bluuebunny/crossref_metadata_2025_split huggingface dataset:
Glucocorticoid-glucocorticoid receptor-HCN1 channels reduce neuronal excitability in dorsal hippocampal CA1 neurons
Authors: Kim Jiwon , Lei Yun , Lu Xin-Yun , Kim Chung Sub 
Published: July 2022

AbstractWhile chronic stress increases hyperpolarization-activated current (Ih) in dorsal hippocampal CA1 neurons, the underlying molecular mechanisms are entirely unknown. Following chronic social defeat stress (CSDS), susceptible mice displayed social avoidance and impaired spatial working memory, which were linked to decreased neuronal excitability, increased perisomatic hyperpolarization-activated cyclic nucleotide-gated (HCN) 1 protein expression, and elevated Ih in dorsal but not ventral CA1 neurons. In control mice, bath application of corticosterone reduced neuronal excitability, increased tetratricopeptide repeat–containing Rab8b-interacting protein (TRIP8b) and HCN1 protein expression, and elevated Ih in dorsal but not ventral CA1 region/neurons. Corticosterone-induced upregulation of functional Ih was mediated by the glucocorticoid receptor (GR), HCN channels, and the protein kinase A (PKA) but not the calcium/calmodulin-dependent protein kinase II (CaMKII) pathway. Three months after the end of CSDS, susceptible mice displayed persistent social avoidance when exposed to a novel aggressor. The sustained behavioral deficit was associated with lower neuronal excitability and higher functional Ih in dorsal CA1 neurons, both of which were unaffected by corticosterone treatment. Our findings show that corticosterone treatment mimics the pathophysiological effects of dorsal CA1 neurons/region found in susceptible mice. The aberrant expression of HCN1 protein along the somatodendritic axis of the dorsal hippocampal CA1 region might be the molecular mechanism driving susceptibility to social avoidance.
Greater functional diversity and redundancy of coral endolithic microbiomes align with lower coral bleaching susceptibility
Authors: Cárdenas Anny , Raina Jean-Baptiste , Pogoreutz Claudia , Rädecker Nils , Bougoure Jeremy , Guagliardo Paul , Pernice Mathieu , Voolstra Christian R 
Published: July 2022

Abstract
The skeleton of reef-building coral harbors diverse microbial communities that could compensate for metabolic deficiencies caused by the loss of algal endosymbionts, i.e., coral bleaching. However, it is unknown to what extent endolith taxonomic diversity and functional potential might contribute to thermal resilience. Here we exposed Goniastrea edwardsi and Porites lutea, two common reef-building corals from the central Red Sea to a 17-day long heat stress. Using hyperspectral imaging, marker gene/metagenomic sequencing, and NanoSIMS, we characterized their endolithic microbiomes together with 15N and 13C assimilation of two skeletal compartments: the endolithic band directly below the coral tissue and the deep skeleton. The bleaching-resistant G. edwardsi was associated with endolithic microbiomes of greater functional diversity and redundancy that exhibited lower N and C assimilation than endoliths in the bleaching-sensitive P. lutea. We propose that the lower endolithic primary productivity in G. edwardsi can be attributed to the dominance of chemolithotrophs. Lower primary production within the skeleton may prevent unbalanced nutrient fluxes to coral tissues under heat stress, thereby preserving nutrient-limiting conditions characteristic of a stable coral-algal symbiosis. Our findings link coral endolithic microbiome structure and function to bleaching susceptibility, providing new avenues for understanding and eventually mitigating reef loss.
Autoregulation of H+/lactate efflux prevents monocarboxylate transport (MCT) inhibitors from reducing glycolytic lactic acid production
Authors: Blaszczak Wiktoria , Williams Hannah , Swietach Pawel 
Published: July 2022

Abstract
Background
Pharmacological inhibition of membrane transporters is expected to reduce the flow of solutes, unless flux is restored (i.e., autoregulated) through a compensatory increase in the transmembrane driving force. Drugs acting on monocarboxylate transporters (MCTs) have been developed to disrupt glycolytic metabolism, but autoregulation would render such interventions ineffective. We evaluated whether small-molecule MCT inhibitors reduce cellular H+/lactate production.

