bluuebunny/crossref_metadata_2025_split huggingface dataset:
Concordance of Immune-Related Markers in Lymphocytes and Prefrontal Cortex in Schizophrenia
Authors: Gatta Eleonora , Saudagar Vikram , Drnevich Jenny , Forrest Marc P , Auta James , Clark Lindsay V , Sershen Henry , Smith Robert C , Grayson Dennis R , Davis John M , Guidotti Alessandro 
Published: January 2021

AbstractSchizophrenia is a severe neuropsychiatric disorder associated with a wide array of transcriptomic and neurobiochemical changes. Genome-wide transcriptomic profiling conducted in postmortem brain have provided novel insights into the pathophysiology of this disorder, and identified biological processes including immune/inflammatory-related responses, metabolic, endocrine, and synaptic function. However, few studies have investigated whether similar changes are present in peripheral tissue. Here, we used RNA-sequencing to characterize transcriptomic profiles of lymphocytes in 18 nonpsychotic controls and 19 individuals with schizophrenia. We identified 2819 differentially expressed transcripts (Pnominal &lt; .05) in the schizophrenia group when compared to controls. Bioinformatic analyses conducted on a subset of 293 genes (Pnominal &lt; .01 and |log2 FC| &gt; 0.5) highlighted immune/inflammatory responses as key biological processes in our dataset. Differentially expressed genes in lymphocytes were highly enriched in gene expression profiles associated with cortex layer 5a and immune cells. Thus, we investigated whether the changes in transcripts levels observed in lymphocytes could also be detected in the prefrontal cortex (PFC, BA10) in a second replication cohort of schizophrenia subjects. Remarkably, mRNA levels detected in the PFC and lymphocytes were in strong agreement, and measurements obtained using RNA-sequencing positively correlated with data obtained by reverse transcriptase-quantitative polymerase chain reaction analysis. Collectively, our work supports a role for immune dysfunction in the pathogenesis of schizophrenia and suggests that peripheral markers can be used as accessible surrogates to investigate putative central nervous system disruptions.
Menopausal symptoms in women with premature ovarian insufficiency: prevalence, severity, and associated factors
Authors: Huang Yizhou , Qi Tongyun , Ma Linjuan , Li Die , Li Chunming , Lan Yibing , Chu Ketan , Chen Peiqiong , Xu Wenxian , Cao Yina , Ying Qian , Xu Ling , Zhou Jianhong 
Published: January 2021

Abstract

Objective:
To comprehensively investigate and evaluate the prevalence, severity, and associated factors of menopausal symptoms in women with premature ovarian insufficiency (POI). In this study, the specific symptomatology experienced by women with POI and women with natural menopause was also compared.

Methods:
In this cross-sectional study, 293 Chinese women with POI from an outpatient clinic were recruited between June 2014 and January 2019. The prevalence and severity of menopausal symptoms were assessed with modified Kupperman Menopausal Index. Participants completed a structured questionnaire, including medical history, menstrual characteristics, and sociodemographic data. Serum levels of reproductive hormones were measured.

Results:
Among 293 women with POI (33.76 ± 5.47 y), the most prevalent symptoms were mood swings (73.4%), insomnia (58.7%), sexual problems (58.7%), and fatigue (57.3%). Moderate-to-severe mood swings were most frequently reported (23.9%), followed by formication (17.4%) and hot flashes/sweating (17.1%). Compared with women with natural menopause, women with POI exhibited significantly higher risks for fatigue (odds ratio  = 1.42; 95% confidence interval, 1.04-1.94), melancholia (3.12; 1.94-5.01), mood swings (3.57; 2.33-5.45), insomnia (1.41; 1.02-1.96), and significantly lower risks for moderate-to-severe sexual problems (0.40; 0.23-0.69), any and moderate-to-severe muscle/joint pain (0.41; 0.27-0.62 and 0.45; 0.25-0.78, respectively). Living in urban areas and higher gravidity were independently associated with menopausal symptoms in women with POI.

