bluuebunny/crossref_metadata_2025 huggingface dataset:
Extracorporeal Membrane Oxygenation for COVID-19: Collaborative Experience From the Texas Medical Center in Houston With 2 Years Follow-Up
Authors: Akkanti Bindu , Suarez Erik E. , O’Neil Erika R. , Rali Aniket S. , Hussain Rahat , Dinh Kha , Tuazon Divina M. , MacGillivray Thomas E. , Diaz-Gomez Jose L. , Simpson Leo , George Joggy K. , Kar Biswajit , Herlihy J. Patrick , Shafii Alexis E. , Gregoric Igor D. , Masud Faisal , Chatterjee Subhasis
Published: September 2022

Patients with severe refractory hypoxemic respiratory failure may benefit from extracorporeal membrane oxygenation (ECMO) for salvage therapy. The Coronavirus disease 2019 (COVID-19) pandemic offered three high-volume independent ECMO programs at a large medical center the chance to collaborate to optimize ECMO care at the beginning of the pandemic in Spring 2020. Between March 15, 2020, and May 30, 2020, 3,615 inpatients with COVID-19 were treated at the Texas Medical Center. During this time, 35 COVID-19 patients were cannulated for ECMO, all but one in a veno-venous configuration. At hospital discharge, 23 (66%) of the 35 patients were alive. Twelve patients died of vasodilatory shock (n = 9), intracranial hemorrhage (n = 2), and cannulation-related bleeding and multiorgan dysfunction (n = 1). The average duration of ECMO was 13.6 days in survivors and 25.0 days in nonsurvivors (p < 0.04). At 1 year follow-up, all 23 discharged patients were still alive, making the 1 year survival rate 66% (23/35). At 2 years follow-up, the overall rate of survival was 63% (22/35). Of those patients who survived 2 years, all were at home and alive and well at follow-up.
Effect of APOB gene polymorphisms on body mass index, blood pressure, and total cholesterol levels: A cross-sectional study in Mexican population
Authors: Colima Fausto Ana Gabriela , Topete Jaqueline , González García Juan Ramón , Hernández Flores Teresita de Jesús , Rodríguez Preciado Sergio Yair , Magaña Torres María Teresa
Published: September 2022

APOB gene polymorphisms are considered risk factors for the development of dyslipidemia, hypertension, and cardiovascular disease (CVD) in several populations. In Mexico, these pathologies are frequent and studies regarding this gene are scarce. The aim of this cross-sectional study was to determined genotype, allele, and haplotype frequencies of APOB polymorphisms and performed analyses of association among the biochemical, hemodynamic, anthropometrical, and genetic variables. Blood samples were taken from 361 subjects from unselected Mexican population for biochemical analysis and for deoxyribonucleic acid extraction; besides blood pressure and body mass index (BMI) were measured. APOB polymorphisms rs934197, rs533617, rs693, and rs1042031 were genotyped by polymerase chain reaction (PCR)-restriction fragment length polymorphism; whereas, rs17240441 and c.66_67insCTGCTG were genotyped by PCR followed by electrophoresis. Genotype and allele frequencies were obtained by simple counting and deviations from Hardy-Weinberg equilibrium (HWE) were calculated by chi-square test. The effect of the polymorphisms on the quantitative variables was determined using analysis of variance, Student’s t test, Pearson’s and Spearman’s correlations and multiple linear regression models. All the polymorphisms were within HWE. Frequencies of mutated alleles were highly heterogeneous: rs934197-T 33.6%, rs17240441-D 39.3%, c.66_67insCTGCTG-I 3.9%, rs533617-G 0.9%, rs693-T 40.5%, and rs1042031-G 17.3%. Chronic degenerative diseases were frequent in the studied population: overweight-obesity 55.1%, dyslipidemia 45.8%, and hypertension 23.5%. The association analyses showed that despite adjustments for age and sex the mutated alleles rs934197-T, rs1042031G, c.66_67-insCTGCTG-I, and rs533617-G, were related to lower values of BMI, total cholesterol (TC), systolic blood pressure, and diastolic blood pressure, respectively. All polymorphisms analyzed except rs533517 and c.66_67insCTGCTG showed high frequencies of the mutated allele, making them useful for association studies. Our results revealed that, APOB gene polymorphisms could be contributing to the development of several chronic diseases, such as essential hypertension, dyslipidemias, obesity, among others. However, specific studies with each pathology are needed to know the possible implications of the polymorphisms.
Correlation between diminished vagal tone and somatic dysfunction severity in very and extremely low birth weight preterm infants assessed with frequency spectrum heart rate variability and salivary cortisol
Authors: Vismara Luca , Gianmaria Tarantino Andrea , Bergna Andrea , Bianchi Giuliana , Bragalini Cristina , Billò Elisa , Dal Farra Fulvio , Buffone Francesca , Agosti Massimo
Published: September 2022

