bluuebunny/crossref_metadata_2025_split huggingface dataset:
Activation of glucagon-like peptide-1 receptors reduces the acquisition of aggression-like behaviors in male mice
Authors: Vestlund Jesper , Zhang Qian , Shevchouk Olesya T. , Hovey Daniel , Sebastian Lundström , Westberg Lars , Jerlhag Elisabet 
Published: October 2022

AbstractAggression is a complex social behavior, which is provoked in the defense of limited resources including food and mates. Recent advances show that the gut-brain hormone ghrelin modulates aggressive behaviors. As the gut-brain hormone glucagon-like peptide-1 (GLP-1) reduces food intake and sexual behaviors its potential role in aggressive behaviors is likely. Therefore, we investigated a tentative link between GLP-1 and aggressive behaviors by combining preclinical and human genetic-association studies. The influence of acute or repeated injections of a GLP-1 receptor (GLP-1R) agonist, exendin-4 (Ex4), on aggressive behaviors was assessed in male mice exposed to the resident-intruder paradigm. Besides, possible mechanisms participating in the ability of Ex4 to reduce aggressive behaviors were evaluated. Associations of polymorphisms inGLP-1Rgenes and overt aggression in males of the CATSS cohort were assessed. In male mice, repeated, but not acute, Ex4 treatment dose-dependently reduced aggressive behaviors. Neurochemical and western blot studies further revealed that putative serotonergic and noradrenergic signaling in nucleus accumbens, specifically the shell compartment, may participate in the interaction between Ex4 and aggression. As high-fat diet (HFD) impairs the responsiveness to GLP-1 on various behaviors the possibility that HFD blunts the ability of Ex4 to reduce aggressive behaviors was explored. Indeed, the levels of aggression was similar in vehicle and Ex4 treated mice consuming HFD. In humans, there were no associations between polymorphisms of theGLP-1Rgenes and overt aggression. Overall, GLP-1 signaling suppresses acquisition of aggressive behaviors via central neurotransmission and additional studies exploring this link are warranted.
Genetic deconvolution of fetal and maternal cell-free DNA in maternal plasma enables next-generation non-invasive prenatal screening
Authors: Xu Chenming , Li Jianli , Chen Songchang , Cai Xiaoqiang , Jing Ruilin , Qin Xiaomei , Pan Dong , Zhao Xin , Ma Dongyang , Xu Xiufeng , Liu Xiaojun , Wang Can , Yang Bingxin , Zhang Lanlan , Li Shuyuan , Chen Yiyao , Pan Nina , Tang Ping , Song Jieping , Liu Nian , Zhang Chen , Zhang Zhiwei , Qiu Xiang , Lu Weiliang , Ying Chunmei , Li Xiaotian , Xu Congjian , Wang Yanlin , Wu Yanting , Huang He-Feng , Zhang Jinglan 
Published: October 2022

AbstractCurrent non-invasive prenatal screening (NIPS) analyzes circulating fetal cell-free DNA (cfDNA) in maternal peripheral blood for selected aneuploidies or microdeletion/duplication syndromes. Many genetic disorders are refractory to NIPS largely because the maternal genetic material constitutes most of the total cfDNA present in the maternal plasma, which hinders the detection of fetus-specific genetic variants. Here, we developed an innovative sequencing method, termed coordinative allele-aware target enrichment sequencing (COATE-seq), followed by multidimensional genomic analyses of sequencing read depth, allelic fraction, and linked single nucleotide polymorphisms, to accurately separate the fetal genome from the maternal background. Analytical confounders including multiple gestations, maternal copy number variations, and absence of heterozygosity were successfully recognized and precluded for fetal variant analyses. In addition, fetus-specific genomic characteristics, including the cfDNA fragment length, meiotic error origins, meiotic recombination, and recombination breakpoints were identified which reinforced the fetal variant assessment. In 1129 qualified pregnancies tested, 54 fetal aneuploidies, 8 microdeletions/microduplications, and 8 monogenic variants were detected with 100% sensitivity and 99.3% specificity. Using the comprehensive cfDNA genomic analysis tools developed, we found that 60.3% of aneuploidy samples had aberrant meiotic recombination providing important insights into the mechanism underlying meiotic nondisjunctions. Altogether, we show that the genetic deconvolution of the fetal and maternal cfDNA enables thorough and accurate delineation of fetal genome which paves the way for the next-generation prenatal screening of essentially all types of human genetic disorders.
INF2-mediated actin filament reorganization confers intrinsic resilience to neuronal ischemic injury
Authors: Calabrese Barbara , Jones Steven L. , Shiraishi-Yamaguchi Yoko , Lingelbach Michael , Manor Uri , Svitkina Tatyana M. , Higgs Henry N. , Shih Andy Y. , Halpain Shelley 
Published: October 2022

