bluuebunny/crossref_metadata_2025_split huggingface dataset:
High performers demonstrate greater neural synchrony than low performers across behavioral domains
Authors: Chamberlain Taylor A. , Corriveau Anna , Song Hayoung , Kwon Young Hye , Yoo Kwangsun , Chun Marvin M. , Rosenberg Monica D. 
Published: June 2023

AbstractHeterogeneity in brain activity gives rise to heterogeneity in behavior, which in turn comprises our distinctive characteristics as individuals. Studying the path from brain to behavior, however, often requires making assumptions about how similarity in behavior scales with similarity in brain activity. Here, we expand upon recent work which proposes a theoretical framework for testing the validity of such assumptions. Using intersubject representational similarity analysis in two independent movie-watching fMRI datasets, we probe how brain-behavior relationships vary as a function of behavioral domain and participant sample. We find evidence that, in some cases, the neural similarity of two individuals is not correlated with behavioral similarity. Rather, individuals with higher behavioral scores are more similar to other high scorers whereas individuals with lower behavioral scores are dissimilar from everyone else. Ultimately, our findings motivate a more extensive investigation of both the structure of brain-behavior relationships and the tacit assumption that people who behave similarly will demonstrate shared patterns of brain activity.
Tessellation of artificial touch via microstimulation of human somatosensory cortex
Authors: Greenspon Charles M. , Shelchkova Natalya D. , Valle Giacomo , Hobbs Taylor G. , Berger-Wolf Ev I. , Hutchison Brianna C. , Dogruoz Efe , Verbarschott Ceci , Callier Thierri , Sobinov Anton R. , Okorokova Elizaveta V. , Jordan Patrick M. , Prasad Dillan , He Qinpu , Liu Fang , Kirsch Robert F. , Miller Jonathan P. , Lee Ray C. , Satzer David , Gonzalez-Martinez Jorge , Warnke Peter C. , Miller Lee E. , Boninger Michael L. , Ajiboye Abidemi B. , Graczyk Emily L. , Downey John E. , Collinger Jennifer L. , Hatsopoulos Nicholas G. , Gaunt Robert A. , Bensmaia Sliman J. 
Published: June 2023

AbstractWhen we interact with objects, we rely on signals from the hand that convey information about the object and our interaction with it. A basic feature of these interactions, the locations of contacts between the hand and object, is often only available via the sense of touch. Information about locations of contact between a brain-controlled bionic hand and an object can be signaled via intracortical microstimulation (ICMS) of somatosensory cortex (S1), which evokes touch sensations that are localized to a specific patch of skin. To provide intuitive location information, tactile sensors on the robotic hand drive ICMS through electrodes that evoke sensations at skin locations matching sensor locations. This approach requires that ICMS-evoked sensations be focal, stable, and distributed over the hand. To systematically investigate the localization of ICMS-evoked sensations, we analyzed the projected fields (PFs) of ICMS-evoked sensations – their location and spatial extent – from reports obtained over multiple years from three participants implanted with microelectrode arrays in S1. First, we found that PFs vary widely in their size across electrodes, are highly stable within electrode, are distributed over large swaths of each participant’s hand, and increase in size as the amplitude or frequency of ICMS increases. Second, while PF locations match the locations of the receptive fields (RFs) of the neurons near the stimulating electrode, PFs tend to be subsumed by the corresponding RFs. Third, multi-channel stimulation gives rise to a PF that reflects the conjunction of the PFs of the component channels. By stimulating through electrodes with largely overlapping PFs, then, we can evoke a sensation that is experienced primarily at the intersection of the component PFs. To assess the functional consequence of this phenomenon, we implemented multi-channel ICMS-based feedback in a bionic hand and demonstrated that the resulting sensations are more localizable than are those evoked via single-channel ICMS.
Mechanistic basis for nigericin-induced NLRP1 inflammasome activation in human epithelial cells
Authors: Rozario Pritisha , Pinilla Miriam , Vind Anna Constance , Robinson Kim S. , Ann Toh Gee , Firdaus Muhammad Jasrie , Martínez José Francisco , Zhewang Lin , Bekker-Jensen Simon , Meunier Etienne , Zhong Franklin 
Published: June 2023

