bluuebunny/crossref_metadata_2025 huggingface dataset:
Decades of Recovery From Sheep Grazing Reveal No Effects on Plant Diversity Patterns Within Icelandic Tundra Landscapes
Authors: Mörsdorf Martin A. , Ravolainen Virve T. , Yoccoz Nigel G. , Thórhallsdóttir Thóra Ellen , Jónsdóttir Ingibjörg Svala
Published: January 2021

Tundra plant communities are often shaped by topography. Contrasting wind exposure, slopes of different inclination and landforms of different curvature affect habitat conditions and shape plant diversity patterns. The majority of tundra is also grazed by ungulates, which may alter topographically induced plant diversity patterns, but such effects may depend on the spatial scales of assessments. Here we ask whether topographically induced patterns of within (alpha) and between (beta) plant community diversity are different in contrasting grazing regimes. We studied plant communities within tundra landscapes that were located in the North and Northwest of Iceland. Half of the studied landscapes were grazed by sheep, whereas the other half was currently un-grazed and recovering for several decades (up to 60 years).Alphaandbetadiversity were assessed on explicitly defined, nested spatial scales, which were determined by topographical units. Although we contrasted currently grazed vegetation to vegetation that witnessed several decades of grazing recovery, we found no statistically significant differences in plant diversity patterns. We relate these findings to the low resilience of our study system toward grazing disturbances, which has important implications for management practices in the tundra. Effects of topography on species richness were only found for specific spatial scales of analyses. Species rich topographical units were associated with relatively large biomass of plant growth forms that promote nutrient availability and potential plant productivity in the tundra, such as forbs. This suggests that biomass of such plant growth forms within habitats can be a useful proxy of potential plant productivity and may predict spatial patterns of plant species richness in tundra.
Induction of SARS-CoV-2 Protein S-Specific CD8+ T Cells in the Lungs of gp96-Ig-S Vaccinated Mice
Authors: Fisher Eva , Padula Laura , Podack Kristin , O’Neill Katelyn , Seavey Matthew M. , Jayaraman Padmini , Jasuja Rahul , Strbo Natasa
Published: January 2021

Given the aggressive spread of COVID-19-related deaths, there is an urgent public health need to support the development of vaccine candidates to rapidly improve the available control measures against SARS-CoV-2. To meet this need, we are leveraging our existing vaccine platform to target SARS-CoV-2. Here, we generated cellular heat shock chaperone protein, glycoprotein 96 (gp96), to deliver SARS-CoV-2 protein S (spike) to the immune system and to induce cell-mediated immune responses. We showed that our vaccine platform effectively stimulates a robust cellular immune response against protein S. Moreover, we confirmed that gp96-Ig, secreted from allogeneic cells expressing full-length protein S, generates powerful, protein S polyepitope-specific CD4+ and CD8+ T cell responses in both lung interstitium and airways. These findings were further strengthened by the observation that protein-S -specific CD8+ T cells were induced in human leukocyte antigen HLA-A2.1 transgenic mice thus providing encouraging translational data that the vaccine is likely to work in humans, in the context of SARS-CoV-2 antigen presentation.
COVID-19 in Association With Development, Course, and Treatment of Systemic Autoimmune Rheumatic Diseases
Authors: Lakota Katja , Perdan-Pirkmajer Katja , Hočevar Alojzija , Sodin-Semrl Snezna , Rotar Žiga , Čučnik Saša , Žigon Polona
Published: January 2021

Autoimmune diseases and infections are often closely intertwined. Patients with autoimmune diseases are more susceptible to infections due to either active autoimmune disease or the medications used to treat them. Based on infections as environmental triggers of autoimmunity, an autoimmune response would also be expected in COVID-19. Although some studies have shown the occurance of autoantibodies and the possible development of autoimmune diseases after SARS-CoV-2 infection, current data suggest that the levels of autoantibodies following SARS-CoV-2 infection is comparable to that of some other known infections and that the autoantibodies might only be transient. The risk of SARS-CoV-2 infection in patients with a systemic autoimmune rheumatic disease (SARD) appears slightly higher compared to the general population and the course of COVID-19 disease does not seem to be very different, however, specific therapies such as glucocorticoids and anti-TNF might modulate the risk of hospitalization/death. Cytokine release syndrome is a severe complication in COVID-19. Many drugs used for the treatment of SARD are directly or indirectly targeting cytokines involved in the cytokine release syndrome, therefore it has been suggested that they could also be effective in COVID-19, but more evidence on the use of these medications for the treatment of COVID-19 is currently being collected.
New Insights Into the Seasonal Movement Patterns of Shortfin Mako Sharks in the Gulf of Mexico
Authors: Gibson Kesley J. , Streich Matthew K. , Topping Tara S. , Stunz Gregory W.
Published: January 2021

