bluuebunny/crossref_metadata_2025_split huggingface dataset:
Proteomics of CKD progression in the chronic renal insufficiency cohort
Authors: Dubin Ruth F. , Deo Rajat , Ren Yue , Wang Jianqiao , Zheng Zihe , Shou Haochang , Go Alan S. , Parsa Afshin , Lash James P. , Rahman Mahboob , Hsu Chi-yuan , Weir Matthew R. , Chen Jing , Anderson Amanda , Grams Morgan E. , Surapaneni Aditya , Coresh Josef , Li Hongzhe , Kimmel Paul L. , Vasan Ramachandran S. , Feldman Harold , Segal Mark R. , Ganz Peter ,   CRIC Study Investigators,   CKD Biomarkers Consortium
Published: October 2023

AbstractProgression of chronic kidney disease (CKD) portends myriad complications, including kidney failure. In this study, we analyze associations of 4638 plasma proteins among 3235 participants of the Chronic Renal Insufficiency Cohort Study with the primary outcome of 50% decline in estimated glomerular filtration rate or kidney failure over 10 years. We validate key findings in the Atherosclerosis Risk in the Communities study. We identify 100 circulating proteins that are associated with the primary outcome after multivariable adjustment, using a Bonferroni statistical threshold of significance. Individual protein associations and biological pathway analyses highlight the roles of bone morphogenetic proteins, ephrin signaling, and prothrombin activation. A 65-protein risk model for the primary outcome has excellent discrimination (C-statistic[95%CI] 0.862 [0.835, 0.889]), and 14/65 proteins are druggable targets. Potentially causal associations for five proteins, to our knowledge not previously reported, are supported by Mendelian randomization: EGFL9, LRP-11, MXRA7, IL-1 sRII and ILT-2. Modifiable protein risk markers can guide therapeutic drug development aimed at slowing CKD progression.
The medial septum controls hippocampal supra-theta oscillations
Authors: Király Bálint , Domonkos Andor , Jelitai Márta , Lopes-dos-Santos Vítor , Martínez-Bellver Sergio , Kocsis Barnabás , Schlingloff Dániel , Joshi Abhilasha , Salib Minas , Fiáth Richárd , Barthó Péter , Ulbert István , Freund Tamás F. , Viney Tim J. , Dupret David , Varga Viktor , Hangya Balázs 
Published: October 2023

AbstractHippocampal theta oscillations orchestrate faster beta-to-gamma oscillations facilitating the segmentation of neural representations during navigation and episodic memory. Supra-theta rhythms of hippocampal CA1 are coordinated by local interactions as well as inputs from the entorhinal cortex (EC) and CA3 inputs. However, theta-nested gamma-band activity in the medial septum (MS) suggests that the MS may control supra-theta CA1 oscillations. To address this, we performed multi-electrode recordings of MS and CA1 activity in rodents and found that MS neuron firing showed strong phase-coupling to theta-nested supra-theta episodes and predicted changes in CA1 beta-to-gamma oscillations on a cycle-by-cycle basis. Unique coupling patterns of anatomically defined MS cell types suggested that indirect MS-to-CA1 pathways via the EC and CA3 mediate distinct CA1 gamma-band oscillations. Optogenetic activation of MS parvalbumin-expressing neurons elicited theta-nested beta-to-gamma oscillations in CA1. Thus, the MS orchestrates hippocampal network activity at multiple temporal scales to mediate memory encoding and retrieval.
Unaltered hepatic wound healing response in male rats with ancestral liver injury
Authors: Beil Johanna , Perner Juliane , Pfaller Lena , Gérard Marie-Apolline , Piaia Alessandro , Doelemeyer Arno , Wasserkrug Naor Adi , Martin Lori , Piequet Aline , Dubost Valérie , Chibout Salah-Dine , Moggs Jonathan , Terranova Rémi 
Published: October 2023

AbstractThe possibility that ancestral environmental exposure could result in adaptive inherited effects in mammals has been long debated. Numerous rodent models of transgenerational responses to various environmental factors have been published but due to technical, operational and resource burden, most still await independent confirmation. A previous study reported multigenerational epigenetic adaptation of the hepatic wound healing response upon exposure to the hepatotoxicant carbon tetrachloride (CCl4) in male rats. Here, we comprehensively investigate the transgenerational effects by repeating the original CCl4 multigenerational study with increased power, pedigree tracing, F2 dose-response and suitable randomization schemes. Detailed pathology evaluations do not support adaptive phenotypic suppression of the hepatic wound healing response or a greater fitness of F2 animals with ancestral liver injury exposure. However, transcriptomic analyses identified genes whose expression correlates with ancestral liver injury, although the biological relevance of this apparent transgenerational transmission at the molecular level remains to be determined. This work overall highlights the need for independent evaluation of transgenerational epigenetic inheritance paradigms in mammals.
Structure of native chromatin fibres revealed by Cryo-ET in situ
Authors: Hou Zhen , Nightingale Frank , Zhu Yanan , MacGregor-Chatwin Craig , Zhang Peijun 
Published: October 2023