Osteopathic manipulative treatment (OMT) is evolving in the neonatal intensive care unit (NICU) setting. Studies showed its efficacy in length of stay and hospitalization costs reduction. Moreover, it was suggested that OMT has a modulatory effect on the preterm infants’ autonomic nervous system (ANS), influencing saturation and heart rate. Even if OMT is based on the palpatory examination of the somatic dysfunctions (SD), there are controversies about its identification and clinical relevance. The objective of this study was to evaluate the inter-rater reliability, clinical characteristics, and functional correlation of the SD Grade score with the heart rate variability (HRV) and the salivary cortisol (sCor) using a multivariate linear model approach. To evaluate those features, we implemented an ad hoc SD examination for preterm infants that was performed by 2 trained osteopaths. It was based on the new variability model of SD that includes an SD Grade assessment procedure. The ANS features were assessed by frequency parameters of HRV studying high frequency (HF), low frequency (LF), and HF/LF, whereas sCor was tested with a radioimmunoassay. The ANS assessment was standardized and performed before SD testing. Sixty-nine premature infants were eligible. SD Grade showed excellent concordance between the blinded raters. Using SD Grade as a grouping variable, the infants presented differences in GA, Apgar, pathological findings, length of stay, and ventilatory assistance. In our multivariate model, HF, LF, and LF/HF resulted linearly correlated with SD Grade. Instead, sCor presented a linear correlation with 5’ Apgar and respiratory distress syndrome but not with SD Grade. SD Grade was in line with the natural history of the underdevelopment due to prematurity. Our models indicate that the cardiac vagal tone is linearly related with SD Grade. This finding may improve the multidisciplinary decision making inside NICU and the management of modifiable factors, like SD, for cardiac vagal tone regulation.
Mental problems and risk factors for depression among medical students during the COVID-19 pandemic: A cross-sectional study
Authors: Pattanaseri Keerati , Atsariyasing Wanlop , Pornnoppadol Chanvit , Sanguanpanich Naratip , Srifuengfung Maytinee
Published: September 2022

Prevalence of depression is high among medical students and several mental problems are identified as risk factors. Coronavirus disease 2019 (COVID-19) pandemic causes difficulties that could adversely affect mental health. However, data concerning prevalence of mental problems, and whether or not these problems remain risk factors for depression during the COVID-19 pandemic in medical students are scarce. To investigate the prevalence of depression, social media addiction, game addiction, sleep quality, eating disorder risk, and perceived stress among Thai medical students, risk factors for depression were investigated. Online surveys via our faculty’s learning portals were advertized to medical students who engaged online learning and 224 respondents provided complete data. Study-related medical students’ data were collected using the Patient Health Questionnaire-9 for depression, the Social-Media Addiction Screening Scale for social media addiction, the Game Addiction Screening Test for game addiction, the Pittsburgh Sleep Quality Index for sleep quality, the Eating Attitudes Test for eating disorder risk, and the Perceived Stress Scale for perceived stress. Depression was reported in 35.7% of medical students, social-media addiction in 22.3%, game addiction in 4.5%, eating disorder risk in 4.9%, poor sleep quality in 80.8%, and moderate-to-high perceived stress in 71.4%. The independent predictors of depression were lower grade point average, social media addiction, and moderate-to-high perceived stress. A high prevalence of depression, stress, and poor sleep was found among medical students during the COVID-19 pandemic. Medical students who are stressed, have lower grades, and/or who are addicted to social media warrant depression screening.
Increased percentage of apoptotic and CTLA-4 (CD152) expressing cells in CD4+/CD8+ cells in COVID-19 patients
Authors: Zahran Asmaa M. , Nafady-Hego Hanaa , Rashad Alaa , El-Badawy Omnia , Nasif Khalid Ali , Mostafa Amr Talat , Osman Heba Ahmed , Dongol Eptehal Mohammed , Hashim Abdelkader Ahmed , Abdelrazek Ghada M. , Abd Elrahman Nehad Hassan , Nafady Asmaa
Published: September 2022

Coronavirus infectious disease 2019 (COVID-19) confirmed cases are characterized by T lymphopenia. Total apoptotic and cytotoxic T-lymphocyte antigen-4 (CTLA-4) expressing cells among CD4+/CD8+ cells were analyzed in 24 COVID-19 patients (16 out-patients and 8 in-patients) and 18 healthy volunteers using flow cytometry to detect their possible role in T lymphopenia. Hospitalized patients did not show significant difference compared to non-hospitalized patients. While the percentage and absolute count of CD4+/CD8+ cells were significantly reduced in COVID-19 cases compared to healthy control (P < .05), the proportion of apoptotic and CTLA-4 expressing CD4+/CD8+ cells were significantly up-regulated in COVID-19 patients (P < .05). In addition, apoptotic and CTLA-4+/CD4+ cells were directly related to dyspnea duration, chest CT score, ferritin, and C-reactive protein and inversely correlated with platelet count in COVID-19 patients. While apoptotic and CTLA-4+/CD8+ cells were directly related to lymphocyte count in COVID-19 patients. The apoptotic and CTLA-4+ cells were directly related to each other in CD4+/CD8+ cells (P < .05). White blood cells (WBCs) (×103/L), eosinophils (ratio and count), lymphocyte ratio, neutrophil ratio, neutrophil/lymphocyte ratio, neutrophil/CD4 ratio, neutrophil/CD8 ratio, CD4+ cells ratio, and CTLA-4+ cells percentage), and CD8+ cells (ratio, count, total apoptotic cell, and CD152 + cells) were all found to be significantly altered in association with COVID-19. Total lymphopenia and depletion of CD4+/CD8+ cells are characterizing COVID-19 patients. Increased apoptosis and CTLA-4 expression in CD4+/CD8+ cells in COVID-19 and their correlations with reduced cell count and severity indicators as CRP and ferritin can be used for diagnosis and follow up of the clinical severity. Our current study proposes promising future diagnostic and therapeutic targets.
Association of glutathione S-transferases (GSTT1, GSTM1 and GSTP1) genes polymorphisms with nonalcoholic fatty liver disease susceptibility: A PRISMA-compliant systematic review and meta-analysis
Authors: Zhu Yi , Yang Jian-Hua , Hu Jun-Ping , Qiao Ming
Published: September 2022

Background:

Glutathione S-transferases (GSTs) genes single-nucleotide polymorphisms (SNPs) have been connected with the susceptibility of nonalcoholic fatty liver disease (NAFLD), but with inconsistent results across the current evidences. The present work was schemed to explore the association between GSTs genes polymorphisms and the NAFLD vulnerability via meta-analysis.

