bluuebunny/crossref_metadata_2025 huggingface dataset:
Correlation between Balthazar CT grading, CECT necrosis volume, attenuation value, and prognosis of patients with acute necrotizing pancreatitis
Authors: Wang Bing , Xia Lu , Zhou Meng , Wang Jiuchen , Huang Shengfei , Xiang Haibo , Huang Zhihua
Published: May 2024

To analyze the correlation between Balthazar CT grading and contrast-enhanced CT necrosis volume and attenuation value and prognosis of patients with acute necrotizing pancreatitis. Ninety-two patients with acute necrotizing pancreatitis who were treated in the hospital were selected between June 2019 and June 2021, and they were divided into the poor prognosis group and the good prognosis group according to the clinical prognosis at 6 months of follow-up. Balthazar CT, contrast-enhanced CT necrosis volume, and attenuation value were compared between the 2 groups. Multivariate logistic regression analysis was used to analyze the influencing factors. Receiver operating characteristic curve was adopted to analyze the predictive value. Among the 92 participants, there were 28 cases with good prognosis (30.43%) and 64 cases with poor prognosis (69.57%). The Acute Physiology and Chronic Health Evaluation II score, C-reactive protein, urea nitrogen, Balthazar CT, necrotic volume, and average attenuation value of the poor prognosis group were significantly higher than those of the good prognosis group (all P values <.05). The results of the multivariate logistic analysis showed that Balthazar CT grade, necrotic volume, and average attenuation value were independent risk factors for poor prognosis in patients with acute necrotizing pancreatitis (all P values <.05). The area under the curve of Balthazar CT grade, necrotic volume, average attenuation value, and the joint detection in predicting the prognosis of patients with acute necrotizing pancreatitis were 0.765, 0.624, 0.764, and 0.861, respectively. The Balthazar CT grading, necrosis volume, and average attenuation value are significantly higher among patients with acute necrotizing pancreatitis complicated with poor prognosis, and they are also independent risk factors for poor prognosis in patients with acute necrotizing pancreatitis, and can help clinically predict the prognosis of patients with acute necrotizing pancreatitis, and the combined detection has better application effects.
Effect of holographic Guasha on sleep quality of older adults with hypertension in the community: A prospective study
Authors: Chen Ling , Li Ruilin , Yang Lianzhao , Gao Hui , Li Wen , Wei Yujuan , Pang Lingling
Published: May 2024

To explore the effect of holographic Guasha therapy on the Pittsburg Sleep Quality Index (PSQI) and Hamilton Anxiety Rating Scale (HAMA) in older adults with hypertension living in the community. This prospective study was conducted from July 2019 to December 2020. Older adults with hypertension (systolic pressure ≥ 140 mm Hg, diastolic pressure ≥ 90 mm Hg) were divided into the control and Guasha groups. The PSQI and HAMA were assessed before and after 4 weeks of intervention. 62 patients were enrolled, with 31/group (Guasha: 72.4 ± 6.9 years, 23.0 ± 3.1 kg/m2; control: 71.4 ± 6.3 years; 22.9 ± 2.9 kg/m2). The total PSQI score did not decrease in the control group after 4 weeks (from 14.8 ± 1.2 to 14.8 ± 1.8, P = .498) but decreased in the Guasha group (from 14.9 ± 1.1 to 6.8 ± 3.5, P < .001). All PSQI subscores decreased in the Guasha group after 4 weeks of Guasha intervention (all P < .05), except for the use of sleep medication, since the use of such drugs was an exclusion criterion. The HAMA index scores did not change in the control or Guasha group (both P > .05). Holographic Guasha appears to achieve better sleep outcomes than conventional treatment in improving the sleep quality of older adults with hypertension living in the community. The participants were not randomly assigned to the treatments, and the results should be confirmed in a formal trial.
Physical Pain Among Urban Native American Emerging Adults: Sociocultural Risk and Protective Factors
Authors: Saba Shaddy K. , Rodriguez Anthony , Dickerson Daniel L. , Mike Lynette , Schweigman Kurt , Arvizu-Sanchez Virginia , Funmaker George , Johnson Carrie L. , Brown Ryan A. , Malika Nipher , D’Amico Elizabeth J.
Published: May 2024

Objective

American Indian/Alaska Native (AI/AN) people have high rates of physical pain. Pain is understudied in urban-dwelling, AI/AN emerging adults, a group with unique sociocultural risk and protective factors. We explore associations between socioeconomic disadvantage, additional sociocultural factors, and pain among urban AI/AN emerging adults.

Methods

AI/AN participants aged 18–25 years (N = 417) were recruited via social media. Regression models tested associations between socioeconomic disadvantage (income and ability to afford health care) and pain as well as additional sociocultural factors (discrimination, historical loss, cultural pride and belonging, visiting tribal lands) and pain. Multigroup regression models tested whether associations between sociocultural factors and pain differed between participants who were socioeconomically disadvantaged and those who were less disadvantaged.

Results

In the full sample, lower income (b = 1.00–1.48, p < .05), inability to afford health care (b = 1.00, p = .011), discrimination (b = 0.12, p = .001), and historical loss (b = 0.24, p = .006) were positively associated with pain, whereas visiting tribal lands was negatively associated with pain (b = −0.86 to −0.42, p < .05). In the multigroup model, visiting tribal lands 31+ days was negatively associated with pain only among the less socioeconomically disadvantaged group (b = −1.48, p < .001).

