bluuebunny/crossref_metadata_2025_split huggingface dataset:
Neuroinflammation in the dorsomedial striatum causes excessive goal-directed action control by disrupting homeostatic astrocyte function
Authors: Abiero Arvie Rodriguez , Gladding Joanne M. , Iredale Jacqueline A. , Drury Hannah R. , Manning Elizabeth E. , Dayas Christopher V. , Dhungana Amolika , Ganesan Kiruthika , Turner Karly , Becchi Serena , Kendig Michael D. , Nolan Christopher , Balleine Bernard , Castorina Alessandro , Cole Louise , Clemens Kelly J. , Bradfield Laura A. 
Published: October 2024

AbstractCompulsive actions have been confusingly described as reflecting both excessive habitual and excessive goal-directed action control. Here we sought to resolve this contradiction by inducing the neuropathology commonly observed in individuals with compulsive disorders and examining the behavioural outcomes. We found that neuroinflammation in the dorsomedial striatum of rats caused them to be excessively goal-directed, as they acquired and maintained goal-directed actions under conditions that would otherwise produce habits. Immunohistochemical analyses suggested that these behaviours were a result of astrocytic proliferation. To investigate further, we chemogenetically activated the Gi-pathway in striatal astrocytes, which altered the firing properties of nearby medium spiny neurons and modulated goal-directed action control. Together, results show that striatal neuroinflammation is sufficient to cause excessive goal-directed control through dysregulated astrocyte function. Our findings suggest that individuals with striatal neuroinflammation are more prone to excessive goal-directed actions than habits, and that future interventions should aim to restore appropriate goal-directed control.
Establishing the green algaeChlamydomonas incertaas a platform for recombinant protein production
Authors: Kang Kalisa , do Espirito Santo Évellin , Diaz Crisandra Jade , Oliver Aaron , Saxton Lisa , May Lauren , Mayfield Stephen , Dutra Molino João Vitor 
Published: October 2024

ABSTRACTChlamydomonas incerta, a genetically close relative of the model green algaChlamydomonas reinhardtii, shows significant potential as a host for recombinant protein expression. Because of the close genetic relationship betweenC. incertaandC. reinhardtii, this species offers an additional reference point for advancing our understanding of photosynthetic organisms, and also provides a potential new candidate for biotechnological applications. This study investigates C. incerta’s capacity to express three recombinant proteins: the fluorescent protein mCherry, the hemicellulose-degrading enzyme xylanase, and the plastic-degrading enzyme PHL7. We have also examined the capacity to target protein expression to various cellular compartments in this alga, including the cytosol, secretory pathway, cytoplasmic membrane, and cell wall. When compared directly withC. reinhardtii,C. incertaexhibited a distinct but notable capacity for recombinant protein production. Cellular transformation with a vector encoding mCherry revealed thatC. incertaproduced approximately 3.5 times higher fluorescence levels and a 3.7-fold increase in immunoblot intensity compared toC. reinhardtii. For xylanase expression and secretion, bothC. incertaandC. reinhardtiishowed similar secretion capacities and enzymatic activities, with comparable xylan degradation rates, highlighting the industrial applicability of xylanase expression in microalgae. Finally,C. incertashowed comparable PHL7 activity levels toC. reinhardtii, as demonstrated by the in vitro degradation of a polyester polyurethane suspension, Impranil® DLN. Finally, we also explored the potential of cellular fusion for the generation of genetic hybrids betweenC. incertaandC. reinhardtiias a means to enhance phenotypic diversity and augment genetic variation. We were able to generate genetic fusion that could exchange both the recombinant protein genes, as well as associated selectable marker genes into recombinant offspring. These findings emphasizeC. incerta’s potential as a robust platform for recombinant protein production, and as a powerful tool for gaining a better understanding of microalgal biology.GRAPHICAL ABSTRACT
Statistical method accounts for microscopic electric field distortions around neurons when simulating activation thresholds
Authors: Weise Konstantin , Makaroff Sergey N. , Numssen Ole , Bikson Marom , Knösche Thomas R. 
Published: October 2024

