bluuebunny/crossref_metadata_2025_split huggingface dataset:
Selective degradation of multimeric proteins via chemically induced proximity to TRIM21
Authors: Lu Panrui , Cheng Yalong , Xue Lei , Ren Xintong , Chen Chenglong , Li Jiao , Wu Qingcui , Sun Shan , Hou Junjie , Jia Wei , Li Chao , Qi Xiangbing , Huang Niu , Han Ting 
Published: February 2024

AbstractTargeted protein degradation (TPD) has emerged as an effective strategy to eliminate disease-causing proteins by inducing their interactions with the protein degradation machinery. First-generation TPD agents exploit a limited set of broadly expressed E3 ubiquitin ligases with constitutive activity, forbidding their application to proteins requiring higher levels of targeting selectivity. Here, by phenotype-based screening, we discovered that the antipsychotic drug acepromazine possesses interferon-enhanced cytotoxicity towards cancer cell lines expressing high levels of aldo-keto reductases 1C. These enzymes convert acepromazine into its stereo-selective metabolite (S)-hydroxyl-acepromazine, which recruits the interferon-induced E3 ubiquitin ligase TRIM21 to the vicinity of the nuclear pore complex, resulting in the degradation of nuclear pore proteins. Co-crystal structures of acepromazine and derivatives in complex with the PRYSPRY domain of TRIM21 revealed a ligandable pocket, which was exploited for designing heterobifunctional degraders. The resulting chemicals selectively degrade multimeric proteins— such as those in biomolecular condensates—without affecting monomeric proteins, consistent with the requirement of substrate-induced clustering for TRIM21 activation. As aberrant protein assemblies have been causally linked to diseases such as neurodegeneration, autoimmunity, and cancer, our findings highlight the potential of TRIM21-based multimer-selective degraders as a strategy to tackle the direct causes of these diseases.
Older individuals do not show task specific variations in EEG band power and finger force coordination
Authors: Eswari Balasubramanian , Balasubramanian Sivakumar , SKM Varadhan 
Published: February 2024

AbstractBackgroundControlling and coordinating finger force is crucial for performing everyday tasks and maintaining functional independence. Aging naturally weakens neural, muscular, and musculoskeletal systems, leading to compromised hand motor function. This decline reduces cortical activity, finger force control and coordination in older adults.ObjectiveTo examine the relationship between EEG band power and finger force coordination in older individuals and compare the results with young adults.MethodsTwenty healthy young adults aged 20–30 (26.96±2.68) and fourteen older adults aged 58–72 (62.57±3.58) participated in this study. Participants held the instrumented handle gently for five seconds then lifted and held it for an additional five seconds in the two conditions: fixed (thumb platform secured) and free condition (thumb platform may slide on slider).ResultsIn the older individuals there was no difference observed in the finger force synergy indices, and EEG beta band power between the two task conditions. However, in the young group synergy indices and EEG beta band power were less in free condition compared to fixed condition. Additionally, in the fixed condition, older adults showed a reduced synergy indices and reduced EEG beta band power than the young adults.ConclusionOlder participants showed consistent synergy indices and beta band power across conditions, unlike young adults who adjusted strategies based on tasks. Young adults exhibited task-dependent finger force synergy indices contrasting with older individuals. These results suggest that the EEG beta band power may serve as a marker for finger force coordination rather than indicating the magnitude of force.
Negative relationship between inter-regional interaction and regional power: a resting fMRI study
Authors: Lee Tien-Wen , Tramontano Gerald 
Published: February 2024

