bluuebunny/crossref_metadata_2025 huggingface dataset:
Negative Clinical Evolution in COVID-19 Patients Is Frequently Accompanied With an Increased Proportion of Undifferentiated Th Cells and a Strong Underrepresentation of the Th1 Subset
Authors: Gutiérrez-Bautista Juan Francisco , Rodriguez-Nicolas Antonio , Rosales-Castillo Antonio , Jiménez Pilar , Garrido Federico , Anderson Per , Ruiz-Cabello Francisco , López-Ruz Miguel Ángel
Published: November 2020

The severity of SARS-CoV-2 infection has been related to uncontrolled inflammatory innate responses and impaired adaptive immune responses mostly due to exhausted T lymphocytes and lymphopenia. In this work we have characterized the nature of the lymphopenia and demonstrate a set of factors that hinder the effective control of virus infection and the activation and arming of effector cytotoxic T CD8 cells and showing signatures defining a high-risk population. We performed immune profiling of the T helper (Th) CD4+ and T CD8+ cell compartments in peripheral blood of 144 COVID-19 patients using multiparametric flow cytometry analysis. On the one hand, there was a consistent lymphopenia with an overrepresentation of non-functional T cells, with an increased percentage of naive Th cells (CD45RA+, CXCR3-, CCR4-, CCR6-, CCR10-) and persistently low frequency of markers associated with Th1, Th17, and Th1/Th17 memory-effector T cells compared to healthy donors. On the other hand, the most profound alteration affected the Th1 subset, which may explain the poor T cells responses and the persistent blood virus load. Finally, the decrease in Th1 cells may also explain the low frequency of CD4+ and CD8+ T cells that express the HLA-DR and CD38 activation markers observed in numerous patients who showed minimal or no lymphocyte activation response. We also identified the percentage of HLA-DR+CD4+ T cells, PD-1+CD+4/CD8+ T cells in blood, and the neutrophil/lymphocyte ratio as useful factors for predicting critical illness and fatal outcome in patients with confirmed COVID-19.
Gut–Liver Immune Response and Gut Microbiota Profiling Reveal the Pathogenic Mechanisms of Vibrio harveyi in Pearl Gentian Grouper (Epinephelus lanceolatus♂ × E. fuscoguttatus♀)
Authors: Deng Yiqin , Zhang Yaqiu , Chen Haoxiang , Xu Liwen , Wang Qian , Feng Juan
Published: November 2020

Vibrio harveyi causes vibriosis in nearly 70% of grouper (Epinephelus sp.), seriously limiting grouper culture. As well as directly inhibiting pathogens, the gut microbiota plays critical roles in immune homeostasis and provides essential health benefits to its host. However, there is still little information about the variations in the immune response to V. harveyi infection and the gut microbiota of grouper. To understand the virulence mechanism of V. harveyi in the pearl gentian grouper, we investigated the variations in the pathological changes, immune responses, and gut bacterial communities of pearl gentian grouper after exposure to differently virulent V. harveyi strains. Obvious histopathological changes were detected in heart, kidney, and liver. In particular, nodules appeared and huge numbers of V. harveyi cells colonized the liver at 12 h postinfection (hpi) with highly virulent V. harveyi. Although no V. harveyi was detected in the gut, the infection simultaneously induced a gut-liver immune response. In particular, the expression of 8 genes associated with cellular immune processes, including genes encoding inflammatory cytokines and receptors, and pattern recognition proteins, was markedly induced by V. harveyi infection, especially with the highly virulent V. harveyi strain. V. harveyi infection also induced significant changes in gut bacterial community, in which Vibrio and Photobacterium increased but Bradyrhizobium, Lactobacillus, Blautia, and Faecalibaculum decreased in the group infected with the highly virulent strain, with accounting for 82.01% dissimilarity. Correspondingly, four bacterial functions related to bacterial pathogenesis were increased by infection with highly virulent V. harveyi, whereas functions involving metabolism and genetic information processing were reduced. These findings indicate that V. harveyi colonizes the liver and induces a gut-liver immune response that substantially disrupts the composition of and interspecies interactions in the bacterial community in fish gut, thereby altering the gut-microbiota-mediated functions and inducing fish death.
Intra-Annual Patterns in the Benthic-Pelagic Fluxes of Dissolved and Particulate Matter
Authors: Rühl Saskia , Thompson Charlie E. L. , Queirós Ana M. , Widdicombe Stephen
Published: November 2020