AbstractIntroductionNotwithstanding advances in computational models of neuromodulation, there are mismatches between simulated and experimental activation thresholds. Transcranial Magnetic Stimulation (TMS) of the primary motor cortex generates motor evoked potentials (MEPs). At the threshold of MEP generation, whole-head models predict macroscopic (at millimeter scale) electric fields (50-70 V/m) which are considerably below conventionally simulated cortical neuron thresholds (175-350 V/m).MethodsWe hypothesize that this apparent contradiction is in part a consequence of electrical field warping by brain microstructure. Classical neuronal models ignore the physical presence of neighboring neurons and microstructure and assume that the macroscopic field directly acts on the neurons. In previous work, we performed advanced numerical calculations considering realistic microscopic compartments (e.g., cells, blood vessels), resulting in locally inhomogeneous (micrometer scale) electric field and altered neuronal activation thresholds. Here we combine detailed neural threshold simulations under homogeneous field assumptions with microscopic field calculations, leveraging a novel statistical approach.ResultsWe show that, provided brain-region specific microstructure metrics, a single statistically derived scaling factor between microscopic and macroscopic electric fields can be applied in predicting neuronal thresholds. For the cortical sample considered, the statistical methods match TMS experimental thresholds.ConclusionsOur approach can be broadly applied to neuromodulation models, where fully coupled microstructure scale simulations may not be computationally tractable.
Snapshots of Mitochondrial Fission Imaged by Cryo-Scanning Transmission Electron Tomography
Authors: Kirchweger Peter , Wolf Sharon Grayer , Varsano Neta , Dadosh Tali , Resch Guenter P. , Elbaum Michael 
Published: October 2024

AbstractMitochondria undergo constant remodeling via fission, fusion, extension, and degradation. Fission, in particular, depends on the accumulation of the mitochondrial fission factor (MFF) and subsequent recruitment of the dynamin-related protein Drp1. We used cryo-scanning transmission electron tomography (cryo-STET) to investigate mitochondrial morphologies in MFF mutant cells (MFF-/-) in ATP-depleting conditions that normally induce fission. The capability of cryo-STET to image through the cytoplasmic volume to a depth of 1 µm provides visualization of mitochondria and their surroundings intact. We imaged changes in mitochondrial morphology and cristae structure and contacts with endoplasmic reticulum, degradative organelles, and cytoskeleton at stalled fission sites. We found disruption of the outer membrane at contact sites with endoplasmic reticulum and degradative organelles at sites of mitophagy. We identified fission sites where the inner mitochondrial membrane is already separated while the outer is still continuous. While MFF is a general fission factor, these observations demonstrate that mitochondrial fission can proceed to the final stage in its absence. The use of cryo-STET allays concerns about the loss of structures due to sample thinning required for cryo-TEM tomography.Summary StatementImaging the whole cytosol in three dimensions greatly aids in understanding cellular processes. Here, we applied cryo-scanning transmission electron tomography to study stages of mitochondrial fission in the absence of the mitochondrial fusion factor protein.
Ybx1guides C/EBPα and cBAF chromatin-remodeling complex to promote adipogenic gene expression in steatotic hepatocytes
Authors: Jordan James M. , Qiao Jixuan , Zou Chenhui , Steensels Sandra , Haczeyni Fahrettin , Fraim Alessandra , Mendoza Arturro , de Jong Ype P. , Ersoy Baran A. 
Published: October 2024

