bluuebunny/crossref_metadata_2025_split huggingface dataset:
Action-sequence learning, habits and automaticity in obsessive-compulsive disorder
Authors: Banca Paula , Ruiz Maria Herrojo , Gonzalez-Zalba Miguel Fernando , Biria Marjan , Marzuki Aleya A. , Piercy Thomas , Sule Akeem , Fineberg Naomi Anne , Robbins Trevor William 
Published: February 2023

AbstractEnhanced habit formation, greater automaticity and impaired goal/habit arbitration in obsessive-com-pulsive disorder (OCD) are key hypotheses from the goal/habit imbalance theory of compulsion which have not been directly investigated. This study tests these hypotheses using a combination of newly developed behavioral tasks. First, we trained both OCD patients and healthy controls, using a smartphone app, to perform chunked action sequences. This motor training was conducted daily for one month. Both groups displayed equivalent procedural learning and attainment of habitual perfor-mance (measured with an objective criterion of automaticity), despite greater subjective habitual tendencies in patients with OCD, self-reported via a recently developed questionnaire. Participants were subsequently tested on a re-evaluation task to assess choice between established automatic and novel goal-directed action sequences. This task showed that both groups were sensitive to re-evaluation based on monetary feedback. However, when re-evaluation was based on physical effort, OCD patients showed a pronounced preference for the previously trained habitual sequence, hypothetically due to its intrinsic value. This was particularly evident in patients with higher compulsive symptoms and habitual tendencies, who also engaged significantly more with the motor habit-training app and reported symptom relief at the end of the study. The tendency to attribute higher intrinsic value to familiar actions may be a potential mechanism leading to compulsions and an important addition to the goal/habit imbalance hypothesis in OCD. We also highlight the potential of the app-training as a habit reversal therapeutic tool.
Epidemiology and aetiology of moderate to severe diarrhoea in hospitalised HIV-infected patients ≥5 years old in South Africa, 2018-2021: a case-control analysis
Authors: Johnstone Siobhan L. , Erasmus Linda , Thomas Juno , Groome Michelle J. , du Plessis Nicolette M. , Avenant Theunis , de Villiers Maryke , Page Nicola A. 
Published: February 2023

AbstractDiarrhoea is a recognised complication of HIV-infection, yet there are limited local aetiological data in this high-risk group. These data are important for informing public health interventions and updating diagnostic and treatment guidelines. This study aimed to determine the pathogenic causes for diarrhoeal admissions in HIV-infected patients compared to hospital controls between July 2018 and November 2021.Admitted diarrhoeal cases (n=243) and non-diarrhoeal hospital controls (n=101) ≥5 years of age were enrolled at Kalafong, Mapulaneng and Matikwana hospitals. Stool specimens/rectal swabs were collected and pathogen screening performed on multiple platforms. Differences in pathogen detections between cases and controls, stratified by HIV status, were investigated.The majority (n=164, 67.5%) of diarrhoeal cases with known HIV status were HIV-infected. Pathogens could be detected in 66.3% (n=228) of specimens, with significantly higher detection in cases compared to controls (72.8% versus 50.5%,p<0.001). Amongst HIV-infected participants, prevalence ofCystoisosporaspp. was significantly higher in cases than controls (17.7% versus 0.0%,p=0.028), whileSchistosomawas detected more often in controls than cases (17.4% versus 2.4%,p=0.009). Amongst the HIV-uninfected participants, prevalence ofShigellaspp.,Salmonellaspp. andHelicobacter pyloriwas significantly higher in cases compared to controls (36.7% versus 12.0%,p=0.002; 11.4% versus 0.0%,p=0.012; 10.1% versus 0.0%,p=0.023).Diarrhoeal aetiology differed by HIV status, withShigellaspp. (36.7%) andSalmonellaspp. (11.4%) having the highest prevalence amongst HIV-uninfected cases andShigellaspp. (18.3%),Cystoisospora(17.7%), andCryptosporidiumspp. (15.9%) having the highest prevalence amongst HIV-infected cases. These differences should be considered for the development of diagnostic and treatment guidelines.
Distribution of Entomopathogenic Nematodes in Some Selected Insect Species in Osogbo Local Government Area of Osun State, Nigeria
Authors: Adeshina Q.O , Rufai A.M , Surakat O.A , Nzeako S.O 
Published: February 2023