Highly mobile apex predators such as the shortfin mako shark (mako shark;Isurus oxyrinchus) serve an important role in the marine ecosystem, and despite their declining populations and vulnerability to overexploitation, this species is frequently harvested in high abundance in both commercial and recreational fisheries. In 2017, the North Atlantic stock was deemed overfished and to be undergoing overfishing and was recently listed in CITES Appendix II. Effective management of this species can benefit from detailed information on their movements and habitat use, which is lacking, especially in the Gulf of Mexico, a potential mating and parturition ground. In this study, we used satellite telemetry to track the movements of mako sharks in the western Gulf of Mexico between 2016 and 2020. In contrast to previous studies that have primarily tagged juvenile mako sharks (>80% juveniles), ∼80% of sharks tagged in this study (7 of 9) were presumed to be mature based on published size-at-maturity data. Sharks were tracked for durations ranging from 10 to 887 days (mean = 359 days; median = 239 days) with three mature individuals tracked for >2 years. Mako sharks tagged in this study used more of the northwestern Gulf of Mexico than reported in previous movement studies on juveniles, suggesting potential evidence of size segregation. While one mature female remained in the Gulf of Mexico over a >2-year period, predominantly on the continental shelf, two mature males demonstrated seasonal migrations ∼2,500 km from the tagging location off the Texas coast to the Caribbean Sea and northeastern United States Atlantic coast, respectively. During these migrations, mako sharks traversed at least 12 jurisdictional boundaries, which also exposed individuals to varying levels of fishing pressure and harvest regulations. Movement ecology of this species, especially for mature individuals in the western North Atlantic, has been largely unknown until recently. These data included here supplement existing information on mako shark movement ecology and potential stock structure that could help improve management of the species.
Developing and Evaluating a Quality Improvement Intervention to Facilitate Patient Navigation in the Accountable Health Communities Model
Authors: Holcomb Jennifer L. , Walton Gretchen H. , Sokale Itunu O. , Ferguson Gayla M. , Schick Vanessa R. , Highfield Linda
Published: January 2021

Introduction:The Accountable Health Communities (AHC) Model was designed to address the health-related social needs of Centers for Medicare & Medicaid Services beneficiaries. Bridge organizations across the AHC Model have identified lack of technical assistance and peer planning as potential barriers to Model success, particularly around patient navigation. The technical assistance and peer planning literature lacks an organizing, conceptual framework, but implementation science frameworks could serve as useful guides. The Strengthening Peer AHC Navigation (SPAN) research protocol seeks to fill this gap and will apply three implementation science frameworks, Consolidated Framework for Implementation Research, Intervention Mapping, and the Expert Recommendations for Implementing Change compilation, to develop a multi-level quality improvement intervention and evaluate the impact of peer planning on Model outcomes. The aims of the SPAN study are to implement and evaluate a novel multi-level quality improvement intervention to improve AHC implementation and navigation milestones through structured peer planning and to provide successful technical assistance for the AHC Model.

Methods and Analysis:The quality improvement intervention is outlined in four Tasks: (1) Assessment – to conduct an assessment of each bridge organization's current implementation, needs, and readiness in AHC Model navigation activities; (2) Planning – to engage in a peer planning approach to build capacity for AHC Model navigation activities; (3) Implementation with technical assistance – Co-creation of a quality improvement protocol for AHC Model navigation activities; and (4) Evaluation – measure the impact of the peer planning and technical assistance approach. Alongside the development and implementation of the quality improvement intervention, this protocol describes a mixed method, convergent parallel study design which will be used to evaluate whether the quality improvement intervention will lead to better outcomes. Tasks will be replicated with five bridge organizations participating in the AHC Model.

Discussion:This research protocol provides a framework that can be used to conduct structured peer planning with technical assistance for social needs programs. This study will provide data on both implementation and outcomes which eventually may impact healthcare cost and utilization.
Antimicrobial Resistance in Enterobacterales and Its Contribution to Sepsis in Sub-saharan Africa
Authors: Tompkins Kathleen , Juliano Jonathan J. , van Duin David
Published: January 2021

Antibiotic resistant Enterobacterales (formerly Enterobactereaceae) are a growing threat to Sub-Saharan Africa. Genes causing antibiotic resistance are easily spread between the environment and humans and infections due to drug resistant organisms contribute to sepsis mortality via delayed time to appropriate antimicrobial therapy. Additionally, second or third-line antibiotics are often not available or are prohibitively expensive in resource-constrained settings leading to limited treatment options. Lack of access to water and sanitation facilities, unregulated use of antibiotics, and malnutrition are contributors to high rates of antibiotic resistance in the region. Improvements in the monitoring of drug resistant infections and antibiotic stewardship are needed to preserve the efficacy of antibiotics for the future.
Serum Prealbumin Concentrations, COVID-19 Severity, and Mortality: A Systematic Review and Meta-Analysis
Authors: Zinellu Angelo , Mangoni Arduino A.
Published: January 2021

Excessive inflammation and malnutrition are associated with coronavirus disease 2019 (COVID-19) severity and mortality. Combined biomarkers of malnutrition and inflammation, such as serum prealbumin, might be particularly attractive for early risk stratification. We conducted a systematic review and meta-analysis of studies reporting serum prealbumin in patients with COVID-19. We searched PubMed, Web of Science and Scopus, between January and November 2020, for studies reporting data on serum prealbumin, COVID-19 severity, defined as severe illness, prolonged viral load, receiving mechanical ventilation or admitted to intensive care unit (ICU), and mortality. Nineteen studies in 4,616 COVID-19 patients were included in the meta-analysis. Pooled results showed that serum prealbumin concentrations were significantly lower in patients with severe disease and non-survivors (standard mean difference, SMD, −0.92, 95% CI, −1.10 to −0.74, P < 0.001). Extreme heterogeneity was observed (I2 = 77.9%; P < 0.001). In sensitivity analysis, the effect size was not significantly affected when each study was in turn removed (range between −0.86 and −0.95). The Begg's (P = 0.06) and Egger's t-tests (P = 0.26) did not show publication bias. Pooled SMD values were significantly and negatively associated with age (t = −2.18, P = 0.045) and C-reactive protein (t = −3.85, P = 0.002). In our meta-analysis, lower serum prealbumin concentrations were significantly associated with COVID-19 severity and mortality. This combined marker of malnutrition and inflammation might assist with early risk stratification and management in this group.
Influences of Seasonal Monsoons on the Taxonomic Composition and Diversity of Bacterial Community in the Eastern Tropical Indian Ocean
Authors: Gao Ping , Du Guangxun , Zhao Duo , Wei Qinsheng , Zhang Xuelei , Qu Lingyun , Gong Xianzhe
Published: January 2021