Conclusions:
Women with POI experienced a high prevalence of menopausal symptoms, particularly related to psychological and sexual domains. Furthermore, women with POI tended to have more distressing menopausal symptoms compared with women with natural menopause.
The influence of gut microbiota in cardiovascular diseases—a brief review
Authors: Almeida Cátia , Barata Pedro , Fernandes Ruben 
Published: January 2021

Abstract
Lately, the gut microbiota has emerged as an important mediator of the development and the outcomes of certain diseases. It's well known that the gut microbiota plays an important role in maintaining human health. Still far from being completely understood and analyzed is the complexity of this ecosystem, although a close relationship between the gut microbiota and cardiovascular diseases (CVD) has been established. A loss of diversity in the microbiota will lead to physiological changes, which can improve inflammatory or infection states like atherosclerosis and hypertension, the basic pathological process of CVD. Targeting the gut microbiota and its metabolites are new and promising strategies for the treatment and prognosis of CVD.
Myroides fluvii sp. nov., isolated from the Han River, Republic of Korea
Authors: Kim Yong-Seok , Jang Seo-Hyeon , Cha Chang-Jun 
Published: January 2021

A Gram-stain-negative, aerobic, short rod-shaped, pale yellow-pigmented, non-motile and gentamycin-resistant bacterial strain designated CJ210T was isolated from the Han River, Republic of Korea. Strain CJ210T grew optimally at 30 °C and pH 7.0 in the absence of NaCl on tryptic soy agar. Flexirubin-type pigments were not produced. Phylogenetic analysis based on 16S rRNA gene sequence similarity showed that strain CJ210T belonged to the genus

Myroides

within the family

Flavobacteriaceae

and was most closely related to

Myroides odoratus

KACC 14347T (98.1 % similarity), followed by

M. injenensis

KCTC 23367T (95.3 % similarity). The average nucleotide identity values between strain CJ210T and two closely related type strains

M. odoratus

KACC 14347T and

M. injenensis

KCTC 23367T were 83.7 and 73.8 %, respectively. The digital DNA–DNA hybridization results between strain CJ210T and the related type strains were 27.5 and 20.2 %, respectively. Strain CJ210T contained menaquinone 6 (MK-6) as the predominant menaquinone. The predominant polar lipids were phosphatidylethanolamine, two unidentified aminolipids and two unidentified lipids. The major fatty acids of strain CJ210T were iso-C15 : 0, iso-C17 : 0 3-OH and summed feature 9 (comprising iso-C17 : 1
ω9c and/or C16 : 0 10-methyl). Whole genome sequencing revealed that strain CJ210T had a genome of 3.8 Mbp with 36.5 % DNA G+C content. The genome contained several antimicrobial resistance genes including an aminoglycoside-resistant gene. On the basis of the polyphasic taxonomic study, strain CJ210T represents a novel species in the genus

Myroides

, for which name Myrodies fluvii sp. nov. is proposed. The type strain is CJ210T (=KACC 19954T=JCM 33306T).
Modelling the effects of cerebral microthrombi on tissue oxygenation and cell death
Authors: Xue Yidan , El-Bouri Wahbi K. , Józsa Tamás I. , Payne Stephen J. 
Published: January 2021

AbstractThrombectomy, the mechanical removal of a clot, is the most common way to treat ischaemic stroke with large vessel occlusions. However, perfusion cannot always be restored after such an intervention. It has been hypothesised that the absence of reperfusion is due to the clot fragments that block the downstream vessels. In this paper, we present a new way of quantifying the effects of cerebral microthrombi on oxygen transport to tissue in terms of hypoxia and ischaemia. The oxygen transport was simulated with the Green’s function method on physiologically accurate microvascular cubes, which was found independent of both microvascular geometry and length scale. The microthrombi occlusions were then simulated in the microvasculature, which were extravasated over time with a new vessel extravasation model. The tissue hypoxic fraction was fitted as a sigmoidal function of vessel blockage fraction, which was then taken to be a function of time after the formation of microthrombi occlusions. A novel hypoxia-based 3-state cell death model was finally proposed to simulate the hypoxic tissue damage over time. Using the cell death model, the impact of a certain degree of microthrombi occlusions on tissue viability and microinfarct volume can be predicted over time. Quantifying the impact of microthrombi on oxygen transport and tissue death will play an important role in full brain models of ischaemic stroke and thrombectomy.
Rise-to-threshold and dynamical systems views of proactive inhibition
Authors: Rawji Vishal , Modi Sachin , Rocchi Lorenzo , Jahanshahi Marjan , Rothwell John C. 
Published: January 2021