ABSTRACTEntomopathogenic nematodes (EPNs) are leading biological control agents used to combat many insect pests in many regions of the world. This study investigated the distribution of entomopathogenic nematodes in four insect species;Zonocerus variegatus, Mantis religiosa, Butterfly and Moth across dry and rainy seasons in Osogbo Local Government Area of Osun State. Insect samples were collected from different sampling stations (cultivated farmlands, vegetation of grasses, and forested lands) using an entomological sweep net. The insects were dissected in a normal saline medium for the presence of EPN. A further verification was made, 60 soil samples were retrieved randomly from the disturbed agroecosystem (where insects were sampled) and an undisturbed agroecosystem (Osun-Osogbo Groove). The soil samples were screened for EPN presence usingTenebrio molitorlarva (mealworm) as baits, while infected baits are placed on modified white traps to recover EPNs. A total of 876 insects samples comprising;Zonocerus variegatus556 (63.5%),Mantis religiosa36 (4.1%), Butterflies 158 (18.0%) and Moths 126 (14.4%) were collected from the disturbed agroecosystem based on sweep net efficiency and species availability. After screening, only 1 (0.1%) insect specimen (Mantis religiosa) specimen successfully harbour an EPN, identified asMermisspp. Result from statistical analysis indicates that both season and insects age do not have influence on the distribution of EPN (P>0.05). Moreover, the low infectivity of EPN in the sampled insect was presumed to be caused by EPNs’ foraging strategies, flooding and other host of factors. This led to further probing through screening of soil samples. Of all 36 soil samples screened from the disturbed agroecosystem, EPNs had zero prevalence. However, from all the (24) soil samples collected from the undisturbed agroecosystem, EPNs belonging to the genusHeterorhabditiswere recovered and identified using morphological and morphometric characters. The absolute frequency of occurrence of EPN in the disturbed agroecosystem was zero compared to 100% recorded for the undisturbed agroecosystem. This study infers that EPN occurrence, dispersal, and persistence in the ecosystem are found to be adversely affected by intense anthropogenic activities.
Neuroprotective effects of hepatoma-derived growth factor in models of Huntington’s disease
Authors: Voelkl Kerstin , Gutiérrez-Ángel Sara , Keeling Sophie , Koyuncu Seda , Arzberger Thomas , Vilchez David , Klein Rüdiger , Dudanova Irina 
Published: February 2023

AbstractHuntington’s disease (HD) is a movement disorder caused by a mutation in the Huntingtin gene, that leads to severe neurodegeneration and inevitable death of the patients. Molecular mechanisms of HD are still not sufficiently understood, and no cure is currently available. Here, we demonstrate neuroprotective effects of hepatoma-derived growth factor (HDGF) in cellular and mouse models of HD. We show that HDGF expression levels in neuronal cell types inversely correlate with cellular vulnerability to HD. Moreover, lack of endogenous HDGF shortened lifespan and worsened rotarod performance of R6/2 HD model mice. AAV-mediated delivery of HDGF into the brain reduced mutant Huntingtin inclusion body load, but had no significant effect on motor behavior or lifespan. Interestingly, both nuclear and cytoplasmic versions of HDGF were equally efficient in rescuing mutant Huntingtin toxicity in cell culture models of HD. Moreover, extracellular application of a recombinant HDGF protein improved viability of mutant Huntingtin-expressing primary neurons and reduced mutant Huntingtin aggregation in neural progenitor cells differentiated from human patient-derived induced pluripotent stem cells (iPSCs). Our findings provide new insights into the pathomechanisms of HD and suggest neuroprotective potential of HDGF in neurodegeneration.
Luminescence-based screening for extracellular vesicle release modulators reveals a role for PI4KIIIβ in exosome biogenesis upon lysosome inhibition
Authors: Bebelman Maarten P. , Crudden Caitrin , Snieder Bart , Thanou Evangelia , Langedijk Catharina J.M. , Viola Margarida , Eleonora Steven , Baginska Urszula , Cotugno Olaf , Bebelman Jan Paul M. , van Eijndhoven Monique A.J. , Bosch Leontien , Li Ka Wan , Smit Martine J. , van Niel Guillaume , Smit August B. , Verweij Frederik J. , Pegtel D. Michiel 
Published: February 2023