Methods:

PubMed, Web of Science, Cochrane Library, China National Knowledge Infrastructure and Wanfang were retrieved for eligible literatures previous to March 10, 2021. The odds ratio (OR) of the dichotomic variables and the standardized mean difference of quantitative variables with corresponding 95% confidence intervals (95%CIs) were computed to evaluate the strength of the associations. The quality of included studies were assessed via using Newcastle-Ottawa Scale (NOS).

Results:

In total, 7 case-control studies encompassing 804 NAFLD patients and 1362 disease-free controls in this meta-analysis. Ultimately, this analysis included 6, 5 and 5 studies for GSTM1, GSTT1 and GSTP1 polymorphisms, respectively. The pooled data revealed that the GSTs genes SNPs had conspicuous associations with NAFLD susceptibility: for GSTM1, null versus present, OR = 1.46, 95%CI 1.20 to 1.79, P = .0002; for GSTT1, null versus present, OR = 1.34, 95%CI 1.06 to 1.68, P = .01; for GSTP1, Ile/Val or Val/Val versus Ile/Ile, OR = 1.60, 95%CI 1.23 to 2.09, P = .0005.

Conclusion:

This work revealed that the GSTM1 null, GSTT1 null and GSTP1-Val genotypes might be related to increased NAFLD susceptibility.
Auricular Reconstruction in Adult Patients With Unprepared Congenital Microtia
Authors: Ma Tengxiao , Li Lei , Wang Xiu , Zhang Zhengwen
Published: September 2022

Background

Because costal cartilage becomes hard and brittle, skin thickens, and elasticity decreases in adult patients with microtia, it is a great challenge for plastic surgeons to reconstruct the auricle with autologous costal cartilage. Therefore, this article concentrates on sharing the experience of auricular reconstruction in adult patients with microtia.

Methods

From January 2015 to January 2021, auricular reconstruction was performed in 38 adult patients (39 ears) of congenital microtia based on autologous costal cartilage. The whole procedure was divided into 2 stages: stage I, the individualized framework carved with autologous costal cartilage was inserted into subcutaneous pocket in the mastoid region; then, the earlobe was transposed backward; and stage II, ear elevation, harvesting the retroauricular fascial flap to cover the support scaffold and closing the defect with free skin graft, was performed.

Results

All patients successfully underwent ear reconstruction. The follow-up time ranged from 3 months to 3 years. Infection occurred in 1 patient. The ear frameworks were partially broken at the helix in 4 cases. Retroauricular graft skin survival was poor in 1 patient. Retroauricular hypertrophic scars occurred in 2 cases. Bad projection of the reconstructed ear occurred in 1 case. Totally 38 patients were satisfied with the results.

Conclusions

According to the physiological characteristics of the costal cartilage and skin soft tissues of adult patients, improvements are made to details based on the Nagata's method, so that the adult patients with microtia can obtain satisfactory surgical results.
Effect of Dopaminergic Therapy on Impulse Control Disorders in Patients With a Prolactinoma
Authors: Ozdeniz Varan Esin , Gurvit Hakan
Published: September 2022

Background:

Studies have reported an increase in the incidence of impulse control disorders (ICDs) in patient groups treated with dopamine agonists (DAAs), especially in Parkinson disease (PD). However, very few studies have reported on ICDs in individuals with a prolactinoma who were treated with DAAs.

Objective:

To see whether a DAA by itself causes ICDs in individuals with a prolactinoma by controlling the susceptibility to impulsivity by excluding individuals with other risk factors for ICDs.

Method:

We compared the performance of 31 individuals with a prolactinoma receiving DAA therapy (DAA+) on various behavioral scales and the Iowa gambling task (IGT), a neuropsychological instrument that measures risky decision-making, with the performance of 20 individuals with a prolactinoma who were not on DAA therapy (DAA−) and 30 healthy controls (HC).

Results:

There was no significant difference among the groups concerning performance on the Zuckerman Sensation Seeking Scale—V, Minnesota Impulse Disorders Interview, Barratt Impulsiveness Scale—11, or IGT. No correlation was found between the scores on these scales and the duration or dose of DAA in the DAA+ group. The incidence of ICDs was 25.8% in the DAA+ group, 15% in the DAA− group, and 16.7% in the HC. The differences among the groups did not reach statistical significance.