Conclusions

Socioeconomic disadvantage may, in part, drive pain disparities among AI/AN emerging adults and act as a barrier to benefitting from visiting tribal lands. Results support a biopsychosocial approach to targeting pain in this population, including addressing socioeconomic challenges and developing culturally informed, strengths-based interventions.
Deinococcus arenicola sp. nov., a novel radiation-resistant bacterium isolated from sandy soil in Antarctica
Authors: Cheng Li , Mu Hongmei , Zhang Xinyu , Jiang Peiqiang , Liu Lukuan , Li Jing
Published: May 2024

A Gram-stain-positive, aerobic, non-mobile and spherical strain, designated ZS9-10T, belonging to the genus Deinococcus was isolated from soil sampled at the Chinese Zhong Shan Station, Antarctica. Growth was observed in the presence of 0–4 % (w/v) NaCl, at pH 7.0–8.0 and at 4–25 °C. Phylogenetic analysis based on 16S rRNA gene sequences showed that strain ZS9-10T formed a lineage in the genus Deinococcus. It exhibited highest sequence similarity (97.4 %) to Deinococcus marmoris DSM 12784T. The major phospholipids of ZS9-10T were unidentified phosphoglycolipid, unidentified glycolipids and unidentified lipids. The major fatty acids were summed feature 3 (C16 : 1
 ω7c and/or C16 : 1
 ω6c), C16 : 0 and C16 : 1
 ω7c. MK-8 was the predominant respiratory quinone. The digital DNA–DNA hybridization and average nucleotide identity values between strain ZS9-10T and its close relative D. marmoris DSM 12784T were 27.4 and 83.9 %, respectively. Based on phenotypic, phylogenetic and genotypic data, a novel species, named Deinococcus arenicola sp. nov., is proposed. The type strain iis ZS9-10T (=CCTCC AB 2019392T=KCTC43192T).
Genetic regulation of lncRNA expression in the whole human brain
Authors: He Yijie , Tang Yaqin , Tan Pengcheng , Huang Dongyu , Wang Yongheng , Wen Tong , Huang Lin , Wang Jia , Shao Lizhen , Cai Qinyu , Li Zhimou , Wang Yueyang , Liu Taihang , Han Zhijie
Published: May 2024

Long non-coding RNAs (lncRNAs) play a key role in the human brain, and genetic variants regulate their expression. Herein, the expression quantitative trait loci (eQTL) of lncRNAs encompassing ten brain regions from 134 individuals was analyzed, and novel variants influencing lncRNA expression (eSNPs) and the respective affected lncRNAs (elncRNAs) were identified. The eSNPs are proximate to their corresponding elncRNAs, enriched in the non-coding genome, and have a high minor allele frequency. The elncRNAs exhibit a high-level and complex pattern of expression. The genetic regulation is more tissue-specific for lncRNAs than for protein-coding genes, with notable differences between cerebrum and cerebellum. However, it shows relatively similar patterns across the cortex regions. Furthermore, we observed a significant enrichment of eSNPs among variants associated with neurological disorders, especially insomnia, and identified insomnia-related lncRNAs involved in immune response functions. Moreover, the present study offers an improved tool for lncRNA quantification, a novel approach for lncRNA function analysis, and a database of lncRNA expression regulation in the human brain. These findings and resources will advance the research on non-coding gene expression regulation in neuroscience.
Cell Maps for Artificial Intelligence: AI-Ready Maps of Human Cell Architecture from Disease-Relevant Cell Lines
Authors: Clark Timothy , Mohan Jillian , Schaffer Leah , Obernier Kirsten , Al Manir Sadnan , Churas Christopher P , Dailamy Amir , Doctor Yesh , Forget Antoine , Hansen Jan Niklas , Hu Mengzhou , Lenkiewicz Joanna , Levinson Maxwell Adam , Marquez Charlotte , Nourreddine Sami , Niestroy Justin , Pratt Dexter , Qian Gege , Thaker Swathi , Bélisle-Pipon Jean-Christophe , Brandt Cynthia , Chen Jake , Ding Ying , Fodeh Samah , Krogan Nevan , Lundberg Emma , Mali Prashant , Payne-Foster Pamela , Ratcliffe Sarah , Ravitsky Vardit , Sali Andrej , Schulz Wade , Ideker Trey
Published: May 2024

This article describes the Cell Maps for Artificial Intelligence (CM4AI) project and its goals, methods, standards, current datasets, software tools, status, and future directions. CM4AI is theFunctional Genomics Data Generation Projectin the U.S. National Institute of Health’s (NIH)Bridge2AIprogram. Its overarching mission is to produce ethical, AI-ready datasets of cell architecture, inferred from multimodal data collected for human cell lines, to enable transformative biomedical AI research.
SMC-mediated dosage compensation inC. elegansevolved in the presence of an ancestral nematode mechanism
Authors: Aharonoff Avrami , Kim Jun , Washington Aaliyah , Ercan Sevinç
Published: May 2024