AbstractThe structure of chromatin plays pivotal roles in regulating gene transcription, DNA replication and repair, and chromosome segregation. This structure, however, remains elusive. Here, using cryo-FIB and cryo-ET, we delineate the 3D architecture of native chromatin fibres in intact interphase human T-lymphoblasts and determine the in situ structures of nucleosomes in different conformations. These chromatin fibres are not structured as uniform 30 nm one-start or two-start filaments but are composed of relaxed, variable zigzag organizations of nucleosomes connected by straight linker DNA. Nucleosomes with little H1 and linker DNA density are distributed randomly without any spatial preference. This work will inspire future high-resolution investigations on native chromatin structures in situ at both a single-nucleosome level and a population level under many different cellular conditions in health and disease.
First demonstration of in-memory computing crossbar using multi-level Cell FeFET
Authors: Soliman Taha , Chatterjee Swetaki , Laleni Nellie , Müller Franz , Kirchner Tobias , Wehn Norbert , Kämpfe Thomas , Chauhan Yogesh Singh , Amrouch Hussam 
Published: October 2023

AbstractAdvancements in AI led to the emergence of in-memory-computing architectures as a promising solution for the associated computing and memory challenges. This study introduces a novel in-memory-computing (IMC) crossbar macro utilizing a multi-level ferroelectric field-effect transistor (FeFET) cell for multi-bit multiply and accumulate (MAC) operations. The proposed 1FeFET-1R cell design stores multi-bit information while minimizing device variability effects on accuracy. Experimental validation was performed using 28 nm HKMG technology-based FeFET devices. Unlike traditional resistive memory-based analog computing, our approach leverages the electrical characteristics of stored data within the memory cell to derive MAC operation results encoded in activation time and accumulated current. Remarkably, our design achieves 96.6% accuracy for handwriting recognition and 91.5% accuracy for image classification without extra training. Furthermore, it demonstrates exceptional performance, achieving 885.4 TOPS/W–nearly double that of existing designs. This study represents the first successful implementation of an in-memory macro using a multi-state FeFET cell for complete MAC operations, preserving crossbar density without additional structural overhead.
Marine viruses disperse bidirectionally along the natural water cycle
Authors: Rahlff Janina , Esser Sarah P. , Plewka Julia , Heinrichs Mara Elena , Soares André , Scarchilli Claudio , Grigioni Paolo , Wex Heike , Giebel Helge-Ansgar , Probst Alexander J. 
Published: October 2023

AbstractMarine viruses in seawater have frequently been studied, yet their dispersal from neuston ecosystems at the air-sea interface towards the atmosphere remains a knowledge gap. Here, we show that 6.2% of the studied virus population were shared between air-sea interface ecosystems and rainwater. Virus enrichment in the 1-mm thin surface microlayer and sea foams happened selectively, and variant analysis proved virus transfer to aerosols collected at ~2 m height above sea level and rain. Viruses detected in rain and these aerosols showed a significantly higher percent G/C base content compared to marine viruses. CRISPR spacer matches of marine prokaryotes to foreign viruses from rainwater prove regular virus-host encounters at the air-sea interface. Our findings on aerosolization, adaptations, and dispersal support transmission of viruses along the natural water cycle.
The accumulation and growth of Pseudomonas aeruginosa on surfaces is modulated by surface mechanics via cyclic-di-GMP signaling
Authors: Wang Liyun , Wong Yu-Chern , Correira Joshua M. , Wancura Megan , Geiger Chris J. , Webster Shanice S. , Touhami Ahmed , Butler Benjamin J. , O’Toole George A. , Langford Richard M. , Brown Katherine A. , Dortdivanlioglu Berkin , Webb Lauren , Cosgriff-Hernandez Elizabeth , Gordon Vernita D. 
Published: October 2023