AbstractSuccessful models of movement should encompass the flexibility of the human motor system to execute movements under different contexts. One such context-dependent modulation is proactive inhibition, a type of behavioural inhibition concerned with responding with restraint. Whilst movement has classically been modelled as a rise-to-threshold process, there exists a lack of empirical evidence for this in limb movements. Alternatively, the dynamical systems view conceptualises activity during motor preparation as setting the initial state of a dynamical system, that evolves into the movement upon receipt of a trigger. We tested these models by measuring how proactive inhibition influenced movement preparation and execution in humans. We changed the orientation (PA: postero-anterior and AP: antero-posterior flowing currents) and pulse width (120 μs and 30 μs) of motor cortex transcranial magnetic stimulation to probe different corticospinal interneuron circuits. PA and AP interneuron circuits represent the dimensions of a state space upon which motor cortex activity unfolds during motor preparation and execution. AP30inputs were inhibited at the go cue, regardless of proactive inhibition, whereas PA120inputs scaled inversely with the probability of successful inhibition. When viewed through a rise-to-threshold model, proactive inhibition was implemented by delaying the trigger to move, suggesting that motor preparation and execution are independent. A dynamical systems perspective showed that proactive inhibition was marked by a shift in the distribution of interneuron networks (trajectories) during movement execution, despite normalisation for reaction time. Viewing data through the rise-to-threshold and dynamical systems models reveal complimentary mechanisms by which proactive inhibition is implemented.Key pointsWe view proactive inhibition through the rise-to-threshold and dynamical systems models.We change the orientation (PA: postero-anterior and AP: antero-posterior flowing currents) and pulse width (120 μs and 30 μs) of transcranial magnetic stimulation to probe interneuron networks in motor cortex during behavioural tasks employing proactive inhibition.When viewed through a rise-to-threshold model, proactive inhibition was implemented by delaying the trigger to move, suggesting that motor preparation and execution are independent.A dynamical systems perspective showed that despite normalisation for reaction time, the trajectory/balance between PA120and AP30interneuron inputs during movement execution depended on proactive inhibition.Viewing data through the rise-to-threshold and dynamical systems models reveal complimentary mechanisms by which proactive inhibition is implemented.
Microfluidic Electric Egg-Laying Assay and Application toIn-vivoToxicity Screening of Microplastics usingC. elegans
Authors: Youssef Khaled , Archonta Daphne , Kubiseseki Terrance J. , Tandon Anurag , Rezai Pouya 
Published: January 2021

AbstractEnvironmental pollutants like microplastics are posing health concerns on aquatic animals and the ecosystem. Microplastic toxicity studies usingC. elegansas a model are evolving but methodologically hindered from obtaining statistically strong data sets, detecting toxicity effects based on microplastics uptake, and correlating physiological and behavioural effects at an individual-worm level. In this paper, we report a novel microfluidic electric egg-laying assay for phenotypical assessment of multiple worms in parallel. The effects of glucose and polystyrene microplastics at various concentrations on the worms’ electric egg-laying, length, diameter, and length contraction during exposure to electric signal were studied. The device contained eight parallel worm-dwelling microchannels called electric traps, with equivalent electrical fields, in which the worms were electrically stimulated for egg deposition and fluorescently imaged for assessment of neuronal and microplastic uptake expression. A new bidirectional stimulation technique was developed, and the device design was optimized to achieve a testing efficiency of 91.25%. Exposure of worms to 100mM glucose resulted in a significant reduction in their egg-laying and size. The effects of 1μm polystyrene microparticles at concentrations of 100 and 1000 mg/L on the electric egg-laying behaviour, size, and neurodegeneration of N2 and NW1229 (expressing GFP pan-neuronally) worms were also studied. Of the two concentrations, 1000 mg/L caused severe egg-laying deficiency and growth retardation as well as neurodegeneration. Additionally, using single-worm level phenotyping, we noticed intra-population variability in microplastics uptake and correlation with the above physiological and behavioural phenotypes, which was hidden in the population-averaged results. Taken together, these results suggest the appropriateness of our microfluidic assay for toxicological studies and for assessing the phenotypical heterogeneity in response to microplastics.
Intracranial electrical stimulation alters meso-scale network integration as a function of network topology
Authors: Thompson WH , Esteban O , Oya H , Nair R , Eberhardt F , Dubois J , Poldrack RA , Adolphs R , Shine JM 
Published: January 2021