In coastal temperate environments, many processes known to affect the exchange of particulate and dissolved matter between the seafloor and the water column follow cyclical patterns of intra-annual variation. This study assesses the extent to which these individual short term temporal variations affect specific direct drivers of seafloor-water exchanges, how they interact with one another throughout the year, and what the resulting seasonal variation in the direction and magnitude of benthic-pelagic exchange is. Existing data from a multidisciplinary long-term time-series from the Western Channel Observatory, United Kingdom, were combined with new experimental andin situdata collected throughout a full seasonal cycle. These data, in combination with and contextualized by time-series data, were used to define an average year, split into five ‘periods’ (winter, pre-bloom, bloom, post-bloom, and autumn) based around the known importance of pelagic primary production and hydrodynamically active phases of the year. Multivariate analyses were used to identify specific sub-sets of parameters that described the various direct drivers of seafloor-water exchanges. Both dissolved and particulate exchange showed three distinct periods of significant flux during the year, although the specific timings of these periods and the cause-effect relationships to the direct and indirect drivers differed between the two types of flux. Dissolved matter exchange was dominated by an upward flux in the pre-bloom period driven by diffusion, then a biologically induced upward flux during the bloom and an autumn downward flux. The latter was attributable to the interactions of hydrodynamic and biological activity on the seafloor. Particulate matter exchanges exhibited a strongly hydrologically influenced upward flux during the winter, followed by a biologically induced downward flux during the bloom and a second period of downward flux throughout post-bloom and autumn periods. This was driven primarily through interactions between biological activity, and physical and meteorological drivers. The integrated, holistic and quantitative data-based analysis of intra-annual variability in benthic/pelagic fluxes presented in this study in a representative temperate coastal environment, demonstrates not only the various process’ inter-connectivity, but also their relative importance to each other. Future investigations or modeling efforts of similar systems will benefit greatly from the relationships and baseline rules established in this study.
Non-precious Melamine/Chitosan Composites for the Oxygen Reduction Reaction: Effect of the Transition Metal
Authors: Aghabarari B. , Martínez-Huerta M. V. , Capel-Sánchez M. C. , Lázaro M. J.
Published: November 2020

The development of active and low-cost electrocatalysts for the oxygen reduction reaction (ORR) is crucial for the sustainable commercialization of fuel cell technologies. In this study, we have synthetized Me/Mo2C (Me = Fe, Co, Cu)-based composites embedded in N- and P-dual doped carbon by means of inexpensive industrial materials, such as melamine and chitosan, as C and N sources, and the heteropolyacid H3PMo12O40 as P and Mo precursor. The effect of the transition metal (Fe, Co, and Cu) on the ORR in alkaline medium has been investigated. The physicochemical properties of the electrocatalysts were performed by X-ray diffraction (XRD), X-ray photoelectron spectroscopy (XPS), Raman spectroscopy, and transmission electron microscopy (TEM). Activity towards ORR was carried out in a three-electrode cell using a ring-disk electrode in 0.1M NaOH. The results obtained clearly show the important role played by each transition metal (Fe, Co, and Cu) in the electrochemical activity. Among them, Fe gives rise to the best performing composite in carrying out the oxygen reduction reaction. The formation Fe3C/Mo2C species embedded in N- and P-dual doped carbon seems to be the determining role in the increase of the ORR performance.
Multistability and Reversibility of Aerobic Granular Sludge Microbial Communities Upon Changes From Simple to Complex Synthetic Wastewater and Back
Authors: Adler Aline , Holliger Christof
Published: November 2020

Aerobic granular sludge (AGS) is a promising alternative wastewater treatment to the conventional activated sludge system allowing space and energy saving. Basic understanding of AGS has mainly been obtained using simple wastewater containing acetate and propionate as carbon source. Yet, the aspect and performances of AGS grown in such model systems are different from those obtained in reactor treating real wastewater. The impact of fermentable and hydrolyzable compounds on already formed AGS was assessed separately by changing the composition of the influent from simple wastewater containing volatile fatty acids to complex monomeric wastewater containing amino acids and glucose, and then to complex polymeric wastewater containing also starch and peptone. The reversibility of the observed changes was assessed by changing the composition of the wastewater from complex monomeric back to simple. The introduction of fermentable compounds in the influent left the settling properties and nutrient removal performance unchanged, but had a significant impact on the bacterial community. The proportion of Gammaproteobacteria diminished to the benefit of Actinobacteria and the Saccharibateria phylum. On the other hand, the introduction of polymeric compounds altered the settling properties and denitrification efficiency, but induced smaller changes in the bacterial community. The changes induced by the wastewater transition were only partly reversed. Seven distinct stables states of the bacterial community were detected during the 921 days of experiment, four of them observed with the complex monomeric wastewater. The transitions between these states were not only caused by wastewater changes but also by operation failures and other incidences. However, the nutrient removal performance and settling properties of the AGS were globally maintained due to the functional redundancy of its bacterial community.
The Mosaic Architecture of NRPS-PKS in the Arbuscular Mycorrhizal Fungus Gigaspora margarita Shows a Domain With Bacterial Signature
Authors: Venice Francesco , Desirò Alessandro , Silva Gladstone , Salvioli Alessandra , Bonfante Paola
Published: November 2020