ABSTRACTBackgroundRegional neural response and network property used to be treated separately. However, evidence has suggested an intimate relationship between the regional and inter-regional profiles. This research aimed to investigate the influence of functional connectivity on regional spontaneous activity.MethodsThirty-six and sixty datasets of structural magnetic resonance imaging (sMRI) and resting state functional MRI (rsfMRI) were selected from the NKI and CAN-BIND database, respectively. The cerebral cortex in rsfMRI was parcellated by MOSI (modular analysis and similarity measurements), which enables multi-resolution exploration. For each parcellated cluster, the mean amplitude of low-frequency fluctuation (ALFF) and its average functional connectivity strength with the remaining cortical analogs were computed. Correlation analyses were exploited to examine their relationship. Supplementary analysis was applied to CAN-BIND EEG data (1 to 30 Hz).ResultsNegative correlation coefficients between inter-regional interaction and regional power were noticed in both MRI datasets. One-sample t-tests revealed robust statistics across different analytic resolutions yielded by MOSI, with individualPvalues at the level 10^-4 to 10^-5. The results suggested that the more intense crosstalk a neural node is embedded in, the less regional power it manifests, and vice versa. The negative relationship was replicated in EEG analysis but limited to delta (1 to 4 Hz) and theta (4 to 8 Hz) frequencies.ConclusionsWe postulate that inhibitory coupling is the mechanism that bridges the local and inter-regional properties, which is more prominent in the lower spectra. The interpretation warrants particular caution since noise may also contribute to the observation.
Screening of associated bacteria ofAlexandrium catenellaon affecting PSTs production and influence mechanism
Authors: Zou Shanmei , Yu Xinke , Sun Tiantian , Wei Lina , Wu Xuemin 
Published: February 2024

AbstractAlexandriumcauses serious food safety and human death due to paralytic shellfish toxins (PSTs) production. The associated bacteria can affect PSTs production ofAlexandrium. However, the influencing mechanism is still unclear. Here we firstly screened functional associated bacteria for affecting PSTs production ofAlexandrium catenellain Yangtze Estuary and further studied their influence on physiological process and molecular regulation ofA. catenella. Thirteen bacteria strains for affecting PSTs production ofA. catenellawere selected. TheA. catenellastrains co-cultured with different functional associated bacteria all produced more PSTs than axenic strain with antibiotic treatment. Compared with axenicA. catenella, the non-axenicA. catenellaproduced more algal cells, soluble sugar, soluble protein and neutral lipid. By RNA-seq, it was found that non-axenicA. catenellaproduced more upregulated functional genes than axenicA. catenella. The biosynthesis of cofactors and spliceosome were the dominant different pathways between axenic and non-axenicA. catenellastrains. The sxtA expression was closely related with Arginine and proline metabolism, Arginine biosynthesis, Fatty acid biosynthesis, TCA cycle and Glutathione metabolism, which were all downregulated in axenicA. catenella. Meantime, the non-axenicA. catenellaunder nitrogen deprivation produced less PSTs and functional genes than non-axenic strain under common culture condition, indicating the nitrogen significance for PSTs production. The detailed signal molecular released by associated bacteria for regulating PSTs ofA. catenellaneeds to be further studied.
Selfish herd effects in aggregated caterpillars and their interaction with warning signals
Authors: Kersh-Mellor Rami , Montgomery Stephen H. , McLellan Callum F. 
Published: February 2024

AbstractLarval Lepidoptera gain survival advantages by aggregating, especially when combined with aposematic warning signals, yet reductions in predation risk may not be experienced equally across all group members. Hamilton’s selfish herd theory predicts that larvae which surround themselves with their group mates should be at lower risk of predation, and those on the periphery of aggregations experience the greatest risk, yet this has rarely been tested. Here, we expose aggregations of artificial ‘caterpillar’ targets to predation from free-flying, wild birds to test for marginal predation when all prey are equally accessible, and for an interaction between warning colouration and marginal predation. We find that targets nearer the centre of the aggregation survived better than peripheral targets and nearby targets isolated from the group. However, there was no difference in survival between peripheral and isolated targets. We also find that grouped targets survived better than isolated targets when both are aposematic, but not when they are non-signalling. Our data suggest that avian predators preferentially target peripheral larvae from aggregations, and that prey warning signals enhance predator avoidance of groups.
Utilising affordable smartphones and open-source time-lapse photography for monitoring pollinators
Authors: Ștefan Valentin , Workman Aspen , Cobain Jared C. , Rakosy Demetra , Knight Tiffany M. 
Published: February 2024