SummaryExcessive lipid accumulation by hepatocytes underlies the pathogenesis of metabolic-dysfunction associated steatotic liver disease (MASLD) and metabolic-dysfunction associated steatohepatitis (MASH) from the earliest stages of the disease. How liver cells regulate the commitment to storing large volumes of fat despite resulting tissue damage is not well understood. Here, we showY box-binding protein 1(Ybx1) is necessary for ectopic activation of an adipocyte-specific gene expression module that potentiates lipid accumulation in hepatocytes. Diet-induced obese (DIO) mice, with liver-specific depletion ofYbx1(Ybx1LKO), are resistant to MASLD without becoming hyperlipidemic.Ybx1LKOlivers exhibit upregulation of hepatocyte markers, like urea processing enzyme carbamoyl phosphate synthetase I (Cps1), and downregulation of adipocyte markers known to be transcriptionally regulated by peroxisome proliferator-activated receptor gamma (PPARγ). In nuclei of DIO mice, YBX1 interacts with CCAAT-enhancer-binding proteins alpha (C/EBPα) and the canonical BRG1/BRM-associated factor complex (cBAF); andC/EBPαis required forYbx1-dependentPPARγexpression in cultured liver cells. The chromatin binding pattern of YBX1 from DIO mouse liver overlaps with those of C/EBPα and cBAF at key adipogenic loci includingPpargandCfd. However, most YBX1-DNA binding occurs on C/EBPα-cBAF-depleted stretches located on chromosomes 16, 18, and 19, spanning up to five Mb, and overlapping regions which are inaccessible in differentiating preadipocytes, thereby bounding activational C/EBPα-cBAF complex-DNA interactions. Moreover, YBX1 expression is increased up to nine-fold in the livers of obese patients with MASLD-MASH compared to healthy obese controls; and adipocyte-specific genes, upregulated byYbx1, are also upregulated in human MASLD-MASH. Overall, our study uncoversYbx1as a critical epigenetic regulator in liver and potential therapeutic target for treatment of MASLD and MASH.
OLIGONUCLEOTIDES TARGETING THE 3’ SPLICE SITE DOWNSTREAM OF A MICROEXON AS AN INNOVATIVE THERAPY FOR AUTISM
Authors: Martinez-Pizarro Ainhoa , Picó Sara , Holm Lise Lolle , Doktor Thomas K , Andresen Brage S , Lucas José J , Desviat Lourdes R 
Published: October 2024

ABSTRACTBackgroundMicroexons are highly conserved and mostly neuronal-specific 3-27 nucleotide exons, enriched in genes linked to autism spectrum disorders (ASD). We have previously shown decreased inclusion of a neuronal specific 24 bp microexon (exon 4) of the translational regulatorCPEB4in brains of idiopathic ASD cases and that this leads to CPEB4 aggregation and subsequent under-expression of multiple high confidence ASD-risk genes. Furthermore, enhanced skipping of theCPEB4microexon is also a novel etiological mechanism in schizophrenia (SCZ).MethodsIn this work we designed and tested in neuroblastoma cells a series of splice switching antisense oligonucleotides (SSO) targeting theCPEB4genomic region surrounding the microexon.ResultsSSOs targeting candidate intronic regions near the microexon resulted in a decrease in microexon inclusion by blocking hnRNPC/PTPB1 binding, thus mimicking the isoform imbalance observed in ASD. However, based on the kinetic coupling model correlating transcriptional elongation with splicing regulation, we identified SSOs targeting downstream 3’ splice site of exon 5 that favoured microexon inclusion in a dose-dependent manner and resulted in increased protein levels ofFOXP1andAUTS2,two high-confidence ASD risk genes that are known targets of CPEB4 and whose protein levels are reduced in ASD.ConclusionsThese results deepen our understanding of the complex splicing regulation of microexons and open new applications of SSOs to treat diseases such as ASD and SCZ that are characterized by altered microexon inclusion.
The Interaction ofUBR4, LRP1, andOPHN1in Refractory Epilepsy:DrosophilaModel to Investigate the Oligogenic Effect on Epilepsy
Authors: Huang Rui-Na , Luo Si-Yuan , Huang Tao , Li Xiong-Sheng , Zhou Fan-Chao , Li Ling-Ying , Chen Ze-Ru , Chen Sheng-Qiang , Tang Bin , Qiao Jing-Da 
Published: October 2024