Mechanisms of X chromosome dosage compensation have been studied extensively in a few model species representing clades of shared sex chromosome ancestry. However, the diversity within each clade as a function of sex chromosome evolution is largely unknown. Here, we anchor ourselves to the nematodeCaenorhabditis elegans, for which a well-studied mechanism of dosage compensation occurs through a specialized structural maintenance of chromosomes (SMC) complex, and explore the diversity of dosage compensation in the surrounding phylogeny of nematodes. Through phylogenetic analysis of theC. elegans dosage compensation complex and a survey of its epigenetic signatures, including X-specific topologically associating domains (TADs) and X-enrichment of H4K20me1, we found that the condensin-mediated mechanism evolved recently in the lineage leading toCaenorhabditisthrough an SMC-4 duplication. Intriguingly, an independent duplication of SMC-4 and the presence of X-specific TADs inPristionchus pacificussuggest that condensin-mediated dosage compensation arose more than once. mRNA-seq analyses of gene expression in several nematode species indicate that dosage compensation itself is ancestral, as expected from the ancient XO sex determination system. Indicative of the ancestral mechanism, H4K20me1 is enriched on the X chromosomes inOscheius tipulae, which does not contain X-specific TADs or SMC-4 paralogs. Together, our results indicate that the dosage compensation system inC. elegansis surprisingly new, and condensin may have been co-opted repeatedly in nematodes, suggesting that the process of evolving a chromosome-wide gene regulatory mechanism for dosage compensation is constrained.

Significance statement

X chromosome dosage compensation mechanisms evolved in response to Y chromosome degeneration during sex chromosome evolution. However, establishment of dosage compensation is not an endpoint. As sex chromosomes change, dosage compensation strategies may have also changed. In this study, we performed phylogenetic and epigenomic analyses surroundingCaenorhabditis elegansand found that the condensin-mediated dosage compensation mechanism inC. elegansis surprisingly new, and has evolved in the presence of an ancestral mechanism. Intriguingly, condensin-based dosage compensation may have evolved more than once in the nematode lineage, the other time inPristionchus. Together, our work highlights a previously unappreciated diversity of dosage compensation mechanisms within a clade, and suggests constraints in evolving new mechanisms in the presence of an existing one.
Discovery of novel RNA viruses in commercially relevant seaweedsAlaria esculentaandSaccharina latissima
Authors: Dekker Rob J. , de Leeuw Wim C. , van Olst Marina , Ensink Wim A. , van Leeuwen Selina , Cohen Job , Timmermans Klaas R. , Breit Timo M. , Jonker Martijs J.
Published: May 2024

Seaweeds are increasingly recognized as sustainable food sources; however, their large-scale cultivation faces challenges similar to land crops, including susceptibility to pathogens. Plant viruses pose a significant threat to global food security, yet little is known about the diversity of viruses in seaweeds. This study investigates virus-associated small interfering RNA (siRNA) responses in commercially relevant seaweed species to understand RNA virus diversity, particularly in edible varieties. Through small RNA sequencing of 16 samples fromSaccharina latissimaandAlaria esculenta, we identified three new RNA viruses Aev-NL1, Slv-NL2 and Slv-NL3, and one new DNA virus (phaeovirus). The partial genome of the new DNA virus was discovered in theA. esculentasamples and shared 67% DNA sequence identity with the major coat protein of the large double-stranded DNA phaeovirusFeldmannia irregularisvirus a. In four out of fiveA. esculentasamples, a new bisegmented ormycovirus-like RNA virus (Aev-NL1) was identified. A similar new virus, Slv-NL1, was found in previously publishedS. latissimaRNA-seq data, sharing 87% sequence identity with Aev-NL1. Lastly, two novel RNA viruses, Slv-NL2 and Slv-NL3, were discovered in all eightS. latissimasamples sharing limited similarity at the genome level but high sequence identity at protein level of both ORFs (>94%). Further investigation of the novel viruses’ presence across our limited set of samples revealed no conclusive associations with diseased seaweed phenotypes. The discovery of four new viruses in only a limited set of samples highlights the presence of previously unrecognized viral diversity in seaweed, thereby underscoring the importance of understanding viral diversity in seaweed as its virome is currently understudied.
Regulation of dopamine release by tonic activity patterns in the striatal brain slice
Authors: Boumhaouad Siham , Makowicz Emily A , Choi Sejoon , Bouhaddou Nezha , Balla Jihane , Taghzouti Khalid , Sulzer David , Mosharov Eugene V.
Published: May 2024

Voluntary movement, motivation, and reinforcement learning depend on the activity of ventral midbrain neurons that extend axons to release dopamine (DA) in the striatum. These neurons exhibit two patterns of action potential activity: a low-frequency tonic activity that is intrinsically generated and superimposed high-frequency phasic bursts that are driven by synaptic inputs.Ex vivoacute striatal brain preparations are widely employed to study the regulation of evoked DA release but exhibit very different DA release kinetics thanin vivorecordings. To investigate the relationship between phasic and tonic neuronal activity, we stimulated the slice in patterns intended to mimic tonic activity, which were interrupted by a series of burst stimuli. Conditioning the striatal slice with low-frequency activity altered DA release triggered by high-frequency bursts and produced kinetic parameters that resemble thosein vivo. In the absence of applied tonic activity, nicotinic acetylcholine receptor and D2 dopamine receptor antagonists had no significant effect on neurotransmitter release driven by repeated burst activity in the striatal brain slice. In contrast, in tonically stimulated slices, D2 receptor blockade decreased the amount of DA released during a single burst and facilitated DA release in subsequent bursts. This experimental system provides a means to reconcile the difference in the kinetics of DA releaseex vivoandin vivoand provides a novel approach to more accurately emulate pre- and post-synaptic mechanisms that control axonal DA releasein vivo.