ABSTRACTNigericin, an ionophore derived fromStreptomyces hygroscopicus, is arguably the most commonly used tool compound to study the NLRP3 inflammasome. Recent findings, however, showed that nigericin also activates the NLRP1 inflammasome in human keratinocytes. In this study, we resolve the mechanistic basis of nigericin-driven NLRP1 inflammasome activation. In multiple non-hematopoietic cell types, nigericin rapidly and specifically inhibits the elongation stage of the ribosome cycle by depleting cytosolic potassium ions. This activates the ribotoxic stress response (RSR) sensor kinase ZAKɑ, p38 and JNK, as well as the hyperphosphorylation of the NLRP1 linker domain. As a result, nigericin-induced pyroptosis in human keratinocytes is blocked by extracellular potassium supplementation, ZAKɑ knockout or pharmacologic inhibitors of ZAKɑ and p38 kinase activities. By surveying a diverse panel of ionophores, we show that the electroneutrality of potassium efflux is essential to activate ZAKɑ-driven RSR, likely because a greater extent of K+ depletion is necessary to activate ZAKɑ-NLRP1 than NLRP3. These findings resolve the mechanism by which nigericin activates NLRP1 in nonhematopoietic cell types and demonstrate an unexpected connection between RSR, perturbations of potassium ion flux and innate immunity.GRAPHICAL ABSTRACTSIGNIFICANCENigericin is familiar to the inflammasome field as the most robust and commonly used NLRP3 inducer. It has enabled numerous breakthroughs in the field linking NLRP3 activation to potassium efflux. In this manuscript, we report that nigericin activates an alternate inflammasome sensor, NLRP1 in primary human skin, nasal and corneal epithelial cells. NLRP1 activation by nigericin requires K+ efflux-driven ribosome stalling and the ribotoxic stress response (RSR) sensor MAP3K, ZAKɑ. We further identify the key biophysical principles that explain why only a subset of K+ ionophores, exemplified by nigericin, function as ‘super’ inflammasome agonists that can activate either NLRP1 or NLRP3, depending on cell type. These results reveal an unexpected connection between RSR, potassium ion flux and innate immunity.
Deficiency of IQCH causes male infertility in humans and mice
Authors: Ruan Tiechao , Zhou Ruixi , Yang Yihong , Guo Junchen , Jiang Chuan , Wang Xiang , Shen Gan , Dai Siyu , Chen Suren , Shen Ying 
Published: June 2023

AbstractIQ motif-containing proteins can be recognized by calmodulin (CaM) and are essential for many biological processes. However, the role of IQ motif-containing proteins in spermatogenesis is largely unknown. In this study, we identified a loss-of-function mutation in the novel gene IQ motif-containing H (IQCH) in a Chinese family with male infertility characterized by a cracked flagellar axoneme and abnormal mitochondrial structure. To verify the function of IQCH,Iqchknockout (KO) mice were generated via CRISPR-Cas9 technology. As expected, theIqchKO male mice exhibited impaired fertility, which was related to deficient acrosome activity and abnormal structures of the axoneme and mitochondria, mirroring the patient phenotypes. Mechanistically, IQCH can bind to CaM and subsequently regulate the expression of RNA-binding proteins (especially HNRPAB), which are indispensable for spermatogenesis. Overall, this study revealed the function of IQCH, expanded the role of IQ motif-containing proteins in reproductive processes, and provided important guidance for genetic counseling and genetic diagnosis of male infertility.
Novel mouse model of Weaver syndrome displays overgrowth and excess osteogenesis reversible with KDM6A/6B inhibition
Authors: Gao Christine W , Lin WanYing , Riddle Ryan C , Kushwaha Priyanka , Boukas Leandros , Björnsson Hans T , Hansen Kasper D , Fahrner Jill A 
Published: June 2023

