bluuebunny/crossref_metadata_2025_split huggingface dataset:
Tight junction membrane proteins regulate the mechanical resistance of the apical junctional complex
Authors: Nguyen Thanh Phuong , Otani Tetsuhisa , Tsutsumi Motosuke , Fujiwara Sachiko , Nemoto Tomomi , Fujimori Toshihiko , Furuse Mikio 
Published: August 2023

AbstractEpithelia must be able to resist mechanical force to preserve tissue integrity. While intercellular junctions are known to be important for the mechanical resistance of epithelia, the roles of tight junctions (TJs) remain to be established. We previously demonstrated that epithelial cells devoid of the TJ membrane proteins claudins and JAM-A completely lack TJs and exhibit focal breakages of their apical junctions. Here, we demonstrate that apical junctions undergo spontaneous fracture when claudin/JAM-A-deficient cells are exposed to mechanical stress. The junction fracture was accompanied by actin disorganization, and actin polymerization was required for apical junction integrity in the claudin/JAM-A-deficient cells. Further deletion of CAR resulted in the disruption of ZO-1 molecule ordering at cell junctions, accompanied by severe defects in apical junction integrity. These results demonstrate that TJ membrane proteins regulate the mechanical resistance of the apical junctional complex in epithelial cells.SummaryTight junction membrane proteins claudins, JAM, and CAR coordinately regulate the nanometer-scale organization of ZO-1 molecules, and are required for the mechanical resistance of apical junctions in epithelial cells.
Human Intelligence and the Connectome are Driven by Structural Brain Network Control
Authors: Anderson Evan D. , Varshney Lav R. , Hemmatian Babak , Robles-Granda Pablo D. , Nayak Anuj Keshava , Wilcox Ramsey R. , Zwilling Christopher E. , Kim Been , Barbey Aron K. 
Published: August 2023

AbstractResearch in network neuroscience demonstrates that human intelligence is shaped by the structural brain connectome, which enables a globally coordinated and dynamic architecture for general intelligence. Building on this perspective, the network neuroscience theory proposes that intelligence arises from system-wide network dynamics and the capacity to flexibly transition between network states. According to this view, network flexibility is made possible by network controllers that move the system into specific network states, enabling solutions to familiar problems by accessing nearby, easy-to-reach network states and adapting to novel situations by engaging distant, difficult-to-reach network states. Although this framework predicts that general intelligence depends on network controllability, the specific cortical regions that serve as network controllers and the nature of their control operations remain to be established. We therefore conducted a comprehensive investigation of the relationship between regional measures of network controllability and general intelligence within a sample of 275 healthy young adults using structural and diffusion-weighted MRI data. Our findings revealed significant associations between intelligence and network controllers located within the frontal, temporal and parietal cortex. Furthermore, we discovered that these controllers collectively enable access to both easy- and difficult-to-reach network states, aligning with the predictions made by the network neuroscience framework. Additionally, our research demonstrated that the identified network controllers are primarily localized within the left hemisphere and do not reside within regions or connections that possess the highest capacity for structural control in general. This discovery suggests that the identified regions may facilitate specialized control operations and motivates further exploration of the network topology and dynamics underlying intelligence in the human brain.SummaryThis study examines the relationship between regional measures of network controllability and general intelligence within a sample of 275 healthy young adults using structural and diffusion-weighted MRI data. We report that individual differences in general intelligence are associated average and modal controllability in specific left-hemisphere cortical regions, and further show that controller regions associated with intelligence are distinct from regions with the highest, centrality, controllability, or communication. These findings reveal a significant structural role for individual regions in controlling the trajectory of the connectome, advancing our understanding of the nature and mechanisms of network controllability in general intelligence.
Unique T cell signatures associated with reducedChlamydia trachomatisreinfection in a highly exposed cohort
Authors: Yount Kacy S , Chen Chi-Jane , Kollipara Avinash , Liu Chuwen , Mokashi Neha V , Zheng Xiaojing , Bagwell C Bruce , Poston Taylor B , Wiesenfeld Harold C , Hillier Sharon L , O’Connell Catherine M , Stanley Natalie , Darville Toni 
Published: August 2023