The Indian Ocean is characterized by its complex physical systems and strong seasonal monsoons. To better understand effects of seasonal monsoon-driven circulation on the bacterioplanktonic community structure in surface waters and the bacterial distribution response to vertical stratification, patterns of seasonal, and vertical distribution of bacterial communities in the Eastern Tropical Indian Ocean were investigated using 16S rRNA gene profiling. Water samples were collected during the Southwest monsoon (from June to August), the fall inter-monsoon (from October and November) and the Northeast monsoon (from December to January), respectively, onboard during three cruises from July 2016 to January 2018. Surface bacterioplankton communities in these three seasons and in the upper water (3–300 m with six depths) during the Northeast monsoon contained a diverse group of taxa, mainly Proteobacteria, Cyanobacteria, Actinobacteria, Bacteroidetes, and Chloroflexi. Redundancy discriminant analysis (RDA) uncovered that temperature, salinity, and dissolved oxygen (DO) were crucial environmental parameters that affected the structure of bacterial community in overall surface samples. However, significant differences in the composition of the bacterial community are likely due to changes in concentrations of salinity during the fall inter-monsoon, while phosphate for both the Southwest monsoon and the Northeast monsoon. Pearson's analysis revealed that the seasonal variation rather than the vertical variation of environmental factors had a more significant impact on the composition of bacterial community. In addition, a clear seasonal pattern of bacterial co-occurrence showed that inter-taxa associations during the fall inter-monsoon were closer than during the Northeast monsoon and the Southwest monsoon. Overall, our results implied clear differences in the composition of bacterial community, with more pronounced seasonal variation compared to the vertical variation in response to environmental changes.
Assessment of Bacterial Community Composition and Dynamics in Alfalfa Silages With and Without Lactobacillus plantarum Inoculation Using Absolute Quantification 16S rRNA Sequencing
Authors: Yang Fengyuan , Zhao Shanshan , Wang Yuan , Fan Xiaomiao , Wang Yanping , Feng Changsong
Published: January 2021

Relative quantification 16S-seq (RQS) has drawn deeper insights into bacterial community compositions in silage. However, it provides no information on dynamics of the total amount of bacterial DNA through the ensiling process and across different treatments. In this study, bacterial compositions in alfalfa silage with and without Lactobacillus plantarum inoculation after 10 and 60days of ensiling were investigated using absolute quantification 16S-seq (AQS), and bacterial composition and its interaction with fermentation properties of silage indicated by AQS and RQS were compared. Variation in total bacterial DNA amounts across different treatments and ensiling periods was illustrated by AQS. AQS indicated higher bacterial richness indices and closer correlations of these indices with fermentation properties than RQS via spearman’s correlation analyses, as well as more taxa with significance on bacterial abundance via lefse analyses. In conclusion, AQS effectively illustrated the dynamics of bacterial communities during the ensiling process.
CLIP4 Shows Putative Tumor Suppressor Characteristics in Breast Cancer: An Integrated Analysis
Authors: Fan Yu , He Lijia , Wang Yu , Fu Shaozhi , Han Yunwei , Fan Juan , Wen Qinglian
Published: January 2021

Background: CAP-Gly domain containing linker protein family member 4 (CLIP4) plays an important role in cancers. However, its expression, prognostic value, and biological effect in breast cancer remain unclear.

Methods: Data on patients diagnosed with breast cancer were retrieved from the TCGA-BRCA and other public omics databases. The expression profile of CLIP4 was analyzed using Oncomine, bc-GenExMiner, and TCGA. The prognostic value of CLIP4 was determined by Kaplan-Meier Plotter and Human Protein Atlas. Identification of genes co-expressed with CLIP4 and potential mechanism analyses were performed using UALCAN, STRING, Metascape, and GSEA. The epigenetic characteristics of CLIP4 were determined by DiseaseMeth and MEXPRESS.

Results: CLIP4 was downregulated and its expression was negatively correlated with estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor type 2 (HER2) status, Nottingham prognostic index (NPI), and Scarff-Bloom-Richardson (SBR) grade in breast cancer, whereas it was positively linked to basal-like and triple negative breast cancer status. Ectopic expression of CLIP4 was related with poor prognosis. In the analysis of genes co-expressed with CLIP4, GSEA showed that the Hedgehog (Hh), JAK-STAT, ERBB, Wnt signaling pathway, cell adhesion molecules, and pathways in cancer were dissimilarly enriched in the CLIP4 expression high phenotype. Analysis of the genetics and epigenetics of CLIP4 indicated that its expression was negatively correlated with DNA methylation.

