bluuebunny/crossref_metadata_2025_split huggingface dataset:
Sulforaphane Effects on Cognition and Symptoms in First and Early Episode Schizophrenia: A Randomized Double-Blind Trial
Authors: Hei Gangrui , Smith Robert C , Li Ranran , Ou Jianjun , Song Xueqing , Zheng Yingjun , He Yiqun , Arriaza Jen , Fahey Jed W , Cornblatt Brian , Kang Dongyu , Yang Ye , Huang Jing , Wang Xiaoyi , Cadenhead Kristin , Zhang Mimei , Davis John M , Zhao Jingping , Jin Hua , Wu Renrong 
Published: March 2022

AbstractObjectiveCognitive symptoms are associated with significant dysfunction in schizophrenia. Oxidative stress and inflammation involving histone deacetylase (HDAC) have been implicated in the pathophysiology of schizophrenia. Sulforaphane has antioxidant properties and is an HDAC inhibitor. The objective of this study was to determine the efficacy of sulforaphane on cognition dysfunction for patients with schizophrenia.MethodsThis double-blind randomized 22-week trial of patients with first-episode schizophrenia was conducted in four psychiatric institutions in China. Patients were randomized to three groups (two doses of sulforaphane vs. placebo) and symptomatic and cognitive assessments were completed at multiple times. The primary outcome measure was change in the MATRICS Composite score. The secondary outcomes were change in MATRICS Domain scores, PANSS Total Scores and change in side-effects.ResultsA total of 172 patients were randomized and 151 patients had at least one follow up evaluation. There were no significant effects of sulforaphane, on the primary outcome, MATRICS overall composite score. However, on secondary outcomes, sulforaphane did significantly improve performance scores on MATRICS battery Domains of spatial working memory (F = 5.68, P = 0.004), reasoning-problem solving (F = 2.82, P = 0.063), and verbal learning (F = 3.56, P = 0.031). There were no effects on PANSS symptom scores. Sulforaphane was well tolerated.ConclusionAlthough the primary outcome was not significant, improvement in three domains of the MATRICS battery, suggests a positive cognitive effect on some cognitive functions, which warrants further clinical trials to further assess whether sulforaphane may be a useful adjunct for treating some types of cognitive deficits in schizophrenia.
Association between COVID-19 Risk-Mitigation Behaviors and Specific Mental Disorders in Youth
Authors: Conway Kevin P. , Bhardwaj Kriti , Michel Emmanuella , Paksarian Diana , Nikolaidis Aki , Kang Minji , Merikangas Kathleen R. , Milham Michael P. 
Published: March 2022

AbstractImportanceAlthough studies of adults show that pre-existing mental disorders increase risk for COVID–19 infection and severity, there is limited information about this association among youth. Mental disorders in general as well as specific types of disorders may influence their ability to comply with risk-mitigation strategies to reduce COVID-19 infection and transmission.ObjectiveTo examine associations between specific mental disorders and COVID-19 risk-mitigation practices among 314 female and 514 male youth.DesignYouth compliance (rated as “Never,” “Sometimes,” “Often,” or “Very often/Always”) with risk mitigation was reported by parents on the CoRonavIruS Health Impact Survey (CRISIS) in January 2021. Responses were summarized using factor analysis of risk mitigation, and their associations with lifetime mental disorders (assessed via structured diagnostic interviews) were identified with linear regression analyses (adjusted for covariates). All analyses used R Project for Statistical Computing for Mac (v.4.0.5).SettingThe Healthy Brain Network (HBN) in New York City Participants. 314 female and 514 male youth (ages 5-21)Main Outcome(s) and Measure(s)COVID-19 risk mitigation behaviors among youthResultsA two-factor model was the best-fitting solution. Factor 1 (avoidance behaviors) included avoiding groups, indoor settings, and other peoples’ homes; avoidance was more likely among youth with any anxiety disorder (p=.01). Factor 2 (hygiene behaviors) included using hand sanitizer, washing hands, and maintaining social distance; practicing hygiene was less likely among youth with ADHD (combined type) (p=.02). Mask wearing, which did not load on either factor, was not associated with any mental health disorder.Conclusion and RelevanceFindings suggest that education and monitoring of risk-mitigation strategies in certain subgroups of youth may reduce risk of exposure to COVID-19 and other contagious diseases. Additionally, they highlight the need for greater attention to vaccine prioritization for individuals with ADHD.Key PointsQuestionAre mental disorders among youth associated with COVID-19 risk-mitigation behaviors?FindingsBased on the parent CoRonavIruS Health Impact Survey (CRISIS) of 314 females and 514 males aged 5-21, youth with anxiety disorders were more likely to avoid high-risk exposure settings, and those with ADHD (combined type) were less likely to follow hygiene practices. In contrast, mask wearing was not associated with youth mental disorders.MeaningSpecific types of disorders in youth may interfere with their ability to employ risk-mitigation strategies that may lead to greater susceptibility to COVID-19.
Nanopore quality score resolution can be reduced with little effect on downstream analysis
Authors: Rivara-Espasandín Martín , Balestrazzi Lucía , Dufort y Álvarez Guillermo , Ochoa Idoia , Seroussi Gadiel , Smircich Pablo , Sotelo-Silveira José , Martín Álvaro 
Published: March 2022