AbstractHuman brain dynamics are organized into a multi-scale network structure that contains multiple tight-knit, meso-scale communities. Recent work has demonstrated that many psychological capacities, as well as impairments in cognitive function secondary to damage, can be mapped onto organizing principles at this mesoscopic scale. However, we still don’t know the rules that govern the dynamic interactions between regions that are constrained by the topology of the broader network. In this preregistered study, we utilized a unique human dataset in which whole brain BOLD-fMRI activity was recorded simultaneously with intracranial electrical stimulation, to characterize the effects of direct neural stimulation on the dynamic reconfiguration of the broader network. Direct neural stimulation increased the extent to which the stimulation site’s own mesoscale community integrated with the rest of the brain. Further, we found that these network changes depended on the topological role of the stimulation site itself: stimulating regions with high participation coefficients led to global integration, whereas stimulating sites with low participation coefficients integrated that regions’ own community with the rest of the brain. These findings provide direct causal evidence for how network topology shapes and constrains inter-regional coordination, and suggest applications for targeted therapeutic interventions in patients with deep-brain stimulation.
Enhanced CICR activity reduces ER Ca2+level in cells expressing CPVT-linked mutant RyR2
Authors: Kurebayashi Nagomi , Murayama Takashi , Ohta Ryosaku , Suzuki Junji , Kanemaru Kazunori , Ohno Seiko , Horie Minoru , Iino Masamitsu , Yamashita Fumiyoshi , Sakurai Takashi 
Published: January 2021

AbstractType 2 ryanodine receptor (RyR2) is a cardiac Ca2+release channel in the endoplasmic reticulum (ER). Mutations in RyR2 are linked to catecholaminergic polymorphic ventricular tachycardia (CPVT), which is considered to be associated with enhanced spontaneous Ca2+release. This spontaneous Ca2+release tends to occur when ER Ca2+([Ca2+]ER) reaches a certain threshold level, and CPVT mutations are reported to lower this threshold. There are two explanations for this lowered threshold: the mutations increase sensitivity to luminal Ca2+or they enhance cytosolic [Ca2+] ([Ca2+]cyt)-induced Ca2+release (CICR) activity. However, no quantitative analysis of this issue has been performed so far. Here, we quantitatively explored how the change in CICR activity of RyR2 affects the threshold [Ca2+]ERexperimentally and by model-based simulation. Wild-type (WT) and CPVT-linked mutant RyR2s were expressed in HEK293 cells. [Ca2+]cytand [Ca2+]ERmeasurements with Ca2+indicators revealed that CPVT RyR2 cells showed higher oscillation frequency and lower threshold [Ca2+]ERin a mutation-specific manner compared with WT cells. The CICR activity of mutant RyR2s was assessed by Ca2+-dependent [3H]ryanodine binding and parameter analysis. CICR activity at resting [Ca2+]cyt, A7.0, was higher in CPVT mutants than in WT and a strong inverse correlation was found between threshold [Ca2+]ERand A7.0. Interestingly, lowering RyR2 expression increased threshold [Ca2+]ER, suggesting that the threshold [Ca2+]ERdepends on net Ca2+release rate via RyR2, a product of A7.0for each mutant and the density of RyR2 molecules. A model-based simulation successfully reproduced the [Ca2+]cytand [Ca2+]ERchanges. Interestingly, the CICR activity associated with specific mutations correlated well with the age of onset of the disease in CPVT patients carrying the mutations. Our data suggest that the reduction in threshold [Ca2+]ERfor spontaneous Ca2+release by CPVT mutation is explained by enhanced CICR activity without considering a change in the [Ca2+]ERsensitivity of RyR2.SummaryCPVT-linked RyR2 mutations are prone to induce spontaneous Ca2+release from ER, which is strongly associated with arrhythmias. Kurebayashi et al. quantitatively explore how the changes in CICR activity by RyR2 mutations affect spontaneous Ca2+experimentally and by model simulation.
A Pan-Respiratory Antiviral Chemotype Targeting a Host Multi-Protein Complex
Authors: Michon Maya , Müller-Schiffmann Andreas , Lingappa Anuradha F. , Yu Shao Feng , Du Li , Deiter Fred , Broce Sean , Mallesh Suguna , Crabtree Jackelyn , Lingappa Usha F. , Macieik Amanda , Müller Lisa , Ostermann Philipp Niklas , Andrée Marcel , Adams Ortwin , Schaal Heiner , Hogan Robert J. , Tripp Ralph A. , Appaiah Umesh , Anand Sanjeev K. , Campi Thomas W. , Ford Michael J. , Reed Jonathan C. , Lin Jim , Akintunde Olayemi , Copeland Kiel , Nichols Christine , Petrouski Emma , Moreira A. Raquel , Jiang I-ting , DeYarman Nicholas , Brown Ian , Lau Sharon , Segal Ilana , Goldsmith Danielle , Hong Shi , Asundi Vinod , Briggs Erica M. , Phyo Ngwe Sin , Froehlich Markus , Onisko Bruce , Matlack Kent , Dey Debendranath , Lingappa Jaisri R. , Prasad M. Dharma , Kitaygorodskyy Anatoliy , Solas Dennis , Boushey Homer , Greenland John , Pillai Satish , Lo Michael K. , Montgomery Joel M. , Spiropoulou Christina F. , Korth Carsten , Selvarajah Suganya , Paulvannan Kumar , Lingappa Vishwanath R. 
Published: January 2021