AbstractAttachment of bacteria onto a surface, consequent signaling, and accumulation and growth of the surface-bound bacterial population are key initial steps in the formation of pathogenic biofilms. While recent reports have hinted that surface mechanics may affect the accumulation of bacteria on that surface, the processes that underlie bacterial perception of surface mechanics and modulation of accumulation in response to surface mechanics remain largely unknown. We use thin and thick hydrogels coated on glass to create composite materials with different mechanics (higher elasticity for thin composites; lower elasticity for thick composites) but with the same surface adhesivity and chemistry. The mechanical cue stemming from surface mechanics is elucidated using experiments with the opportunistic human pathogen Pseudomonas aeruginosa combined with finite-element modeling. Adhesion to thin composites results in greater changes in mechanical stress and strain in the bacterial envelope than does adhesion to thick composites with identical surface chemistry. Using quantitative microscopy, we find that adhesion to thin composites also results in higher cyclic-di-GMP levels, which in turn result in lower motility and less detachment, and thus greater accumulation of bacteria on the surface than does adhesion to thick composites. Mechanics-dependent c-di-GMP production is mediated by the cell-surface-exposed protein PilY1. The biofilm lag phase, which is longer for bacterial populations on thin composites than on thick composites, is also mediated by PilY1. This study shows clear evidence that bacteria actively regulate differential accumulation on surfaces of different stiffnesses via perceiving varied mechanical stress and strain upon surface engagement.
Revealing inherent quantum interference and entanglement of a Dirac particle
Authors: Ning Wen , Zheng Ri-Hua , Xia Yan , Xu Kai , Li Hekang , Zheng Dongning , Fan Heng , Wu Fan , Yang Zhen-Biao , Zheng Shi-Biao 
Published: October 2023

AbstractAlthough originally predicted in relativistic quantum mechanics, Zitterbewegung can also appear in some classical systems, which leads to the important question of whether Zitterbewegung of Dirac particles is underlain by a more fundamental and universal interference behavior without classical analogs. We here reveal such an interference pattern in phase space, which underlies but goes beyond Zitterbewegung, and whose nonclassicality is manifested by the negativity of the phase space quasiprobability distribution, and the associated pseudospin-momentum entanglement. We confirm this discovery by numerical simulation and an on-chip experiment, where a superconducting qubit and a quantized microwave field respectively emulate the internal and external degrees of freedom of a Dirac particle. The measured quasiprobability negativities agree well with the numerical simulation. Besides being of fundamental importance, the demonstrated nonclassical effects are useful in quantum technology.
γ-Aminobutyric acids (GABA) and serum GABA/AABA (G/A) ratio as potential biomarkers of physical performance and aging
Authors: Lyssikatos Charalampos , Wang Zhiying , Liu Ziyue , Warden Stuart J. , Bonewald Lynda , Brotto Marco 
Published: October 2023

AbstractDeclining physical performance with age and disease is an important indicator of declining health. Biomarkers that identify declining physical performance would be useful in predicting treatment outcomes and identifying potential therapeutics. γ-aminobutyric acid (GABA), a muscle autocrine factor, is a potent inhibitor of muscle function and works as a muscle relaxant. L-α-aminobutyric acid (L-AABA) is a biomarker for malnutrition, liver damage, and depression. We sought to determine if GABA and L-AABA may be useful for predicting physical performance. Serum levels of GABA and L-AABA were quantified in 120 individuals divided by age, sex, and physical capacity into low, average, and high performer groups. Analyses explored correlations between serum levels and physical performance. Both GABA and the ratio of GABA/AABA (G/A), but not AABA, were highly positively associated with age (Pearson correlations r = 0.35, p = 0.0001 for GABA, r = 0.31, p = 0.0007 for G/A, n = 120). GABA showed negative associations in the whole cohort with physical performance [fast gait speed, 6 min walk test (6MWT), PROMIS score, and SF36PFS raw score] and with subtotal and femoral neck bone mineral density. L-AABA was positively associated with usual gait speed, 6MWT, total SPPB score, and SF36PFS raw score in the total cohort of 120 human subjects, also with 6MWT and SF36PFS raw score in the 60 male subjects, but no associations were observed in the 60 females. As both GABA and L-AABA appear to be indicative of physical performance, but in opposite directions, we examined the G/A ratio. Unlike GABA, the G/A ratio showed a more distinct association with mobility tests such as total SPPB score, usual and fast gait speed, 6MWT, and SF36PFS raw score in the males, regardless of age and metabolic status. Serum G/A ratio could be potentially linked to physical performance in the male population. Our findings strongly suggest that GABA, L-AABA, and the G/A ratio in human serum may be useful markers for both age and physical function. These new biomarkers may significantly enhance the goal of identifying universal biomarkers to accurately predict physical performance and the beneficial effects of exercise training for older adults.
rs67047829 genotypes of ERV3-1/ZNF117 are associated with lower body mass index in the Polish population
Authors: Clark Jeremy S. C. , Podsiadło Konrad , Sobalska-Kwapis Marta , Marciniak Błażej , Rydzewska Kamila , Ciechanowicz Andrzej , van de Wetering Thierry , Strapagiel Dominik 
Published: October 2023