AbstractWe investigate the effect of quality score information loss on downstream analysis from nanopore sequencing FASTQ files. We polished denovo assemblies for a mock microbial community and a human genome, and we called variants on a human genome. We repeated these experiments using various pipelines, under various coverage level scenarios, and various quality score quantizers. In all cases we found that the quantization of quality scores cause little difference on (or even improves) the results obtained with the original (non-quantized) data. This suggests that the precision that is currently used for nanopore quality scores is unnecessarily high, and motivates the use of lossy compression algorithms for this kind of data. Moreover, we show that even a non-specialized compressor, like gzip, yields large storage space savings after quantization of quality scores.
Reduced childhood social attention in an autism model marmoset predicts impaired social skills and inflexible behavior in adulthood
Authors: Nakagami Akiko , Yasue Miyuki , Nakagaki Keiko , Nakamura Madoka , Kawai Nobuyuki , Ichinohe Noritaka 
Published: March 2022

AbstractAutism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by social and communication impairments and restricted and repetitive behavior. Although currently no established cure exists for ASD, early intervention to the deficits of attention to other individuals is expected to reduce the progression of ASD symptoms in later life. In order to confirm this hypothesis and improve early therapeutic interventions, it is desirable to develop an animal model of ASD in which social attention is impaired in childhood and ASD-like social behavior is observed in adulthood. However, rodent models of ASD have difficulty in recapitulating the deficit of gaze-based social attention. In this study, we examined the direction of gaze towards other conspecifics during childhood and puberty in a three-chamber test setting using an ASD model of marmoset produced by maternal exposure to valproic acid (VPA). We also conducted a reversal learning test in an adult VPA-exposed marmoset as an indicator of perseveration, a core symptom of ASD that has not previously been investigated in this model. The results showed that time spent gazing at other conspecifics was reduced in VPA-exposed marmosets in childhood, and adults displayed rigidity of response. In a longitudinal study using the same animals, deficits in social attention in childhood correlated well with ASD-like social disturbance (inequity aversion and third-party reciprocity) and inflexible behavior in adulthood. Since VPA-exposed marmosets exhibit these diverse ASD-like behaviors that are coherent from childhood to adulthood, VPA-exposed marmosets will provide a valuable opportunity to elucidate mechanisms for early intervention and contribute to the development of early therapies.
Periventricular nodular heterotopia is functionally coupled with the neocortex during resting and task states
Authors: Gao Yayue , Chen Guanpeng , Teng Pengfei , Zhang Xin , Fang Fang , Englot Dario J. , Luan Guoming , Wang Xiongfei , Wang Qian 
Published: March 2022