AbstractWeaver syndrome is a Mendelian disorder of the epigenetic machinery (MDEM) caused by germline pathogenic variants inEZH2, which encodes the predominant H3K27 methyltransferase and key enzymatic component of Polycomb repressive complex 2 (PRC2). Weaver syndrome is characterized by striking overgrowth and advanced bone age, intellectual disability, and distinctive facies. We generated a mouse model for the most common Weaver syndrome missense variant,EZH2p.R684C.Ezh2R684C/R684Cmouse embryonic fibroblasts (MEFs) showed global depletion of H3K27me3.Ezh2R684C/+mice had abnormal bone parameters indicative of skeletal overgrowth, andEzh2R684C/+osteoblasts showed increased osteogenic activity. RNA-seq comparing osteoblasts differentiated fromEzh2R684C/+andEzh2+/+bone marrow mesenchymal stem cells (BM-MSCs) indicated collective dysregulation of the BMP pathway and osteoblast differentiation. Inhibition of the opposing H3K27 demethylases Kdm6a/6b substantially reversed the excessive osteogenesis inEzh2R684C/+cells both at the transcriptional and phenotypic levels. This supports both the ideas that writers and erasers of histone marks exist in a fine balance to maintain epigenome state, and that epigenetic modulating agents have therapeutic potential for the treatment of MDEMs.
Multi-night naturalistic cortico-basal recordings reveal mechanisms of NREM slow wave suppression and spontaneous awakenings in Parkinson’s disease
Authors: Anjum Md Fahim , Smyth Clay , Dijk Derk-Jan , Starr Philip , Denison Timothy , Little Simon 
Published: June 2023

ABSTRACTBackgroundSleep disturbance is a prevalent and highly disabling comorbidity in individuals with Parkinson’s disease (PD) that leads to worsening of daytime symptoms, accelerated disease progression and reduced quality of life.ObjectivesWe aimed to investigate changes in sleep neurophysiology in PD particularly during non-rapid eye movement (NREM) sleep, both in the presence and absence of deep brain stimulation (DBS).MethodsMulti-night (n=58) intracranial recordings were performed at-home, from chronic electrocorticography and subcortical electrodes, with sensing-enabled DBS pulse generators, paired with portable polysomnography. Four people with PD and one person with cervical dystonia were evaluated to determine the neural structures, signals and connections modulated during NREM sleep and prior to spontaneous awakenings. Recordings were performed both ON and OFF DBS in the presence of conventional dopaminergic replacement medications.ResultsWe demonstrate an increase in cortico-basal slow wave activity in delta (1-4 Hz) and a decrease in beta (13-31 Hz) during NREM (N2 and N3) versus wakefulness in PD. Cortical-subcortical coherence was also found to be higher in the delta range and lower in the beta range during NREM versus wakefulness. DBS stimulation resulted in a further elevation in cortical delta and a decrease in alpha (8-13 Hz) and low beta (13-15 Hz) power compared to the OFF stimulation state. During NREM sleep, we observed a strong inverse interaction between subcortical beta and cortical slow wave activity and found that subcortical beta increases prior to spontaneous awakenings.ConclusionsChronic, multi-night recordings in PD reveal opposing sleep stage specific modulations of cortico-basal slow wave activity in delta and subcortical beta power and connectivity in NREM, effects that are enhanced in the presence of DBS. Within NREM specifically, subcortical beta and cortical delta are strongly inversely correlated and subcortical beta power is found to increase prior to and predict spontaneous awakenings. We find that DBS therapy appears to improve sleep in PD partially through direct modulation of cortico-basal beta and delta oscillations. Our findings help elucidate a contributory mechanism responsible for sleep disturbances in PD and highlight potential biomarkers for future precision neuromodulation therapies targeting sleep and spontaneous awakenings.
Field phenomics reveals genetic variation for transpiration response to vapor pressure deficit in sorghum
Authors: Raymundo Rubí , Wang Xu , Felderhoff Terry , Sexton-Bowser Sarah , Poland Jesse , Lipka Alexander E. , Morris Geoffrey P. 
Published: June 2023

ABSTRACTDrought adaptation for water-limited environments relies on traits that optimize plant water budgets. Limited transpiration (LT) reduces water demand under high vapor pressure deficit (VPD) (i.e., dry air condition), conserving water for efficient use during the reproductive stage. Although studies in controlled environments report genetic variation for LT, confirming its replicability in field conditions is critical for developing water-resilient crops. Here we test the existence of genetic variation for LT in sorghum in field trials and whether canopy temperature (TC) is a surrogate method to discriminate this trait. We phenotyped transpiration response to VPD (TR-VPD) via stomatal conductance (gs), canopy temperature (TC) from fixed IRT sensors (TCirt), and unoccupied aerial system thermal imagery (TCimg) in 11 genotypes. Replicability among phenomic approaches for three genotypes revealed genetic variability for TR-VPD. Genotypes BTx2752 and SC979 carry the LT trait, while genotype DKS54-00 has the non-LT trait. TCcan determine differences in TR-VPD. However, the broad sense heritability (H2) and correlations suggest that canopy architecture and stand count hampers TCirtand TCimgmeasurement. Unexpectedly, observations of gsand VPD showed non-linear patterns for genotypes with LT and non-LT traits. Our findings provide further insights into the genetics of plant water dynamics.
Assembly of tight junction belts by surface condensation and actin elongation
Authors: Sun Daxiao , Zhao Xueping , Wiegand Tina , Bartolucci Giacomo , Martin-Lemaitre Cecilie , Grill Stephan W. , Hyman Anthony A. , Weber Christoph , Honigmann Alf 
Published: June 2023