As obligate biotrophic symbionts, arbuscular mycorrhizal fungi (AMF) live in association with most land plants. Among them, Gigaspora margarita has been deeply investigated because of its peculiar features, i.e., the presence of an intracellular microbiota with endobacteria and viruses. The genome sequencing of this fungus revealed the presence of some hybrid non-ribosomal peptide synthases-polyketide synthases (NRPS-PKS) that have been rarely identified in AMF. The aim of this study is to describe the architecture of these NRPS-PKS sequences and to understand whether they are present in other fungal taxa related to G. margarita. A phylogenetic analysis shows that the ketoacyl synthase (KS) domain of one G. margarita NRPS-PKS clusters with prokaryotic sequences. Since horizontal gene transfer (HGT) has often been advocated as a relevant evolutionary mechanism for the spread of secondary metabolite genes, we hypothesized that a similar event could have interested the KS domain of the PKS module. The bacterial endosymbiont of G. margarita, Candidatus Glomeribacter gigasporarum (CaGg), was the first candidate as a donor, since it possesses a large biosynthetic cluster involving an NRPS-PKS. However, bioinformatics analyses do not confirm the hypothesis of a direct HGT from the endobacterium to the fungal host: indeed, endobacterial and fungal sequences show a different evolution and potentially different donors. Lastly, by amplifying a NRPS-PKS conserved fragment and mining the sequenced AMF genomes, we demonstrate that, irrespective of the presence of CaGg, G. margarita, and some other related Gigasporaceae possess such a sequence.
Microbiota and Metabolite Profiling Combined With Integrative Analysis for Differentiating Cheeses of Varying Ripening Ages
Authors: Afshari Roya , Pillidge Christopher J. , Dias Daniel A. , Osborn A. Mark , Gill Harsharn
Published: November 2020

Cheese maturation and flavor development results from complex interactions between milk substrates, cheese microbiota and their metabolites. In this study, bacterial 16S rRNA-gene sequencing, untargeted metabolomics (gas chromatography-mass spectrometry) and data integration analyses were used to characterize and differentiate commercial Cheddar cheeses of varying maturity made by the same and different manufacturers. Microbiota and metabolite compositions varied between cheeses of different ages and brands, and could be used to distinguish the cheeses. Individual amino acids and carboxylic acids were positively correlated with the ripening age for some brands. Integration and Random Forest analyses revealed numerous associations between specific bacteria and metabolites including a previously undescribed positive correlation between Thermus and phenylalanine and a negative correlation between Streptococcus and cholesterol. Together these results suggest that multi-omics analyses has the potential to be used for better understanding the relationships between cheese microbiota and metabolites during ripening and for discovering biomarkers for validating cheese age and brand authenticity.
Functional Characterization of Calcineurin-Responsive Transcription Factors Fg01341 and Fg01350 in Fusarium graminearum
Authors: Zhang Xiangxiang , Cao Shulin , Li Wei , Sun Haiyan , Deng Yuanyu , Zhang Aixiang , Chen Huaigu
Published: November 2020

Ca2 +/calmodulin-dependent phosphatase calcineurin is one of the important regulators of intracellular calcium homeostasis and has been investigated extensively in Saccharomyces cerevisiae. However, only a few reports have explored the function of the Crz1 homolog in filamentous fungi, especially in Fusarium graminearum. In this study, we identified Fg01341 as a potential ortholog of yeast Crz1. Fg01341 could interact with calcineurin and initiate nuclear transport in a calcineurin-dependent manner. The ΔFg01341 mutant exhibited normal hyphal growth on basic medium and conidia formation, but sexual reproduction was partially blocked. Pathogenicity assays showed that the virulence of the ΔFg01341 mutant in flowering wheat heads and corn silks dramatically decreased and was thus consistent with the reduction in deoxynivalenol production. Unexpectedly, the sensitivity to osmotic stress of the deletion mutant and that of the wild-type strain did not present any differences. The deletion mutant showed higher sensitivity to tebuconazole than the wild-type strain. Results also showed that the transcription factor Fg01350 might be the calcineurin target and was independent of Crz1. Furthermore, ΔFg01350 showed defects in hyphal growth, sexual production, virulence, and deoxynivalenol production. Collectively, the results indicate that these two proteins functionally redundant and that the calcineurin–Crz1-independent pathway is particularly important in F. graminearum.
Cobalt Resistance via Detoxification and Mineralization in the Iron-Reducing Bacterium Geobacter sulfurreducens
Authors: Dulay Hunter , Tabares Marcela , Kashefi Kazem , Reguera Gemma
Published: November 2020

Bacteria in the genus Geobacter thrive in iron- and manganese-rich environments where the divalent cobalt cation (CoII) accumulates to potentially toxic concentrations. Consistent with selective pressure from environmental exposure, the model laboratory representative Geobacter sulfurreducens grew with CoCl2 concentrations (1 mM) typically used to enrich for metal-resistant bacteria from contaminated sites. We reconstructed from genomic data canonical pathways for CoII import and assimilation into cofactors (cobamides) that support the growth of numerous syntrophic partners. We also identified several metal efflux pumps, including one that was specifically upregulated by CoII. Cells acclimated to metal stress by downregulating non-essential proteins with metals and thiol groups that CoII preferentially targets. They also activated sensory and regulatory proteins involved in detoxification as well as pathways for protein and DNA repair. In addition, G. sulfurreducens upregulated respiratory chains that could have contributed to the reductive mineralization of the metal on the cell surface. Transcriptomic evidence also revealed pathways for cell envelope modification that increased metal resistance and promoted cell-cell aggregation and biofilm formation in stationary phase. These complex adaptive responses confer on Geobacter a competitive advantage for growth in metal-rich environments that are essential to the sustainability of cobamide-dependent microbiomes and the sequestration of the metal in hitherto unknown biomineralization reactions.
6S-1 RNA Contributes to Sporulation and Parasporal Crystal Formation in Bacillus thuringiensis
Authors: Li Zhou , Zhu Li , Yu Zhaoqing , Liu Lu , Chou Shan-Ho , Wang Jieping , He Jin
Published: November 2020

