, demonstrating that butyrate acts intracellularly. Our work identified butyrate as novel regulator of intestinal Mg2+ uptake that works independently from metabolic regulation. This finding further highlights the role of microbial fermentation in the regulation of mineral absorption.
Familial history and prevalence of BRCA1, BRCA2 and TP53 pathogenic variants in HBOC Brazilian patients from a public healthcare service
Authors: Matta Bruna Palma , Gomes Renan , Mattos Daniel , Olicio Renata , Nascimento Caroline Macedo , Ferreira Gerson Moura , Brant Ayslan Castro , Boroni Mariana , Furtado Carolina , Lima Valdirene , Moreira Miguel Ângelo Martins , dos Santos Anna Cláudia Evangelista 
Published: November 2022

AbstractSeveral studies have demonstrated the cost-effectiveness of genetic testing for surveillance and treatment of carriers of germline pathogenic variants associated with hereditary breast/ovarian cancer syndrome (HBOC). In Brazil, seventy percent of the population is assisted by the public Unified Health System (SUS), where genetic testing is still unavailable. And few studies were performed regarding the prevalence of HBOC pathogenic variants in this context. Here, we estimated the prevalence of germline pathogenic variants in BRCA1, BRCA2 and TP53 genes in Brazilian patients suspected of HBOC and referred to public healthcare service. Predictive power of risk prediction models for detecting mutation carriers was also evaluated. We found that 41 out of 257 tested patients (15.9%) were carriers of pathogenic variants in the analyzed genes. Most frequent pathogenic variant was the founder Brazilian mutation TP53 c.1010G > A (p.Arg337His), adding to the accumulated evidence that supports inclusion of TP53 in routine testing of Brazilian HBOC patients. Surprisingly, BRCA1 c.5266dupC (p.Gln1756fs), a frequently reported pathogenic variant in Brazilian HBOC patients, was not observed. Regarding the use of predictive models, we found that familial history of cancer might be used to improve selection or prioritization of patients for genetic testing, especially in a context of limited resources.
The moderating role of physical fitness in the relationship between sugar-sweetened beverage consumption and adiposity in schoolchildren
Authors: López-Gil José Francisco , Cavero-Redondo Iván , Sánchez-López Mairena , Martínez-Hortelano José Alberto , Berlanga-Macias Carlos , Soriano-Cano Alba , Martínez-Vizcaíno Vicente 
Published: November 2022

AbstractThe mediating and moderating associations of cardiorespiratory fitness (CRF) and handgrip strength on the association between dietary patterns and several health outcomes have been previously studied. For instance, handgrip strength has been found as a moderator of the relationship between excess weight and cardiometabolic risk factors in young adults. Similarly, CRF has been shown as a mediator of the association between diet and obesity in children. However, to our knowledge, the role of CRF and handgrip strength on the association between sugar-sweetened beverage (SSB) consumption and adiposity is still unclear. The aim of this study was to determine whether CRF and handgrip strength moderate the association between SSB consumption and adiposity in a population-based sample of Spanish schoolchildren. This cross-sectional study involved 475 schoolchildren (52.0% girls), aged 8–12, from ten schools in Cuenca (Spain). Adiposity was determined as body fat (in kg), which was measured using a bioimpedance analysis system. Data on SSB consumption were gathered by using the Children’s Eating Habits Questionnaire, which was completed by parents. The CRF level was determined by the 20-m Shuttle Run test and Nevill’s curvilinear allometric model. Handgrip strength was determined using a digital dynamometer with adjustable grip. For each unit (in ml/kg/min) of CRF increased, the association between SSB consumption and adiposity was moderated (B = − 0.09, CI 95% − 0.14 to − 0.04). This significant moderation was also found for each 0.01 unit of increased normalized handgrip strength (B = − 0.07; CI 95% − 0.11 to − 0.02). Similarly, the Johnson-Neymann technique established three different regions. The first region shows that the association of SSB consumption on adiposity in participants who had levels of CRF < 43.4 ml/kg/min or handgrip strength < 0.34 was greater and statistically significant. The second region (43.4–57.4 ml/kg/min for CRF; 0.34–0.58 for normalized handgrip strength) depicted that the association between SSB consumption and adiposity was not statistically significant in those with a CRF level or normalized handgrip strength between the lower and upper thresholds. The third region was found at > 57.4 ml/kg/min (for CRF level) and > 0.58 (for normalized handgrip strength), indicating that the association between SSB consumption and adiposity was lower and statistically significant in children above these moderator values. Our results showed that certain levels of CRF and normalized handgrip strength moderate the association between SSB consumption and adiposity in a sample of Spanish schoolchildren. It might be possible that higher physical fitness level in childhood may contribute to reducing the association between SSB consumption and adiposity.
Glycosylated clusterin species facilitate Aβ toxicity in human neurons
Authors: Foster Evangeline M. , Fernandes Marco , Dangla-Valls Adria , Hublitz Philip , Pangalos Menelaos , Lovestone Simon , Ribe Elena M. , Buckley Noel J. 
Published: November 2022