AbstractDuring early ischemic brain injury, glutamate receptor hyperactivation mediates neuronal death via osmotic cell swelling. Here we show that ischemia and excess NMDA receptor activation cause actin to rapidly and extensively reorganize within the somatodendritic compartment. Normally, F-actin is concentrated within dendritic spines. However, <5 min after bath-applied NMDA, F-actin depolymerizes within spines and polymerizes into stable filaments within the dendrite shaft and soma. A similar actinification occurs after experimental ischemia in culture, and photothrombotic stroke in mouse. Following transient NMDA incubation, actinification spontaneously reverses. Na+, Cl−, water, and Ca2+ influx, and spine F-actin depolymerization are all necessary, but not individually sufficient, for actinification, but combined they induce activation of the F-actin polymerization factor inverted formin-2 (INF2). Silencing of INF2 renders neurons vulnerable to cell death and INF2 overexpression is protective. Ischemia-induced dendritic actin reorganization is therefore an intrinsic pro-survival response that protects neurons from death induced by cell edema.
The deglacial forest conundrum
Authors: Dallmeyer Anne , Kleinen Thomas , Claussen Martin , Weitzel Nils , Cao Xianyong , Herzschuh Ulrike 
Published: October 2022

AbstractHow fast the Northern Hemisphere (NH) forest biome tracks strongly warming climates is largely unknown. Regional studies reveal lags between decades and millennia. Here we report a conundrum: Deglacial forest expansion in the NH extra-tropics occurs approximately 4000 years earlier in a transient MPI-ESM1.2 simulation than shown by pollen-based biome reconstructions. Shortcomings in the model and the reconstructions could both contribute to this mismatch, leaving the underlying causes unresolved. The simulated vegetation responds within decades to simulated climate changes, which agree with pollen-independent reconstructions. Thus, we can exclude climate biases as main driver for differences. Instead, the mismatch points at a multi-millennial disequilibrium of the NH forest biome to the climate signal. Therefore, the evaluation of time-slice simulations in strongly changing climates with pollen records should be critically reassessed. Our results imply that NH forests may be responding much slower to ongoing climate changes than Earth System Models predict.
Traceless cysteine-linchpin enables precision engineering of lysine in native proteins
Authors: Reddy Neelesh C. , Molla Rajib , Joshi Pralhad Namdev , T. K. Sajeev , Basu Ipsita , Kawadkar Jyotsna , Kalra Neetu , Mishra Ram Kumar , Chakrabarty Suman , Shukla Sanjeev , Rai Vishal 
Published: October 2022

AbstractThe maintenance of machinery requires its operational understanding and a toolbox for repair. The methods for the precision engineering of native proteins meet a similar requirement in biosystems. Its success hinges on the principles regulating chemical reactions with a protein. Here, we report a technology that delivers high-level control over reactivity, chemoselectivity, site-selectivity, modularity, dual-probe installation, and protein-selectivity. It utilizes cysteine-based chemoselective Linchpin-Directed site-selective Modification of lysine residue in a protein (LDMC-K). The efficiency of the end-user-friendly protocol is evident in quantitative conversions within an hour. A chemically orthogonal C-S bond-formation and bond-dissociation are essential among multiple regulatory attributes. The method offers protein selectivity by targeting a single lysine residue of a single protein in a complex biomolecular mixture. The protocol renders analytically pure single-site probe-engineered protein bioconjugate. Also, it provides access to homogeneous antibody conjugates (AFC and ADC). The LDMC-K-ADC exhibits highly selective anti-proliferative activity towards breast cancer cells.
Single cell analysis of cribriform prostate cancer reveals cell intrinsic and tumor microenvironmental pathways of aggressive disease
Authors: Wong Hong Yuen , Sheng Quanhu , Hesterberg Amanda B. , Croessmann Sarah , Rios Brenda L. , Giri Khem , Jackson Jorgen , Miranda Adam X. , Watkins Evan , Schaffer Kerry R. , Donahue Meredith , Winkler Elizabeth , Penson David F. , Smith Joseph A. , Herrell S. Duke , Luckenbaugh Amy N. , Barocas Daniel A. , Kim Young J. , Graves Diana , Giannico Giovanna A. , Rathmell Jeffrey C. , Park Ben H. , Gordetsky Jennifer B. , Hurley Paula J. 
Published: October 2022