AbstractFormation of biomolecular condensates via phase separation enables compartmentation of many cellular processes. However, how cells can control condensation at specific locations to create complex cellular structures remains poorly understood. Here, we investigated the mechanism of tight junction formation, which involves condensation of scaffold proteins at cell-cell contacts and elongation of the condensates into a belt around the cellular perimeter. Using cell biology, reconstitution, and thermodynamic theory, we discovered that cells use surface phase transitions to control local condensation at the membrane far below bulk saturation. Surface condensation of junctional ZO-scaffold proteins is mediated by receptor binding and regulated by the receptor’s oligomerization state. Functionally, ZO surface condensation is directly coupled to actin polymerization and bundling, which drives elongation of receptor-ZO-actin condensates similar to tight junction belt formation in cells. We conclude that surface phase transitions provide a robust mechanism to control the position and shape of protein condensates.One-Sentence SummaryLocal surface binding of cytosolic scaffold proteins provides spatial control of protein condensation to assemble adhesion junctions.
Rethinking simultaneous suppression in visual cortex via compressive spatiotemporal population receptive fields
Authors: Kupers Eline R , Kim Insub , Grill-Spector Kalanit 
Published: June 2023

1AbstractWhen multiple visual stimuli are presented simultaneously in the receptive field, the neural response is suppressed compared to presenting the same stimuli sequentially. The prevailing hypothesis suggests that this suppression is due to competition among multiple stimuli for limited resources within receptive fields, governed by task demands. However, it is unknown how stimulus-driven computations may give rise to simultaneous suppression. Using fMRI, we find simultaneous suppression in single voxels, which varies with both stimulus size and timing, and progressively increases up the visual hierarchy. Using population receptive field (pRF) models, we find that compressive spatiotemporal summation rather than compressive spatial summation predicts simultaneous suppression, and that increased simultaneous suppression is linked to larger pRF sizes and stronger compressive nonlinearities. These results necessitate a rethinking of simultaneous suppression as the outcome of stimulus-driven compressive spatiotemporal computations within pRFs, and open new opportunities to study visual processing capacity across space and time.
Antimicrobial Evaluation ofSalvadora persicaMethanolic Stem Extract andIn vivoModelling of its Identified Constituting Compounds Revealed Antibacterial Effect of 2-[(5-Iodosalicylidene)hydrazino]-4-morpholino-6-(1-pyrrolidinyl)-1,3,5-triazine in the Treatment of Dental Plague
Authors: Adigun Temidayo Olamide , Muhammed Maikarfi , Funmilayo Adisa Mofoluwaso , Alli Abdulhameed Oluwatomi , Olufunke Fagboro Oluwayemisi , Oluwatosin Oyebamiji Samson , Ayodeji Akinsehinwa Samuel , Oyebola Aina Kehinde 
Published: June 2023

AbstractChallenges of resistance to synthetic antimicrobials have opened new vistas in the search for natural products. This research rigorously reviews plant used in oral health. The antimicrobial activities ofSalvadora persicacommonly used as chewing stick was investigated against 3 clinical strains ofEscherichia coli, Staphylococcus aureus, Aspergillus nigar. The antibacterial and antifungal activities of the extracts were determined using the agar well diffusion.Salvadora persica, was active against all the isolates especially on the bacteria with a MIC and MBC of 12.5mg/mL and 25mg/mL respectively. Phytochemical screening revealed the presence of alkaloids, tannins, flavonoids, saponins and traces of terpenoids.In silicomodelling of the compounds identified in the chewing stick extract reveals that the aromatic nitrogen-rich compound with PubChem ID: 135580681 is likely responsible for the mechanistic inhibition associated with antibacterial effect of the plant material against dental plagues
Proteasome condensate formation is driven by multivalent interactions with shuttle factors and K48-linked ubiquitin chains
Authors: Waite Kenrick A. , Vontz Gabrielle , Lee Stella Y. , Roelofs Jeroen 
Published: June 2023