AbstractClusterin (CLU) is one of the most significant genetic risk factors for late onset Alzheimer’s disease (AD). However, the mechanisms by which CLU contributes to AD development and pathogenesis remain unclear. Studies have demonstrated that the trafficking and localisation of glycosylated CLU proteins is altered by CLU-AD mutations and amyloid-β (Aβ), which may contribute to AD pathogenesis. However, the roles of non-glycosylated and glycosylated CLU proteins in mediating Aβ toxicity have not been studied in human neurons. iPSCs with altered CLU trafficking were generated following the removal of CLU exon 2 by CRISPR/Cas9 gene editing. Neurons were generated from control (CTR) and exon 2 −/− edited iPSCs and were incubated with aggregated Aβ peptides. Aβ induced changes in cell death and neurite length were quantified to determine if altered CLU protein trafficking influenced neuronal sensitivity to Aβ. Finally, RNA-Seq analysis was performed to identify key transcriptomic differences between CLU exon 2  −/− and CTR neurons. The removal of CLU exon 2, and the endoplasmic reticulum (ER)-signal peptide located within, abolished the presence of glycosylated CLU and increased the abundance of intracellular, non-glycosylated CLU. While non-glycosylated CLU levels were unaltered by Aβ25–35 treatment, the trafficking of glycosylated CLU was altered in control but not exon 2  −/− neurons. The latter also displayed partial protection against Aβ-induced cell death and neurite retraction. Transcriptome analysis identified downregulation of multiple extracellular matrix (ECM) related genes in exon 2  −/− neurons, potentially contributing to their reduced sensitivity to Aβ toxicity. This study identifies a crucial role of glycosylated CLU in facilitating Aβ toxicity in human neurons. The loss of these proteins reduced both, cell death and neurite damage, two key consequences of Aβ toxicity identified in the AD brain. Strikingly, transcriptomic differences between exon 2  −/− and control neurons were small, but a significant and consistent downregulation of ECM genes and pathways was identified in exon 2  −/− neurons. This may contribute to the reduced sensitivity of these neurons to Aβ, providing new mechanistic insights into Aβ pathologies and therapeutic targets for AD.
Fragmentation by major dams and implications for the future viability of platypus populations
Authors: Mijangos Jose L. , Bino Gilad , Hawke Tahneal , Kolomyjec Stephen H. , Kingsford Richard T. , Sidhu Harvinder , Grant Tom , Day Jenna , Dias Kimberly N. , Gongora Jaime , Sherwin William B. 
Published: November 2022

AbstractThe evolutionarily unique platypus (Ornithorhynchus anatinus) has experienced major declines and extinctions from a range of historical and recent interacting human-mediated threats. Although spending most of their time in the water, platypuses can move over land. Nevertheless, uncertainties remain whether dams are barriers to movement, thus limiting gene flow and dispersal, essential to evolution and ecology. Here we examined disruption of gene flow between platypus groups below and above five major dams, matched to four adjacent rivers without major dams. Genetic differentiation (FST) across dams was 4- to 20-fold higher than along similar stretches of adjacent undammed rivers; FST across dams was similar to differentiation between adjacent river systems. This indicates that major dams represent major barriers for platypus movements. Furthermore, FST between groups was correlated with the year in which the dam was built, increasing by 0.011 every generation, reflecting the effects of these barriers on platypus genetics. This study provides evidence of gene flow restriction, which jeopardises the long-term viability of platypus populations when groups are fragmented by major dams. Mitigation strategies, such as building of by-pass structures and translocation between upstream and downstream of the dam, should be considered in conservation and management planning.
SARS-CoV-2 spike opening dynamics and energetics reveal the individual roles of glycans and their collective impact
Authors: Pang Yui Tik , Acharya Atanu , Lynch Diane L. , Pavlova Anna , Gumbart James C. 
Published: November 2022

AbstractThe trimeric spike (S) glycoprotein, which protrudes from the SARS-CoV-2 viral envelope, binds to human ACE2, initiated by at least one protomer’s receptor binding domain (RBD) switching from a "down” (closed) to an "up” (open) state. Here, we used large-scale molecular dynamics simulations and two-dimensional replica exchange umbrella sampling calculations with more than a thousand windows and an aggregate total of 160 μs of simulation to investigate this transition with and without glycans. We find that the glycosylated spike has a higher barrier to opening and also energetically favors the down state over the up state. Analysis of the S-protein opening pathway reveals that glycans at N165 and N122 interfere with hydrogen bonds between the RBD and the N-terminal domain in the up state, while glycans at N165 and N343 can stabilize both the down and up states. Finally, we estimate how epitope exposure for several known antibodies changes along the opening path. We find that the BD-368-2 antibody’s epitope is continuously exposed, explaining its high efficacy.
Blib is a multi-module simulation platform for genetics studies and intelligent breeding
Authors: Zhang Luyan , Li Huihui , Wang Jiankang 
Published: November 2022

AbstractSimulation is an efficient approach for the investigation of theoretical and applied issues in population and quantitative genetics, and animal and plant breeding. In this study, we report a multi-module simulation platform called Blib, that is able to handle more complicated genetic effects and models than existing tools. Two derived data types are first defined in Blib, one to hold the required information on genetic models, and the other one to represent the genetics and breeding populations. A number of subroutines are then developed to perform specific tasks. Four case studies are present as examples to show the applications of Blib, i.e., genetic drift of multiple alleles in randomly mating populations, joint effects of neutral mutation and genetic drift, comparison of mass versus family selection, and choice of testers in hybrid breeding. Blib together with its application modules, has great potential to benefit theoretical genetic studies and intelligent breeding by simulating and predicting outcomes in a large number of scenarios, and identifying the best optimum selection and crossing schemes.
Extension of the short wavelength side of fluorescent proteins using hydrated chromophores, and its application
Authors: Sugiura Kazunori , Nagai Takeharu 
Published: November 2022

AbstractTo perform correlation analysis between different physiological parameters using fluorescent protein-based functional probes, diversification of wavelength properties of fluorescent proteins is underway. However, the shortest emission wavelength of fluorescent proteins has not been updated for more than 10 years. Here, we report the development of Sumire, a fluorescent protein emitting 414 nm violet fluorescence from a hydrated chromophore. The Sumire’s fluorescence property allows for the creation of FRET probes that can be used simultaneously with CFP-YFP based FRET probes for multi-parameter analysis.