ABSTRACTMonitoring plant-pollinator interactions is crucial for understanding factors that influence these relationships across space and time. While traditional methods in pollination ecology are time-consuming and resource-intensive, the growing availability of photographic technology, coupled with advancements in artificial intelligence classification, offers the potential for non-destructive and automated techniques. However, it is important that the photographs are of high enough quality to enable insects to be identified at lower taxonomic levels, preferably genus or species levels. This study assessed the feasibility of using smartphones to automatically capture images of insects visiting flowers and evaluated whether the captured images offered sufficient resolution for precise insect identification. Smartphones were positioned above target flowers from various plant species to capture time-lapse images of any flower visitor in urban green areas around Leipzig and Halle, Germany. We present the proportions of insect identifications achieved at different taxonomic levels, such as order, family, genus, and species, and discuss whether limitations stem from the automated approach (e.g., inability to observe distinguishing features in images despite high image quality) or low image quality. Practical recommendations are provided to address these challenges. Our results indicate that for bee families, nearly three quarters of all cases could be identified to genus level. Flies were more difficult, due to the small size of many individuals and the more challenging features needed for identification (e.g., in the wing veins). Overall, we suggest that smartphones are an effective tool when optimised by researchers. As technology continues to advance, smartphones are becoming increasingly accessible, affordable, and user-friendly, rendering them an appealing option for pollinator monitoring.
The role of hidden hearing loss in tinnitus: insights from early markers of peripheral hearing damage
Authors: Devolder Pauline , Keppler Hannah , Keshishzadeh Sarineh , Taghon Baziel , Dhooge Ingeborg , Verhulst Sarah 
Published: February 2024

AbstractSince the presence of tinnitus is not always associated with audiometric hearing loss, it has been hypothesized that hidden hearing loss may act as a potential trigger for increased central gain along the neural pathway leading to tinnitus perception. In recent years, the study of hidden hearing loss has improved with the discovery of cochlear synaptopathy and several objective diagnostic markers. This study investigated three potential markers of peripheral hidden hearing loss in subjects with tinnitus: extended high-frequency audiometric thresholds, the auditory brainstem response, and the envelope following response. In addition, speech intelligibility was measured as a functional outcome measurement of hidden hearing loss. To account for age-related hidden hearing loss, participants were grouped according to age, presence of tinnitus, and audiometric thresholds. Group comparisons were conducted to differentiate between age- and tinnitus-related effects of hidden hearing loss. All three markers revealed age-related differences, whereas no differences were observed between the tinnitus and non-tinnitus groups. However, the older tinnitus group showed improved performance on low-pass filtered speech in noise tests compared to the older non-tinnitus group. These low-pass speech in noise scores were significantly correlated with tinnitus distress, as indicated using questionnaires, and could be related to the presence of hyperacusis. Based on our observations, cochlear synaptopathy does not appear to be the underlying cause of tinnitus. The improvement in low-pass speech-in-noise could be explained by enhanced temporal fine structure encoding or hyperacusis. Therefore, we recommend that future tinnitus research takes into account age-related factors, explores low-frequency encoding, and thoroughly assesses hyperacusis.
MXRA8 promotes adipose tissue whitening to drive obesity
Authors: Jia Wentong , Giwa Rocky , Moley John R. , Smith Gordon I. , Petersen Max C. , Field Rachael L , Abousaway Omar , Kim Arthur S. , Coffey Sarah R. , Varnum Stella , Wright Jasmine M. , Zhang Xinya , Krysa Samantha , Lodhi Irfan J. , Abumrad Nada A. , Klein Samuel , Diamond Michael S. , Brestoff Jonathan R. 
Published: February 2024