AbstractWe present a novel small molecule antiviral chemotype that was identified by an unconventional cell-free protein synthesis and assembly-based phenotypic screen for modulation of viral capsid assembly. Activity of PAV-431, a representative compound from the series, has been validated against infectious virus in multiple cell culture models for all six families of viruses causing most respiratory disease in humans. In animals this chemotype has been demonstrated efficacious for Porcine Epidemic Diarrhea Virus (a coronavirus) and Respiratory Syncytial Virus (a paramyxovirus). PAV-431 is shown to bind to the protein 14-3-3, a known allosteric modulator. However, it only appears to target the small subset of 14-3-3 which is present in a dynamic multi-protein complex whose components include proteins implicated in viral lifecycles and in innate immunity. The composition of this target multi-protein complex appears to be modified upon viral infection and largely restored by PAV-431 treatment. Our findings suggest a new paradigm for understanding, and drugging, the host-virus interface, which leads to a new clinical therapeutic strategy for treatment of respiratory viral disease.
Intact synapse structure and function after combined knockout of PTPδ, PTPσ and LAR
Authors: Emperador-Melero Javier , de Nola Giovanni , Kaeser Pascal S. 
Published: January 2021

AbstractIt has long been proposed that Leukocyte common Antigen-Related Receptor Protein Tyrosine Phosphatases (LAR-RPTPs) are cell-adhesion proteins for the control of synapse assembly. Their synaptic nanoscale localization, however, has not been established, and the fine structure of synapses after knockout of the three vertebrate genes for LAR-RPTPs (PTPδ, PTPσ and LAR) has not been tested. Here, we find that PTPδ is precisely apposed to postsynaptic scaffolds at excitatory and inhibitory synapses using superresolution microscopy. We generated triple-conditional knockout mice for PTPδ, PTPσ and LAR to test whether they are essential for synapse structure. While mild effects on synaptic vesicle clustering and active zone architecture were detected, synapse numbers and their overall structure were unaffected, membrane anchoring of the active zone persisted, and vesicle docking and release were normal. We conclude that LAR-RPTPs, despite their localization at synaptic appositions, are dispensable for the organization and function of presynaptic nerve terminals.
Local Shape Descriptors for Neuron Segmentation
Authors: Sheridan Arlo , Nguyen Tri , Deb Diptodip , Lee Wei-Chung Allen , Saalfeld Stephan , Turaga Srini , Manor Uri , Funke Jan 
Published: January 2021

AbstractWe present a simple, yet effective, auxiliary learning task for the problem of neuron segmentation in electron microscopy volumes. The auxiliary task consists of the prediction of Local Shape Descriptors (LSDs), which we combine with conventional voxel-wise direct neighbor affinities for neuron boundary detection. The shape descriptors are designed to capture local statistics about the neuron to be segmented, such as diameter, elongation, and direction. On a large study comparing several existing methods across various specimen, imaging techniques, and resolutions, we find that auxiliary learning of LSDs consistently increases segmentation accuracy of affinity-based methods over a range of metrics. Furthermore, the addition of LSDs promotes affinity-based segmentation methods to be on par with the current state of the art for neuron segmentation (Flood-Filling Networks, FFN), while being two orders of magnitudes more efficient—a critical requirement for the processing of future petabyte-sized datasets. Implementations of the new auxiliary learning task, network architectures, training, prediction, and evaluation code, as well as the datasets used in this study are publicly available as a benchmark for future method contributions.