Conclusion:

Individuals who are under treatment with low-dose, D2-selective DAAs for a prolactinoma do not face an increased risk for ICDs, especially when they are carefully screened for any psychiatric comorbidity that may also display impulsivity.
Knowledge Mapping of Nigeria’s Scientific Contribution to Antimicrobial Resistance Research: A visualized investigation using VOS viewer and Cite Space
Authors: Adeiza Shuaibu Suleiman , Shuaibu Mohammed Gazali , Shuaibu Bello Abdulmalik
Published: September 2022

Objective

A comprehensive overview of the research output, including conceptual and temporal trends, is required to address the growing AMR burden in Nigeria, which was previously lacking. This study uses bibliometric analysis to show this.

Methods

Data from a query of AMR articles in the Dimensions database (PubMed included) were subjected to bibliometric analysis (1972–2022). Bibliometric indicators, topic networks were established and topic trends were analysed by frequency, relevance scores, and trends over time.

Results

A total of 0.2% of the papers on AMR published worldwide were written by authors or institutions from Nigeria. In 2021, publications grew by 13.6%, highlighting the field’s increased vigour. The vast majority of publications (57.18%) were in the field of Medical and Health Sciences, with 2428 papers. The top journal for AMR papers with at least one Nigerian institution affiliation was African Journal of Clinical and Experimental Microbiology, which published 1.8% of these papers. Antimicrobial stewardship, Clinical and laboratory practices on AMR, Public health implications, Traditional and molecular methods, and Phytomedicine and drug discovery were prominent areas of focus for Nigerian researchers.

Conclusion

This study provides a comprehensive overview of the AMR research output, highlighting the need of increased research capacity to address the burden of AMR in Nigeria. Because Nigeria is overly reliant on conventional methods of discovery and development, innovation is essential for the future of antibiotics.
SRF transcriptionally regulates the oligodendrocyte cytoskeleton during CNS myelination
Authors: Iram Tal , Garcia Miguel A. , Amand Jérémy , Kaur Achint , Iyer Manasi , Lam Mable , Ambiel Nicolas , Keller Andreas , Wyss-Coray Tony , Kern Fabian , Zuchero J. Bradley
Published: September 2022

Myelination of neuronal axons is essential for nervous system development. Myelination requires dramatic cytoskeletal dynamics in oligodendrocytes, but how actin is regulated during myelination is poorly understood. We recently identified serum response factor (SRF)—a transcription factor known to regulate expression of actin and actin regulators in other cell types—as a critical driver of myelination in the aged brain. Yet, a major gap remains in understanding the fundamental role of SRF in oligodendrocyte lineage cells. Here we show that SRF is required cell autonomously in oligodendrocytes for myelination during development. Combining ChIP-seq with RNA-seq identifies SRF-target genes in OPCs and oligodendrocytes that include actin and other key cytoskeletal genes. Accordingly, SRF knockout oligodendrocytes exhibit dramatically reduced actin filament levels early in differentiation, consistent with its role in actin-dependent myelin sheath initiation. Together, our findings identify SRF as a transcriptional regulator that controls the expression of cytoskeletal genes required in oligodendrocytes for myelination. This study identifies a novel pathway regulating oligodendrocyte biology with high relevance to brain development, aging, and disease.

Highlights

Developmental CNS myelination requires the transcription factor SRF in oligodendrocytes.

SRF targets actin and actin-regulatory but not myelin related genes.

SRF drives oligodendrocyte actin cytoskeleton dynamics during early stages of myelination.
Parasite gene flow in riverine habitats: ascertaining the roles of stream drift, river bifurcations and host dispersal
Authors: Janecka Mary J.
Published: September 2022

Determining the factors that shape parasite gene flow across complex landscapes is central to understanding the coevolutionary process. In rivers, unidirectional currents, stream drift, may facilitate downstream parasite dispersal, while bifurcating branches may cause population subdivision among branches. The generative habitat processes in rivers can potentially interact with host dispersal to determine gene flow within the aquatic ecosystem. We examined the population genetic structure and gene flow of a trematode infecting semi-aquatic snakes to determine the relative contributions of stream drift, river bifurcations and host dispersal in shaping parasite gene flow in three connected riverine ecosystems. We found the strongest population structure immediately below a recently constructed reservoir at the confluence of the two rivers, with mild structure between one out the the three reaches of the river. Patterns of isolation by distance along linear pathways were not uniform, despite similar path network path lengths. We found the strongest evidence for isolation by distance associated with the river bifurcation. The comparison of terrestrial versus within river network dispersal indicates that parasite transmission between branches occurs along river networks. Short-distance terrestrial dispersal however may be important along some linear networks. Our results highlight the complexity of host-habitat interactions shaping parasite gene flow and the need for empirical data from natural systems to develop accurate models of parasite transmission in rivers.
Targeted Protein Degradation via Nanoparticles
Authors: Liu Yang , Liu Runhan , Dong Jiawei , Xia Xue , Yang Haoying , Wei Sijun , Fan Linlin , Fang Mengke , Zou Yan , Zheng Meng , Leong Kam W. , Shi Bingyang
Published: September 2022

Strategies that hijack selective proteins of interest (POIs) to the intracellular protein recycling machinery for targeted protein degradation (TPD) have recently emerged as powerful tools for undruggable targets in biomedical research and the pharmaceutical industry. However, targeting any new POI with current TPD tools requires laborious case-by-case design for different diseases and cell types, especially for those extracellular targets. Here, we observed that nanoparticles (NPs) can mediate the receptor-free internalization of hijacked protein and further developed a generic paradigm for both intra- and extracellular POI degradation, by making full use of clinically approved components. The phenomenon is general, as we found nanostructures such as lipid nanoparticle (LNP), liposomes, exosomes, polymeric nanoparticles, inorganic nanoparticles and their hybrid nanoparticles modified with POI-recognizing moiety (antibody, peptides, small molecule drugs) can mediate TPD for a wide range of extracellular/membrane and intracellular targets. The super flexible and feasible-to-synthesize TPD-NPs paradigm may revolutionize the current TPD tools development landscape and it provides fundamental knowledge to receptor mediated drug therapies.