6S RNA is a kind of high-abundance non-coding RNA that globally regulates bacterial transcription by interacting with RNA polymerase holoenzyme. Through bioinformatics analysis, we found that there are two tandem 6S RNA-encoding genes in the genomes of Bacillus cereus group bacteria. Using Bacillus thuringiensis BMB171 as the starting strain, we have explored the physiological functions of 6S RNAs, and found that the genes ssrSA and ssrSB encoding 6S-1 and 6S-2 RNAs were located in the same operon and are co-transcribed as a precursor that might be processed by specific ribonucleases to form mature 6S-1 and 6S-2 RNAs. We also constructed two single-gene deletion mutant strains ΔssrSA and ΔssrSB and a double-gene deletion mutant strain ΔssrSAB by means of the markerless gene knockout method. Our data show that deletion of 6S-1 RNA inhibited the growth of B. thuringiensis in the stationary phase, leading to lysis of some bacterial cells. Furthermore, deletion of 6S-1 RNA also significantly reduced the spore number and parasporal crystal content. Our work reveals that B. thuringiensis 6S RNA played an important regulatory role in ensuring the sporulation and parasporal crystal formation.
Nanoparticle Surface Functionalization: How to Improve Biocompatibility and Cellular Internalization
Authors: Sanità Gennaro , Carrese Barbara , Lamberti Annalisa
Published: November 2020

The use of nanoparticles (NP) in diagnosis and treatment of many human diseases, including cancer, is of increasing interest. However, cytotoxic effects of NPs on cells and the uptake efficiency significantly limit their use in clinical practice. The physico-chemical properties of NPs including surface composition, superficial charge, size and shape are considered the key factors that affect the biocompatibility and uptake efficiency of these nanoplatforms. Thanks to the possibility of modifying physico-chemical properties of NPs, it is possible to improve their biocompatibility and uptake efficiency through the functionalization of the NP surface. In this review, we summarize some of the most recent studies in which NP surface modification enhances biocompatibility and uptake. Furthermore, the most used techniques used to assess biocompatibility and uptake are also reported.
Frontal and Cerebellar Atrophy Supports FTSD-ALS Clinical Continuum
Authors: Pizzarotti Beatrice , Palesi Fulvia , Vitali Paolo , Castellazzi Gloria , Anzalone Nicoletta , Alvisi Elena , Martinelli Daniele , Bernini Sara , Cotta Ramusino Matteo , Ceroni Mauro , Micieli Giuseppe , Sinforiani Elena , D’Angelo Egidio , Costa Alfredo , Gandini Wheeler-Kingshott Claudia A. M.
Published: November 2020

Background

Frontotemporal Spectrum Disorder (FTSD) and Amyotrophic Lateral Sclerosis (ALS) are neurodegenerative diseases often considered as a continuum from clinical, epidemiologic, and genetic perspectives. We used localized brain volume alterations to evaluate common and specific features of FTSD, FTSD-ALS, and ALS patients to further understand this clinical continuum.

Methods

We used voxel-based morphometry on structural magnetic resonance images to localize volume alterations in group comparisons: patients (20 FTSD, seven FTSD-ALS, and 18 ALS) versus healthy controls (39 CTR), and patient groups between themselves. We used mean whole-brain cortical thickness (CT¯) to assess whether its correlations with local brain volume could propose mechanistic explanations of the heterogeneous clinical presentations. We also assessed whether volume reduction can explain cognitive impairment, measured with frontal assessment battery, verbal fluency, and semantic fluency.

Results

Common (mainly frontal) and specific areas with reduced volume were detected between FTSD, FTSD-ALS, and ALS patients, confirming suggestions of a clinical continuum, while at the same time defining morphological specificities for each clinical group (e.g., a difference of cerebral and cerebellar involvement between FTSD and ALS). CT¯ values suggested extensive network disruption in the pathological process, with indications of a correlation between cerebral and cerebellar volumes and CT¯ in ALS. The analysis of the neuropsychological scores indeed pointed toward an important role for the cerebellum, along with fronto-temporal areas, in explaining impairment of executive, and linguistic functions.

Conclusion

We identified common elements that explain the FTSD-ALS clinical continuum, while also identifying specificities of each group, partially explained by different cerebral and cerebellar involvement.
Multimodal Imaging and Analysis of the Neuroanatomical Organization of the Primary Olfactory Inputs in the Brownbanded Bamboo Shark, Chiloscyllium punctatum
Authors: Camilieri-Asch Victoria , Caddy Harrison T. , Hubbard Alysia , Rigby Paul , Doyle Barry , Shaw Jeremy A. , Mehnert Andrew , Partridge Julian C. , Yopak Kara E. , Collin Shaun P.
Published: November 2020