AbstractStress conditions can cause the relocalization of proteasomes to condensates in yeast and mammalian cells. The interactions that facilitate the formation of proteasome condensates, however, are unclear. Here, we show that the formation of proteasome condensates in yeast depends on long K48-linked ubiquitin chains together with the proteasome shuttle factors Rad23 and Dsk2. These shuttle factors colocalize to these condensates. Strains deleted for the third shuttle factor gene,DDI1, show proteasome condensates in the absence of cellular stress, consistent with the accumulation of substrates with long K48-linked ubiquitin chains that accumulate in this mutant. We propose a model where the long K48-linked ubiquitin chains function as a scaffold for the ubiquitin binding domains of the shuttle factors and the proteasome, allowing for the multivalent interactions that further drive condensate formation. Indeed, we determined different intrinsic ubiquitin receptors of the proteasome (Rpn1, Rpn10, and Rpn13) are critical under different condensate inducing conditions. In all, our data support a model where the cellular accumulation of substrates with long ubiquitin chains, potentially due to reduced cellular energy, allows for proteasome condensate formation. This suggests that proteasome condensates are not simply for proteasome storage, but function to sequester soluble ubiquitinated substrates together with inactive proteasomes.SignificanceStress conditions can cause the relocalization of proteasomes to condensates in yeast as well as mammalian cells. Our work shows that the formation of proteasome condensates in yeast depends on long K48-linked ubiquitin chains, the proteasome binding shuttle factors Rad23 and Dsk2 and proteasome intrinsic ubiquitin receptors. Here, different receptors are critical for different condensate inducers. These results indicate distinct condensates can form with specific functionality. Our identification of key factors involved in the process is crucial for understanding the function of proteasome relocalization to condensates. We propose that cellular accumulation of substrates with long ubiquitin chains results in the formation of condensates comprising those ubiquitinated substrates, proteasomes, and proteasome shuttle factors, where the ubiquitin chains serve as the scaffold for condensate formation.
Intrinsically Disordered Regions Promote Protein Refoldability and Facilitate Retrieval from Biomolecular Condensates
Authors: To Philip , Bhagwat Atharva M. , Tarbox Haley E. , Ecer Ayse , Wendorff Hannah , Jamieson Zanya , Trcek Tatjana , Fried Stephen D. 
Published: June 2023

AbstractMany eukaryotic proteins contain intrinsically disordered regions (IDRs) that intersperse globular folded domains, in contrast with bacterial proteins which are typically highly globular1, 2. Recent years have seen great progress in identifying biological functions associated with these elusive protein sequence: in specific cases, they mediate liquid liquid phase separation3, perform molecular recognition4, or act as sensors to changes in the environment5. Nevertheless, only a small number of IDRs have annotated functions6despite their presence in 64% of yeast proteins,7stimulating some to question what ‘general purpose’ they may serve8, 9. Here, by interrogating the refoldability of two fungal proteomes (Saccharomyces cerevisiaeandNeurosporra crassa), we show that IDRs render their host proteins more refoldable from the denatured state, allowing them to cohere more closely to Anfinsen’s thermodynamic hypothesis10, 11. The data provide an exceptionally clear picture of which biophysical and topological characteristics enable refoldability. Moreover, we find that almost all yeast proteins that partition into stress granules during heat shock are refoldable, a finding that holds for other condensates such as P-bodies and the nucleolus. Finally, we find that the Hsp104 unfoldase12is the principal actor in mediating disassembly of heat stress granules and that the efficiency with which condensed proteins are returned to the soluble phase is also well explained by refoldability. Hence, these studies establish spontaneous refoldability as an adaptive trait that endows proteins with the capacity to reform their native soluble structures following their extraction from condensates. Altogether, our results provide an intuitive model for the function of IDRs in many multidomain proteins and clarifies their relationship to the phenomenon of biomolecular condensation.