bluuebunny/crossref_metadata_2025 huggingface dataset:
Perfil ideal do professor do século XXI
Authors: Silva Dayvane Oliveira da , Santos Ronielle Batista Oliveira , Queiróz Nívia Rodrigues de
Published: June 2021

Falar de educação na atualidade é quase impossível sem falar nas inúmeras transformações ocorridas ao longo dos anos, transformações essas que tem demandado um esforço extra daqueles que fazem ela acontecer “o professor”. O professor muitas vezes precisa se reinventar para conseguir acompanhar uma sociedade em transformações diárias e todas essas transformações em especial no campo educacional tem gerado inquietações na busca de uma melhor qualidade na relação do professor com o processo de ensino aprendizagem. Ensinar na atualidade é um desafio de proporções gigantescas, tem muito mais haver com a formação do cidadão do que com a transmissão de conteúdos prontos e acabados, acredito que essa tenha sido a principal mudança no campo educacional quando nos referimos a prática docente. Mas afinal o que o professor do século XXI deve ter para se encaixar nesse novo modelo de sociedade? A leitura deste artigo permitirá uma reflexão sobre esse perfil ideal de professor.
Modeling ringed seal Pusa hispida habitat and lair emergence timing in the eastern Bering and Chukchi Seas
Authors: Lindsay JM , Laidre KL , Conn PB , Moreland EE , Boveng PL
Published: June 2021

Ringed seals Pusa hispida are reliant on snow and sea ice for denning, and a better understanding of ringed seal habitat selection and timing of emergence from snow dens (also called lairs) is needed to quantify and predict effects of climate change in the Arctic. We used generalized additive models to assess relationships between ringed seal counts, from spring aerial surveys in the Bering Sea (2012 and 2013) and Chukchi Sea (2016), and spatiotemporal covariates including survey date, remotely sensed snow and sea-ice values, and short-term weather data. We produced separate models for total ringed seal counts and for pup counts within each region. Our models showed that in both areas, total ringed seal counts increased over the course of the spring, especially after 15 May, indicating emergence from lairs and/or the onset of basking behavior. For the more northerly Chukchi Sea, we found a substantial unimodal effect of snow melt progression and a positive effect of snow depth on total ringed seal counts. In contrast, Bering Sea total ringed seal counts and pup counts in both regions were affected much more strongly by date than by habitat variables. Overall, our findings demonstrate that snow depth and melt play an important role in the timing of ringed seal den emergence, particularly in the Chukchi Sea, and suggest that ringed seal denning may be affected by continued shifts in melt and snow depth associated with climate change.
Elevated nutrients and herbivory negatively affect Dictyota growth dynamics
Authors: Ramseyer TN , Tronholm A , Turner T , Brandt ME , Smith TB
Published: June 2021

Caribbean coral reefs are experiencing a shift to algal dominance at the expense of stony corals. Determining the factors leading to algal phase shifts is crucial for assuring the survival of Caribbean coral reefs. In this study, factors controlling the growth of the abundant brown macroalgae Dictyota spp. were investigated by varying herbivory pressure (caging) and nutrients (fertilizer addition) on coral reefs near St. Thomas (US Virgin Islands). Experiment 1 measured Dictyota heights and percent cover at 3 sites (11-20 m depth) and showed no growth response to nutrient addition and a weak negative response to herbivory. To confirm results of Experiment 1, a caging and nutrient manipulation (Experiment 2) was conducted at one site (14 m depth) using the dependent variable Dictyota biomass. A strong negative response of growth to nutrient addition was shown, presumably because of nutrient inhibition, and an equally negative response to herbivory (loss of ~50% biomass over 21 d). The inhibitory effect of fertilization on growth was confirmed in a third experiment that showed increasing biomass loss over 4 treatment levels of increasing fertilizer addition (0 [ambient], 5, 10, 20 g). Overall, Dictyota was not nutrient limited at any sites, and was weakly controlled by herbivore populations. Factors responsible for Dictyota abundance on Caribbean reefs may reflect decreased herbivory caused by overfishing and reductions in coral cover and do not appear to be affected by recent changes in nitrogen or phosphorus load. This study reinforces the need for conservation and management of herbivores in coral reef ecosystems, to mitigate the effects from anthropogenic stressors.
Quantifying sponge host and microbial symbiont contribution to dissolved organic matter uptake through cell separation
Authors: Hudspith M , van der Sprong J , Rix L , Víg D , Schoorl J , de Goeij JM
Published: June 2021