AbstractPeriventricular nodular heterotopia (PVNH) is a well-defined developmental disorder characterized by failed neuronal migration, which forms ectopic neuronal nodules along the ventricular walls. Previous studies mainly focus on clinical symptoms caused by the PVNH tissue, such as seizures. However, little is known about whether and how neurons in the PVNH tissue functionally communicate with neurons in the neocortex. To probe this, we applied magnetoencephalography (MEG) and stereo-electroencephalography (sEEG) recordings to patients with PVNH during resting and task states. By estimating frequency-resolved phase coupling strength of the source-reconstructed neural activities, we found that the PVNH tissue was spontaneously coupled with the neocortex in the α to β frequency range, which was consistent with the synchronization pattern within the neocortical network. Furthermore, the coupling strength between PVNH and sensory areas effectively modulated the local neural activity in sensory areas. In both MEG and sEEG visual experiments, the PVNH tissue exhibited visual evoked responses, with a similar pattern and latency as the ipsilateral visual cortex. These findings demonstrate that PVNH is functionally integrated into cognition-related cortical circuits, suggesting a co-development perspective of ectopic neurons after their migration failure.
Thoracic crop formation is spatiotemporally coordinated with flight muscle histolysis during claustral colony foundation of a Lasius japonicus queen
Authors: Kurihara Yuta , Ogawa Kota , Chiba Yudai , Hayashi Yoshinobu , Miyazaki Satoshi 
Published: March 2022

ABSTRACTIn a majority of ants, a newly mated queen independently founds a colony and claustrally raises her first brood without foraging outside the nest. During claustral independent colony foundation (ICF) in several ants, the esophagus of the founding queen expands and develops into a thoracic crop, which is then filled with a liquid substrate for larval feeding. It has been suggested that these substrates are converted from her body reserves (e.g., histolyzed flight muscles) or redistributed from a gastral crop. Here, we examined thoracic crop development in Lasius japonicus during claustral ICF. The foundresses claustrally fed their larvae from week 2 to 5 after ICF onset, and the first worker emerged at week 6. The development proceeded as follows: in week 0, foundress dorsal esophagus wall was pleated and thickened. Then, from week 2 to 5, the esophagus expanded dorsally toward where flight muscles had been present, following flight muscle histolysis. Gastral crop expansion followed esophagus expansion. Thus, thoracic crop formation may be spatiotemporally coordinated with flight muscle histolysis in Lasius japonicus queens, and similar developmental regulations might be common in other claustral ICF ants.
Deep Learning for MYC binding site recognition
Authors: Fioresi R. , Demurtas P. , Perini G. 
Published: March 2022

AbstractMotivationThe definition of the genome distribution of the Myc transcription factor is extremely important since it may help predict its transcriptional activity particularly in the context of cancer. Myc is among the most powerful oncogenes involved in the occurrence and development of more than 80% of different types of pediatric and adult cancers. Myc regulates thousands of genes which can be in part different, depending on the type of tissues and tumours. Myc distribution along the genome has been determined experimentally through chromatin immunoprecipitation This approach, although powerful, is very time consuming and cannot be routinely applied to tumours of individual patients. Thus, it becomes of paramount importance to develop in-silico tools that can effectively and rapidly predict its distribution on a given cell genome. New advanced computational tools (DeeperBind) can then be successfully employed to determine the function of Myc in a specific tumour, and may help to devise new directions and approaches to experiments first and personalized and more effective therapeutic treatments for a single patient later on.ResultsThe use of DeeperBind with DeepRAM on Colab platform can effectively predict the binding sites for the MYC factor with an accuracy above 0.96 AUC, when trained with multiple cell lines. The analysis of the filters in DeeperBind trained models shows, besides the consensus sequence CACGTG classically associated to the MYC factor, also the other consensus sequences G/C box or TGGGA, respectively bound by the SP1 and MIZ-1 transcription factors, which are known to mediate the MYC repressive response. Overall, our findings suggest a stronger sinergy between the machine learning tools as DeeperBind and biological experiments, which may reduce the time consuming experiments by providing a direction to guide them.
Host control and species interactions jointly determine microbiome community structure
Authors: Abbasi Eeman , Akçay Erol 
Published: March 2022