Abstract Figure
Anin vivo“turning model” reveals new RanBP9 interactions in lung macrophages
Authors: Kajimura Yasuko , Tessari Anna , Orlacchio Arturo , Thoms Alexandra , Cufaro Maria Concetta , Marco Federica Di , Amari Foued , Chen Min , Soliman Shimaa H.A. , Rizzotto Lara , Zhang Liwen , Amann Joseph , Carbone David P. , Ahmed Amer , Fiermonte Giuseppe , Freitas Mike , Lodi Alessia , Boccio Piero Del , Palmieri Dario , Coppola Vincenzo
Published: May 2024

The biological functions of the scaffold protein Ran Binding Protein 9 (RanBP9) remain elusive in macrophages or any other cell type where this protein is expressed together with its CTLH (C-terminal to LisH) complex partners. We have engineered a new mouse model, named RanBP9-TurnX, where RanBP9 fused to three copies of the HA tag (RanBP9-3xHA) can be turned into RanBP9-V5 tagged upon Cre-mediated recombination. We created this model to enable stringent biochemical studies at cell type specific level throughout the entire organism. Here, we have used this tool crossed with LysM-Cre transgenic mice to identify RanBP9 interactions in lung macrophages. We show that RanBP9-V5 and RanBP9-3xHA can be both co-immunoprecipitated with the known members of the CTLH complex from the same whole lung lysates. However, more than ninety percent of the proteins pulled down by RanBP9-V5 differ from those pulled-down by RanBP9-HA. The lung RanBP9-V5 associated proteome includes previously unknown interactions with macrophage-specific proteins as well as with players of the innate immune response, DNA damage response, metabolism, and mitochondrial function. This work provides the first lung specific RanBP9-associated interactome in physiological conditions and reveals that RanBP9 and the CTLH complex could be key regulators of macrophage bioenergetics and immune functions.
Detection of Nontoxic BoNT/A Levels in Post-Facial Botox Injection Breastmilk using a Multi-technique Approach
Authors: Gu Helene , Xu Zhenyu , Koviazina Renata , Tan Pengcheng , Zheng Changcheng , Kappes Ferdinand , Kotsifaki Domna G. , Shen Fangrong , Tsigkou Anastasia
Published: May 2024

Background

The use of cosmetic Botox (Botulinum Neurotoxin Type A, BoNT/A ) has become increasingly prevalent. Particularly after pregnancy, postpartum depression represents one major factor motivating women to use Botox even during the lactation and breastfeeding period. Currently, there is limited understanding of the impact of Botox on lactation and the potential of its active component passing into breastmilk and affecting the infant.

Methods

Breastmilk samples were acquired from five women aged between 28 - 45 through a clinic in Suzhou, Jiangsu, P.R. China. Three sample sets ranged from 1 hour to 1 year after facial Botox treatments (64 U), whereas the remaining two sample sets were from women who never received Botox treatment. BoNT/A concentrations in samples were detected using standard Enzyme-Linked Immunosorbent Assay (ELISA), unreduced and reduced Western Blotting, confocal micro-Raman Spectroscopy, and Mass Spectrometry(LC-MS).

Findings

From ELISA, breastmilk BoNT/A concentrations peaked at 33.4 pg/mL 4 days after Botox injection. BoNT/A concentrations were highest overall in the first week and around two months after injection. While non-reducing polyacrylamide gel electrophoresis (PAGE) showed a protein band of 150 kDa peaking at 48 hours, reduced SDS-PAGE detected a 100 kDa protein first peaking at 72 hours, then re-emerging after 7 days, respectively, and in line with previous observations by others. Interestingly, micro-Raman spectroscopy indicated additional Raman peaks at 6 hours and 48 hours that were not present in other breastmilk samples which were evaluated in this study. However, no clear indication of BoNT/A was detected in Mass Spectrometry (LC-MS).

Interpretation

The amount of BoNT/A in breastmilk peaks around 48 hours, and at 2 months after facial injection. Even over a year after injection, BoNT/A can be detected. However, all quantities of BoNT/A detected in this study are highly likely to be safe for infants. Additionally, our study suggests that alternative methods, besides ELISA, may be utilized for the rapid detection of low concentrations of BoNT/A in body fluid samples.

Funding

Duke Kunshan University Start-Up funds, Duke Kunshan University Undergraduate Studies Signature Work Research Grant, Synear and Wang-Cai Biochemistry grants, and Kunshan Municipal Government research funding.

Graphical Abstract

Highlights

BoNT/A was detected in the breastmilk of 3 women after facial Botox injections of 64 U.

Toxin levels peaked in the first week and at around 2 months after injection.

All detected levels (up to 33.40 pg/mL) were significantly below the lethal dose for newborns.
Laboratory tests for influenza and the respiratory syncytial virus may be used as a proxy for associated hospitalizations in Canada
Authors: Champredon David
Published: May 2024

In Canada, the national number of hospital admissions associated with influenza and respiratory syncytial virus (RSV) is usually available about three months after admission. This delay hampers real-time analysis involving hospitalization data, like, for example, epidemic forecasting. Here, using a mixed-effects model on 15 years of data covering about 70% of the Canadian population, we show that these hospitalizations can be approximated using the number of laboratory tests positive for influenza A and RSV, a data stream publicly reported much more rapidly, about two weeks after symptoms onset.
Clostridioides difficilebinary toxin CDT induces biofilm-like persisting microcolonies
Authors: Meza Torres Jazmin , Tinevez Jean-Yves , Crozouls Aline , Mary Héloïse , Kim Minhee , Hunault Lise , Chamorro-Rodriguez Susan , Lejal Emilie , Altamirano-Silva Pamela , Gobaa Samy , Peltier Johann , Chassaing Benoit , Dupuy Bruno
Published: May 2024