Highlights

Nanoparticle mediated targeted protein degradation (TPD-NP) can be constructed by “Mix-and-Match” and do not requirede novosynthesis or specific internalization design.

TPD-NPs can be equipped with specific cell type targeting capacity, loading and controlled release of therapeutic cargos, as well as biological barrier penetration capacity.

Assembling components can be clinical-approved or biodegradable for translational medicine.

TPD-NP highly boosted current application platforms of nano-delivery and TPD.
Predicting Phenotypes From Novel Genomic Markers Using Deep Learning
Authors: Sehrawat Shivani , Najafian Keyhan , Jin Lingling
Published: September 2022

Genomic selection models use Single Nucleotide Polymorphism (SNP) markers to predict phenotypes. However, these predictive models face challenges due to the high dimensionality of genome-wide SNP marker data. Thanks to recent breakthroughs in DNA sequencing and decreased sequencing cost, the study of novel genomic variants such as Structural Variations (SVs) and Transposable Elements (TEs) become increasingly prevalent. In this paper, we develop a deep convolutional neural network model,NovGMDeep, to predict phenotypes using SVs and TEs markers for genomic selection. The proposed model is trained and tested on samples ofA. thalianaandO. sativausingk-fold cross-validation. The prediction accuracy is evaluated using Pearson’s Correlation Coefficient (PCC), Mean Absolute Error (MAE), and Standard Deviation (SD) of MAE. The predicted results showed higher correlation when the model is trained with SVs and TEs than with SNPs.NovGMDeepalso has higher prediction accuracy when comparing with conventional statistical models. This work sheds light on the unrecognized function of SVs and TEs in genotype-to-phenotype associations, as well as their extensive significance and value in crop development.
Feature detecting columnar neurons mediate object tracking saccades in Drosophila
Authors: Frighetto Giovanni , Frye Mark A.
Published: September 2022

Tracking visual objects while stabilizing the visual background is complicated by the different computational requirements for object tracking and motion vision. In fruit fly, directionally selective motion detectors T4 and T5 cells supply wide-field neurons of the lobula plate, which control smooth gaze stabilization behavior. Here, we hypothesized that an anatomically parallel pathway supplied by T3, which encodes small moving objects and innervates the lobula, drives body saccades toward objects. We combined physiological and behavioral experiments to show that T3 neurons respond omnidirectionally to contrast changes induced by the visual stimuli that elicit tracking saccades, and silencing T3 reduced the frequency of tracking saccades. By contrast, optogenetic manipulation of T3 increased the number of tracking saccades. Our results represent the first evidence that parallel motion detection and feature detection pathways coordinate smooth gaze stabilization and saccadic object tracking behavior during flight.
Optical modulation of excitation-contraction coupling in human induced pluripotent stem cell-derived cardiomyocytes
Authors: Vurro Vito , Federici Beatrice , Ronchi Carlotta , Florindi Chiara , Sesti Valentina , Crasto Silvia , Maniezzi Claudia , Galli Camilla , Antognazza Maria Rosa , Bertarelli Chiara , Di Pasquale Elisa , Lanzani Guglielmo , Lodola Francesco
Published: September 2022

Non-genetic photostimulation is a novel and rapidly growing multidisciplinary field of research that aims to induce light sensitivity in living systems by exploiting exogeneous phototransducers.

Here we propose a recently synthetized intramembrane photoswitch, based on an azobenzene derivative (Ziapin2), for optical pacing of human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs).

The light-mediated stimulation process has been studied by applying several characterization techniques to detect the effect on the cell properties. In particular, we recorded changes in membrane capacitance, in membrane potential (Vm), and modulation of intracellular Ca2+dynamics. Finally, cell contractility was analyzed using a custom MATLAB algorithm.

Photostimulation of intramembrane Ziapin2 causes a transient Vmhyperpolarization followed by a delayed depolarization and action potential firing. The observed initial electrical modulation nicely correlates with changes in Ca2+dynamics and contraction rate.

This work represents the proof of principle that Ziapin2 can modulate electrical activity and contractility in hiPSC-CMs, opening up a future development in cardiac physiology.
Biomechanics and neural circuits for vestibular-induced fine postural control in larval zebrafish
Authors: Sugioka Takumi , Tanimoto Masashi , Higashijima Shin-ichi
Published: September 2022

Land-walking vertebrates maintain a desirable posture by finely controlling muscles. It is unclear whether fish also finely control posture in the water. Here, we showed that larval zebrafish have fine posture control. When roll-tilted, fish recovered their upright posture using a reflex behavior, which was a slight body bend near the swim bladder. The vestibular-induced body bend produces a misalignment between gravity and buoyancy, generating a moment of force that recovers the upright posture. We identified the neural circuits for the reflex, including the vestibular nucleus (tangential nucleus) through reticulospinal neurons (neurons in the nucleus of the medial longitudinal fasciculus) to the spinal cord, and finally to the posterior hypaxial muscles, a special class of muscles near the swim bladder. These results suggest that fish maintain a dorsal-up posture by frequently performing the body bend reflex and demonstrate that the reticulospinal pathway plays a critical role in fine postural control.
The Mechanisms Underlying Colour Afterimages
Authors: Witzel Christoph
Published: September 2022