AbstractCribriform prostate cancer, found in both invasive cribriform carcinoma (ICC) and intraductal carcinoma (IDC), is an aggressive histological subtype that is associated with progression to lethal disease. To delineate the molecular and cellular underpinnings of ICC/IDC aggressiveness, this study examines paired ICC/IDC and benign prostate surgical samples by single-cell RNA-sequencing, TCR sequencing, and histology. ICC/IDC cancer cells express genes associated with metastasis and targets with potential for therapeutic intervention. Pathway analyses and ligand/receptor status model cellular interactions among ICC/IDC and the tumor microenvironment (TME) including JAG1/NOTCH. The ICC/IDC TME is hallmarked by increased angiogenesis and immunosuppressive fibroblasts (CTHRC1+ASPN+FAP+ENG+) along with fewer T cells, elevated T cell dysfunction, and increased C1QB+TREM2+APOE+-M2 macrophages. These findings support that cancer cell intrinsic pathways and a complex immunosuppressive TME contribute to the aggressive phenotype of ICC/IDC. These data highlight potential therapeutic opportunities to restore immune signaling in patients with ICC/IDC that may afford better outcomes.
Quorum-sensing control of matrix protein production drives fractal wrinkling and interfacial localization of Vibrio cholerae pellicles
Authors: Qin Boyang , Bassler Bonnie L. 
Published: October 2022

AbstractBacterial cells at fluid interfaces can self-assemble into collective communities with stunning macroscopic morphologies. Within these soft, living materials, called pellicles, constituent cells gain group-level survival advantages including increased antibiotic resistance. However, the regulatory and structural components that drive pellicle self-patterning are not well defined. Here, using Vibrio cholerae as our model system, we report that two sets of matrix proteins and a key quorum-sensing regulator jointly orchestrate the sequential mechanical instabilities underlying pellicle morphogenesis, culminating in fractal patterning. A pair of matrix proteins, RbmC and Bap1, maintain pellicle localization at the interface and prevent self-peeling. A single matrix protein, RbmA, drives a morphogenesis program marked by a cascade of ever finer wrinkles with fractal scaling in wavelength. Artificial expression of rbmA restores fractal wrinkling to a ΔrbmA mutant and enables precise tuning of fractal dimensions. The quorum-sensing regulatory small RNAs Qrr1-4 first activate matrix synthesis to launch pellicle primary wrinkling and ridge instabilities. Subsequently, via a distinct mechanism, Qrr1-4 suppress fractal wrinkling to promote fine modulation of pellicle morphology. Our results connect cell-cell signaling and architectural components to morphogenic patterning and suggest that manipulation of quorum-sensing regulators or synthetic control of rbmA expression could underpin strategies to engineer soft biomaterial morphologies on demand.
Chronic intake of high dietary sucrose induces sexually dimorphic metabolic adaptations in mouse liver and adipose tissue
Authors: Stephenson Erin J. , Stayton Amanda S. , Sethuraman Aarti , Rao Prahlad K. , Meyer Alice , Gomes Charles Klazer , Mulcahy Molly C. , McAllan Liam , Puchowicz Michelle A. , Pierre Joseph F. , Bridges Dave , Han Joan C. 
Published: October 2022

AbstractAlmost all effective treatments for non-alcoholic fatty liver disease (NAFLD) involve reduction of adiposity, which suggests the metabolic axis between liver and adipose tissue is essential to NAFLD development. Since excessive dietary sugar intake may be an initiating factor for NAFLD, we have characterized the metabolic effects of liquid sucrose intake at concentrations relevant to typical human consumption in mice. We report that sucrose intake induces sexually dimorphic effects in liver, adipose tissue, and the microbiome; differences concordant with steatosis severity. We show that when steatosis is decoupled from impairments in insulin responsiveness, sex is a moderating factor that influences sucrose-driven lipid storage and the contribution of de novo fatty acid synthesis to the overall hepatic triglyceride pool. Our findings provide physiologic insight into how sex influences the regulation of adipose-liver crosstalk and highlight the importance of extrahepatic metabolism in the pathogenesis of diet-induced steatosis and NAFLD.
Coemissive luminescent nanoparticles combining aggregation-induced emission and quenching dyes prepared in continuous flow
Authors: Li Chong , Liu Qi , Tao Shengyang 
Published: October 2022