AbstractDysregulated extracellular vesicle (EV) release has been implicated in various pathologies, including cancer, neurodegenerative disease and osteoarthritis. Despite clear therapeutic potential, drug screening for EV release modulators has yielded limited success due to the lack of a sensitive and scalable EV read-out system. Here, we employed CRISPR-Cas9 to engineer HEK293 cells expressing HA-NanoLuciferase-(NL)-tagged endogenous CD63. We found that under basal culture conditions, CD63-containing EVs are released via a mechanism that is independent of the exocytic SNARE protein SNAP23, presumably by direct budding from the plasma membrane. Endo-lysosome inhibition by chemical or genetic perturbation of vATPase strongly increased SNAP23 and nSmase2-dependent exosome secretion from intracellular compartments. Proteomic analysis revealed these exosomes are enriched for early- and late endosomal markers, but also for autophagosomal proteins. This suggests that a proportion of these exosomes originate from amphisomes, although chemical inhibition of canonical autophagy did not affect exosome secretion upon lysosome inhibition. Using a broad- spectrum kinase inhibitor screen, we identified and subsequently validated the lipid kinase PI4KIIIβ as a critical mediator of exosome secretion and amphisome-mediated secretory autophagy, upon lysosome inhibition. We conclude that tagging of endogenous CD63 with NanoLuciferase represents a sensitive, scalable reporter strategy that enables identification of (druggable) modulators of EV biogenesis and release under physiological and pathological conditions.
Fractal Structure of Human and Primate Social Networks Optimizes Information Flow
Authors: West B.J. , Culbreth G. , Dunbar R.I.M. , Grigolini P. 
Published: February 2023

AbstractPrimate and human social groups exhibit a fractal structure that has a very limited range of preferred layer sizes, with groups of 5, 15, 50 and (in humans) 150 and 500 predominating. This same fractal distribution is also observed in the distribution of species mean group sizes in primates. Here we demonstrate that this preferential numbering arises because of the critical nature of dynamic self-organization within complex social networks. We calculate the size dependence of the scaling properties of complex social network models and argue that this aggregate behaviour exhibits a form of collective intelligence. Direct calculation establishes that the complexity of social networks as measured by their scaling behaviour is non-monotonic, peaking globally around 150 with a secondary peak at 500 and tertiary peaks centred on 15 and 50, thereby providing a theory-based rationale for the fractal layering of primate and human social groups.
MousePZT: A Simple, Reliable, Low-Cost Device for Vital Sign Monitoring and Respiratory Gating in Mice Under Anesthesia
Authors: Rivera Daniel A. , Buglione Anne E. , Schaffer Chris B. 
Published: February 2023

AbstractSmall animal studies in biomedical research often require anesthesia to reduce pain or stress experienced by research animals and to minimize motion artifact for imaging or other measurements. Anesthetized animals should be closely monitored to avoid complications and unintended effects of altered physiology during such procedures. Many currently available monitoring devices can be expensive, invasive, or interfere with experimental design. Here, we present a low-cost device, based on a simple piezoelectric sensor, with a custom circuit and computer software that allows for measurements of both respiratory rate and heart rate in a non-invasive, minimal contact manner. We find the accuracy of the MousePZT device in measuring respiratory and heart rate under anesthesia and with pharmacologically induced changes in heart rate match those of commercial or more invasive systems. We also demonstrate that changes in respiratory rate can precede changes in heart rate associated with alterations in anesthetic depth. Additional circuitry on the device outputs a respiration locked trigger signal for respiratory-gating of imaging or other data acquisition that has high sensitivity and specificity for detecting respiratory cycles. We provide detailed construction documents and all necessary microcontroller and computer software, enabling straightforward adoption of this device.
Complete Workflow for High Throughput Human Single Skeletal Muscle Fiber Proteomics
Authors: Momenzadeh Amanda , Jiang Yuming , Kreimer Simion , Teigen Laura E. , Zepeda Carlos S. , Haghani Ali , Mastali Mitra , Song Yang , Hutton Alexandre , Parker Sarah J , Van Eyk Jennifer E. , Sundberg Christopher W. , Meyer Jesse G. 
Published: February 2023