Methods
Cellular assays measured the relationship between MCT activity (expressed as membrane H+/lactate permeability; PHLac) and lactic acid production (inferred from H+ and lactate excretion; JHLac) in a panel of pancreatic ductal adenocarcinoma (PDAC) cells spanning a range of glycolytic phenotype.

Results
MCT activity did not correlate with lactic acid production, indicating that it is not set by membrane permeability properties. MCT inhibitors did not proportionately reduce JHLac because of a compensatory increase in the transmembrane [lactate] driving force. JHLac was largely insensitive to [lactate], therefore its cytoplasmic build-up upon MCT inhibition does not hinder glycolytic production. Extracellular acidity, an MCT inhibitor, reduced JHLac but this was via cytoplasmic acidification blocking glycolytic enzymes.

Conclusions
We provide mathematically verified evidence that pharmacological and physiological modulators of MCTs cannot proportionately reduce lactic acid production because of the stabilising effect of autoregulation on overall flux.
The EGFR-STYK1-FGF1 axis sustains functional drug tolerance to EGFR inhibitors in EGFR-mutant non-small cell lung cancer
Authors: Eggermont Carolien , Giron Philippe , Noeparast Maxim , Vandenplas Hugo , Aza-Blanc Pedro , Gutierrez Gustavo J. , De Grève Jacques 
Published: July 2022

AbstractNon-small cell lung cancer (NSCLC) patients harboring activating mutations in epidermal growth factor receptor (EGFR) are sensitive to therapy with EGFR tyrosine kinase inhibitors (TKI). Despite remarkable clinical responses using EGFR TKI, surviving drug tolerant cells serve as a reservoir from which drug resistant tumors may emerge. This study addresses the need for improved efficacy of EGFR TKI by identifying targets involved in functional drug tolerance against them. To this aim, a high-throughput siRNA kinome screen was performed using two EGFR TKI-sensitive EGFR-mutant NSCLC cell lines in the presence/absence of the second-generation EGFR TKI afatinib. From the screen, Serine/Threonine/Tyrosine Kinase 1 (STYK1) was identified as a target that when downregulated potentiates the effects of EGFR inhibition in vitro. We found that chemical inhibition of EGFR combined with the siRNA-mediated knockdown of STYK1 led to a significant decrease in cancer cell viability and anchorage-independent cell growth. Further, we show that STYK1 selectively interacts with mutant EGFR and that the interaction is disrupted upon EGFR inhibition. Finally, we identified fibroblast growth factor 1 (FGF1) as a downstream effector of STYK1 in NSCLC cells. Accordingly, downregulation of STYK1 counteracted the afatinib-induced upregulation of FGF1. Altogether, we unveil STYK1 as a valuable target to repress the pool of surviving drug tolerant cells arising upon EGFR inhibition. Co-targeting of EGFR and STYK1 could lead to a better overall outcome for NSCLC patients.
Cryo-EM structure of the human Kv3.1 channel reveals gating control by the cytoplasmic T1 domain
Authors: Chi Gamma , Liang Qiansheng , Sridhar Akshay , Cowgill John B. , Sader Kasim , Radjainia Mazdak , Qian Pu , Castro-Hartmann Pablo , Venkaya Shayla , Singh Nanki Kaur , McKinley Gavin , Fernandez-Cid Alejandra , Mukhopadhyay Shubhashish M. M. , Burgess-Brown Nicola A. , Delemotte Lucie , Covarrubias Manuel , Dürr Katharina L. 
Published: July 2022

AbstractKv3 channels have distinctive gating kinetics tailored for rapid repolarization in fast-spiking neurons. Malfunction of this process due to genetic variants in the KCNC1 gene causes severe epileptic disorders, yet the structural determinants for the unusual gating properties remain elusive. Here, we present cryo-electron microscopy structures of the human Kv3.1a channel, revealing a unique arrangement of the cytoplasmic tetramerization domain T1 which facilitates interactions with C-terminal axonal targeting motif and key components of the gating machinery. Additional interactions between S1/S2 linker and turret domain strengthen the interface between voltage sensor and pore domain. Supported by molecular dynamics simulations, electrophysiological and mutational analyses, we identify several residues in the S4/S5 linker which influence the gating kinetics and an electrostatic interaction between acidic residues in α6 of T1 and R449 in the pore-flanking S6T helices. These findings provide insights into gating control and disease mechanisms and may guide strategies for the design of pharmaceutical drugs targeting Kv3 channels.
Somatic cell fate maintenance in mouse fetal testes via autocrine/paracrine action of AMH and activin B
Authors: Rodriguez Karina F. , Brown Paula R. , Amato Ciro M. , Nicol Barbara , Liu Chia-Feng , Xu Xin , Yao Humphrey Hung-Chang 
Published: July 2022