There is currently a limited understanding of the morphological and functional organization of the olfactory system in cartilaginous fishes, particularly when compared to bony fishes and terrestrial vertebrates. In this fish group, there is a clear paucity of information on the characterization, density, and distribution of olfactory receptor neurons (ORNs) within the sensory olfactory epithelium lining the paired olfactory rosettes, and their functional implications with respect to the hydrodynamics of incurrent water flow into the nares. This imaging study examines the brownbanded bamboo sharkChiloscyllium punctatum(Elasmobranchii) and combines immunohistochemical labeling using antisera raised against five G-protein α-subunits (Gαs/olf, Gαq/11/14, Gαi–1/2/3, Gαi–3, Gαo) with light and electron microscopy, to characterize the morphological ORN types present. Three main ORNs (“long”, “microvillous” and “crypt-like”) are confirmed and up to three additional microvilli-bearing types are also described; “Kappe-like” (potential or homologous “Kappe” as in teleosts), “pear-shaped” and “teardrop-shaped” cells. These morphotypes will need to be confirmed molecularly in the future. Using X-ray diffusible iodine-based contrast-enhanced computed tomography (diceCT), high-resolution scans of the olfactory rosettes, olfactory bulbs (OBs), peduncles, and telencephalon reveal a lateral segregation of primary olfactory inputs within the OBs, with distinct medial and lateral clusters of glomeruli, suggesting a potential somatotopic organization. However, most ORN morphotypes are found to be ubiquitously distributed within the medial and lateral regions of the olfactory rosette, with at least three microvilli-bearing ORNs labeled with anti-Gαofound in significantly higher densities in lateral lamellae [in lateral lamellae] and on the anterior portion of lamellae (facing the olfactory cavity). These microvilli-bearing ORN morphotypes (microvillous, “Kappe-like,” “pear-shaped,” and “teardrop-shaped”) are the most abundant across the olfactory rosette of this species, while ciliated ORNs are less common and crypt cells are rare. Spatial simulations of the fluid dynamics of the incurrent water flow into the nares and within the olfactory cavities indicate that the high densities of microvilli-bearing ORNs located within the lateral region of the rosette are important for sampling incoming odorants during swimming and may determine subsequent tracking behavior.
Robust Trajectory Generation for Robotic Control on the Neuromorphic Research Chip Loihi
Authors: Michaelis Carlo , Lehr Andrew B. , Tetzlaff Christian
Published: November 2020

Neuromorphic hardware has several promising advantages compared to von Neumann architectures and is highly interesting for robot control. However, despite the high speed and energy efficiency of neuromorphic computing, algorithms utilizing this hardware in control scenarios are still rare. One problem is the transition from fast spiking activity on the hardware, which acts on a timescale of a few milliseconds, to a control-relevant timescale on the order of hundreds of milliseconds. Another problem is the execution of complex trajectories, which requires spiking activity to contain sufficient variability, while at the same time, for reliable performance, network dynamics must be adequately robust against noise. In this study we exploit a recently developed biologically-inspired spiking neural network model, the so-called anisotropic network. We identified and transferred the core principles of the anisotropic network to neuromorphic hardware using Intel's neuromorphic research chip Loihi and validated the system on trajectories from a motor-control task performed by a robot arm. We developed a network architecture including the anisotropic network and a pooling layer which allows fast spike read-out from the chip and performs an inherent regularization. With this, we show that the anisotropic network on Loihi reliably encodes sequential patterns of neural activity, each representing a robotic action, and that the patterns allow the generation of multidimensional trajectories on control-relevant timescales. Taken together, our study presents a new algorithm that allows the generation of complex robotic movements as a building block for robotic control using state of the art neuromorphic hardware.
Learning-Dependent Dendritic Spine Plasticity Is Reduced in the Aged Mouse Cortex
Authors: Huang Lianyan , Zhou Hang , Chen Kai , Chen Xiao , Yang Guang
Published: November 2020

Aging is accompanied by a progressive decrease in learning and memory function. Synaptic loss, one of the hallmarks of normal aging, likely plays an important role in age-related cognitive decline. But little is known about the impact of advanced age on synaptic plasticity and neuronal function in vivo. In this study, we examined the structural dynamics of postsynaptic dendritic spines as well as calcium activity of layer 5 pyramidal neurons in the cerebral cortex of young and old mice. Using transcranial two-photon microscopy, we found that in both sensory and motor cortices, the elimination rates of dendritic spines were comparable between young (3–5 months) and mature adults (8–10 months), but seemed higher in old mice (>20 months), contributing to a reduction of total spine number in the old brain. During the process of motor learning, old mice compared to young mice had fewer new spines formed in the primary motor cortex. Motor training-evoked somatic calcium activity in layer 5 pyramidal neurons of the motor cortex was also lower in old than young mice, which was associated with the decline of motor learning ability during aging. Together, these results demonstrate the effects of aging on learning-dependent synapse remodeling and neuronal activity in the living cortex and suggest that synaptic deficits may contribute to age-related learning impairment.
Association of the Plasma Long Non-coding RNA MEG3 With Parkinson's Disease
Authors: Quan Yi , Wang Jia , Wang Shuo , Zhao Jizong
Published: November 2020

Objective: To investigate the expression level of the maternally expressed gene-3 (MEG3) of the free long non-coding RNA (lncRNAs) in the plasma of Parkinson's disease (PD) patients and its relationship with the disease.