Negative colour afterimages incorporate the most fundamental tenets of human colour perception (adaptation, opponency, complementary colours, context-dependence, dependence on the beholder), but despite their fundamental importance, the underlying mechanisms are controversial. The key question is whether the afterimages are attributable to adaptation in the cone photoreceptors, of colour-opponent neurons in the subcortical pathway, or require the assumption of yet unknown cortical mechanisms. The most common assumption in textbooks and contemporary research is that negative afterimages are cone-opponent. It has not previously been recognised that the role of those mechanisms can be distinguished because they make fundamentally different predictions about the hue and saturation of afterimages. To test these predictions, we developed experimental paradigms to measure the exact colours perceived in afterimages. The results reveal that afterimages do not align with cone-opponency but closely follow a well-founded model of cone adaptation (cone contrasts). Our findings establish that cone-adaptation is the sole origin of negative colour afterimages. The quantitative cone-contrast model provides a comprehensive, straight-forward explanation of the adaptive mechanisms underlying colour afterimages that resolves apparent contradictions and debunks wide-spread misconceptions. This model has far-reaching implications for longstanding mysteries about visual perception.
Normative models for neuroimaging markers: Impact of model selection, sample size and evaluation criteria
Authors: Bozek Jelena , Griffanti Ludovica , Lau Stephan , Jenkinson Mark
Published: September 2022

Modelling population reference curves or normative modelling is increasingly used with the advent of large neuroimaging studies. In this paper we assess the performance of fitting methods from the perspective of clinical applications and investigate the influence of the sample size. Further, we evaluate linear and nonlinear models for percentile curve estimation and highlight how the bias-variance trade-off manifests in typical neuroimaging data.

We created plausible ground truth distributions of hippocampal volumes in the age range of 45 to 80 years, as an example application. Based on these distributions we repeatedly simulated samples for sizes between 50 and 50,000 data points, and for each simulated sample we fitted a range of normative models. We compared the fitted models and their variability across repetitions to the ground truth, with specific focus on the outer percentiles (1th, 5th, 10th) as these are the most clinically relevant.

Our results quantify the expected decreasing trend in variance of the volume estimates with increasing sample size. However, bias in the volume estimates only decreases a modest amount, without much improvement at large sample sizes. The uncertainty of model performance is substantial for what would often be considered large samples in a neuroimaging context and rises dramatically at the ends of the age range, where fewer data points exist. Flexible models perform better across sample sizes, especially for nonlinear ground truth.

Surprisingly large samples of several thousand data points are needed to accurately capture outlying percentiles across the age range for applications in research and clinical settings. Performance evaluation methods should assess both, bias and variance. Furthermore, extreme caution is needed when attempting to extrapolate beyond the age range included in the source dataset. To help with such evaluations of normative models we have made our code available to guide researchers developing or utilising normative models.
Yeast NDI1 expression prevents the unfolded protein response and reconfigures metabolism to restore neuronal function in mitochondrial complex I deficiency
Authors: Granat Lucy , Ranson Daniel , Hamer Emma , Chakrabarty Ram Prosad , Mattedi Francesca , Fort-Aznar Laura , Hirth Frank , Sweeney Sean T. , Vagnoni Alessio , Chandel Navdeep S. , Bateman Joseph M.
Published: September 2022

Mutations in mitochondrial complex I cause mitochondrial complex I deficiency, a group of severe neurological diseases that can result in death in infancy. The mechanisms underlying complex I deficiency pathogenesis remain poorly understood, and as a result there are currently no available treatments. To better understand the causes of neuronal dysfunction in complex I deficiency, we modelled complex I deficiency inDrosophilaby knocking down the mitochondrial complex I subunit ND-75 (NDUFS1) specifically in neurons. Neuronal complex I deficiency causes locomotor defects, seizures and reduced lifespan. At the cellular level, complex I deficiency leads to mitochondrial morphology defects, reduced endoplasmic reticulum-mitochondria contacts and activation of the endoplasmic reticulum unfolded protein response (UPR) in neurons. Remarkably, we find that expression of the yeast non-proton translocating NADH dehydrogenase NDI1 in neurons, which couples NADH oxidation to transfer of electrons into the respiratory chain, reinstates endoplasmic reticulum-mitochondria contacts, prevents UPR activation and rescues the behavioural and lifespan phenotypes caused by complex I deficiency. Metabolomic analysis shows that NDI1 expression also reconfigures neuronal metabolism and implicates increased GABA levels as a contributor to the neurological manifestations of complex I deficiency. Together, these data indicate that NDI1 abrogates UPR signalling and reprogrammes metabolism to alleviate neuronal dysfunction caused by neuronal complex I deficiency.
In-silico and in-vitro evaluation of anti-oxidant and anti-hypertensive activities ofChenopodium ambrosoides LINN. ethanol leaf extract
Authors: Olaniyi Ayinde , Oluwatobi Oguntoye , Oluwabunmi Alabi
Published: September 2022