AbstractAchieving an ideal light-harvesting system at a low cost remains a challenge. Herein, we report the synthesis of a hybrid dye system based on tetraphenylene (TPE) encapsulated organic dyes in a continuous flow microreactor. The composite dye nanoparticles (NPs) are synthesized based on supramolecular self-assembly to achieve the co-emission of aggregation-induced emission dyes and aggregation-caused quenching dyes (CEAA). Numerical simulations and molecular spectroscopy were used to investigate the synthesis mechanism of the CEAA dyes. Nanoparticles of CEAA dyes provide a platform for efficient cascade Förster resonance energy transfer (FRET). Composite dye nanoparticles of TPE and Nile red (NiR) are synthesized for an ideal light-harvesting system using coumarin 6 (C-6) as an energy intermediate. The light-harvesting system has a considerable red-shift distance (~126 nm), high energy-transfer efficiency (ΦET) of 99.37%, and an antenna effect of 26.23. Finally, the versatility of the preparation method and the diversity of CEAA dyes are demonstrated.
Nonlinear germanium-silicon photodiode for activation and monitoring in photonic neuromorphic networks
Authors: Shi Yang , Ren Junyu , Chen Guanyu , Liu Wei , Jin Chuqi , Guo Xiangyu , Yu Yu , Zhang Xinliang 
Published: October 2022

AbstractSilicon photonics is promising for artificial neural networks computing owing to its superior interconnect bandwidth, low energy consumption and scalable fabrication. However, the lack of silicon-integrated and monitorable optical neurons limits its revolution in large-scale artificial neural networks. Here, we highlight nonlinear germanium-silicon photodiodes to construct on-chip optical neurons and a self-monitored all-optical neural network. With specifically engineered optical-to-optical and optical-to-electrical responses, the proposed neuron merges the all-optical activation and non-intrusive monitoring functions in a compact footprint of 4.3 × 8 μm2. Experimentally, a scalable three-layer photonic neural network enables in situ training and learning in object classification and semantic segmentation tasks. The performance of this neuron implemented in a deep-scale neural network is further confirmed via handwriting recognition, achieving a high accuracy of 97.3%. We believe this work will enable future large-scale photonic intelligent processors with more functionalities but simplified architecture.
Algal photosystem I dimer and high-resolution model of PSI-plastocyanin complex
Authors: Naschberger Andreas , Mosebach Laura , Tobiasson Victor , Kuhlgert Sebastian , Scholz Martin , Perez-Boerema Annemarie , Ho Thi Thu Hoai , Vidal-Meireles André , Takahashi Yuichiro , Hippler Michael , Amunts Alexey 
Published: October 2022

AbstractPhotosystem I (PSI) enables photo-electron transfer and regulates photosynthesis in the bioenergetic membranes of cyanobacteria and chloroplasts. Being a multi-subunit complex, its macromolecular organization affects the dynamics of photosynthetic membranes. Here we reveal a chloroplast PSI from the green alga Chlamydomonas reinhardtii that is organized as a homodimer, comprising 40 protein subunits with 118 transmembrane helices that provide scaffold for 568 pigments. Cryogenic electron microscopy identified that the absence of PsaH and Lhca2 gives rise to a head-to-head relative orientation of the PSI–light-harvesting complex I monomers in a way that is essentially different from the oligomer formation in cyanobacteria. The light-harvesting protein Lhca9 is the key element for mediating this dimerization. The interface between the monomers is lacking PsaH and thus partially overlaps with the surface area that would bind one of the light-harvesting complex II complexes in state transitions. We also define the most accurate available PSI–light-harvesting complex I model at 2.3 Å resolution, including a flexibly bound electron donor plastocyanin, and assign correct identities and orientations to all the pigments, as well as 621 water molecules that affect energy transfer pathways.
Impaired amino acid uptake leads to global metabolic imbalance of Candida albicans biofilms
Authors: Böttcher Bettina , Driesch Dominik , Krüger Thomas , Garbe Enrico , Gerwien Franziska , Kniemeyer Olaf , Brakhage Axel A. , Vylkova Slavena 
Published: October 2022

AbstractCandida albicans biofilm maturation is accompanied by enhanced expression of amino acid acquisition genes. Three state-of-the-art omics techniques were applied to detail the importance of active amino acid uptake during biofilm development. Comparative analyses of normoxic wild-type biofilms were performed under three metabolically challenging conditions: aging, hypoxia, and disabled amino acid uptake using a strain lacking the regulator of amino acid permeases Stp2. Aging-induced amino acid acquisition and stress responses to withstand the increasingly restricted environment. Hypoxia paralyzed overall energy metabolism with delayed amino acid consumption, but following prolonged adaptation, the metabolic fingerprints aligned with aged normoxic biofilms. The extracellular metabolome of stp2Δ biofilms revealed deficient uptake for 11 amino acids, resulting in extensive transcriptional and metabolic changes including induction of amino acid biosynthesis and carbohydrate and micronutrient uptake. Altogether, this study underscores the critical importance of a balanced amino acid homeostasis for C. albicans biofilm development.
Blood pressure variability and plasma Alzheimer’s disease biomarkers in older adults
Authors: Sible Isabel J. , Yew Belinda , Jang Jung Yun , Alitin John Paul M. , Li Yanrong , Gaubert Aimée , Nguyen Amy , Dutt Shubir , Blanken Anna E. , Ho Jean K. , Marshall Anisa J. , Kapoor Arunima , Shenasa Fatemah , Rodgers Kathleen E. , Sturm Virginia E. , Head Elizabeth , Martini Alessandra , Nation Daniel A. 
Published: October 2022