AbstractSkeletal muscle is a major regulatory tissue of whole-body metabolism and is composed of a diverse mixture of cell (fiber) types. Aging and several diseases differentially affect the various fiber types, and therefore, investigating the changes in the proteome in a fiber-type specific manner is essential. Recent breakthroughs in isolated single muscle fiber proteomics have started to reveal heterogeneity among fibers. However, existing procedures are slow and laborious requiring two hours of mass spectrometry time per single muscle fiber; 50 fibers would take approximately four days to analyze. Thus, to capture the high variability in fibers both within and between individuals requires advancements in high throughput single muscle fiber proteomics. Here we use a single cell proteomics method to enable quantification of single muscle fiber proteomes in 15 minutes total instrument time. As proof of concept, we present data from 53 isolated skeletal muscle fibers obtained from two healthy individuals analyzed in 13.25 hours. Adapting single cell data analysis techniques to integrate the data, we can reliably separate type 1 and 2A fibers. Sixty-five proteins were statistically different between clusters indicating alteration of proteins involved in fatty acid oxidation, muscle structure and regulation. Our results indicate that this method is significantly faster than prior single fiber methods in both data collection and sample preparation while maintaining sufficient proteome depth. We anticipate this assay will enable future studies of single muscle fibers across hundreds of individuals, which has not been possible previously due to limitations in throughput.
Incomplete transcriptional dosage compensation of vertebrate sex chromosomes is balanced by post-transcriptional compensation
Authors: Lister Nicholas C , Milton Ashley M , Patel Hardip R , Waters Shafagh A , Hanrahan Benjamin J , McIntyre Kim L , Livernois Alexandra M , Wee Lee Kian , Ringel Alessa R. , Mundlos Stefan , Robson Michael I. , Shearwin-Whyatt Linda , Grützner Frank , Marshall Graves Jennifer A. , Ruiz-Herrera Aurora , Waters Paul D 
Published: February 2023

AbstractHeteromorphic sex chromosomes (XY or ZW) present problems of gene dosage imbalance between the sexes, and with the autosomes. Mammalian X chromosome inactivation was long thought to imply a critical need for dosage compensation in vertebrates. However, the universal importance of sex chromosome dosage compensation was questioned by mRNA abundance measurements that demonstrated sex chromosome transcripts are neither balanced between the sexes or with autosomes in monotreme mammals or birds. Here, we demonstrate unbalanced mRNA levels of X genes in platypus males and females that correlate with differential loading of histone modifications, and confirm that transcripts of Z genes are unbalanced between males and females also in chicken. However, we found that in both species, median male to female protein abundance ratios were 1:1, implying an additional level of post-transcriptional control. We conclude that parity of sex chromosome output is achieved in birds, as well as all mammal groups, by a combination of transcriptional and post-transcriptional control, consistent with an essential role for sex chromosome dosage compensation in vertebrates.
MAP9/MAPH-9 supports axonemal microtubule doublets and modulates motor movement
Authors: Tran Michael V. , Ferguson James W. , Cote Lauren E. , Khuntsariya Daria , Fetter Richard D. , Wang Jennifer T. , Wellard Stephen R. , Sallee Maria D. , Genova Mariya , Eskinazi Sani , Magiera Maria M. , Janke Carsten , Stearns Tim , Lansky Zdenek , Shen Kang , Magescas Jérémy , Feldman Jessica L. 
Published: February 2023

SummaryMicrotubule doublets (MTDs) are a well conserved compound microtubule structure found primarily in cilia. However, the mechanisms by which MTDs form and are maintainedin vivoremain poorly understood. Here, we characterize microtubule-associated protein 9 (MAP9) as a novel MTD-associated protein. We demonstrate thatC. elegansMAPH-9, a MAP9 homolog, is present during MTD assembly and localizes exclusively to MTDs, a preference that is in part mediated by tubulin polyglutamylation. Loss of MAPH-9 caused ultrastructural MTD defects, dysregulated axonemal motor velocity, and perturbed cilia function. As we found that the mammalian ortholog MAP9 localized to axonemes in cultured mammalian cells and mouse tissues, we propose that MAP9/MAPH-9 plays a conserved role in supporting the structure of axonemal MTDs and regulating ciliary motors.
Similarity in Functional Connectome Architecture Predicts Teenage Grit
Authors: Park Sujin , Park Daeun , Kim M. Justin 
Published: February 2023