Conclusion: Methylated CLIP4 may be a novel prognostic and therapeutic biomarker for breast cancer.
The Involvement of Aquaporin-4 in the Interstitial Fluid Drainage Impairment Following Subarachnoid Hemorrhage
Authors: Liu E. , Peng Xianlong , Ma Haowen , Zhang Yan , Yang Xiaomei , Zhang Yixuan , Sun Linlin , Yan Junhao
Published: January 2021

The mechanism of brain injury following subarachnoid hemorrhage (SAH) has not yet been clarified. The glymphatic system (GS), a glia-dependent waste clearance pathway, drains away soluble waste proteins and metabolic products, even some toxic factors from the brain. Aquaporin-4 (Aqp4) is highly expressed on the astrocyte foot processes and facilitates the interstitial fluid (ISF) transportation in the GS system. In this study, the role of Aqp4 in the GS injury after SAH was explored using Aqp4 gene knockout (Aqp4−/−) Sprague Dawley rats. The results of MRI, fluorescent imaging, and transmission electron microscopy (TEM) indicated that, after SAH, the inflow of cerebrospinal fluid (CSF) into the brain and the clearance of ISF from the brain were both significantly decreased. Meanwhile, the expression level of Aqp4 around the artery was markedly higher than that around the vein following SAH. Aqp4 knockout exacerbated the GS damage after SAH. In summary, after SAH, there was an apparent GS impairment, and Aqp4 played key roles in modulating the function of GS in the brain.
Identification of Heterogeneous Subtypes of Mild Cognitive Impairment Using Cluster Analyses Based on PET Imaging of Tau and Astrogliosis
Authors: Lee Hyun Jeong , Lee Eun-Chong , Seo Seongho , Ko Kwang-Pil , Kang Jae Myeong , Kim Woo-Ram , Seo Ha-Eun , Lee Sang-Yoon , Lee Yeong-Bae , Park Kee Hyung , Yeon Byeong Kil , Okamura Nobuyuki , Na Duk L. , Seong Joon-Kyung , Noh Young
Published: January 2021

Background: Mild cognitive impairment (MCI) is a condition with diverse causes and clinical outcomes that can be categorized into subtypes. [18F]THK5351 has been known to detect reactive astrogliosis as well as tau which is accompanied by neurodegenerative changes. Here, we identified heterogeneous groups of MCI patients using THK retention patterns and a graph theory approach, allowing for the comparison of risk of progression to dementia in these MCI subgroups.

Methods: Ninety-seven participants including 60 MCI patients and individuals with normal cognition (NC, n = 37) were included and undertook 3T MRI, [18F]THK5351 PET, and detailed neuropsychological tests. [18F]Flutemetamol PET was also performed in 62 participants. We calculated similarities between MCI patients using their regional standardized uptake value ratio of THK retention in 75 ROIs, and clustered subjects with similar retention patterns using the Louvain method based on the modularity of the graph. The clusters of patients identified were compared with an age-matched control group using a general linear model. Dementia conversion was evaluated after a median follow-up duration of 34.6 months.

Results: MCI patients were categorized into four groups according to their THK retention patterns: (1) limbic type; (2) diffuse type; (3) sparse type; and (4) AD type (retention pattern as in AD). Subjects of the limbic type were characterized by older age, small hippocampal volumes, and reduced verbal memory and frontal/executive functions. Patients of the diffuse type had relatively large vascular burden, reduced memory capacity and some frontal/executive functions. Co-morbidity and mortality were more frequent in this subgroup. Subjects of the sparse type were younger and declined only in terms of visual memory and attention. No individuals in this subgroup converted to dementia. Patients in the AD type group exhibited the poorest cognitive function. They also had the smallest hippocampal volumes and the highest risk of progression to dementia (90.9%).

Conclusion: Using cluster analyses with [18F]THK5351 retention patterns, it is possible to identify clinically-distinct subgroups of MCI patients and those at greater risk of progression to dementia.
Impact of High Fat Diet and Ethanol Consumption on Neurocircuitry Regulating Emotional Processing and Metabolic Function
Authors: Coker Caitlin R. , Keller Bailey N. , Arnold Amy C. , Silberman Yuval
Published: January 2021

The prevalence of psychiatry disorders such as anxiety and depression has steadily increased in recent years in the United States. This increased risk for anxiety and depression is associated with excess weight gain, which is often due to over-consumption of western diets that are typically high in fat, as well as with binge eating disorders, which often overlap with overweight and obesity outcomes. This finding suggests that diet, particularly diets high in fat, may have important consequences on the neurocircuitry regulating emotional processing as well as metabolic functions. Depression and anxiety disorders are also often comorbid with alcohol and substance use disorders. It is well-characterized that many of the neurocircuits that become dysregulated by overconsumption of high fat foods are also involved in drug and alcohol use disorders, suggesting overlapping central dysfunction may be involved. Emerging preclinical data suggest that high fat diets may be an important contributor to increased susceptibility of binge drug and ethanol intake in animal models, suggesting diet could be an important aspect in the etiology of substance use disorders. Neuroinflammation in pivotal brain regions modulating metabolic function, food intake, and binge-like behaviors, such as the hypothalamus, mesolimbic dopamine circuits, and amygdala, may be a critical link between diet, ethanol, metabolic dysfunction, and neuropsychiatric conditions. This brief review will provide an overview of behavioral and physiological changes elicited by both diets high in fat and ethanol consumption, as well as some of their potential effects on neurocircuitry regulating emotional processing and metabolic function.
Implementation-Independent Representation for Deep Convolutional Neural Networks and Humans in Processing Faces
Authors: Song Yiying , Qu Yukun , Xu Shan , Liu Jia
Published: January 2021