ABSTRACTChlamydia trachomatis(CT) is the most common bacterial sexually transmitted infection globally. Understanding natural immunity to CT will inform vaccine design. This study aimed to profile immune cells and associated functional features in CT-infected women, and determine immune profiles associated with reduced risk of ascended endometrial CT infection and CT reinfection. PBMCs from CT-exposed women were profiled by mass cytometry and random forest models identified key features that distinguish outcomes. CT+ participants exhibited higher frequencies of CD4+ Th2, Th17, and Th17 DN CD4 T effector memory (TEM) cells than uninfected participants with decreased expression of T cell activation and differentiation markers. No significant differences were detected between women with or without endometrial CT infection. Participants who remained follow-up negative (FU-) showed higher frequencies of CD4 T central memory (TCM) Th1, Th17, Th1/17, and Th17 DN but reduced CD4 TEM Th2 cells than FU+ participants. Expression of markers associated with central memory and Th17 lineage were increased on T cell subsets among FU- participants. These data indicate that peripheral T cells exhibit distinct features associated with resistance to CT reinfection. The highly plastic Th17 lineage appears to contribute to protection. Addressing these immune nuances could promote efficacy of CT vaccines.GRAPHICAL ABSTRACT
Membrane molecule bouncer enables follicle fertilization in a viviparous teleost:Poecilia reticulata(guppy)
Authors: Yoshida Junki , Tajika Yuki , Uchida Kazuko , Kuwahara Makoto , Sano Kaori , Suzuki Takayuki , Hondo Eiichi , Iida Atsuo 
Published: August 2023

AbstractFertilization is a fundamental mechanism of sexual reproduction. Generally, oocytes are ovulated from the ovarian follicles and contact the sperm outside the ovarian medulla. Unlike this, follicle fertilization which means the egg contact with sperm in the ovarian medulla without ovulation is known in the viviparous teleost species belonging to the Poeciliidae. In this study, we focused on a viviparous teleost species,Poecilia reticulata(guppy). Our sperm tracking assay indicated that the sperm reached the immature oocytes with a germinal vesicle, and the fertilized immature oocytes were presumed to contribute to littermates. The binding between immature oocytes and sperm is a specific trait in the guppy, which was not observed inDanio rerio(zebrafish) orOryzias latipes(medaka). The loss- and gain-of-function assays indicated that bouncer plays a critical role in immature oocyte-to-sperm binding. This fertilization trait in immature oocytes may provide certain advantages for females with respect to nutrition or other gestation costs. Our findings shed light on the unique reproductive strategies of guppy and contribute to our understanding of the diverse reproductive mechanisms in vertebrates.Summary statementUnlike general vertebrates, guppy’s oocyte fertilizes with sperm in the ovarian medulla at the immature stages. The distinctive trait depends on the Ly6/uPAR protein bouncer.
m6A mRNA Methylation Regulates Early Pancreatic β-Cell Differentiation
Authors: Kahraman Sevim , De Jesus Dario F , Wei Jiangbo , Brown Natalie K. , Zou Zhongyu , Hu Jiang , He Chuan , Kulkarni Rohit N 
Published: August 2023

SUMMARYN6-methyladenosine (m6A) is the most abundant chemical modification in mRNA, and plays important roles in human and mouse embryonic stem cell pluripotency, maintenance, and differentiation. We have recently reported, for the first time, the role of m6A in the postnatal control of β-cell function in physiological states and in Type 1 and 2 Diabetes. However, the precise mechanisms by which m6A acts to regulate the development of human and mouse β-cells are unexplored. Here, we show that the m6A landscape is dynamic during human pancreas development, and that METTL14, one of the m6A writer complex proteins, is essential for the early differentiation of both human and mouse β-cells.
Metabolic reprogramming duringCandida albicansplanktonic-biofilm transition is modulated by theZCF15andZCF26paralogs
Authors: Rai Laxmi Shanker , Chauvel Murielle , Sanchez Hiram , van Wijlick Lasse , Maufrais Corinne , Cokelaer Thomas , Sertour Natacha , Legrand Mélanie , Andes David R , Bachellier-Bassi Sophie , d’Enfert Christophe 
Published: August 2023