Clinical symptoms ofClostridioides difficileinfection (CDI) range from diarrhea to pseudomembranous colitis. A major challenge in managing CDI is the high rate of relapse. Several studies correlate production of CDT binary toxin by clinical strains ofClostridioides difficilewith higher relapse rates. Although the mechanism of action of CDT on host cells is known, its exact contribution to CDI is still unclear. To understand the physiological role of CDT during CDI, we established two hypoxic relevant intestinal models, Transwell and Microfluidic Intestine-on-Chip systems. Both were challenged with the epidemic strain UK1 CDT+and its isogenic CDT-mutant. We report that CDT binary toxin induces mucin-associated microcolonies that increaseC. difficilecolonization and display biofilm-like properties by enhancingC. difficileresistance to vancomycin but not to fidaxomicin, a biofilm disrupting antibiotic. Importantly, biofilm- like CDT-dependent microcolonies were also observed in the caecum and colon of infected mice. Hence, our study shows that CDT toxin induces biofilm-like microcolonies, increasingC. difficilecolonization and persistence.
SH3BP2 regulates the organization of the neuromuscular synapses through protein-driven phase separation
Authors: Pradhan Bhola Shankar , Bernadzki Krzysztof , Bandaruk Yauhen , Siudzińska Anna , De Cicco Teresa , Gawor Marta , Krzemień Joanna , Chodaczek Grzegorz , Hashemolhosseini Said , Prószyński Tomasz J.
Published: May 2024

The molecular mechanisms underlying the development and maintenance of the neuromuscular junction are poorly understood, even though the malfunction of these specialized synapses is associated with severe genetic and autoimmune disorders. The identity of factors controlling the maintenance mechanisms of postsynaptic acetylcholine receptors (AChR) in high-density has been elusive and is of great interest to the pharma industry, searching for possible new targets for disease interventions. Here, we report the identification of a scaffold protein SH3BP2, which exhibits polyvalent interaction with the dystrophin-glycoprotein complex (DGC) and AChR pentamers, promoting AChR clustering through phase separation. Muscle-specific SH3BP2 deletion in mice leads to impaired organization of the neuromuscular synapses, defects in synaptic transmission, and reduced muscle strength. Our studies identified a novel regulator of the postsynaptic machinery involved in clustering AChR and linking it to the DGC.
Multifaceted confidence in exploratory choice
Authors: Solopchuk Oleg , Dayan Peter
Published: May 2024

Our choices are typically accompanied by a feeling of confidence - an internal estimate that they are correct. Correctness, however, depends on our goals. For example, exploration-exploitation problems entail a tension between short- and long-term goals: finding out about the value of one option could mean foregoing another option that is apparently more rewarding. Here, we hypothesised that after making an exploratory choice that involves sacrificing an immediate gain, subjects will be confident that they chose a better option for long-term rewards, but not confident that it was a better option for immediate reward. We asked 250 subjects across 2 experiments to perform a varying-horizon two-arm bandits task, in which we asked them to rate their confidence that their choice would lead to more immediate, or more total reward. Confirming previous studies, we found a significant increase in exploration with increasing trial horizon, but, contrary to our predictions, we found no difference between confidence in immediate or total reward. This dissociation is further evidence for a separation in the mechanisms involved in choices and confidence judgements.
Meta-Control Demands at the Beginning of Extended Tasks are Categorically Different from Control Demands During Their Subsequent Execution
Authors: Akgur Berhan F. , Gezici Tamer , Oymagil Elif , Farooqui Ausaf A.
Published: May 2024

The well-known activation of frontoparietal regions forms the basis of neuroscientific accounts of cognitive control. Control interventions that activate frontoparietal regions also generate a characteristic psychophysiological signature that, amongst others, is accompanied by increased pupil size. Here, we characterize a distinct but key aspect of cognitive control that deactivates these frontoparietal regions and decreases pupil size.

Our goals are completed through extended tasks that are hierarchically controlled and executed as a single entity despite consisting of numerous steps (e.g., ‘preparing coffee’, ‘writing emails’). This is achieved through higher-level programs instantiated at the beginning of their execution that will go on to organize cognition and instantiate various control interventions during the ensuing task execution.

Difficult episodes begin with the instantiation of more complex higher-level programs that will go on to organize a more complex set of control interventions. However, the demands related to instantiating these more complex programs are likely to be distinct from those related to control interventions. Control interventions, like selective attention, inhibition, etc., involve making goal-directed changes in sensory and motor regions to select the correct incoming information and action. In contrast, instantiating higher-level programs involves embodying the set of commands that will go on to make the relevant goal-directed neurocognitive changes later in the ensuing extended task by organizing and instantiating the correct set of control interventions.