AbstractRefractory epilepsy is an intractable neurological disorder that is currently difficult to achieve effective pharmacological control in clinical practice and can result in poor quality of life as well as increased mortality. Genetic factors are important causes of epilepsy, especially idiopathic epilepsy. In the clinical gene sequencing work, we identified one refractory epileptic patient who carried three epileptogenic candidate genes:UBR4, LRP1, andOPHN1variants. To clarify the epileptogenicity and interactions ofUBR4, LRP1, andOPHN1variants, as well as explore the role of each mutant gene in eliciting epilepsy, we established single-knockdown, double-knockdown, and triple-knockdownDrosophilamodels by suppressing the gene expression of these three epileptogenic candidate genes. After conducting behavioral testing for epilepsy in the sevenDrosophilaknockdown models, regression equations illustrating the causal connection between genotype and phenotype were developed. The mutations of the three epileptogenic candidate genes:UBR4, LRP1, andOPHN1, were proved to be epileptogenic at the animal level both in seizure rates and logistic regression results. Moreover, significant negative interactions inUBR4-OPHN1KD andLRP1-OPHN1KD were found in the trigenic KD system as well as theUBR4-OPHN1andLRP1-OPHN1digenic KD system according to the logistic regression analysis result. However, despite the existence of negative interaction, three groups of digenic KD flies and one group of trigenic KD flies presented higher seizure rates than that of the corresponding monogenic KD flies.LRP1-OPHN1KD together with its negative interaction was regarded as the main causative factors for seizure in theUBR4-LRP1-OPHN1KD.
Principles of nutrition-dependent root-microbiome engineering for regulating crop yield via live microbial inoculants
Authors: Huang Yuxiao , Tang Shengyue , Liu Rumeng , Liu Ju , Xiao Ting , Ni Bin 
Published: October 2024

AbstractAs the second genome, host-associated microbiota can enhance the functions of host immune systems, improve host nutrient availability and acquisition capacity, and increase host resistance to abiotic stress. Constructing host-associated microbiomes by applying various bioinoculants has become an attractive tool for promoting human health and increasing food production. However, despite their promising properties, the efficacy of bioinoculants vary significantly in actual field and clinical practices. Understanding the global design principles that shape the outcomes of interactions between bioinoculants and target host–microbiome symbionts remains a considerable challenge. In this study, we used a wheat production system as a case study to quantitatively understand how soil nutrient status impacts the establishment of host–microbiome interaction networks and their subsequent interactions with external bioinoculants. We found that soil organic carbon, one of the most general soil properties for global crop productivity and resilience, could affect the outcome of bioinoculant applications in wheat production systems, which led to functional instability in bioinoculant application outcomes. The results of this study significantly improved our understanding of the global design principles of nutrition-dependent root-microbiome engineering for regulating crop yield via the application of live microbial inoculants and provide theoretical guidance for bioinoculant applications in agricultural practice.
The impact of dwell time on the contextual effect of visual and passive lead-in movements
Authors: Alvarez-Hidalgo Laura , Franklin David W. , Howard Ian S. 
Published: October 2024

ABSTRACTContextual cues arising from distinct movements are crucial in shaping control strategies for human movement. Here, we examine the impact of visual and passive lead-in movement cues on unimanual motor learning, focusing on the influence of “dwell time”, in which two-part movements are separated by the interval between the end of the first movement and the start of the second. We used a robotic manipulandum to implement a point-to-point interference task with switching opposing viscous curl-fields in male and female human participants. Consistent with prior research, in both visual and passive lead-in conditions, participants showed significant adaptation to opposing dynamics with short dwell times. As dwell time increased for both visual and passive signals, past movement information had less contextual influence. However, the efficacy of visual movement cues declined faster as dwell times increased. At dwell times greater than 800ms, the contextual influence of prior visual movement was small, whereas the effectiveness of passive lead-in movement was found to be significantly greater. This indicates that the effectiveness of sensory movement cues in motor learning is modality-dependent. We hypothesize that such differences may arise because proprioceptive signals directly relate to arm movements, whereas visual inputs can relate to many aspects of movement in the environment and not just to our own arm movements. Therefore, the motor system may not always find them as relevant for predictive control of dynamics.Significance StatementThis study reveals the critical role of contextual cues from distinct movements in shaping motor learning. Here, we examined the influence of “dwell time”, the interval between the end of the first and the start of the second movement. Notably, visual lead-in movement cues lose their effectiveness sooner than passive lead-in movement cues as dwell time increases. This is possibly due to their lesser relevance to self-generated movements and the longer processing delays in visual information. This finding underscores the modality-dependent nature of sensory cues in motor learning. Understanding these effects can inform the development of more effective rehabilitation and training programs by leveraging the strengths of different sensory modalities to optimize motor learning.News & NoteworthyThis research uncovers, for the first time, how visual and proprioceptive sensory cues affect motor learning as a function of the pause or “dwell time” in two-part movements. The study has shown that visual lead-in movement cues lose their effectiveness sooner than passive lead-in movement cues as dwell time increases. By revealing the modality-dependent nature of sensory information, this study enhances our understanding of motor control and opens new possibilities for improving therapeutic interventions.
Prevalence of Key Spike Protein Mutations and Their Limited Effect on COVID-19 Clinical Manifestations in Sylhet, Bangladesh
Authors: Akter Shahina , Zeba Zebunnesa , Hossain Md. Anwar , Ofori Michael Arthur , Shahab Muhammad , Rolim Silva Gabriel Vinícius , Nobre Oliveira Jonas Ivan , Akash Shopnil , Banu Tanjina Akhtar , Islam Mousona , Sarkar Murshed Hasan , Goswami Barna , Chowdhury Sanjana Fatema , Habib Md. Ahashan , Khan Md. Salim 
Published: October 2024