AbstractCandida albicansis a commensal of the human microbiota that can form biofilms on implanted medical devices. These biofilms are tolerant to antifungals and to the host immune system. To identify novel genes modulatingC. albicansbiofilm formation, we performed a large-scale screen with 2454C. albicansdoxycycline-dependent overexpression strains and identified 16 genes whose overexpression significantly hampered biofilm formation. Among those, overexpression of theZCF15andZCF26paralogs that encode transcription factors and have orthologs only in biofilm-forming species of theCandidaclade, caused impaired biofilm formation bothin vitroandin vivo. Interestingly, overexpression ofZCF15specifically impeded biofilm formation without any defect in hyphal growth. Transcript profiling, transcription factor binding, and phenotypic microarray analyses conducted upon overexpression ofZCF15andZCF26demonstrated their direct role in reprogramming cellular metabolism by regulating glycolytic cycle and tricarboxylic acid cycle genes. Taken together, this study has identified a new set of biofilm regulators, includingZCF15andZCF26,that appear to control biofilm development through their specific role in metabolic remodeling.
A force-sensitive mutation reveals a spindle assembly checkpoint-independent role for dynein in anaphase progression
Authors: Salvador-Garcia David , Jin Li , Hensley Andrew , Gölcük Mert , Gallaud Emmanuel , Chaaban Sami , Port Fillip , Vagnoni Alessio , Planelles-Herrero Vicente José , McClintock Mark A. , Derivery Emmanuel , Carter Andrew P. , Giet Régis , Gür Mert , Yildiz Ahmet , Bullock Simon L. 
Published: August 2023

ABSTRACTThe cytoplasmic dynein-1 (dynein) motor organizes cells by shaping microtubule networks and moving a large variety of cargoes along them. However, dynein’s diverse roles complicatein vivostudies of its functions significantly. To address this issue, we have used gene editing to generate a series of missense mutations inDrosophilaDynein heavy chain (Dhc). We find that mutations associated with human neurological disease cause a range of defects in larval and adult flies, including impaired cargo trafficking in neurons. We also describe a novel mutation in the microtubule-binding domain (MTBD) of Dhc that, remarkably, causes metaphase arrest of mitotic spindles in the embryo but does not impair other dynein-dependent processes. We demonstrate that the mitotic arrest is independent of dynein’s well-established roles in silencing the spindle assembly checkpoint.In vitroreconstitution and optical trapping assays reveal that the mutation only impairs the performance of dynein under load.In silicoall-atom molecular dynamics simulations show that this effect correlates with increased flexibility of the MTBD, as well as an altered orientation of the stalk domain, with respect to the microtubule. Collectively, our data point to a novel role of dynein in anaphase progression that depends on the motor operating in a specific load regime. More broadly, our work illustrates how cytoskeletal transport processes can be dissectedin vivoby manipulating mechanical properties of motors.
Hemispheric asymmetries in auditory cortex reflect discriminative responses to temporal details or summary statistics of stationary sounds
Authors: Berto Martina , Reisinger Patrick , Ricciardi Emiliano , Weisz Nathan , Bottari Davide 
Published: August 2023