AbstractBlood pressure variability is an emerging risk factor for Alzheimer’s disease in older adults, independent of average blood pressure levels. Growing evidence suggests increased blood pressure variability is linked to Alzheimer’s disease pathophysiology indexed by cerebrospinal fluid and positron emission tomography markers, but relationships with plasma Alzheimer’s disease markers have not been investigated. In this cross-sectional study of 54 community-dwelling older adults (aged 55–88, mean age 69.9 [8.2 SD]), elevated blood pressure variability over 5 min was associated with lower levels of plasma Aβ1–42 (standardized ß =  − 0.36 [95% CI − 0.61, − 0.12]; p = 0.005; adjusted R2 = 0.28) and Aβ1–42: Aβ1–40 ratio (ß =  − 0.49 [95% CI − 0.71, − 0.22]; p < 0.001; adjusted R2 = 0.28), and higher levels of total tau (ß = 0.27 [95% CI 0.01, 0.54]; p = 0.04; adjusted R2 = 0.19) and Ptau181:Aβ1–42 ratio (ß = 0.26 [95% CI 0.02, 0.51]; p = 0.04; adjusted R2 = 0.22). Findings suggest higher blood pressure variability is linked to plasma biomarkers of increased Alzheimer’s disease pathophysiology.
Probing patterning in microbial consortia with a cellular automaton for spatial organisation
Authors: Venkatraghavan Sankalpa , Anantakrishnan Sathvik , Raman Karthik 
Published: October 2022

AbstractMicrobial consortia exhibit spatial patterning across diverse environments. Since probing the self-organization of natural microbial communities is limited by their inherent complexity, synthetic models have emerged as attractive alternatives. In this study, we develop novel frameworks of bacterial communication and explore the emergent spatiotemporal organization of microbes. Specifically, we built quorum sensing-mediated models of microbial growth that are utilized to characterize the dynamics of communities from arbitrary initial configurations and establish the effectiveness of our communication strategies in coupling the growth rates of microbes. Our simulations indicate that the behavior of quorum sensing-coupled consortia can be most effectively modulated by the rates of secretion of acyl homoserine lactones. Such a mechanism of control enables the construction of desired relative populations of constituent species in spatially organized populations. Our models accurately recapitulate previous experiments that have investigated pattern formation in synthetic multi-cellular systems. Additionally, our software tool enables the easy implementation and analysis of our frameworks for a variety of initial configurations and simplifies the development of sophisticated gene circuits facilitating distributed computing. Overall, we demonstrate the potential of spatial organization as a tunable parameter in synthetic biology by introducing a communication paradigm based on the location and strength of coupling of microbial strains.
Synergetic synchronized oscillation by distributed neural integrators to induce dynamic equilibrium in energy dissipation systems
Authors: Hayashibe Mitsuhiro , Shimoda Shingo 
Published: October 2022

AbstractThe synchronization phenomenon is common to many natural mechanical systems. Joint friction and damping in humans and animals are associated with energy dissipation. A coupled oscillator model is conventionally used to manage multiple joint torque generations to form a limit cycle in an energy dissipation system. The coupling term design and the frequency and phase settings become issues when selecting the oscillator model. The relative coupling relationship between oscillators needs to be predefined for unknown dynamics systems, which is quite challenging problem. We present a simple distributed neural integrators method to induce the limit cycle in unknown energy dissipation systems without using a coupled oscillator. The results demonstrate that synergetic synchronized oscillation could be produced that adapts to different physical environments. Finding the balanced energy injection by neural inputs to form dynamic equilibrium is not a trivial problem, when the dynamics information is not priorly known. The proposed method realized self-organized pattern generation to induce the dynamic equilibrium for different mechanical systems. The oscillation was managed without using the explicit phase or frequency knowledge. However, phase, frequency, and amplitude modulation emerged to form an efficient synchronized limit cycle. This type of distributed neural integrator can be used as a source for regulating multi-joint coordination to induce synergetic oscillations in natural mechanical systems.