Sponge-microbe symbioses underpin the ecological success of sponges in many aquatic benthic ecosystems worldwide. These symbioses are often described as mutually beneficial, but identifying positive symbiotic interactions and quantifying the contribution of partners to physiological processes is challenging. For example, our understanding of the relative contribution of sponge cells and their microbial symbionts to the uptake and exchange of dissolved organic matter (DOM)—a major component of sponge diet—is limited. Here, we combined host-symbiont cell separation with pulse-chase isotopic labelling in order to trace the uptake of13C- and15Nenriched DOM into sponge cells and microbial symbionts of the encrusting Caribbean spongesHaliclona vansoestiandScopalina ruetzleri, which are low microbial abundance (LMA) species. Sponge cells were responsible for >99% of DOM assimilation during the pulse-chase experiment for both sponge species, while the contribution of symbiotic microbes to total DOM uptake was negligible (<1%). Nitrogen derived from DOM was translocated from sponge cells to microbial cells over time, indicating processing of host nitrogenous wastes by microbial endosymbionts. Thus, host cells drive DOM uptake in these species, while microbial symbionts may aid in the recycling of host-waste products. Our findings highlight the ability of sponges to derive nutrition by internalizing dissolved compounds from their environment and retaining nutrients via host-microbe interactions.
Risk Assessment and Analysis in Health, Safety and Environmental (HSE) Hazards of Bitumenous Waterproofing Industry Using HAZID Technique
Authors: Dadgar Parisa
Published: June 2021

Today, the use of risk assessment methods in various industries is expanding so that there are currently more than 70 types of different risk assessment methods in the world. These methods are usually used to identify, control and reduce the consequences of risks. The main methods of risk assessment are appropriate methods for risk assessment and their results can be used for management and decision-making to control and reduce its consequences. The purpose of this study is to identify and evaluate the risks to safety, health and the environment and to provide proposed and corrective solutions to reduce or eliminate HSE risks using the HAZID method. This descriptive cross-sectional study was performed for 4 months to identify the risks. For this purpose, a list of possible safety, health and environmental risks was prepared and the risk was evaluated by HAZID technique. In total, 5.15% of the identified risks are unacceptable, 20.62% are undesirable, 50.51% are acceptable, but 23.72% of the need for revision is minor. The results of this research include the implementation of measures such as safety training - professional training - inspection monitoring system - personnel safety management - preventive maintenance system management and forming a safety audit team - establishing regular House  Keeping  programs, etc. in identifying and Controls identified risks.
A Porcine Congenital Single-Sided Deafness Model, Its Population Statistics and Degenerative Changes
Authors: Ren Wei , Xu Cong , Zheng Fan-jun , Lin Ting-ting , Jin Peng , Zhang Yue , Guo Wei-wei , Liu Chuan-hong , Zhou Xiao-yang , Wang Lu-lu , Wang Yong , Zhao Hui , Yang Shi-ming
Published: June 2021

Objective

To describe and study the population statistics, hearing phenotype, and pathological changes of a porcine congenital single-sided deafness (CSSD) pedigree.

Methods

Click auditory brainstem response (ABR), full-frequency ABR, and distortion product otoacoustic emission (DPOAE) were used to assess the hearing phenotype of the strain. Tympanogram was used to assess the middle ear function since birth. Celloidin embedding–hematoxylin–eosin (CE-HE) stain and scanning electron microscopy (SEM) were used to study the pathological changes of cochlear microstructures. Chi-square analysis was used to analyze the relation between hearing loss and other phenotypes.

Results

The mating mood of CSSD with CSSD was most efficient in breeding-targeted CSSD phenotype (47.62%), and the prevalence of CSSD reached 46.67% till the fifth generation, where 42.22% were bilateral hearing loss (BHL) and 9.00% were normal hearing (NH) individuals. Hearing loss was proved to have no relation with coat color (P = 0.0841 > 0.05) and gender (P = 0.4621 > 0.05) by chi-square analysis. The deaf side of CSSD offspring in the fifth generation had no relation with that of their maternal parent (P = 0.2387 > 0.05). All individuals in this strain exhibited congenital severe to profound sensorineural hearing loss with no malformation and dysfunction of the middle ear. The good hearing ear of CSSD stayed stable over age. The deaf side of CSSD and BHL presented cochlear and saccular degeneration, and the hair cell exhibited malformation since birth and degenerated from the apex to base turn through time. The pathology in BHL cochlea progressed more rapidly than CSSD and till P30, the hair cell had been totally gone. The stria vascularis (SV) was normal since birth and degenerated through time and finally exhibited disorganization of three layers of cells.