Across four experiments, we show that while executing difficult episodes activates frontoparietal regions and increases pupil size, the beginning of these difficult episodes, i.e., junctures where more complex higher-level programs are instantiated, deactivates these same frontoparietal regions and decreases pupil size. We thus show that cognitive control related to difficult extended tasks involves categorically different demands at the beginning compared to during their subsequent execution.
Altered striosome-matrix distribution and activity of striatal cholinergic interneurons in a model of autism-linked repetitive behaviors
Authors: Molitor Jordan , Graniou Juliette , Salin Pascal , Castets Francis , Fatmi Ahmed , Kerkerian-Le Goff Lydia , Fasano Laurent , Caubit Xavier , Gubellini Paolo
Published: May 2024

Repetitive behaviors are cardinal features of many brain disorders, including autism spectrum disorder (ASD). We previously associated dysfunction of striatal cholinergic interneurons (SCINs) with repetitive behaviors in a mouse model based on conditional deletion of the ASD-related geneTshz3in cholinergic neurons (Chat-cKO). Here, we provide evidence linking SCIN abnormalities to the unique organization of the striatum into striosome and matrix compartments, whose imbalances are implicated in several pathological conditions.Chat-cKOmice exhibit altered relationship between the embryonic birthdate of SCINs and their adult striosome-matrix distribution, leading to an increased proportion of striosomal SCINs. In addition, the ratio of striosomal SCINs with slow-irregularvs. sustained-regular firing is increased, which translates into decreased activity, further stressing the striosome-matrix imbalance. These findings provide novel insights onto the pathogenesis of ASD-related stereotyped behaviors by pointing to abnormal developmental compartmentalization and activity of SCINs as a substrate.
Navigating directed evolution efficiently: optimizing selection conditions and selection output analysis
Authors: Handal-Marquez Paola , Nguyen Hoai , Pinheiro Vitor B.
Published: May 2024

Directed evolution is a powerful tool that can bypass gaps in our understanding of the sequence-function relationship of proteins and still isolate variants with desired activities, properties, and substrate specificities. The rise of directed evolution platforms for polymerase engineering has accelerated the isolation of xenobiotic nucleic acids (XNAs) synthetases and reverse transcriptases (RTs) capable of processing a wide array of unnatural XNAs which have numerous therapeutic and biotechnological applications. Still, the current generation of XNA polymerases functions with significantly lower efficiency than the natural counterparts and retains a significant level of DNA polymerase activity which limits theirin vivoapplications. Although directed evolution approaches are continuously being developed and implemented to improve XNA polymerase engineering, the field lacks an in-depth analysis of the effect of selection parameters, library construction biases and sampling biases. Focusing on the directed evolution pipeline for DNA and XNA polymerase engineering, this work sets out a method for understanding the impact of selection conditions on selection success and efficiency. We also explore the influence of selection conditions on fidelity at the population and individual mutant level. Additionally, we explore the sequencing coverage requirements in directed evolution experiments, which differ from genome assembly and other-omicsapproaches. This analysis allowed us to identify the sequencing coverage threshold for the accurate and precise identification of significantly enriched mutants. Overall, this study introduces a robust methodology for optimizing selection protocols, which effectively streamlines selection processes by employing small libraries and cost-effective NGS sequencing. It provides valuable insights into critical considerations, thereby enhancing the overall effectiveness and efficiency of directed evolution strategies applicable to enzymes other than the ones considered here.
PotentialL-asparaginaseproducingE.colisources among River water and cafeteria sewage: The case of Wabe River and Wolkite University students’ cafeteria in Wolkite, Ethiopia
Authors: Tufa Kajelcha Fikadu , Mosisa Senbeto Beri , FikaduTufa Aklilu , Beriso Admas Berhanu
Published: May 2024

L-asparaginaseis a promising enzyme for cancer treatment and is found in plants, animals and microbes. This enzyme is of great medical and industrial importance. It is used with inside the remedy of acute lymphoblastic leukemia and helps in reducing the acryl amide substances found in fried and baked foods. Its source varies from bacteria to yeast and fungi. This study aimed to screen the potentialL-asparaginaseproducing E. coli isolates among river water and cafeteria sewage samples near the Gubryie area, SNNPR-Ethiopia. In this study,E. coliisolates were isolated from sewage from the Wabe River and Wolkite University student cafeteria. During the study, 14 isolates, 11 from cafeteria sewage and 3 from Wabe River, were confirmed to beE. coliusing IMViC, TSI, SCA, and Gram tests. For theE. coli-positive samples, screening ofL-asparaginasewas performed using the phenol red indicator. The change in color from yellow to pink in M9 media due to the acidic environment created whenL-asparaginewas degraded to urea indicates the presence ofL-asparginasein the potentE. colicells. The production ofL-asparaginasewas carried out using submerged fermentation method. Mechanical cell disruption method, high speed centrifugation, was used to separate the secreted enzyme from cells. The potential of theE. colicells to produceL-asparginasewas also checked using a rapid plate assay method with the indicator dye phenol red. The zone of inhibition for the intracellular enzyme activity ranges from 16.5 mm up to 22.25 mm while that of extracellular enzyme ranged from 7.5 mm up to 9 mm. The commonly used software system is SPSS version 23. The PCR result depicted that theansAgene presence was confirmed in 50% of the isolates. The result confirmed that theE.coliisolates from sewage showed betterL-asparaginaseproduction potency than the Wabe River isolates. This study indicated thatE. colistrains are promising sources ofL-Asparginasefor food and pharmacological companies if the scale-up of this work has been completed in the future.
Continuous and discrete decoding of overt speech with electroencephalography
Authors: Craik Alexander , Dial Heather , Contreras-Vidal Jose Luis
Published: May 2024