1AbstractThe host microbiome can be considered an ecological community of microbes present inside a complex and dynamic host environment. The host is under selective pressure to ensure that its microbiome remains beneficial. The host can impose a range of ecological filters including the immune response that can influence the assembly and composition of the microbial community. How the host immune response interacts with the within-microbiome community dynamics to affect the assembly of the microbiome has been largely unexplored. We present here a mathematical framework to elucidate the role of host immune response and its interaction with the balance of ecological interactions types within the microbiome community. We find that highly mutualistic microbial communities characteristic of high community density are most susceptible to changes in immune control and become invasion prone as host immune control strength is increased. Whereas highly competitive communities remain relatively stable in resisting invasion to changing host immune control. Our model reveals that the host immune control can interact in unexpected ways with a microbial community depending on the prevalent ecological interactions types for that community. We stress the need to incorporate the role of host-control mechanisms to better understand microbiome community assembly and stability.
Control of contextual memory through interneuronal α5-GABAAreceptors
Authors: Zhu Mengwen , Abdulzahir Alifayaz , Perkins Mark G , Chu Chan C , Krause Bryan M , Casey Cameron , Lennertz Richard , Ruhl David , Hentschke Harald , Nagarajan Rajasekar , Chapman Edwin R , Rudolph Uwe , Fanselow Michael S , Pearce Robert A 
Published: March 2022

Abstractγ-aminobutyric acid type A receptors that incorporate α5 subunits (α5-GABAARs) are highly enriched in the hippocampus and are strongly implicated in control of learning and memory. Receptors located on pyramidal neuron dendrites have long been considered responsible, but here we report that their selective knockout from either interneurons (α5-i-KO) or pyramidal neurons (α5-pyr-KO) interferes with the ability of the general anesthetic etomidate to suppress contextual conditioning. Using Ca2+imaging of CA1 pyramidal neuron activity in freely exploring mice to assess hippocampal function directly, we found that etomidate blocked the development of place cells and spatial engrams in wild type (WT) and α5-pyr-KO mice, but not in α5-i-KO mice. In addition, α5-i-KO mice developed weaker spatial engrams than WT mice under control conditions. These findings show that interneuronal α5-GABAARs serve a physiological role in promoting spatial learning, and that they mediate the suppression of hippocampus-dependent memory by etomidate.
Stimulation-Evoked Effective Connectivity (SEEC): An in-vivo approach for defining mesoscale corticocortical connectivity
Authors: Bundy David T. , Barbay Scott , Hudson Heather M. , Frost Shawn B. , Nudo Randolph J. , Guggenmos David J. 
Published: March 2022

AbstractBackgroundCortical electrical stimulation has been a versatile technique for examining the structure and function of cortical regions as well as for implementing novel therapies. While electrical stimulation has been used to examine the local spread of neural activity, it may also enable longitudinal examination of mesoscale interregional connectivity. Recent studies have used focal intracortical microstimulation (ICMS) with optical imaging to show cross-region spread of neural activity, but techniques are limited to utilizing hemodynamic responses within anesthetized preparations.ObjectiveHere, we sought to use ICMS in conjunction with recordings of multi-unit action potentials to assess the mesoscale effective connectivity within sensorimotor cortex.MethodsNeural recordings were made from multielectrode arrays placed into sensory, motor, and premotor regions during surgical experiments in three squirrel monkeys. During each recording, single-pulse ICMS was repeatably delivered to a single region. Mesoscale effective connectivity was calculated from ICMS-evoked changes in multi-unit firing.ResultsMulti-unit action potentials were able to be detected on the order of 1 ms after each ICMS pulse. Across sensorimotor regions, short-latency (< 2.5 ms) ICMS-evoked neural activity strongly correlated with known anatomic connections. Additionally, ICMS-evoked responses remained stable across the experimental period, despite small changes in electrode locations and anesthetic state.ConclusionsThese results show that monitoring ICMS-evoked neural activity, in a technique we refer to as Stimulation-Evoked Effective Connectivity (SEEC), is a viable way to longitudinally assess effective connectivity enabling studies comparing the time course of connectivity changes with the time course of changes in behavioral function.HighlightsShort-latency neural responses to ICMS were evaluated in multiple cortical regions.Neural responses strongly correlated with known anatomical connections.Stimulation-evoked neural responses were maintained across repeated tests.ICMS-evoked activity can show longitudinal changes in effective connectivity.
Development of a dual fluorescent reporter system in Clostridioides difficile reveals a division of labor between virulence and transmission gene expression
Authors: Donnelly M. Lauren , Shrestha Shailab , Ribis John , Kuhn Pola , Krasilnikov Maria , Feliciano Carolina Alves , Shen Aimee 
Published: March 2022