Conclusion

This inbred porcine strain exhibited high and stable prevalence of CSSD, which highly resembled human non-syndromic CSSD disease. This porcine model could be used to further explore the etiology of CSSD and serve as an ideal tool for the studies of the effects of single-sided hearing deprivation on neural, cognitive, and behavioral developments and the benefits brought by CI in CSSD individuals.
A Regulatory Loop Involving Notch and Wnt Signaling Maintains Leukemia Stem Cells in T-Cell Acute Lymphoblastic Leukemia
Authors: Zhang Ling , Wu Jieying , Feng Yashu , Khadka Bijay , Fang Zhigang , Gu Jiaming , Tang Baoqiang , Xiao Ruozhi , Pan Guangjin , Liu Jia-Jun
Published: June 2021

Leukemia-initiating cells play critical role in relapse, resistance to therapies and metastases but the mechanism remains largely elusive. We report that β-catenin is over-expressed in almost all T-ALL patients and flow sorted β-cateninhigh fractions are highly resistant to therapy, leading to liver metastases in nude mice as well as dysregulated lncRNAs. Pharmacological inhibition through XAV-939 as well as si-RNA mediated inhibition of β-catenin is initially effective in re-sensitization to therapy, however, prolonged inhibition shifts dependency from β-catenin to Notch signaling, with particularly high levels of receptors Notch 1 and Notch 2. The results are verifiable in a cohort of T-ALL patients comprising of responders vs. those who have progressed, with β-catenin, Notch 1 and Notch 2 elevated in progressed patients. Further, in patients-derived cells, silencing of Notch 1 or Notch 2 does not counter resistance to β-catenin inhibition, rather pharmacological pan-Notch inhibition is needed to overcome resistance and its effect on in vitro tumor sphere formations as well as in vivo liver metastases. Thus, wnt and Notch signaling are part of a regulatory loop mutually compensating for each other in T-ALL, while ensuring the maintenance of stem cell phenotype.
Leveraging 16S rRNA Microbiome Sequencing Data to Identify Bacterial Signatures for Irritable Bowel Syndrome
Authors: Liu Yuxia , Li Wenhui , Yang Hongxia , Zhang Xiaoying , Wang Wenxiu , Jia Sitong , Xiang Beibei , Wang Yi , Miao Lin , Zhang Han , Wang Lin , Wang Yujing , Song Jixiang , Sun Yingjie , Chai Lijuan , Tian Xiaoxuan
Published: June 2021

Irritable bowel syndrome (IBS) is a chronic gastrointestinal disorder characterized by abdominal pain or discomfort. Previous studies have illustrated that the gut microbiota might play a critical role in IBS, but the conclusions of these studies, based on various methods, were almost impossible to compare, and reproducible microorganism signatures were still in question. To cope with this problem, previously published 16S rRNA gene sequencing data from 439 fecal samples, including 253 IBS samples and 186 control samples, were collected and processed with a uniform bioinformatic pipeline. Although we found no significant differences in community structures between IBS and healthy controls at the amplicon sequence variants (ASV) level, machine learning (ML) approaches enabled us to discriminate IBS from healthy controls at genus level. Linear discriminant analysis effect size (LEfSe) analysis was subsequently used to seek out 97 biomarkers across all studies. Then, we quantified the standardized mean difference (SMDs) for all significant genera identified by LEfSe and ML approaches. Pooled results showed that the SMDs of nine genera had statistical significance, in which the abundance of Lachnoclostridium, Dorea, Erysipelatoclostridium, Prevotella 9, and Clostridium sensu stricto 1 in IBS were higher, while the dominant abundance genera of healthy controls were Ruminococcaceae UCG-005, Holdemanella, Coprococcus 2, and Eubacterium coprostanoligenes group. In summary, based on six published studies, this study identified nine new microbiome biomarkers of IBS, which might be a basis for understanding the key gut microbes associated with IBS, and could be used as potential targets for microbiome-based diagnostics and therapeutics.
Cardiac Dysfunction in a Mouse Vascular Dementia Model of Bilateral Common Carotid Artery Stenosis
Authors: An Lulu , Chopp Michael , Zacharek Alex , Shen Yi , Chen Zhili , Qian Yu , Li Wei , Landschoot-Ward Julie , Liu Zhongwu , Venkat Poornima
Published: June 2021

Background:Cardiac function is associated with cognitive function. Previously, we found that stroke and traumatic brain injury evoke cardiac dysfunction in mice. In this study, we investigate whether bilateral common carotid artery stenosis (BCAS), a model that induces vascular dementia (VaD) in mice, induces cardiac dysfunction.