Deep convolutional neural networks (DCNN) nowadays can match human performance in challenging complex tasks, but it remains unknown whether DCNNs achieve human-like performance through human-like processes. Here we applied a reverse-correlation method to make explicit representations of DCNNs and humans when performing face gender classification. We found that humans and a typical DCNN, VGG-Face, used similar critical information for this task, which mainly resided at low spatial frequencies. Importantly, the prior task experience, which the VGG-Face was pre-trained to process faces at the subordinate level (i.e., identification) as humans do, seemed necessary for such representational similarity, because AlexNet, a DCNN pre-trained to process objects at the basic level (i.e., categorization), succeeded in gender classification but relied on a completely different representation. In sum, although DCNNs and humans rely on different sets of hardware to process faces, they can use a similar and implementation-independent representation to achieve the same computation goal.
Long-Term Risk Factors for Intracranial In-Stent Restenosis From a Multicenter Trial of Stenting for Symptomatic Intracranial Artery Stenosis Registry in China
Authors: Guo Xu , Ma Ning , Gao Feng , Mo Da-Peng , Luo Gang , Miao Zhong-Rong
Published: January 2021

Background: For patients with symptomatic intracranial artery stenosis (sICAS), endovascular treatment has been shown to be feasible and safe in recent studies. However, in-stent restenosis (ISR) risks the recurrence of ischemic stroke. We attempt to elucidate the risk factors for ISR.

Methods: We retrospectively analyzed 97 patients with sICAS from a prospective registry trial that included 20 centers from September 2013 to January 2015. Cases were classified into the ISR≥ 50% group or the ISR < 50% group. The baseline characteristics and long-term follow-up were compared between the two groups. Binary logistic regression analyses were identified as an association between ISR and endovascular technique factors.

Results: According to whether ISR was detected by CT angiography, 97 patients were divided into the ISR group (n = 24) and the non-ISR group (n = 73). The admission baseline features and lesion angiography characteristics were similar, while plasma hs-CRP (mg/L) was higher in the ISR≥ 50% group at admission (8.2 ± 11.4 vs. 2.8 ± 4.1, p = 0.032). Binary logistic regression analysis identified the longer stents (adjusted OR 0.816, 95% CI 0.699–0.953; p = 0.010), balloon-mounted stents (adjusted OR 5.748, 95% CI 1.533–21.546; p = 0.009), and local anesthesia (adjusted OR 6.000, 95% CI 1.693–21.262; p = 0.006) as predictors of ISR at the 1-year follow-up.

Conclusions: The longer stents, balloon-mounted stents implanted in the intracranial vertebral or basilar artery, and local anesthesia were significantly associated with in-stent restenosis. Further studies are required to identify accurate biomarkers or image markers associated with ISR in ICAS patients.

Clinical Trial Registration:www.ClinicalTrials.gov, identifier: NCT01968122.
Seizure-Induced Acute Glial Activation in the in vitro Isolated Guinea Pig Brain
Authors: Vila Verde Diogo , de Curtis Marco , Librizzi Laura
Published: January 2021

Introduction: It has been proposed that seizures induce IL-1β biosynthesis in astrocytes and increase blood brain barrier (BBB) permeability, even without the presence of blood borne inflammatory molecules and leukocytes. In the present study we investigate if seizures induce morphological changes typically observed in activated glial cells. Moreover, we will test if serum albumin extravasation into the brain parenchyma exacerbates neuronal hyperexcitability by inducing astrocytic and microglial activation.

Methods: Epileptiform seizure-like events (SLEs) were induced in limbic regions by arterial perfusion of bicuculline methiodide (BMI; 50 μM) in the in vitro isolated guinea pig brain preparation. Field potentials were recorded in both the hippocampal CA1 region and the medial entorhinal cortex. BBB permeability changes were assessed by analyzing extravasation of arterially perfused fluorescein isothiocyanate (FITC)–albumin. Morphological changes in astrocytes and microglia were evaluated with tridimensional reconstruction and Sholl analysis in the ventral CA1 area of the hippocampus following application of BMI with or without co-perfusion of human serum albumin.

Results: BMI-induced SLE promoted morphological changes of both astrocytes and microglia cells into an activated phenotype, confirmed by the quantification of the number and length of their processes. Human-recombinant albumin extravasation, due to SLE-induced BBB impairment, worsened both SLE duration and the activated glia phenotype.

Discussion: Our study provides the first direct evidence that SLE activity per se is able to promote the activation of astro- and microglial cells, as observed by their changes in phenotype, in brain regions involved in seizure generation; we also hypothesize that gliosis, significantly intensified by h-recombinant albumin extravasation from the bloodstream to the brain parenchyma due to SLE-induced BBB disruption, is responsible for seizure activity reinforcement.
Age and Tumor Differentiation-Associated Gene Expression Based Analysis of Non-Familial Prostate Cancers
Authors: Sharad Shashwat , Allemang Travis C. , Li Hua , Nousome Darryl , Ku Anson Tai , Whitlock Nichelle C. , Sowalsky Adam G. , Cullen Jennifer , Sesterhenn Isabell A. , McLeod David G. , Srivastava Shiv , Dobi Albert
Published: January 2021