Neurological disorders affecting speech production adversely impact quality of life for over 7 million individuals in the US. Traditional speech interfaces like eye-tracking devices and P300 spellers are slow and unnatural for these patients. An alternative solution, speech Brain-Computer Interfaces (BCIs), directly decodes speech characteristics, offering a more natural communication mechanism. This research explores the feasibility of decoding speech features using non-invasive EEG. Nine neurologically intact participants were equipped with a 63-channel EEG system with additional sensors to eliminate eye artifacts. Participants read aloud sentences displayed on a screen selected for phonetic similarity to the English language. Deep learning models, including Convolutional Neural Networks and Recurrent Neural Networks with/without attention modules, were optimized with a focus on minimizing trainable parameters and utilizing small input window sizes. These models were employed for discrete and continuous speech decoding tasks, achieving above-chance participant-independent decoding performance for discrete classes and continuous characteristics of the produced audio signal. A frequency sub-band analysis highlighted the significance of certain frequency bands (delta, theta, and gamma) for decoding performance, and a perturbation analysis identified crucial channels. Assessed channel selection methods did not significantly improve performance, but they still outperformed chance levels, suggesting a distributed representation of speech information encoded in the EEG signals. Leave-One-Out training demonstrated the feasibility of utilizing common speech neural correlates, reducing data collection requirements from individual participants.
Endogenous ZAP is associated with altered Zika virus infection phenotype
Authors: Le Nguyen Phuong Khanh , Singh Prince Pal , Sabir Ahmad Jawad , Trus Ivan , Karniychuk Uladzimir
Published: May 2024

The zinc finger antiviral protein 1 (ZAP) has broad antiviral activity. ZAP is an interferon (IFN)-stimulated gene, which itself may enhance type I IFN antiviral response. In a previous study, Zika virus was identified as ZAP-resistant and not sensitive to ZAP antiviral activity. Here, we found that ZAP was associated with the inhibition of Zika virus in Vero cells, in the absence of a robust type I IFN system because Vero cells are deficient for IFN-alpha and -beta. Also, quantitative RNA-seq data indicated that endogenous ZAP is associated with altered global gene expression both in the steady state and during Zika virus infection. Further studies are warranted to elucidate this IFN-alpha and -beta independent anti-Zika virus activity and involvement of ZAP.
Automated inference of disease mechanisms in patient-hiPSC-derived neuronal networks
Authors: Doorn Nina , van Putten Michel J.A.M. , Frega Monica
Published: May 2024

Human induced pluripotent stem cells (hiPSCs)-derived neurons offer a valuable platform for studying neurological disorders in a patient-specific manner. These neurons can be rapidly differentiated into excitatory neuronal networks, whose activity is measurable using multi-electrode arrays (MEAs). Neuronal networks derived from patients exhibit distinct characteristics, reflecting underlying pathological molecular mechanisms. However, elucidating these mechanisms traditionally requires extensive and hypothesis-driven additional experiments. Computational models can link observable network activity to underlying molecular mechanisms by identifying biophysical model parameters that simulate the activity, but this identification process is challenging. Here, we address this challenge by using simulation-based inference (SBI), a machine-learning approach, to automatically identify the full range of model parameters able to explain the patient-derived MEA activity.

Our study demonstrates that SBI can accurately identify ground-truth parameters in simulated data, and successfully estimate the parameters that replicate the network activity of healthy hiPSC-derived neuronal networks. Furthermore, we show that SBI can pinpoint molecular mechanisms affected by pharmacological agents and identify key disease mechanisms in neuronal networks derived from patients. These findings underscore the potential of SBI to automate and enhance the identification of disease mechanisms from MEA measurements, offering a robust and scalable method for advancing research with hiPSC-derived neuronal networks.
Potential Benefits of Ketone Therapy as a Novel Immunometabolic Treatment for Schizophrenia
Authors: Huizer Karin , Soni Shubham , Schmidt Mya A. , Çakici Nuray , de Haan Lieuwe , Dyck Jason R. B. , van Beveren Nico J. M.
Published: May 2024

Rationale

Current treatment options for patients with schizophrenia-spectrum disorders (SSD) remain unsatisfactory, leaving patients with persistent negative and cognitive symptoms and metabolic side effects. Therapeutic ketosis was recently hypothesized to target the bio-energetic pathophysiology of SSD. However, neuro-inflammation plays an important role in the pathobiology of SSD as well. Ideally, novel treatments would target both the bio-energetic, and the inflammatory aspects of SSD. In this study, we aimed to investigate the effects of ketone bodies on neuro-inflammation in an acute inflammation mouse model.

Methods

8-week-old male C57BL/6 N mice (n=11) were treated with either ketone ester (KE) or vehicle for 3 days. On day 3, a single intraperitoneal injection of lipopolysaccharide (LPS) or phosphate buffered saline (PBS) was administered. Mice were euthanized 24 h after LPS/PBS injection. Whole brain gene expression analysis using RT-PCR was done forTnf-a, Il-6andIl-1b.

Results

LPS caused a potent transcriptional upregulation ofTnf-a, Il-6andIl-1bin the vehicle-treated mouse brain compared to PBS-injected controls. KE strongly and significantly attenuated the increased transcription of pro-inflammatory cytokines (Tnf-a, Il-6andIl-1b) in the brain upon LPS injection compared to vehicle.