Methods: Thirty PD patients (PD group) who treated at Xuanwu Hospital of Capital University of Medical Sciences between January 2017 and December 2019 were selected as the research objects and 30 healthy subjects were enrolled in the study during the same period as the control group. Cognitive function was assessed according to the Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA) were used to evaluate cognitive function, Non-Motor Symptoms Scale (NMSS) was used to evaluate severity of non-motor symptoms. The relative expression of lncRNAs MEG3 in plasma was measured by PCR, and the levels of neuron-specific enolase (NSE), nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF) in plasma were measured by ELISA, and the relationship with these all indexes was analyzed.

Results: The NMSS score of PD group was significantly higher than that of the control group, while the MMSE and MoCA scores were significantly lower than that of the control group (P < 0.05); The relative expression of lncRNAs MEG3, NGF and BDNF levels of PD group were significantly lower than that of the control group, and NSE level was significantly higher than that of the control group (P < 0.05); The H&Y stage and NMSS score in PD group were negatively correlated with the relative expression of lncRNAs MEG3, the levels of NGF and BDNF (P < 0.05), and positively correlated with NSE (P < 0.05); The MMSE and MoCA scores in PD group were positively correlated with the relative expression of lncRNAs MEG3, NGF, BDNF levels (P < 0.05), and negatively correlated with NSE (P < 0.05); The relative expression of lncRNAs MEG3 in PD group was positively correlated with NGF, BDNF levels (P < 0.05), and negatively correlated with NSE (P < 0.05).

Conclusion: The expression of lncRNAs MEG3 in the plasma of PD patients was downregulated compared to that of healthy control subjects, and its expression level was closely related to the aggravation of non-motor symptoms, cognitive decline, and PD stage. These associations may reflect the synergism of the increase of NSE and decrease of NGF and BDNF levels, highlighting plasma lncRNA MEG3 as a new candidate biomarker of PD.
Evidence Limitations in Determining Sexually Dimorphic Outcomes in Pediatric Post-Traumatic Hypopituitarism and the Path Forward
Authors: West Alina Nico , Diaz-Thomas Alicia M. , Shafi Nadeem I.
Published: November 2020

Neuroendocrine dysfunction can occur as a consequence of traumatic brain injury (TBI), and disruptions to the hypothalamic-pituitary axis can be especially consequential to children. The purpose of our review is to summarize current literature relevant to studying sex differences in pediatric post-traumatic hypopituitarism (PTHP). Our understanding of incidence, time course, and impact is constrained by studies which are primarily small, are disadvantaged by significant methodological challenges, and have investigated limited temporal windows. Because hormonal changes underpin the basis of growth and development, the timing of injury and PTHP testing with respect to pubertal stage gains particular importance. Reciprocal relationships among neuroendocrine function, TBI, adverse childhood events, and physiological, psychological and cognitive sequelae are underconsidered influencers of sexually dimorphic outcomes. In light of the tremendous heterogeneity in this body of literature, we conclude with the common path upon which we must collectively arrive in order to make progress in understanding PTHP.
Hand Focused Upper Extremity Rehabilitation in the Subacute Phase Post-stroke Using Interactive Virtual Environments
Authors: Merians Alma S. , Fluet Gerard G. , Qiu Qinyin , Yarossi Mathew , Patel Jigna , Mont Ashley J. , Saleh Soha , Nolan Karen J. , Barrett AM , Tunik Eugene , Adamovich Sergei V.
Published: November 2020

Introduction:Innovative motor therapies have attempted to reduce upper extremity impairment after stroke but have not made substantial improvement as over 50% of people post-stroke continue to have sensorimotor deficits affecting their self-care and participation in daily activities. Intervention studies have focused on the role of increased dosing, however recent studies have indicated that timing of rehabilitation interventions may be as important as dosing and importantly, that dosing and timing interact in mediating effectiveness. This study is designed to empirically test dosing and timing.

Methods and Analysis:In this single-blinded, interventional study, subjects will be stratified on two dimensions, impairment level (Fugl-Meyer Upper Extremity Assessment (FM) and presence or absence of Motor Evoked Potentials (MEPs) as follows; (1) Severe, FM score 10–19, MEP+, (2) Severe, FM score 10–19, MEP–, (3) Moderate, FM score 20–49, MEP+, (4) Moderate, FM score 20–49, MEP–. Subjects not eligible for TMS will be assigned to either group 2 (if severe) or group 3 (if moderate). Stratified block randomization will then be used to achieve a balanced assignment. Early Robotic/VR Therapy (EVR) experimental group will receive in-patient usual care therapy plus an extra 10 h of intensive upper extremity therapy focusing on the hand using robotically facilitated rehabilitation interventions presented in virtual environments and initiated 5–30 days post-stroke. Delayed Robotic/VR Therapy (DVR) experimental group will receive the same intervention but initiated 30–60 days post-stroke. Dose-matched usual care group (DMUC) will receive an extra 10 h of usual care initiated 5–30 days post-stroke. Usual Care Group (UC) will receive the usual amount of physical/occupational therapy.

Outcomes:There are clinical, neurophysiological, and kinematic/kinetic measures, plus measures of daily arm use and quality of life. Primary outcome is the Action Research Arm Test (ARAT) measured at 4 months post-stroke.

Discussion:Outcome measures will be assessed to determine whether there is an early time period in which rehabilitation will be most effective, and whether there is a difference in the recapture of premorbid patterns of movement vs. the development of an efficient, but compensatory movement strategy.