Oxidative stress and free radicals have been implicated in ethno-pathogenesis of hypertension and cardiovascular disease.C. ambrosoidesLinn. is a popular plant used in the management of oxidative stress related diseases such as hypertension and obesity in Nigeria and West African countries; however, studies validating the antioxidant and antihypertensive potential of this plant is scanty in literature. Thus, this study was designed to investigate the antioxidant and antihypertensive activities ofC. ambrosoidesethanolic leaf extract usingin-vitro(vis-à-vis) DPPH free radical scavenging assay, nitric oxide radical inhibition assay, lipid peroxidation inhibition assay, ferric reducing power assay and angiotensin converting enzyme inhibition assay) andin-silico(Molecular docking) techniques and results analyzed using GraphPad prism8 software and Multiple test as criteria for statistical comparison and significance. Gas chromatography mass spectrometry (GCMS) analysis was employed to identify constituent bioactive compounds in the extract. The results of thein-vitroanti-oxidants assays show dose dependent inhibition with the highest activity observed at 2.5 mg/ml. The ferric reducing power activity of the extract significantly (P<0.05) shows higher activity than the ascorbic acid standard at all concentration with the highest activity observed at 2.5mg/ml (77.030% against 69.159%).

The extract significantly scavenged DPPH radical than ascorbic acid standard at 2.5mg/ml (81.161% against 75.378%), however at low concentration (1.5mg/ml-0.5mg/ml) the standard shows higher activity than the extract, however dose dependence was maintained. Ascorbic acid standard significantly shows higher activity than the extracts lipid peroxidation inhibition and nitric oxide inhibition activity at all concentration.

The extract exhibited high angiotensin converting enzyme (ACE) inhibited in a dose dependent manner with the highest activity at 2.5mg/ml (95.990%). The ACE inhibitory potential ofC. ambrosoidesextract was corroborated by in-silicostudies which revealed that 14 out of the 96 identified bioactive compounds through GCMS exhibited higher negative binding affinities than lisinopril (−6.8 Kcal/mol), with the compound 2,4-Diamino-6,8-bis[3,4-dichlorophenyl]-5,6-dihydro-8H-thiapyrano[4’,3’4,5]thieno[2,3d]pyrimidine having the highest binding affinity (−8.0Kcal/mol) In conclusion, it is suggested that the anti-hypertensive activity demonstrated by C.ambrosoidesmight be mediated via its anti-oxidant ability and ACE inhibitory potential.
Comparison Between Gradients and Parcellations for Functional Connectivity Prediction of Behavior
Authors: Kong Ru , Rui Tan Yan , Wulan Naren , Qi Rong Ooi Leon , Farahibozorg Seyedeh-Rezvan , Harrison Samuel , Bijsterbosch Janine D. , Bernhardt Boris C. , Eickhoff Simon , Thomas Yeo B.T.
Published: September 2022

Resting-state functional connectivity (RSFC) is widely used to predict behavioral measures. To predict behavioral measures, representing RSFC with parcellations and gradients are the two most popular approaches. Here, we compare parcellation and gradient approaches for RSFC-based prediction of a broad range of behavioral measures in the Human Connectome Project (HCP) and Adolescent Brain Cognitive Development (ABCD) datasets. Among the parcellation approaches, we consider group-average “hard” parcellations (Schaefer et al., 2018), individual-specific “hard” parcellations (Kong et al., 2021a), and an individual-specific “soft” parcellation (spatial independent component analysis with dual regression; Beckmann et al., 2009). For gradient approaches, we consider the well-known principal gradients (Margulies et al., 2016) and the local gradient approach that detects local RSFC changes (Laumann et al., 2015). Across two regression algorithms, individual-specific hard-parcellation performs the best in the HCP dataset, while the principal gradients, spatial independent component analysis and group-average “hard” parcellations exhibit similar performance. On the other hand, principal gradients and all parcellation approaches perform similarly in the ABCD dataset. Across both datasets, local gradients perform the worst. Finally, we find that the principal gradient approach requires at least 40 to 60 gradients to perform as well as parcellation approaches. While most principal gradient studies utilize a single gradient, our results suggest that incorporating higher order gradients can provide significant behaviorally relevant information. Future work will consider the inclusion of additional parcellation and gradient approaches for comparison.
A SHR-IDD-PIN regulatory network mediates minor vein differentiation in rice
Authors: Liu Qiming , Teng Shouzhen , Deng Chen , Wu Suting , Li Haoshu , Wang Yanwei , Wu Jinxia , Cui Xuean , Zhang Zhiguo , Quick William Paul , Brutnell Thomas P. , Sun Xuehui , Lu Tiegang
Published: September 2022

C3 and C4 grasses directly and indirectly provide the vast majority of calories to the human diet, yet our understanding of the molecular mechanisms driving photosynthetic productivity in grasses is largely unexplored. Here we define a genetic circuit comprised of SHR, IDD and PIN family members that specify vascular identify and ground cell proliferation in leaves of both C3 and C4 grasses. Ectopic expression and loss-of-function mutant studies of SHORT ROOT (SHR) paralogs in C3Oryza sativa (rice) and C4Setaria viridis (green millet) revealed a role in both minor vein formation and ground cell differentiation. Genetic and in vitro studies further suggest that SHR regulates this process through its interaction with Indeterminate Domain (IDD) IDD 12 and 13. We further show a direct interaction of these IDD proteins with a putative regulatory element within the auxin transporter PIN5c gene. Collectively, these studies indicated that a SHR-IDD regulatory circuit mediates auxin flow through the negative regulation of PIN protein expression to modulate minor vein patterning in the grasses.
Investigation of reversible histone acetylation and dynamics in gene expression regulation using 3D liver spheroid model
Authors: Stransky Stephanie , Cutler Ronald , Aguilan Jennifer , Nieves Edward , Sidoli Simone
Published: September 2022

Background

Three-dimensional (3D) cell culture has emerged as an alternative approach to 2D flat culture to model more accurately the phenotype of solid tissue in laboratories. Culturing cells in 3D more precisely recapitulates physiological conditions of tissues, as these cells reduce activities related to proliferation, focusing their energy consumption towards metabolism and homeostasis.