Prostate cancer incidence in young men has increased. Patients diagnosed at an earlier age are likely to have aggressive prostate cancer and treatment decisions are continuing to be weighted by patient age and life expectancy. Identification of age-associated gene-expression signatures hold great potential to augment current and future treatment modalities. To investigate age-specific tumor associated gene signatures and their potential biomarkers for disease aggressiveness, this study was designed and stratified into well and poorly differentiated tumor types of young (42–58 years) and old (66–73 years) prostate cancer patients. The differentially expressed genes related to tumor-normal differences between non-familial prostate cancer patients were identified and several genes uniquely associated with the age and tumor differentiation are markedly polarized. Overexpressed genes known to be associated with somatic genomic alterations was predominantly found in young men, such as TMPRESS2-ERG and c-MYC. On the other hand, old men have mostly down-regulated gene expressions indicating the loss of protective genes and reduced cell mediated immunity indicated by decreased HLA-A and HLA-B expression. The normalization for the benign signatures between the age groups indicates a significant age and tumor dependent heterogeneity exists among the patients with a great potential for age-specific and tumor differentiation-based therapeutic stratification of prostate cancer.
Case Report: IL-21 and Bcl-6 Regulate the Proliferation and Secretion of Tfh and Tfr Cells in the Intestinal Germinal Center of Patients With Inflammatory Bowel Disease
Authors: Yang Youguang , Lv Xiaodan , Zhan Lingling , Chen Lan , Jin Hui , Tang Xinping , Shi Qingqing , Zou Qiyuan , Xiang Jiqiao , Zhang WeiWei , Zeng Zhaojing , Jiang Haixing , Lv Xiaoping
Published: January 2021

Objective: This study aimed to investigate the effect of interleukin (IL)-21 and B cell lymphoma protein-6 on germinal center follicular helper T (Tfh) cells and follicular regulatory T (Tfr) cells and its relationship with the clinical features of inflammatory bowel disease (IBD).

Methods: The expression of peripheral blood cytokines IL-21 and Bcl-6 mRNA was detected by reverse transcription–polymerase chain reaction. The distribution characteristics of Tfh and Tfr cells were detected using the triple immunofluorescence staining analysis.

Results: The expression of IL-21 and Bcl-6 mRNA was upregulated in the ulcerative colitis (UC) and Crohn disease (CD) groups compared with that in the control group. Triple immunofluorescence staining showed that the number of Tfh cells in the intestinal germinal center obviously increased in the UC and CD groups compared with that in the control group, whereas the number of Tfr cells reduced.

Conclusion: This study suggested that the Tfr and Tfh cells might be involved in the regulation of IBD. Bcl-6 and IL-21 can regulate the Tfh/Tfr ratio in the intestinal germinal center, promoting the occurrence and development of IBD.
Epidermal Growth Factor Receptor: A Potential Therapeutic Target for Diabetic Kidney Disease
Authors: Sheng Lili , Bayliss George , Zhuang Shougang
Published: January 2021

Diabetic kidney disease (DKD) is a leading cause of end-stage renal disease worldwide and the major cause of renal failure among patients on hemodialysis. Numerous studies have demonstrated that transient activation of epidermal growth factor receptor (EGFR) pathway is required for promoting kidney recovery from acute injury whereas its persistent activation is involved in the progression of various chronic kidney diseases including DKD. EGFR-mediated pathogenesis of DKD is involved in hemodynamic alteration, metabolic disturbance, inflammatory response and parenchymal cellular dysfunction. Therapeutic intervention of this receptor has been available in the oncology setting. Targeting EGFR might also hold a therapeutic potential for DKD. Here we review the functional role of EGFR in the development of DKD, mechanisms involved and the perspective about use of EGFR inhibitors as a treatment for DKD.
Low-Level Vagus Nerve Stimulation Reverses Obstructive Sleep Apnea-Related Atrial Fibrillation by Ameliorating Sympathetic Hyperactivity and Atrial Myocyte Injury
Authors: Guo Yankai , Xiaokereti Jiasuoer , Meng Qingjun , Cao Guiqiu , Sun Huaxin , Zhou Xianhui , Zhang Ling , Tang Baopeng
Published: January 2021

Background: Previous studies have proved that low-level vagus nerve stimulation (LLVS) could suppress acute obstructive sleep apnea (OSA), which is associated with atrial fibrillation (AF).

Objective: This study investigates the underlying electrophysiological, neural, and cardiomyocyte injury mechanisms on acute OSA-induced AF, examining whether LLVS can attenuate or reverse this remodeling.

Methods and Results: Eighteen mongrel dogs received endotracheal intubation under general anesthesia and were randomly divided into three groups: the OSA group (simulated OSA with clamping of the trachea cannula at the end of expiration for 2min followed ventilation 8min, lasting 6h, n=6), the OSA+LLVS group (simulated OSA plus LLVS, n=6), and a control group (sham clamping the trachea cannula without stimulation, n=6). In the OSA+LLVS group, the atrial effective refractory period was significantly lengthened while the sinus node recovery time and AF duration decreased after the 4th hour, and the expression level of Cx40 and Cx43 was significantly increased compared to the OSA group. Norepinephrine, TH, and ChAT were significantly decreased in the OSA+LLVS group compared with the OSA group. Mitochondrial swelling, cardiomyocyte apoptosis, and glycogen deposition, along with a higher concentration of TNF-α, IL-6 were observed in the OSA group, and the LLVS inhibited the structural remodeling and expression of inflammatory cytokines.