Methods:Late-adult (6–8 months) C57BL/6J mice were subjected to sham surgery (n= 6) or BCAS (n= 8). BCAS was performed by applying microcoils (0.16 mm internal diameter) around both common carotid arteries. Cerebral blood flow and cognitive function tests were performed 21–28 days post-BCAS. Echocardiography was conducted in conscious mice 29 days after BCAS. Mice were sacrificed 30 days after BCAS. Heart tissues were isolated for immunohistochemical evaluation and real-time PCR assay.

Results:Compared to sham mice, BCAS in mice significantly induced cerebral hypoperfusion and cognitive dysfunction, increased cardiac hypertrophy, as indicated by the increased heart weight and the ratio of heart weight/body weight, and induced cardiac dysfunction and left ventricular (LV) enlargement, indicated by a decreased LV ejection fraction (LVEF) and LV fractional shortening (LVFS), increased LV dimension (LVD), and increased LV mass. Cognitive deficits significantly correlated with cardiac deficits. BCAS mice also exhibited significantly increased cardiac fibrosis, increased oxidative stress, as indicated by 4-hydroxynonenal and NADPH oxidase-2, increased leukocyte and macrophage infiltration into the heart, and increased cardiac interleukin-6 and thrombin gene expression.

Conclusions:BCAS in mice without primary cardiac disease provokes cardiac dysfunction, which, in part, may be mediated by increased inflammation and oxidative stress.
Analysis of the Impact of the 2019–20 Australian Bushfire Season on the Atmospheric Environment
Authors: Zhang Jie , Sheng Zheng , He Yang , Zuo Xinjie , Jin Bo , He Mingyuan
Published: June 2021

The 2019–20 Australian bushfire produced strong plumes that carried massive quantities of gases and aerosols through the tropopause into the stratosphere. The 2019 El Niño and a rare sudden stratospheric warming (SSW) in the Southern Hemisphere (SH) that occurred in austral spring 2019 caused reduced precipitation in eastern Australia, which caused the strongest bushfire in history in terms of area and disaster degree. High-intensity bushfires triggered chemical reactions, including the rapid secondary formation of formic acid (FA). The strong intensity of the bushfire and the isolated environment allowed their impacts to be well detected. We identified the most active bushfire period (December 30–January 1) and its impacts on atmospheric components. The trajectory and lifetime of bushfire plumes were analysed to reveal the bushfire process and most active period. Based on multiple satellite and reanalysis products, unique variations in atmospheric components were identified and attributed to three main factors: bushfire development period, stratospheric heating mechanism and rapid secondary formation of FA. The bushfire gradually increased in intensity from June, reached its most active period from December 30–January 1, and then weakened. The bushfire development period caused delays in the plumes and peak values of gases (CO, SO2, FA and ozone) and temperature. The diurnal cycle, particle concentration and time restricted the total radiative forcing of aerosols and gases, which prevented a high rate of temperature increase similar to that of gas input from plumes. The strong intensity of the bushfire caused rapid secondary formation of FA, which caused a sharp increase in FA production from December 30–January 1.
The Enigmatic N-Terminal Domain of Proglucagon; A Historical Perspective
Authors: Conlon J. Michael
Published: June 2021