AbstractThe processing of stationary sounds relies on both local features and compact representations. As local information is compressed into summary statistics, abstract representations emerge. Whether the brain is endowed with distinct neural architectures overseeing such computations is unknown.In this magnetoencephalography (MEG) study, we employed a validated protocol to localize cortical correlates of local and summary representations, exposing participants to triplets of synthetic sound textures systematically varying for either local details or summary statistics. Sounds also varied for their sound duration, specifically short (40ms) or long (478ms). Results revealed clear distinct activation patterns for local features and summary statistics changes. Such activations diverged in magnitude, spatiotemporal distribution, and hemispheric lateralization. For short sounds, a change in local features, compared to summary statistics, predominantly activated the right hemisphere. Conversely, for long sounds, a change in summary statistics elicited higher activation than a change in local features in both hemispheres.Specifically, while the right auditory cortex was responding more to changes in local features or summary statistics depending on sound duration (short or long, respectively), the left frontal lobe was selectively engaged in processing a change in summary statistics at a long sound duration. These findings provide insights into the neural mechanisms underlying the computation of local and summary acoustic information and highlight the involvement of distinct cortical pathways and hemispheric lateralization in auditory processing at different temporal resolutions.Significant StatementWe revealed hemispheric specializations for auditory computations at high (local) and low (summary statistics) temporal resolutions. The right hemisphere was engaged for both computations, while the left hemisphere responded more to summary statistics changes. These findings highlight the multifaceted functions of the right hemisphere in capturing acoustic properties of stationary sounds and the left hemisphere’s involvement in processing abstract representations.
FAM210A mediates an inter-organelle crosstalk essential for protein synthesis and muscle growth in mouse
Authors: Chen Jingjuan , Yue Feng , Kim Kun Ho , Zhu Peipei , Qiu Jiamin , Tao W. Andy , Kuang Shihuan 
Published: August 2023

AbstractMitochondria are not only essential for energy production in eukaryocytes but also a key regulator of intracellular signaling. Here, we report an unappreciated role of mitochondria in regulating cytosolic protein translation in skeletal muscle cells (myofibers). We show that the expression of mitochondrial protein FAM210A (Family With Sequence Similarity 210 Member A) is positively associated with muscle mass in mice and humans. Muscle-specificMyl1Cre-drivenFam210aknockout (Fam210aMKO) in mice reduces mitochondrial density and function, leading to progressive muscle atrophy and premature death. Metabolomic and biochemical analyses reveal thatFam210aMKOreverses the oxidative TCA cycle towards the reductive direction, resulting in acetyl-CoA accumulation and hyperacetylation of cytosolic proteins. Specifically, hyperacetylation of several ribosomal proteins leads to disassembly of ribosomes and translational defects. Transplantation ofFam210aMKOmitochondria into wildtype myoblasts is sufficient to elevate protein acetylation in recipient cells. These findings reveal a novel crosstalk between the mitochondrion and ribosome mediated by FAM210A.
Conserved regulatory motifs in the juxtamembrane domain and kinase N-lobe revealed through deep mutational scanning of the MET receptor tyrosine kinase domain
Authors: Estevam Gabriella O. , Linossi Edmond M. , Macdonald Christian B. , Espinoza Carla A. , Michaud Jennifer M. , Coyote-Maestas Willow , Collisson Eric A. , Jura Natalia , Fraser James S. 
Published: August 2023

AbstractMET is a receptor tyrosine kinase (RTK) responsible for initiating signaling pathways involved in development and wound repair. MET activation relies on ligand binding to the extracellular receptor, which prompts dimerization, intracellular phosphorylation, and recruitment of associated signaling proteins. Mutations, which are predominantly observed clinically in the intracellular juxtamembrane and kinase domains, can disrupt typical MET regulatory mechanisms. Understanding how juxtamembrane variants, such as exon 14 skipping (METΔEx14), and rare kinase domain mutations can increase signaling, often leading to cancer, remains a challenge. Here, we perform a parallel deep mutational scan (DMS) of the MET intracellular kinase domain in two fusion protein backgrounds: wild type and METΔEx14. Our comparative approach has revealed a critical hydrophobic interaction between a juxtamembrane segment and the kinase ⍺C-helix, pointing to potential differences in regulatory mechanisms between MET and other RTKs. Additionally, we have uncovered a β5 motif that acts as a structural pivot for the kinase domain in MET and other TAM family of kinases. We also describe a number of previously unknown activating mutations, aiding the effort to annotate driver, passenger, and drug resistance mutations in the MET kinase domain.
Host-pathogen coevolution promotes the evolution of general, broad-spectrum resistance and reduces foreign pathogen spillover risk
Authors: Hulse Samuel V. , Antonovics Janis , Hood Michael E. , Bruns Emily L. 
Published: August 2023