Results

Here, we demonstrate that 3D liver spheroids are a suitable system to model chromatin dynamics and response to epigenetics inhibitors. To delay necrotic tissue formation despite proliferation arrest, we utilize rotating bioreactors that apply active media diffusion and low shearing forces. We demonstrate that the proteome and the metabolome of our model resemble typical liver functions. We prove that spheroids respond to sodium butyrate (NaBut) treatment, an inhibitor of histone deacetylases (HDACi), by upregulating histone acetylations and transcriptional activation. As expected, NaBut treatment impaired specific cellular functions, including the energy metabolism. More importantly, we demonstrate that spheroids reestablish their original proteome and transcriptome, including pre-treatment levels of histone acetylation, metabolism, and protein expression once the standard culture condition is restored after treatment. Given the slow replication rate (>40 days) of cells in 3D spheroids, our model enables to monitor the recovery of approximately the same cells that underwent treatment, demonstrating that NaBut does not have long-lasting effects on histone acetylation and gene expression. These results suggest that histone acetylation has minimal epigenetics memory in our spheroids culture.

Conclusion

Together, we established an innovative cell culture system that can be used to model anomalously decondensing chromatin in physiological cell growth and rule out epigenetics inheritance if cells recover the original phenotype after treatment. The transient epigenetics effects demonstrated here highlights the relevance of using a 3D culture model system that could be very useful in studies requiring long term drug treatment conditions that would not be possible using a 2D cell monolayer system.
Growth cone advance requires EB1 as revealed by genomic replacement with a light-sensitive variant
Authors: Dema Alessandro , Charafeddine Rabab , Rahgozar Shima , van Haren Jeffrey , Wittmann Torsten
Published: September 2022

A challenge in analyzing dynamic intracellular cell biological processes is the dearth of methodologies that are sufficiently fast and specific to perturb intracellular protein activities. We previously developed a light-sensitive variant of the microtubule plus end tracking protein EB1 by inserting a blue light-controlled protein dimerization module between functional domains. Here we describe an advanced method to replace endogenous EB1 with this light-sensitive variant in a single genome editing step enabling this approach in human induced pluripotent stem cells and derived neurons. We demonstrate that acute and local optogenetic EB1 inactivation in developing cortical neurons induces microtubule depolymerization in the growth cone periphery and subsequent neurite retraction. In addition, advancing growth cones are repelled from areas of blue light exposure. These phenotypes were independent of the neuronal EB1 homolog EB3, revealing a direct dynamic role of EB1-mediated microtubule plus end interactions in neuron morphogenesis and neurite guidance.
Identification and structural modeling of the chlamydial RNA polymerase omega subunit
Authors: Cheng Andrew , Wan Danny , Ghatak Arkaprabha , Wang Chengyuan , Feng Deyu , Fondell Joseph D. , Ebright Richard H. , Fan Huizhou
Published: September 2022

Gene transcription in bacteria is carried out by the multisubunit RNA polymerase (RNAP), which is composed of a catalytic core enzyme and a promoter-recognizing σ factor. RNAP core enzyme comprises two α subunits, one β subunit, one β’
s subunit, and one ω (omega) subunit. Across multiple bacterial taxa, the RNAP ω subunit plays critical roles in the assembly of RNAP core enzyme and in other cellular functions, including regulation of bacterial growth, stress response, and biofilm formation. However, for several intracellular bacterium, including the obligate intracellular bacterium Chlamydia, no RNAP ω subunit previously has been identified. Here, we report the identification of Chlamydia trachomatis hypothetical protein CTL0286 as the chlamydial RNAP ω ortholog, based on sequence, synteny, and AlphaFold and AlphaFold-Multimer three-dimensional-structure predictions. We conclude that CTL0286 functions as the previously missing chlamydial ω ortholog. Extensions of our analysis indicate that all obligate intracellular bacteria have ω orthologs.

IMPORTANCE

Chlamydiae are common mammalian pathogens. Chlamydiae have a unique developmental cycle characterized with an infectious but nondividing elementary body (EB), which can temporarily survive outside host cells, and a noninfectious reticulate body (RB), which replicates only intracellularly. Chlamydial development inside host cells can be arrested during persistence in response to adverse environmental conditions. Transcription plays a central role in the progression of the chlamydial developmental cycle as well as entry into and recovery from persistence. The identification of the elusive ω subunit of chlamydial RNAP makes possible future study of its regulatory roles in gene expression during chlamydial growth, development, and stress responses. This discovery also paves the way to prepare and study the intact chlamydial RNAP and its interactions with inhibitors in vitro.