AbstractFate determination and maintenance of fetal testes in most mammals occur cell autonomously as a result of the action of key transcription factors in Sertoli cells. However, the cases of freemartin, where an XX twin develops testis structures under the influence of an XY twin, imply that hormonal factor(s) from the XY embryo contribute to sex reversal of the XX twin. Here we show that in mouse XY embryos, Sertoli cell-derived anti-Mullerian hormone (AMH) and activin B together maintain Sertoli cell identity. Sertoli cells in the gonadal poles of XY embryos lacking both AMH and activin B transdifferentiate into their female counterpart granulosa cells, leading to ovotestis formation. The ovotestes remain to adulthood and produce both sperm and oocytes, although there are few of the former and the latter fail to mature. Finally, the ability of XY mice to masculinize ovaries is lost in the absence of these two factors. These results provide insight into fate maintenance of fetal testes through the action of putative freemartin factors.
SLITRK2 variants associated with neurodevelopmental disorders impair excitatory synaptic function and cognition in mice
Authors: El Chehadeh Salima , Han Kyung Ah , Kim Dongwook , Jang Gyubin , Bakhtiari Somayeh , Lim Dongseok , Kim Hee Young , Kim Jinhu , Kim Hyeonho , Wynn Julia , Chung Wendy K. , Vitiello Giuseppina , Cutcutache Ioana , Page Matthew , Gecz Jozef , Harper Kelly , Han Ah-reum , Kim Ho Min , Wessels Marja , Bayat Allan , Jaén Alberto Fernández , Selicorni Angelo , Maitz Silvia , de Brouwer Arjan P. M. , Silfhout Anneke Vulto-van , Armstrong Martin , Symonds Joseph , Küry Sébastien , Isidor Bertrand , Cogné Benjamin , Nizon Mathilde , Feger Claire , Muller Jean , Torti Erin , Grange Dorothy K. , Willems Marjolaine , Kruer Michael C. , Ko Jaewon , Piton Amélie , Um Ji Won 
Published: July 2022

AbstractSLITRK2 is a single-pass transmembrane protein expressed at postsynaptic neurons that regulates neurite outgrowth and excitatory synapse maintenance. In the present study, we report on rare variants (one nonsense and six missense variants) in SLITRK2 on the X chromosome identified by exome sequencing in individuals with neurodevelopmental disorders. Functional studies showed that some variants displayed impaired membrane transport and impaired excitatory synapse-promoting effects. Strikingly, these variations abolished the ability of SLITRK2 wild-type to reduce the levels of the receptor tyrosine kinase TrkB in neurons. Moreover, Slitrk2 conditional knockout mice exhibited impaired long-term memory and abnormal gait, recapitulating a subset of clinical features of patients with SLITRK2 variants. Furthermore, impaired excitatory synapse maintenance induced by hippocampal CA1-specific cKO of Slitrk2 caused abnormalities in spatial reference memory. Collectively, these data suggest that SLITRK2 is involved in X-linked neurodevelopmental disorders that are caused by perturbation of diverse facets of SLITRK2 function.
Hypoxia induces HIF1α-dependent epigenetic vulnerability in triple negative breast cancer to confer immune effector dysfunction and resistance to anti-PD-1 immunotherapy
Authors: Ma Shijun , Zhao Yue , Lee Wee Chyan , Ong Li-Teng , Lee Puay Leng , Jiang Zemin , Oguz Gokce , Niu Zhitong , Liu Min , Goh Jian Yuan , Wang Wenyu , Bustos Matias A. , Ehmsen Sidse , Ramasamy Adaikalavan , Hoon Dave S. B. , Ditzel Henrik J. , Tan Ern Yu , Chen Qingfeng , Yu Qiang 
Published: July 2022