AbstractThere is now substantial evidence that zinc-finger proteins are implicated in adiposity. Aims were to datamine for high-frequency (near-neutral selection) pretermination-codon (PTC) single-nucleotide polymorphisms (SNPs; n = 141) from a database with > 550,000 variants and analyze possible association with body mass index in a large Polish sample (n = 5757). BMI was regressed (males/females together or separately) against genetic models. Regression for rs67047829 uncovered an interaction-independent association with BMI with both sexes together: mean ± standard deviation, kg/m2: [G];[G], 25.4 ± 4.59 (n = 3650); [G](;)[A], 25.0 ± 4.28 (n = 731); [A];[A], 23.4 ± 3.60 (n = 44); additive model adjusted for age and sex: p = 4.08 × 10–5; beta: − 0.0458, 95% confidence interval (CI) − 0.0732 : − 0.0183; surviving Bonferroni correction; for males: [G];[G], 24.8 ± 4.94 (n = 1878); [G](;)[A], 24.2 ± 4.31 (n = 386); [A];[A], 22.4 ± 3.69 (n = 23); p = 4.20 × 10–4; beta: − 0.0573, CI − 0.0947 : − 0.0199. For average-height males the difference between [G];[G] and [A];[A] genotypes would correspond to ~ 6 kg, suggesting considerable protection against increased BMI. rs67047829 gives a pretermination codon in ERV3-1 which shares an exonic region and possibly promoter with ZNF117, previously associated with adiposity and type-2 diabetes. As this result occurs in a near-neutral Mendelian setting, a drug targetting ERV3-1/ZNF117 might potentially provide considerable benefits with minimal side-effects. This result needs to be replicated, followed by analyses of splice-variant mRNAs and protein expression.
Association between the MTNR1B, HHEX, SLC30A8, and TCF7L2 single nucleotide polymorphisms and cardiometabolic risk profile in a mixed ancestry South African population
Authors: Ngwa Ndonwi Elvis , Matshazi Don Makwakiwe , Davison Glenda Mary , Kengne Andre Pascal , Matsha Tandi Edith 
Published: October 2023

AbstractSingle nucleotide polymorphisms of theTCF7L2,HHEX,SLC30A8,MTNR1B,SLC2A2andGLIS3genes are well established candidate genes for cardiometabolic diseases (CMDs) across different ethnic populations. We investigated their association with CMDs in a mixed ancestry population of South Africa. rs10830963, rs1111875, rs11920090, rs13266634, rs7034200 and rs7903146 SNPs were genotyped by quantitative real time PCR in 1650 participants and Hardy–Weinberg equilibrium (HWE) analyses performed on the SNPs. Diabetes, obesity, hypertension and cardiometabolic traits were compared across genotypes of SNPs in HWE. Linear and logistic regressions adjusting for age, gender and body mass index were used to determine the risk of T2DM, obesity and hypertension. rs7903146 (p = 0.055), rs1111875 (p = 0.465), rs13266634 (p = 0.828), and rs10830963 (p = 0.158) were in HWE. The rs10830963 recessive genotype was able to predict FPG, insulin and HOMA-IR, while the rs1111875 recessive genotype was able to predict total cholesterol, triglyceride, LDL cholesterol and FPG. The rs7903146 recessive genotype was able to predict SBP and LDL cholesterol. The recessive genotypes ofMTNRIBandHHEXSNPs were associated with T2DM traits in the study population and could partially explain the high prevalence of T2DM. Further studies are required to confirm these findings and establish candidate genes in the African population.
Quantifying intracellular glucose levels when yeast is grown in glucose media
Authors: Li Xiang , Heinemann Matthias 
Published: October 2023