Ethical Considerations:The IRBs of New Jersey Institute of Technology, Rutgers University, Northeastern University, and Kessler Foundation reviewed and approved all study protocols. Study was registered inhttps://ClinicalTrials.gov(NCT03569059) prior to recruitment. Dissemination will include submission to peer-reviewed journals and professional presentations.
Impact of Lower Limb Active Movement Training in Individuals With Spastic Type Cerebral Palsy on Neuromuscular Control Outcomes: A Systematic Review
Authors: O'Brien Shari M. , Lichtwark Glen A. , Carroll Timothy J. , Barber Lee A.
Published: November 2020

Background: Cerebral Palsy (CP) is a non-progressive neurological condition that results in motor impairment which increases proximally to distally along the lower extremity (i.e., greatest impairment at the ankle). Consequently, motor impairment and reduced voluntary muscle activation results in reduced neuromuscular control of the lower limb in this population. CP rehabilitation traditionally aims to improve movement proficiency for functional activities, such as walking, by using a range of active movement modalities that require volitional effort; however, the underlying neural mechanisms of improved control and function remain unknown. The primary purpose of this study was to systematically determine the efficacy of lower limb active movement interventions to improve neuromuscular control in individuals with CP.

Methodology: A search for studies involving an active lower limb intervention and neurophysiological outcome measures in individuals with CP was performed in five electronic databases. Studies were assessed for methodological quality using the Downs and Black assessment tool.

Results: Nine of 6,263 articles met the inclusion criteria. Methodological quality of all studies was poor, ranging from 2 to 27 out of a possible score of 32 points on the Downs and Black assessment tool. The study interventions varied extensively in modality and prescription as well as in the outcome measures used.

Conclusions: Whether active movement improves neuromuscular control of the lower limb in CP is unclear due to high variability in intervention protocols and selected outcomes measures. Future active intervention studies must carefully consider the selection of neurophysiological outcome measures.
Electroencephalographic Abnormalites in SARS-CoV-2 Patients
Authors: Besnard Stephane , Nardin Clotilde , Lyon Elsa , Debroucker Thomas , Arjmand Roxana , Moretti Raffaella , Pochat Hervé
Published: November 2020

Viral infection with SARS-CoV-2 has a neurological tropism that may induce an encephalopathy. In this context, electroencephalographic exploration (EEG) is indicated as a diagnostic argument correlated with lumbar puncture, biology, and imaging. We performed a retrospective analysis of 42 patients explored by EEG and infected by COVID-19, according to the EEG abnormalities and clinical signs that motivated the examination. Confusion and epileptic seizures were the most common clinical indications, with 64% of the patients displaying these symptoms. The EEG was altered in 85% of the cases of confusion, in 57% of the cases of epileptic symptoms (general or focal seizure or prolonged loss of contact) and 20% of the cases of malaise or brief loss of consciousness. Nine EEG (21%) were in favor of an encephalopathy, two had de novo alterations in persistent consciousness and two had alterations in general states of confusion; one was very agitated and without history of epilepsy and combined eyelids clonia while a second one exhibited unconsciousness with left hemicorpus clonus. Two were being investigated for delayed awakening without sedation for more than 24 h. All of these patients were diagnosed COVID-19, some of them with associated mild to severe respiratory disorders. This work shows the interest of the EEG in exploring COVID-19 patients suffering from neurological or general symptoms looking for cerebral alteration.
Neuromuscular Diseases Care in the Era of COVID-19
Authors: Bertran Recasens Bernat , Rubio Miguel Angel
Published: November 2020

The COVID-19 pandemic has pushed health systems to their limit and forced readjustment of standards of care for different pathologies. Management of neuromuscular diseases becomes a challenge since most of them are chronic, disabling, progressive, and/or require immunosuppressive drugs. There are three main aspects of COVID-19 that affect neuromuscular diseases care. The first one relates to how SARS-CoV2 directly affects different neuromuscular pathologies. Respiratory weakness, as seen in myasthenia gravis, amyotrophic lateral sclerosis, and myopathies, and the use of immunomodulatory drugs (Myasthenia Gravis and Chronic Inflammatory Demyelinating Polyneuropathy) make this group of patients potentially more vulnerable. Secondly, safety measures also affect proper care, limiting care continuity, and physical rehabilitation (one of the essential aspects of myopathies treatment). Telemedicine can partially solve the problem allowing for a continuum of close care, avoiding unnecessary visits, and even guaranteeing the attention of professionals from tertiary care centers. However, one of the crucial steps in neuromuscular diseases is diagnosis, and in most scenarios, more than one face-to-face visit is needed. Lastly, the global COVID-19 situation will also have an economic impact on patients and their families. This situation is of particular concern given that neuromuscular diseases already present difficulties due to the scarcity of resources in terms of public healthcare and research.
Decreased Proliferation in the Neurogenic Niche, Disorganized Neuroblast Migration, and Increased Oligodendrogenesis in Adult Netrin-5-Deficient Mice
Authors: Ikegaya Shunsuke , Iga Yurika , Mikawa Sumiko , Zhou Li , Abe Manabu , Sakimura Kenji , Sato Kohji , Yamagishi Satoru
Published: November 2020