AbstractSARS-CoV-2 is the virus responsible for the COVID-19 pandemic, which has spread rapidly around the world and had a significant impact on public health and the economy worldwide. This study investigated the correlation between SARS-CoV-2 spike protein mutations, clinical outcomes and patient demographics in the Sylhet region of Bangladesh. We looked at the full genome sequences of 37 SARS-CoV-2 samples that were collected between January and June 2020. Specifically, we looked at five major spike protein mutations: D614G, A570D, D1118H, A222V, and P681R. The D614G mutation was the most prevalent (94.6%), followed by A570D and D1118H (both 32.4%), A222V (29.7%), and P681R (13.5%). Despite their high prevalence, we found no statistically significant associations between these mutations and clinical outcomes or demographic variables, except for possible trends for the P681R mutation. We found that age played a decisive role in recovery from COVID-19, with older patients exhibiting slower recovery rates. In terms of predictors of outcome, gender differences were observed: clinical symptoms and viral genetic mutations were more influential for men, while age and disease progression were more important for women. Common nucleotide substitutions (A23403G, C3037T, and C14408T) associated with European strains were identified, suggesting possible routes of transmission. This study contributes to our understanding of the genetics, clinical manifestations and epidemiology of SARS-CoV-2 in the Sylhet region and emphasizes the need for continuous genomic surveillance and adaptive public health strategies.
Simulated microgravity accelerates alpha-synuclein aggregation and induces oxidative stress in anin vitroParkinson’s disease model
Authors: Lentini Veronica , Uras Giuseppe , Manca Alessia , El Faqir Mohammed Amine , Lucas-Del-Pozo Sara , Deiana Nicola , Cao Giacomo , Schapira Anthony HV , Pantaleo Antonella 
Published: October 2024

AbstractParkinson’s disease (PD) is a neurodegenerative disorder characterized by the accumulation of alpha-synuclein aggregates and progressive neuronal loss in the substantia nigra, with aging being its primary risk factor. The current available models to study PD mechanisms are largely relying on genetic mutations to recapitulate PD typical hallmarks, such as increased alpha-synuclein aggregation. However, they do not model the aging features associated with the disease.Microgravity, a condition experience by astronauts during space missions, is known to induce ageing-like modifications on both systemic and cellular physiology.To replicate the aging-related stress observed in PD patients, we exposed SH-SY5Y and 3K-SNCA mutant cell lines to simulated microgravity.Our findings revealed that simulated microgravity enhanced PD alterations, with a significant increase in misfolded and phosphorylated a-syn. This was accompanied by heightened oxidative stress, as evidenced by increased levels of reactive oxygen species, without a sufficient antioxidant response. These results suggest that simulated microgravity effectively mimics and accelerate the stress associated with aging in PD cell models, regardless of the presence of PD mutation. This study highlights the potential of simulated microgravity as a tool for investigating aging processes in neurodegenerative diseases.