Conclusion: LLVS decreased the inducibility of AF partly by ameliorating sympathetic hyperactivity and atrial myocyte injury after acute OSA-induced AF.
Exercise Limitation in Children and Adolescents With Severe Refractory Asthma: A Lack of Asthma Control?
Authors: Faleiro Rita C. , Mancuzo Eliane V. , Lanza Fernanda C. , Queiroz Mônica V. N. P. , de Oliveira Luciano F. L. , Ganem Vinicius O. , Lasmar Laura B.
Published: January 2021

Background

Patients with severe refractory asthma (SRA), even when using high doses of multiple controller medications in a regular and appropriate way, can have persistent complaints of exercise limitation.

Methods

This was a cross-sectional study involving patients with SRA (treated with ≥ 800 μg of budesonide or equivalent, with ≥ 80% adherence, appropriate inhaler technique, and comorbidities treated), who presented no signs of a lack of asthma control other than exercise limitation. We also evaluated healthy controls, matched to the patients for sex, age, and body mass index. All participants underwent cardiopulmonary exercise testing (CPET) on a cycle ergometer, maximum exertion being defined as ≥ 85% of the predicted heart rate, with a respiratory exchange ratio ≥ 1.0 for children and ≥ 1.1 for adolescents. Physical deconditioning was defined as oxygen uptake (VO2) < 80% of predicted at peak exercise, without cardiac impairment or ventilatory limitation. Exercise-induced bronchoconstriction (EIB) was defined as a forced expiratory volume in one second ≥ 10% lower than the baseline value at 5, 10, 20, and 30 minutes after CPET.

Results

We evaluated 20 patients with SRA and 19 controls. In the sample as a whole, the mean age was 12.9 ± 0.4 years. The CPET was considered maximal in all participants. In terms of the peak VO2 (VO2peak), there was no significant difference between the patients and controls, (P = 0.10). Among the patients, we observed isolated EIB in 30%, isolated physical deconditioning in 25%, physical deconditioning accompanied by EIB in 25%, and exercise-induced symptoms not supported by the CPET data in 15%.

Conclusion and Clinical Relevance

Physical deconditioning, alone or accompanied by EIB, was the determining factor in reducing exercise tolerance in patients with SRA and was not therefore found to be associated with a lack of asthma control.
COVID 19-Induced Smell and Taste Impairments: Putative Impact on Physiology
Authors: Meunier Nicolas , Briand Loïc , Jacquin-Piques Agnès , Brondel Laurent , Pénicaud Luc
Published: January 2021

Smell and taste impairments are recognized as common symptoms in COVID 19 patients even in an asymptomatic phase. Indeed, depending on the country, in up to 85–90% of cases anosmia and dysgeusia are reported. We will review briefly the main mechanisms involved in the physiology of olfaction and taste focusing on receptors and transduction as well as the main neuroanatomical pathways. Then we will examine the current evidences, even if still fragmented and unsystematic, explaining the disturbances and mode of action of the virus at the level of the nasal and oral cavities. We will focus on its impact on the peripheral and central nervous system. Finally, considering the role of smell and taste in numerous physiological functions, especially in ingestive behavior, we will discuss the consequences on the physiology of the patients as well as management regarding food intake.
Targeting Endolysosomal Two-Pore Channels to Treat Cardiovascular Disorders in the Novel COronaVIrus Disease 2019
Authors: Moccia Francesco , Negri Sharon , Faris Pawan , Perna Angelica , De Luca Antonio , Soda Teresa , Berra-Romani Roberto , Guerra Germano
Published: January 2021

Emerging evidence hints in favor of a life-threatening link between severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) and the cardiovascular system. SARS-CoV-2 may result in dramatic cardiovascular complications, whereas the severity of COronaVIrus Disease 2019 (COVID-19) and the incidence of fatalities tend to increase in patients with pre-existing cardiovascular complications. SARS-CoV-2 is internalized into the host cells by endocytosis and may then escape the endolysosomal system via endosomes. Two-pore channels drive endolysosomal trafficking through the release of endolysosomal Ca2+. Recent evidence suggested that the pharmacological inhibition of TPCs prevents Ebola virus and Middle East Respiratory Syndrome COronaVirus (MERS-CoV) entry into host cells. In this perspective, we briefly summarize the biophysical and pharmacological features of TPCs, illustrate their emerging role in the cardiovascular system, and finally present them as a reliable target to treat cardiovascular complications in COVID-19 patients.
Domain Unknown Function DUF1668-Containing Genes in Multiple Lineages Are Responsible for F1 Pollen Sterility in Rice
Authors: Sakata Mitsukazu , Takano-Kai Noriko , Miyazaki Yuta , Kanamori Hiroyuki , Wu Jianzhong , Matsumoto Takashi , Doi Kazuyuki , Yasui Hideshi , Yoshimura Atsushi , Yamagata Yoshiyuki
Published: January 2021