Conclusions

KE potently dampened neuro-inflammation in this acute inflammation mouse model. Ketone therapy holds great promise as a treatment for SSD patients by simultaneously targeting two main pathophysiological disease pathways. We encourage more research into the immunometabolic potential of therapeutic ketosis in SSD.

Highlights

A brain bio-energetic deficit and neuro-inflammation are involved in schizophrenia

Ketone therapy is being investigated as a bio-energetic treatment of schizophrenia

Ketone ester inhibits neuro-inflammation in an acute inflammation mouse mode

Therapeutic ketosis could target both pathophysiological pathways in SSD

The Immunometabolic potential of ketone therapy for SSD warrants further attention
Re-focusing visual working memory during expected and unexpected memory tests
Authors: Wang Sisi , van Ede Freek
Published: May 2024

A classic distinction from the domain of external attention is that between anticipatory orienting and subsequent re-orienting of attention to unexpected events. Whether and how humans also re-orient attention ‘in mind’ following expected and unexpected working-memory tests remains elusive. We leveraged spatial modulations in neural activity and gaze to isolate re-orienting within the spatial layout of visual working memory following central memory tests of certain, expected, or unexpected mnemonic content. Besides internal orienting after predictive cues, we unveil a second stage of internal attentional deployment following both expected and unexpected memory tests. Following expected tests, internal attentional deployment was not contingent on prior orienting, suggesting an additional verification – “double checking” – in memory. Following unexpected tests, re-focusing of alternative memory content was prolonged. This brings attentional re-orienting to the domain of working memory and underscores how memory tests can invoke either a verification or a revision of our internal focus.
Cortical tracking of speakers’ spectral changes predicts selective listening
Authors: Constantino Francisco Cervantes , Caputi Ángel A.
Published: May 2024

A social scene is particularly informative when people are distinguishable. To understand somebody amid a ‘cocktail party’ chatter, we automatically index their voice. This ability is underpinned by parallel processing of vocal spectral contours from speech sounds, but it has not yet been established how this occurs in the brain’s cortex. We investigate single-trial neural tracking of slow frequency modulations in speech using electroencephalography. Participants briefly listened to unfamiliar single speakers, and in addition, they performed a cocktail party comprehension task. Quantified through stimulus reconstruction methods, robust tracking was found in neural responses to slow (delta-theta range) modulations of frequency contours in the fourth and fifth formant band, equivalent to the 3.5–5 KHz audible range. Instantaneous frequency spacing (ΔF), which also yields indexical information from the vocal tract, was similarly decodable. Moreover, EEG evidence of listeners’ spectral tracking abilities predicted their chances of succeeding at selective listening when faced with two-speaker speech mixtures. In summary, the results indicate that the communicating brain can rely on locking of cortical rhythms to major changes led by upper resonances of the vocal tract. Their corresponding articulatory mechanics hence continuously issue a fundamental credential for listeners to target in real time.
Decreased cellular excitability of pyramidal tract neurons in primary motor cortex leads to paradoxically increased network activity in simulated parkinsonian motor cortex
Authors: Doherty Donald W , Chen Liqiang , Smith Yoland , Wichmann Thomas , Chu Hong-yuan , Lytton William W
Published: May 2024

Decreased excitability of pyramidal tract neurons in layer 5B (PT5B) of primary motor cortex (M1) has recently been shown in a dopamine-depleted mouse model of parkinsonism. We hypothesized that decreased PT5B neuron excitability would substantially disrupt oscillatory and non-oscillatory firing patterns of neurons in layer 5 (L5) of primary motor cortex (M1). To test this hypothesis, we performed computer simulations using a previously validated computer model of mouse M1. Inclusion of the experimentally identified parkinsonism-associated decrease of PT5B excitability into our computational model produced a paradoxical increase in rest-state PT5B firing rate, as well as an increase in beta-band oscillatory power in local field potential (LFP). In the movement-state, PT5B population firing and LFP showed reduced beta and increased high-beta, low-gamma activity of 20-35 Hz in the parkinsonian, but not in control condition. The appearance of beta-band oscillations in parkinsonism would be expected to disrupt normal M1 motor output and contribute to motor activity deficits seen in patients with Parkinson’s disease (PD).
Norepinephrine changes behavioral state via astroglial purinergic signaling
Authors: Chen Alex B. , Duque Marc , Wang Vickie M. , Dhanasekar Mahalakshmi , Mi Xuelong , Rymbek Altyn , Tocquer Loeva , Narayan Sujatha , Prober David , Yu Guoqiang , Wyart Claire , Engert Florian , Ahrens Misha B.
Published: May 2024

Both neurons and glia communicate via diffusible neuromodulatory substances, but the substrates of computation in such neuromodulatory networks are unclear. During behavioral transitions in the larval zebrafish, the neuromodulator norepinephrine drives fast excitation and delayed inhibition of behavior and circuit activity. We find that the inhibitory arm of this feedforward motif is implemented by astroglial purinergic signaling. Neuromodulator imaging, behavioral pharmacology, and perturbations of neurons and astroglia reveal that norepinephrine triggers astroglial release of adenosine triphosphate, extracellular conversion into adenosine, and behavioral suppression through activation of hindbrain neuronal adenosine receptors. This work, along with a companion piece by Lefton and colleagues demonstrating an analogous pathway mediating the effect of norepinephrine on synaptic connectivity in mice, identifies a computational and behavioral role for an evolutionarily conserved astroglial purinergic signaling axis in norepinephrine-mediated behavioral and brain state transitions.