AbstractIn Saccharomyces cerevisiae, intracellular glucose levels impact glucose transport and regulate carbon metabolism via various glucose sensors. To investigate mechanisms of glucose sensing, it is essential to know the intracellular glucose concentrations. Measuring intracellular glucose concentrations, however, is challenging when cells are grown on glucose, as glucose in the water phase around cells or stuck to the cell surface can be carried over during cell sampling and in the following attributed to intracellular glucose, resulting in an overestimation of intracellular glucose concentrations. Using lactose as a carryover marker in the growth medium, we found that glucose carryover originates from both the water phase and from sticking to the cell surface. Using a hexokinase null strain to estimate the glucose carryover from the cell surface, we found that glucose stuck on the cell surface only contributes a minor fraction of the carryover. To correct the glucose carryover, we revisited l-glucose as a carryover marker. Here, we found that l-glucose slowly enters cells. Thus, we added l-glucose to yeast cultures growing on uniformly 13C-labeled d-glucose only shortly before sampling. Using GC–MS to distinguish between the two differently labeled sugars and subtracting the carryover effect, we determined the intracellular glucose concentrations among two yeast strains with distinct kinetics of glucose transport to be at 0.89 mM in the wild-type strain and around 0.24 mM in a mutant with compromised glucose uptake. Together, our study provides insight into the origin of the glucose carryover effect and suggests that l-glucose added to the culture shortly before sampling is a possible method that yet has limitations with regard to measurement accuracy.
Exploring the role of our contacts with pets in broadening concerns for animals, nature, and fellow humans: a representative study
Authors: Amiot Catherine E. , Gagné Christophe , Bastian Brock 
Published: October 2023

AbstractWhile pet ownership is normative in many occidental countries, whether humans’ proximal contacts with pets have implications for attitudes and behaviors toward other (non pet) animals, nature, and fellow humans, has received limited empirical attention. In a large representative sample, we investigate whether pet ownership and positive contact with pets are associated with more positive attitudes and heightened concerns for non-pet animals, nature, and human outgroups. A cross-sectional questionnaire survey was conducted among Canadian adults (619 pet owners, 450 non-pet owners). Pet owners reported more positive attitudes toward non-pet animals (e.g., wild, farm animals), higher identification with animals, more positive attitudes toward human outgroups, higher biospheric environmental concerns, higher human–environment interdependence beliefs, and lower usual meat consumption. Positive contact with pets was also associated with most of these outcomes. Solidarity with animals, a dimension of identification with animals, emerged as a particularly clear predictor of these outcomes and mediated the associations between positive contact with pets and positive attitudes toward non-pet animals, biospheric, egoistic, and altruistic environmental concerns, human–environment interdependence beliefs, and diet. Our results provide support for the capacity of pets to shape human consideration for a broad range of social issues, beyond the specific context of human-pet relations.
Sodium-glucose co-transporter 2 inhibitor add-on therapy for metformin delays diabetic retinopathy progression in diabetes patients: a population-based cohort study
Authors: Li Jing-Xing , Hung Yu-Tung , Bair Henry , Hsu Shu-Bai , Hsu Chung-Yi , Lin Chun-Ju 
Published: October 2023

AbstractTo investigate how sodium-glucose co-transporter 2 inhibitors (SGLT2is) add-on therapy for metformin affects diabetic retinopathy (DR) progression in patients with type 2 diabetes mellitus (T2DM). This nationwide population-based study conducted from January 1, 2016, to December 31, 2018 involved 3,432,911 adults with T2DM in Taiwan. To adjust for potential confounders, data on sex, age, income, comorbidities, diabetes complication severity index score, staging of kidney disease, anti-diabetic medications, and index year were included. The outcome was DR progression, determined by procedure codes or the addition of ICD-9-CM or ICD-10-CM codes to the medical records of the patients during the study. Sensitivity analyses were performed to validate the findings. The adjusted hazard ratio (aHR) of DR progression was 0.89 for the SGLT2is add-on group, relative to the control group [95% confidence interval (CI) 0.81–0.99, P = 0.026]. The Kaplan–Meier curve of the cumulative incidence rate showed that the cumulative incidence of DR progression was considerably decreased in the SGLT2is cohort (log-rank P = 0.0261). The use of SGLT2is for less than 1 year and 1–2 years were associated with a significant increase in the risk of DR progression (aHR 1.56 and 1.88, respectively); however, the risk markedly reduced if the SGLT2is regimen was used for more than 2 years (aHR 0.41, 95% Cl 0.35–0.48; P < 0.001). The serial sensitivity analysis showed consistent findings. The aHR of DR progression was 0.82 for the SGLT2is cohort relative to the non-SGLT2is cohort based on the fundoscopy or indirect ophthalmoscopy findings within 1 year before the outcome date (95% Cl 0.71–0.95; P = 0.009). Co-administration of metformin and SGLT2is may reduce the risk of DR progression. Short-term use of SGLT2is may markedly increase the risk of DR, whereas prolonged use SGLT2is may significantly decrease it.