In the adult mouse brain, neurogenesis occurs mainly in the ventricular-subventricular zone (V-SVZ) and the subgranular zone of the hippocampal dentate gyrus. Neuroblasts generated in the V-SVZ migrate to the olfactory bulb via the rostral migratory stream (RMS) in response to guidance molecules, such as netrin-1. We previously showed that the related netrin-5 (NTN5) is expressed in Mash1-positive transit-amplifying cells and doublecortin-positive neuroblasts in the granule cell layer of the olfactory bulb, the RMS, and the subgranular zone of the adult mouse brain. However, the precise role of NTN5 in adult neurogenesis has not been investigated. In this study, we show that proliferation in the neurogenic niche is impaired in NTN5 knockout mice. The number of proliferating (EdU-labeled) cells in NTN5 KO mice was significantly lower in the V-SVZ, whereas the number of Ki67-positive proliferating cells was unchanged, suggesting a longer cell cycle and decreased cell division in NTN5 KO mice. The number of EdU-labeled cells in the RMS and olfactory bulb was unchanged. By contrast, the numbers of EdU-labeled cells in the cortex, basal ganglia/lateral septal nucleus, and corpus callosum/anterior commissure were increased, which largely represented oligodendrocyte lineage cells. Lastly, we found that chain migration in the RMS of NTN5 KO mice was disorganized. These findings suggest that NTN5 may play important roles in promoting proliferation in the V-SVZ niche, organizing proper chain migration in the RMS, and suppressing oligodendrogenesis in the brain.
An in vitro Model of Human Retinal Detachment Reveals Successive Death Pathway Activations
Authors: Potic Jelena , Mbefo Martial , Berger Adeline , Nicolas Michael , Wanner Dana , Kostic Corinne , Matet Alexandre , Behar-Cohen Francine , Moulin Alexandre , Arsenijevic Yvan
Published: November 2020

Purpose

was to create an in vitro model of human retinal detachment (RD) to study the mechanisms of photoreceptor death.

Methods

Human retinas were obtained through eye globe donations for research purposes and cultivated as explants. Cell death was investigated in retinas with (control) and without retinal pigment epithelium (RPE) cells to mimic RD. Tissues were studied at different time points and immunohistological analyses for TUNEL, Cleaved caspase3, AIF, CDK4 and the epigenetic mark H3K27me3 were performed. Human and monkey eye globes with retinal detachment served as controls.

Results

The number of TUNEL-positive cells, compared between 1 and 7 days, increased with time in both retinas with RPE (from 1.2 ± 0.46 to 8 ± 0.89, n = 4) and without RPE (from 2.6 ± 0.73 to 16.3 ± 1.27, p < 0.014). In the group without RPE, cell death peaked at day 3 (p = 0.014) and was high until day 7. Almost no Cleaved-Caspase3 signal was observed, whereas a transient augmentation at day 3 of AIF-positive cells was observed to be about 10-fold in comparison to the control group (n = 2). Few CDK4-positive cells were found in both groups, but significantly more in the RD group at day 7 (1.8 ± 0.24 vs. 4.7 ± 0.58, p = 0.014). The H3K27me3 mark increased by 7-fold after 5 days in the RD group (p = 0.014) and slightly decreased at day 7 and was also observed to be markedly increased in human and monkey detached retina samples.

Conclusion

AIF expression coincides with the first peak of cell death, whereas the H3K27me3 mark increases during the cell death plateau, suggesting that photoreceptor death is induced by different successive pathways after RD. This in vitro model should permit the identification of neuroprotective drugs with clinical relevance.
Comparing the Impact of Laparoscopic Sleeve Gastrectomy and Gastric Cancer Surgery on Resting-State Brain Activity and Functional Connectivity
Authors: Gu Yong , Li Guanya , Wang Jia , von Deneen Karen M. , Wu Kaichun , Yang Yan , She Junjun , Ji Gang , Nie Yongzhan , Cui Guangbin , Zhang Yi , He Shuixiang
Published: November 2020

Laparoscopic sleeve gastrectomy (LSG) is one of the most performed bariatric surgeries in clinical practice. Growing neuroimaging evidence shows that LSG induces brain functional and structural alterations accompany with sustained weight-loss. Meanwhile, for clinical treatment of gastric cancer, stomach removal surgery is a similar procedure to LSG. It is unclear if the gastric cancer surgery (GCS) would induce the similar alterations in brain functions and structures as LSG, and it would help to clarify the specificity of the LSG. We recruited 24 obese patients who received LSG in the LSG group and 16 normal weight patients with gastric cancer who received GCS as the control group. Functional magnetic resonance imaging was employed to investigate the differences and similarity of surgery’s impact on resting-state brain activity and functional connectivity (RSFC) between LSG and GCS groups. Both LSG and GCS groups showed increased activities in the posterior cingulate cortex (PCC) and supplementary motor area (SMA) as well as the decreased RSFC of PCC- dorsomedial prefrontal cortex and SMA- dorsolateral prefrontal cortex. There were decreased resting-state activity of hippocampus and putamen in LSG group and increases in GCS group. In LSG group, resting-state activities of hippocampus and putamen were correlated with craving for high-caloric food and body mass index after surgery, respectively. These findings suggest LSG induced alterations in resting-state activity and RSFC of hippocampus and putamen specifically regulate the obese state and overeating behaviors in obese patients.