AbstractGrit is a personality trait that encapsulates the tendency to persevere and maintain consistent interest for long-term goals. While prior studies found that grit predicts positive behavioral outcomes, there is a paucity of work providing explanatory evidence from a neurodevelopmental perspective. Based on previous research suggesting the utility of the functional connectome as a developmental measure, we tested the idea that individual differences in grit might be, in part, rooted in brain development in adolescence and emerging adulthood (N= 64, 11-19 years of age). Our analysis showed that grit was associated with connectome stability across conditions and connectome similarity across individuals. Notably, inter-subject representational similarity analysis revealed that teenagers who were grittier shared similar functional connectome architecture with each other, more so than those with lower grit. Our findings suggest that gritty individuals are more likely to follow a specific neurodevelopmental trajectory, which may underpin subsequent beneficial behavioral outcomes.Statement of RelevanceMaintaining consistent effort and passion for long-term, personally meaningful goals – often referred to as grit – is suggested to be associated with a wide range of positive outcomes such as academic achievement, career success and subjective well-being. Although grit has gained substantial amount of interest not only in the academia but also from the general population, only a handful of studies have examined its neural underpinnings. Here, we examined whether putative developmental measures using whole-brain functional connectivity patterns (i.e., functional connectome) explain individual differences in grit. Using publicly available developmental neuroimaging dataset ranging from early adolescence to emerging adulthood, we found that functional connectome stability within individuals and similarity between individuals uniquely explained self-reported grit. Confirmatory analyses demonstrated the existence of common neural representations shared among gritty teenagers, which were unveiled during movie-watching. These findings highlight that grit may be embedded in the functional connectome architecture during adolescence and emerging adulthood.
Perturbed neurochemical and microstructural organization in a mouse model of prenatal opioid exposure: a multi-modal magnetic resonance study
Authors: Shahid Syed Salman , Grecco Gregory G. , Atwood Brady K. , Wu Yu-Chien 
Published: February 2023

AbstractMethadone-based treatment for pregnant women with opioid use disorder is quite prevalent in the clinical environment. A number of clinical and animal model-based studies have reported cognitive deficits in infants prenatally exposed to methadone-based opioid treatments. However, the long-term impact of prenatal opioid exposure (POE) on pathophysiological mechanisms that govern neurodevelopmental impairment is not well understood. Using a translationally relevant mouse model of prenatal methadone exposure (PME), the aim of this study is to investigate the role of cerebral biochemistry and its possible association with regional microstructural organization in PME offspring. To understand these effects, 8- week-old male offspring with PME (n=7) and prenatal saline exposure (PSE) (n=7) were scanned in vivo on 9.4 Tesla small animal scanner. Single voxel proton magnetic resonance spectroscopy (1H-MRS) was performed in the right dorsal striatum (RDS) region using a short echo time (TE) Stimulated Echo Acquisition Method (STEAM) sequence. Neurometabolite spectra from the RDS was first corrected for tissue T1 relaxation and then absolute quantification was performed using the unsuppressed water spectra. High-resolution in vivo diffusion MRI (dMRI) for region of interest (ROI) based microstructural quantification was also performed using a multi-shell dMRI sequence. Cerebral microstructure was characterized using diffusion tensor imaging (DTI) and Bingham-neurite orientation dispersion and density imaging (Bingham-NODDI). MRS results in the RDS showed significant decrease in N-acetyl aspartate (NAA), taurine (tau), glutathione (GSH), total creatine (tCr) and glutamate (Glu) concentration levels in PME, compared to PSE group. In the same RDS region, mean orientation dispersion index (ODI) and intracellular volume fraction (VFIC) demonstrated positive associations with tCr in PME group. ODI also exhibited significant positive association with Glu levels in PME offspring. Significant reduction in major neurotransmitter metabolites and energy metabolism along with strong association between the neurometabolites and perturbed regional microstructural complexity suggest a possible impaired neuroadaptation trajectory in PME offspring which could be persistent even into late adolescence and early adulthood.