ABSTRACTMatrix-remodeling associated 8 (MXRA8), also known as Dual immunoglobulin domain cell adhesion molecule (DICAM), is a type 1 transmembrane protein that reportedly binds the αVβ3integrin1and regulates the differentiation of osteoclasts2and chondrocytes3, tumor growth4, T cell trafficking5, and angiogenesis6. MXRA8 is also an essential entry receptor for chikungunya virus and other related arthritogenic alphaviruses.7-9We compared MXRA8 expression in 51 tissues in the Human Protein Atlas and found it is most highly expressed in white adipose tissue (WAT), however the function of MXRA8 in WAT is unknown. Here, we found that MXRA8 expression in WAT is increased in people with obesity and that this response is also observed in a mouse model of high fat-diet (HFD)-induced obesity. Single-nucleus RNA sequencing and high-dimensional spectral flow cytometry analyses revealed that MXRA8 is expressed predominantly by adipocyte progenitor (AP) cells and mature adipocytes. MXRA8 mutant primary adipocytes from inguinal (i)WAT exhibited increased expression of Uncoupling protein 1 (UCP1), a thermogenic protein expressed by beige and brown adipocytes that limits obesity pathogenesis.10-12Indeed, MXRA8 mutant mice fed a HFD had preserved UCP1+beige and brown adipocytes and were protected from HFD-induced obesity in a UCP1-dependent manner. Collectively, these findings indicate that MXRA8 promotes whitening of beige and brown adipose tissues to drive obesity pathogenesis and identify MXRA8 as a possible therapeutic target to treat obesity and associated metabolic diseases.
FoxO factors are essential for maintaining organ homeostasis by acting as stress sensors in airway epithelial cells
Authors: Uliczka Karin , Bossen Judith , Zissler Ulrich M. , Fink Christine , Niu Xiao , Pieper Mario , Prange Ruben D. , Vock Christina , Wagner Christina , Knop Mirjam , Abdelsadik Ahmed , Franzenburg Sören , Bruchhaus Iris , Wegmann Michael , Schmidt-Weber Carsten B. , König Peter , Pfefferle Petra , Heine Holger , Roeder Thomas 
Published: February 2024

AbstractAirway epithelia have the challenging task of maintaining functional and structural homeostasis, even when exposed to various stress factors. Transcription factors of the FoxO family can fulfill this complex task, as they act as integration hubs that translate extrinsic and intrinsic information into a physiologically appropriate response. We could show that FoxO factors inDrosophila, mouse, and human airway epithelial cells (AECs) respond to stressors like hypoxia, temperature, or oxidative stress by nuclear translocation. A complex activation pattern is revealed in human cell culture systems, which differs between individual hFOXO factors and cell types. Studies withDrosophilashowed that hypoxia was the only stressor that induced a dfoxo-dependent, local immune response activation. SinceDrosophilahas only one ortholog of FoxO, it was possible to show that the absence of dfoxo in the airways strongly increases the stress sensitivity of the airways. This stress sensitivity finds its counterpart in mouse models of chronic and acute asthma, with reduced mFoxO expression in the lung, particularly mFoxO1 and mFoxO3A. Finally, it is also reflected in asthma patients who show reduced hFOXO transcripts in their sputum samples. We conclude that active FoxO signaling in AECs is necessary to respond appropriately to stressors. Impaired FoxO signaling limits this ability and thus promotes disease development.
Individualized functional connectivity markers associated with motor and mood symptoms of Parkinson’s disease
Authors: Dahmani Louisa , Bai Yan , Zhang Wei , Ren Jianxun , Li Shiyi , Hu Qingyu , Fu Xiaoxuan , Ma Jianjun , Wei Wei , Wang Meiyun , Liu Hesheng , Wang Danhong 
Published: February 2024