AbstractGenetic variation for disease resistance within host populations can strongly impact the spread of endemic pathogens. In plants, recent work has shown that within-population variation in resistance can also affect the transmission of foreign spillover pathogens if that resistance is general. However, most hosts also possess specific resistance mechanisms that provide strong defenses against coevolved endemic pathogens. Here we use a modeling approach to ask how antagonistic coevolution between hosts and their endemic pathogen at the specific resistance locus can affect the frequency of general resistance, and therefore a host’s vulnerability to foreign pathogens. We develop a two-locus model with variable recombination that incorporates both general (resistance to all pathogens) and specific (resistance to endemic pathogens only). We find that introducing coevolution into our model greatly expands the regions where general resistance can evolve, decreasing the risk of foreign pathogen invasion. Furthermore, coevolution greatly expands which conditions maintain polymorphisms at both resistance loci, thereby driving greater genetic diversity within host populations. This genetic diversity often leads to positive correlations between host resistance to foreign and endemic pathogens, similar to those observed in natural populations. However, if resistance loci become linked, the resistance correlations can shift to negative. If we include a third, linkage modifying locus into our model, we find that selection often favors complete linkage. Our model demonstrates how coevolutionary dynamics with an endemic pathogen can mold the resistance structure of host populations in ways that affect its susceptibility to foreign pathogen spillovers, and that the nature of these outcomes depends on resistance costs, as well as the degree of linkage between resistance genes.
The rapid decline in interaural-time-difference sensitivity for pure tones can be explained by peripheral filtering
Authors: Goupell Matthew J. , Stecker G. Christopher , Williams Brittany T. , Bilokon Anhelina , Tollin Daniel J. 
Published: August 2023

ABSTRACTPurposeThe interaural time difference (ITD) is a primary horizontal-plane sound localization cue computed in the auditory brainstem. ITDs are accessible in the temporal fine structure of pure tones with a frequency of no higher than about 1400 Hz. Explaining how listeners’ ITD sensitivity transitions from very best sensitivity near 700 Hz to impossible to detect within 1 octave currently lacks a fully compelling physiological explanation. Here, it was hypothesized that the rapid decline in ITD sensitivity is dictated not by a central neural limitation but by initial peripheral sound encoding, specifically, the low-frequency (apical) edge of the cochlear excitation pattern produced by a pure tone.MethodsITD sensitivity was measured in 16 normal-hearing listeners as a joint function of frequency (900-1500 Hz) and level (10-50 dB sensation level).ResultsPerformance decreased with increasing frequency and decreasing sound level. The slope of performance decline was 90 dB/octave, consistent with the low-frequency slope of the cochlear excitation pattern.ConclusionFine-structure ITD sensitivity near 1400 Hz may be conveyed primarily by “off-frequency” activation of neurons tuned to lower frequencies near 700 Hz. Physiologically, this could be realized by having neurons sensitive to fine-structure ITD up to only about 700 Hz. A more extreme model would have only a single narrow channel near 700 Hz that conveys fine-structure ITDs. Such a model is a major simplification and departure from the classic formulation of the binaural display, which consists of a matrix of neurons tuned to a wide range of relevant frequencies and ITDs.
Open datasets and code for multi-scale relations on structure, function and neuro-genetics in the human brain
Authors: Jimenez-Marin Antonio , Diez Ibai , Erramuzpe Asier , Stramaglia Sebastiano , Bonifazi Paolo , Cortes Jesus M 
Published: August 2023

ABSTRACTThe human brain is an extremely complex network of structural and functional connections that operate at multiple spatial and temporal scales. Investigating the relationship between these multi-scale connections is critical to advancing our comprehension of brain function and disorders. However, accurately predicting structural connectivity from its functional counterpart remains a challenging pursuit. One of the major impediments is the lack of public repositories that integrate structural and functional networks at diverse resolutions. Addressing this issue, we provide open datasets and code enabling the examination of the correspondence between structural and functional connectivities at different scales. We present a module-level strategy that overcomes region-level approaches in understanding the structure-function correspondence. Moreover, we also provide additional resources focused on neuro-genetic associations of module-level network metrics, which present promising opportunities to further advance research in the field of network neuroscience, particularly concerning brain disorders.