AbstractThe hypoxic tumor microenvironment has been implicated in immune escape, but the underlying mechanism remains elusive. Using an in vitro culture system modeling human T cell dysfunction and exhaustion in triple-negative breast cancer (TNBC), we find that hypoxia suppresses immune effector gene expression, including in T and NK cells, resulting in immune effector cell dysfunction and resistance to immunotherapy. We demonstrate that hypoxia-induced factor 1α (HIF1α) interaction with HDAC1 and concurrent PRC2 dependency causes chromatin remolding resulting in epigenetic suppression of effector genes and subsequent immune dysfunction. Targeting HIF1α and the associated epigenetic machinery can reverse the immune effector dysfunction and overcome resistance to PD-1 blockade, as demonstrated both in vitro and in vivo using syngeneic and humanized mice models. These findings identify a HIF1α-mediated epigenetic mechanism in immune dysfunction and provide a potential strategy to overcome immune resistance in TNBC.
Spin-related symmetry breaking induced by half-disordered hybridization in BixEr2-xRu2O7 pyrochlores for acidic oxygen evolution
Authors: Zhou Gang , Wang Peifang , Hu Bin , Shen Xinyue , Liu Chongchong , Tao Weixiang , Huang Peilin , Liu Lizhe 
Published: July 2022

AbstractWhile acidic oxygen evolution reaction plays a critical role in electrochemical energy conversion devices, the sluggish reaction kinetics and poor stability in acidic electrolyte challenges materials development. Unlike traditional nano-structuring approaches, this work focuses on the structural symmetry breaking to rearrange spin electron occupation and optimize spin-dependent orbital interaction to alter charge transfer between catalysts and reactants. Herein, we propose an atomic half-disordering strategy in multistage-hybridized BixEr2-xRu2O7 pyrochlores to reconfigure orbital degeneracy and spin-related electron occupation. This strategy involves controlling the bonding interaction of Bi-6s lone pair electrons, in which partial atom rearrangement makes the active sites transform into asymmetric high-spin states from symmetric low-spin states. As a result, the half-disordered BixEr2-xRu2O7 pyrochlores demonstrate an overpotential of ~0.18 V at 10 mA cm−2 accompanied with excellent stability of 100 h in acidic electrolyte. Our findings not only provide a strategy for designing atom-disorder-related catalysts, but also provides a deeper understanding of the spin-related acidic oxygen evolution reaction kinetics.
The database of eye-movement measures on words in Chinese reading
Authors: Zhang Guangyao , Yao Panpan , Ma Guojie , Wang Jingwen , Zhou Junyi , Huang Linjieqiong , Xu Pingping , Chen Lijing , Chen Songlin , Gu Junjuan , Wei Wei , Cheng Xi , Hua Huimin , Liu Pingping , Lou Ya , Shen Wei , Bao Yaqian , Liu Jiayu , Lin Nan , Li Xingshan 
Published: July 2022

AbstractEye movements are one of the most fundamental behaviors during reading. A growing number of Chinese reading studies have used eye-tracking techniques in the last two decades. The accumulated data provide a rich resource that can reflect the complex cognitive mechanisms underlying Chinese reading. This article reports a database of eye-movement measures of words during Chinese sentence reading. The database contains nine eye-movement measures of 8,551 Chinese words obtained from 1,718 participants across 57 Chinese sentence reading experiments. All data were collected in the same experimental environment and from homogenous participants, using the same protocols and parameters. This database enables researchers to test their theoretical or computational hypotheses concerning Chinese reading efficiently using a large number of words. The database can also indicate the processing difficulty of Chinese words during text reading, thus providing a way to control or manipulate the difficulty level of Chinese texts.
Trustors’ disregard for trustees deciding quickly or slowly in three experiments with time constraints
Authors: Cabrales Antonio , Espín Antonio M. , Kujal Praveen , Rassenti Stephen 
Published: July 2022

AbstractMany decisions in the economic and social domain are made under time constraints, be it under time pressure or forced delay. Requiring individuals to decide quickly or slowly often elicit different responses. Time pressure has been associated with inefficiency in market settings and market regulation often requires individuals to delay their decisions via cooling-off periods. Yet, recent research suggests that people who make reflective decisions are met with distrust. If this extends toexternaltime constraints, then forcing individuals to delay their decisions may be counterproductive in scenarios where trust considerations are important, such as in market and organizational design. In three Trust Game experiments (total number of participants = 1872), including within- and between-subjects designs, we test whether individuals trust (more) someone who is forced to respond quickly (intuitively) or slowly (reflectively). We find that trustors do not adjust their behavior (or their beliefs) to the trustee’s time conditions. This seems to be an appropriate response because time constraints do not affect trustees’ behavior, at least when the game decisions are binary (trust vs. don’t trust; reciprocate vs. don’t reciprocate) and therefore mistakes cannot explain choices. Thus, delayed decisions per se do not seem to elicit distrust.
Free hand hitting of stone-like objects in wild gorillas
Authors: Masi Shelly , Pouydebat Emmanuelle , San-Galli Aurore , Meulman Ellen , Breuer Thomas , Reeves Jonathan , Tennie Claudio 
Published: July 2022