ABSTRACTParkinson’s disease (PD) is a complex neurological disorder characterized by many motor and non-motor symptoms. While most studies focus on the motor symptoms of the disease, it is important to identify markers that underlie different facets of the disease. In this case-control study, we sought to discover reliable, individualized functional connectivity markers associated with both motor and mood symptoms of PD. Using functional MRI, we extensively sampled 166 patients with PD (64 women, 102 men; mean age=61.8 years, SD=7.81) and 51 healthy control participants (32 women, 19 men; mean age=55.68 years, SD=7.62). We found that a model consisting of 44 functional connections predicted both motor (UPDRS-III: Pearsonr=0.21, FDR-adjustedp=0.006) and mood symptoms (HAMD: Pearsonr=0.23, FDR-adjustedp=0.006; HAMA: Pearsonr=0.21, FDR-adjustedp=0.006). Two sets of connections contributed differentially to these predictions. Between-network connections, mainly connecting the sensorimotor and visual large-scale functional networks, substantially contributed to the prediction of motor measures, while within-network connections in the insula and sensorimotor network contributed more so to mood prediction. The middle to posterior insula region played a particularly important role in predicting depression and anxiety scores. We successfully replicated and generalized our findings in two independent PD datasets. Taken together, our findings indicate that sensorimotor and visual network markers are indicative of PD brain pathology, and that distinct subsets of markers are associated with motor and mood symptoms of PD.
Open-Source Platform for Kinematic Analysis of Mouse Forelimb Movement
Authors: Berezhnoi Daniil , Chehade Hiba Douja , Chu Hong-Yuan 
Published: February 2024

SummaryWe present an open-source behavioral platform and software solution for studying fine motor skills in mice performing reach-to-grasp task. The behavioral platform uses readily available and 3D-printed components and was designed to be affordable and universally reproducible. The protocol describes how to assemble the box, train mice to perform the task and process the video with the custom software pipeline to analyze forepaw kinematics. All the schematics, 3D models, code and assembly instructions are provided in the open GitHub repository.Graphical abstract
Modeling nearshore-offshore water exchange in Lake Ontario
Authors: Hlevca Bogdan , Howell Todd , Valipour Reza , Madani Mohammad 
Published: February 2024

AbstractThe water quality and resources of Lake Ontario’s nearshore ecosystem undergo heightened stress, particularly along the northwest shoreline. Hydrodynamic processes linking the distinct nearshore and offshore trophic structures play a crucial role in transporting nutrient-loaded water along and across the shore. Despite the pivotal connection between algae growth and the development of nuisance proportions, the scales over which these processes operate remain poorly understood. This study delves into the exchange dynamics between nearshore and offshore areas of Lake Ontario throughout 2018, employing a validated three-dimensional numerical model. A virtual passive age tracer is utilized to discern horizontal mixing time scales between nearshore regions of the lake (water depth < 30 m) and offshore locations. The dispersal pattern, as revealed by a passive tracer released from eight points around the model lake’s perimeter, indicates more extensive diffusion in late summer when lake-wide stratification is established, compared to the mixed period. Coastal upwelling events, leading to intrusions of hypolimnetic waters, significantly contribute to net cross-shore transport, with the most pronounced effects observed in May and June when the offshore thermocline is shallow. In the northern part of the lake, dispersal predominantly occurs alongshore, mirroring the prevailing cyclonic (counterclockwise) coastal circulation during the stratified season. This pattern is a consequence of a 45% increase in upwelling events compared to three decades ago. In the northwestern and southern sectors of the lake, elevated cross-shore mixing is attributed to geomorphology-induced cross-basin currents.
Physicochemical Principles Driving Small Molecule Binding to RNA
Authors: Allen Timothy E. H. , McDonagh James L. , Broncel Malgorzata , Bryant Carson J. , Incarnato Danny , Vasudevan Anil , Khan Rabia T. 
Published: February 2024

AbstractThe possibility of using RNA-targeting small molecules to treat diseases is gaining traction as the next frontier of drug discovery and development. The chemical characteristics of small molecules that bind to RNA are still relatively poorly understood, particularly in comparison to protein-targeting small molecules. To fill this gap, we have generated an unprecedented amount of RNA-small molecule binding data, and used it to derive physicochemical rules of thumb that could be used to define areas of chemical space enriched for RNA binders - the Small molecules Targeting RNA (STaR) rules of thumb. These rules have been applied to publicly available RNA-small molecule datasets and found to be largely generalizable. Furthermore, a number of patented RNA-targeting compounds and FDA-approved compounds also pass these rules, as well as key RNA binding approved drug case studies including Risdiplam. We anticipate this work will significantly accelerate the exploration of the RNA-targeted chemical space, towards unlocking RNA’s potential as a small molecule drug target.Graphical Abstract