Enteroglucagon refers to the predominant peptide with glucagon-like immunoreactivity (GLI) that is released by the intestine into the circulation in response to nutrients. Development of a radioimmunoassay for glucagon revealed issues that were not apparent in applications of the insulin radioimmunoassay. The fact that some antisera raised against glucagon recognized glucagon-related peptides in extracts of both pancreas and gut whereas others recognized only components in the pancreas remained a mystery until it was realized that the “gut GLI cross-reactive” antisera were directed against an epitope in the N-terminal to central region of glucagon whereas the “pancreatic glucagon specific” antisera were directed against an epitope in the C-terminal region. Unlike the cross-reactive antisera, the glucagon specific antisera did not recognize components in which glucagon was extended from its C-terminus by additional amino acids. Initial attempts to purify enteroglucagon from porcine ileum led to the erroneous conclusion that enteroglucagon comprised 100 amino acids with an apparent molecular mass of 12,000 Da and was consequently given the name glicentin. Subsequent work established that the peptide constituted residues (1-69) of proglucagon (Mr 8128). In the 40 years since the structural characterization of glicentin, attempts to establish an unambiguous physiological function for enteroglucagon have not been successful. Unlike the oxyntomodulin domain at the C-terminus of enteroglucagon, the primary structure of the N-terminal domain (glicentin-related pancreatic peptide) has been poorly conserved among mammals. Consequently, most investigations of the bioactivity of porcine glicentin may have been carried out in inappropriate animal models. Enteroglucagon may simply represent an inactive peptide that ensures that the intestine does not release equimolar amounts of a hyperglycemic agent (glucagon) and a hypoglycemic agent (GLP-1) after ingestion of nutrients.
Potential Post-Fire Impacts on a Water Supply Reservoir: An Integrated Watershed-Reservoir Approach
Authors: Basso Marta , Mateus Marcos , Ramos Tiago B. , Vieira Diana C. S.
Published: June 2021

Wildfires are an increasing threat in the Mediterranean region, causing frequent losses of goods and human lives. Not only are wildfires a concern due to their immediate effects on vegetation and soil, but they can also have substantial impacts on surface water quality. Approximately one-third of the world’s largest cities obtain their drinking water from forest catchments. The removal of vegetation and consequent runoff increase with a high concentration of ash and sediment often leads to increased nutrient and contaminant loads to downstream reservoirs, damaging the aquatic ecosystem and threatening human health. This study focused on the post-fire degradation of surface water in Castelo de Bode reservoir, a strategic freshwater supply for Lisbon’s metropolitan area (2,000,000 inhabitants), Portugal. Output data from the catchment model Soil and Water Assessment Tool were used as inputs to the CE-QUAL-W2 reservoir model. CE-QUAL-W2 was then calibrated for water level, temperature, nutrients, total suspended solids, chlorophyll-a, and dissolved oxygen. The post-fire impacts were assessed by adjusting land use features (curve number, crop vegetation management factor), and soil properties (soil erodibility) in the catchment model, considering the different impacts of fire (low, medium, and high severity). The reservoir model was able to perform temperature seasonality and stratification while a weak performance was found for chlorophyll-a probably for having considered only a group of algae. Simulations showed a deterioration of water quality at the dam wall during the first year after the forest fire. Nevertheless, contamination did not appear worrisome with regards to water quality standards likely due to the capability of the reservoir to attenuate inflow concentrations.
Whole-Exome Sequencing Analysis of Human Semen Quality in Russian Multiethnic Population
Authors: Kolmykov Semyon , Vasiliev Gennady , Osadchuk Ludmila , Kleschev Maxim , Osadchuk Alexander
Published: June 2021

The global trend toward the reduction of human spermatogenic function observed in many countries, including Russia, raised the problem of extensive screening and monitoring of male fertility and elucidation of its genetic and ethnic mechanisms. Recently, whole-exome sequencing (WES) was developed as a powerful tool for genetic analysis of complex traits. We present here the first Russian WES study for identification of new genes associated with semen quality. The experimental 3 × 2 design of the WES study was based on the analysis of 157 samples including three ethnic groups—Slavs (59), Buryats (n = 49), and Yakuts (n = 49), and two different semen quality groups—pathozoospermia (n = 95) and normospermia (n = 62). Additionally, our WES study group was negative for complete AZF microdeletions of the Y-chromosome. The normospermia group included men with normal sperm parameters in accordance with the WHO-recommended reference limit. The pathozoospermia group included men with impaired semen quality, namely, with any combined parameters of sperm concentration <15 × 106/ml, and/or progressive motility <32%, and/or normal morphology <4%. The WES was performed for all 157 samples. Subsequent calling and filtering of variants were carried out according to the GATK Best Practices recommendations. On the genotyping stage, the samples were combined into four cohorts: three sets corresponded to three ethnic groups, and the fourth set contained all the 157 whole-exome samples. Association of the obtained polymorphisms with semen quality parameters was investigated using the χ2 test. To prioritize the obtained variants associated with pathozoospermia, their effects were determined using Ensembl Variant Effect Predictor. Moreover, polymorphisms located in genes expressed in the testis were revealed based on the genomic annotation. As a result, the nine potential SNP markers rs6971091, rs557806, rs610308, rs556052, rs1289658, rs278981, rs1129172, rs12268007, and rs17228441 were selected for subsequent verification on our previously collected population sample (about 1,500 males). The selected variants located in seven genes FAM71F1, PPP1R15A, TRIM45, PRAME, RBM47, WDFY4, and FSIP2 that are expressed in the testis and play an important role in cell proliferation, meiosis, and apoptosis.
Prognostic Value of Germline Copy Number Variants and Environmental Exposures in Non-small Cell Lung Cancer
Authors: Chen Shizhen , Lu Liming , Xian Jianfeng , Shi Changhong , Chen Jinbin , Rao Boqi , Qiu Fuman , Lu Jiachun , Yang Lei
Published: June 2021