AbstractThe earliest stone tool types, sharp flakes knapped from stone cores, are assumed to have played a crucial role in human cognitive evolution. Flaked stone tools have been observed to be accidentally produced when wild monkeys use handheld stones as tools. Holding a stone core in hand and hitting it with another in the absence of flaking,free hand hitting,has been considered a requirement for producing sharp stone flakes by hitting stone on stone,free hand percussion. We report on five observations offree hand hittingbehavior in two wild western gorillas, using stone-like objects (pieces of termite mound). Gorillas are therefore the second non-human lineage primate showing free-hand hitting behavior in the wild, and ours is the first report for free hand hitting behavior in wild apes. This study helps to shed light on the morphofunctional and cognitive requirements for the emergence of stone tool production as it shows that a prerequisite for free hand percussion (namely, free hand hitting) is part of the spontaneous behavioral repertoire of one of humans’ closest relatives (gorillas). However, the ability to combine free hand hitting with the force, precision, and accuracy needed to facilitate conchoidal fracture in free hand percussion may still have been a critical watershed for hominin evolution.
Accurate image-based CSF volume calculation of the lateral ventricles
Authors: Yepes-Calderon Fernando , McComb J. Gordon 
Published: July 2022

AbstractThe size/volume of the brain’s ventricles is essential in diagnosing and treating many neurological disorders, with various forms of hydrocephalus being some of the most common. Initial ventricular size and changes, if any, in response to disease progression or therapeutic intervention are monitored by serial imaging methods. Significant variance in ventricular size is readily noted, but small incremental changes can be challenging to appreciate. We have previously reported using artificial intelligence to determine ventricular volume. The values obtained were compared with those calculated using the inaccurate manual segmentation as the “gold standard”. This document introduces a strategy to measure ventricular volumes where manual segmentation is not employed to validate the estimations. Instead, we created 3D printed models that mimic the lateral ventricles and measured those 3D models’ volume with a tuned water displacement device. The 3D models are placed in a gel and taken to the magnetic resonance scanner. Images extracted from the phantoms are fed to an artificial intelligence-based algorithm. The volumes yielded by the automation must equal those yielded by water displacement to assert validation. Then, we provide certified volumes for subjects in the age range (1–114) months old and two hydrocephalus patients.
Ultrafast optical control of surface and bulk magnetism in magnetic topological insulator/antiferromagnet heterostructure
Authors: Liu Peiwen , Eckberg Chris , Pan Lei , Zhang Peng , Wang Kang L. , Lüpke Gunter 
Published: July 2022

AbstractOptical control of the magnetic properties in topological insulator systems is an important step in applying these materials in ultrafast optoelectronic and spintronic schemes. In this work, we report the experimental observation of photo-induced magnetization dynamics in the magnetically doped topological insulator (MTI)/antiferromagnet (AFM) heterostructure composed of Cr-(Bi,Sb)2Te3/CrSb. Through proximity coupling to the AFM layer, the MTI displays a dramatically enhanced magnetism, with robust perpendicular magnetic anisotropy. When subjected to intense laser irradiation, both surface and bulk magnetism of the MTI are weakened by laser-induced heating of the lattice, however, at the surface, the deleterious heat effect is compensated by the strengthening of Dirac-hole-mediated exchange coupling as demonstrated by an unconventional pump-fluence-dependent exchange-bias effect. Through theoretical analyses, the sizes of exchange coupling energies are estimated in the MTI/AFM bilayer structure. The fundamentally different mechanisms supporting the surface and bulk magnetic order in MTIs allow a novel and distinctive photo-induced transient magnetic state with antiparallel spin configuration, which broadens the understanding of the magnetization dynamics of MTIs under ultrashort and intense optical excitation.