ABSTRACTThe bacterial pathogen Clostridioides difficile causes gastroenteritis through its production of toxins and transmits disease through its production of resistant spores. Toxin and spore production are energy-expensive processes that are regulated by multiple transcription factors in response to many nutritional inputs. While toxin and sporulation genes are both heterogeneously expressed in only a subset of C. difficile cells, the relationship between these two sub-populations remains unclear. To address whether C. difficile coordinates the generation of these sub-populations, we developed a dual transcriptional reporter system that allows toxin and sporulation gene expression to be simultaneously visualized at the single-cell level using chromosomally-encoded mScarlet and mNeonGreen fluorescent transcriptional reporters. We then adapted an automated image analysis pipeline to quantify toxin and sporulation gene expression in thousands of individual cells in different media conditions and genetic backgrounds. These analyses revealed that toxin and sporulation gene expression rarely overlap during growth on agar plates, but broth culture increases this overlap in a manner dependent on the multifunctional RstA transcriptional regulator. Our results suggest that certain growth conditions promote a “division of labor” between transmission and virulence gene expression, highlighting how these subpopulations are influenced by environmental inputs. Given that recent work has revealed population-wide heterogeneity for numerous cellular processes in C. difficile, we anticipate that our dual reporter system will be broadly useful for determining the overlap in these subpopulations.IMPORTANCEClostridioides difficile is an important nosocomial pathogen that causes severe diarrhea by producing toxins and is transmitted by producing spores. While both processes are crucial for C. difficile disease, only a subset of cells express toxins and/or undergo sporulation. Whether C. difficile coordinates the relationship between these energy-expensive processes remains unknown. We developed a dual fluorescent reporter system coupled with an automated image analysis pipeline to rapidly characterize expression two genes of interest across thousands of bacterial cells. Using this reporter system, we discovered that toxin and sporulation gene expression appear to undergo a “division of labor” in certain growth conditions, particularly during growth on agar plates. Since C. difficile specializes into subpopulations for numerous vital cellular processes, this novel dual reporter system will enable future studies aimed at understanding how C. difficile coordinates various subpopulations throughout its infectious disease cycle.
High salt intake activates the hypothalamic-pituitary-adrenal axis, amplifies the stress response, and alters tissue glucocorticoid exposure in mice
Authors: Costello Hannah M , Krilis Georgios , Grenier Celine , Severs David , Ivy Jessica R. , Nixon Mark , Holmes Megan C , Livingstone Dawn E.W. , Hoorn Ewout J , Dhaun Neeraj , Bailey Matthew A 
Published: March 2022

ABSTRACTHigh salt intake is common and contributes to poor cardiovascular health. Sustained cortisol excess also induces an adverse cardiovascular profile. Urinary cortisol excretion positively correlates with urinary sodium excretion. We hypothesised that this was due to hypothalamic-pituitary-adrenal axis activation by high salt intake.In male C57BL6/J mice, 2 weeks of high salt intake increased Crh and Pomc mRNA abundance in the hypothalamus and anterior pituitary, respectively and caused a sustained rise in plasma corticosterone. Plasma copeptin and anterior pituitary V1b receptor mRNA expression was elevated, which may contribute to basal HPA axis activation. Additionally, high salt intake amplified glucocorticoid response to restraint stress, indicative of enhanced HPA axis sensitivity. In the periphery, high salt intake reduced the binding capacity of corticosteroid-binding globulin, enhancing glucocorticoid bioavailability. Within several tissues, the expression of glucocorticoid-regenerating enzyme, 11β-hydroxysteroid dehydrogenase type 1, was increased and the glucocorticoid receptor downregulated. Overall, high salt intake increased glucocorticoid exposure in the hippocampus, anterior pituitary and liver.Chronic high salt intake amplifies basal and stress-induced glucocorticoid levels and resets glucocorticoid biology centrally, peripherally and within cells. This shows direct connectivity between salt homeostasis and HPA axis function. The cumulative effect is likely maladaptive and may contribute to the long-term health consequences of a high salt diet.