Postzygotic reproductive isolation maintains species integrity and uniformity and contributes to speciation by restricting the free gene flow between divergent species. In this study we identify causal genes of two Mendelian factors S22A and S22B on rice chromosome 2 inducing F1 pollen sterility in hybrids between Oryza sativa japonica-type cultivar Taichung 65 (T65) and a wild relative of rice species Oryza glumaepatula. The causal gene of S22B in T65 encodes a protein containing DUF1668 and gametophytically expressed in the anthers, designated S22B_j. The O. glumaepatula allele S22B-g, allelic to S22B_j, possesses three non-synonymous substitutions and a 2-bp deletion, leading to a frameshifted translation at the S22B C-terminal region. Transcription level of S22B-j and/or S22B_g did not solely determine the fertility of pollen grains by genotypes at S22B. Western blotting of S22B found that one major band with approximately 46 kDa appeared only at the mature stage and was reduced on semi-sterile heterozygotes at S22B, implying that the 46 kDa band may associated in hybrid sterility. In addition, causal genes of S22A in T65 were found to be S22A_j1 and S22A_j3 encoding DUF1668-containing protein. The allele of a wild rice species Oryza meridionalis Ng at S22B, designated S22B_m, is a loss-of-function allele probably due to large deletion of the gene lacking DUF1668 domain and evolved from the different lineage of O. glumaepatula. Phylogenetic analysis of DUF1668 suggested that many gene duplications occurred before the divergence of current crops in Poaceae, and loss-of-function mutations of DUF1668-containing genes represent the candidate causal genetic events contributing to hybrid incompatibilities. The duplicated DUF1668-domain gene may provide genetic potential to induce hybrid incompatibility by consequent mutations after divergence.
Eating Disorder Symptoms in Elite Spanish Athletes: Prevalence and Sport-Specific Weight Pressures
Authors: Teixidor-Batlle Clara , Ventura Carles , Andrés Ana
Published: January 2021

We determined the prevalence of eating disorder (ED) symptoms among elite Spanish athletes from a broad range of sports and levels of competition and examined the associations between the presence of symptoms and perceived sport-specific weight pressures. We surveyed 646 elite athletes (16.7 ± 4.4 years; 51.08% females) representing 33 sports from top-division teams and two elite athlete training centers in Catalonia. Based on the results of the Eating Attitudes Test-26 responses, 5.1% of athletes (7.6% of females and 2.5% of males) were at risk of EDs. The highest rates of ED symptoms were observed in male endurance athletes and female esthetic athletes. Competition level was not a risk factor. The only gender differences in the presence of ED symptoms by competing level were observed in athletes competing at the national level. Female athletes with ED symptoms scored higher on the two subscales of the Spanish version of the Weight Pressures in Sport (WPS) tool: coach and sport-specific pressures and pressures from teammates and due to uniform. Male athletes with ED symptoms scored higher on the pressures due to uniform subscale. Finally, symptomatic female but not male athletes competing at international and national levels also perceived greater sport-specific weight pressures.
The Mediating Role of Meaning in Life in the Effects of Calling on Posttraumatic Stress Symptoms and Growth: A Longitudinal Study of Navy Soldiers Deployed to the Gulf of Aden
Authors: Seol Jeong Hoon , Park Yonguk , Choi Jinsoo , Sohn Young Woo
Published: January 2021

This study examined the mediating role of meaning in life in the effect of calling on posttraumatic stress disorder (PTSD) and posttraumatic growth (PTG) among navy soldiers of the Republic of Korea deployed to the Gulf of Aden, Somalia. Participants responded to the questionnaire survey three times (pre-deployment, deployment, and post-deployment) at 4-month intervals. From the first, second, and third surveys, data were collected for 223, 195, and 103 respondents, respectively. Results showed that calling had a negative effect on PTSD, fully mediated by meaning in life, whereas calling had a positive effect on PTG, partially mediated by meaning in life. Our findings suggest that calling acts as a positive psychological resource for maintaining the meaning in life throughout stressful events experienced during deployment, thereby reducing posttraumatic stress symptoms and promoting post-deployment psychological growth. Finally, theoretical and practical implications and the need for follow-up studies are discussed.
Functionally Flexible Signaling and the Origin of Language
Authors: Oller D. Kimbrough , Griebel Ulrike
Published: January 2021

At the earliest break of ancient hominins from their primate relatives in vocal communication, we propose a selection pressure on vocal fitness signaling by hominin infants. Exploratory vocalizations, not tied to expression of distress or immediate need, could have helped persuade parents of the wellness and viability of the infants who produced them. We hypothesize that hominin parents invested more in infants who produced such signals of fitness plentifully, neglecting or abandoning them less often than infants who produced the sounds less frequently. Selection for such exploratory vocalization provided a critically important inclination and capability relevant to language, we reason, because the system that encouraged spontaneous vocalization also made vocalization functionally flexible to an extent that has not been observed in any other animal. Although this vocal flexibility did not by itself create language, it provided an essential foundation upon which language would evolve through a variety of additional steps. In evaluating this speculation, we consider presumable barriers to evolving language that are thought to be implications of Darwinian Theory. It has been claimed that communication always involves sender self-interest and that self-interest leads to deceit, which is countered through clever detection by receivers. The constant battle of senders and receivers has been thought to pose an insuperable challenge to honest communication, which has been viewed as a requirement of language. To make communication honest, it has been proposed that stable signaling requires costly handicaps for the sender, and since language cannot entail high cost, the reasoning has suggested an insurmountable obstacle to the evolution of language. We think this presumed honesty barrier is an illusion that can be revealed by recognition of the fact that language is not inherently honest and in light of the distinction between illocutionary force and semantics. Our paper also considers barriers to the evolution of language (not having to do with honesty) that we think may have actually played important roles in preventing species other than humans from evolving language.