Germline copy number variant (gCNV) has been studied as a genetic determinant for prognosis of several types of cancer, but little is known about how it affects non-small cell lung cancer (NSCLC) prognosis. We aimed to develop a prognostic nomogram for NSCLC based on gCNVs. Promising gCNVs that are associated with overall survival (OS) of NSCLC were sorted by analyzing the TCGA data and were validated in a small Chinese population. Then the successfully verified gCNVs were determined in a training cohort (n = 570) to develop a prognostic nomogram, and in a validation cohort (n = 465) to validate the nomogram. Thirty-five OS-related gCNVs were sorted and were reduced to 15 predictors by the Lasso regression analysis. Of them, only CNVR395.1 and CNVR2239.1 were confirmed to be associated with OS of NSCLC in the Chinese population. High polygenic risk score (PRS), which was calculated by the hazard effects of CNVR395.1 and CNVR2239.1, exerted a significantly higher death rate in the training cohort (HR = 1.41, 95%CI: 1.16–1.74) and validation cohort (HR = 1.42, 95%CI: 1.13–1.77) than low PRS. The nomogram incorporating PRS and surrounding factors, achieved admissible concordance indexes of 0.678 (95%CI: 0.664–0.693) and 0.686 (95%CI: 0.670–0.702) in predicting OS in the training and validation cohorts, respectively, and had well-fitted calibration curves. Moreover, an interaction between PRS and asbestos exposure was observed on affecting OS (Pinteraction = 0.042). Our analysis developed a nomogram that achieved an admissible prediction of NSCLC survival, which would be beneficial to the personalized intervention of NSCLC.
Thromboplasminflammation in COVID-19 Coagulopathy: Three Viewpoints for Diagnostic and Therapeutic Strategies
Authors: Gando Satoshi , Wada Takeshi
Published: June 2021

Thromboplasminflammation in coronavirus disease 2019 (COVID-19) coagulopathy consists of angiotensin II (Ang II)-induced coagulopathy, activated factor XII (FXIIa)- and kallikrein, kinin system-enhanced fibrinolysis, and disseminated intravascular coagulation (DIC). All three conditions induce systemic inflammation via each pathomechanism-developed production of inflammatory cytokines. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) downregulates angiotensin-converting enzyme 2, leading to an increase in Ang II levels. Ang II-induced coagulopathy comprising platelet activation, thrombin generation, plasminogen activator inhibitor-1 expression and endothelial injury causes thrombosis via the angiotensin II type 1 receptor. SARS-CoV-2 RNA and neutrophil extracellular trap (NET) DNA activate FXII, resulting in plasmin generation through FXIIa- and kallikrein-mediated plasminogen conversion to plasmin and bradykinin-induced tissue-type plasminogen activator release from the endothelium via the kinin B2 receptor. NETs induce immunothrombosis at the site of infection (lungs), through histone- and DNA-mediated thrombin generation, insufficient anticoagulation control, and inhibition of fibrinolysis. However, if the infection is sufficiently severe, immunothrombosis disseminates into the systemic circulation, and DIC, which is associated with the endothelial injury, occurs. Inflammation, and serine protease networks of coagulation and fibrinolysis, militate each other through complement pathways, which exacerbates three pathologies of COVID-19 coagulopathy. COVID-19 coagulopathy causes microvascular thrombosis and bleeding, resulting in multiple organ dysfunction and death in critically ill patients. Treatment targets for improving the prognosis of COVID-19 coagulopathy include thrombin, plasmin, and inflammation, and SARS-CoV-2 infection. Several drugs are candidates for controlling these conditions; however, further advances are required to establish robust treatments based on a clear understanding of molecular mechanisms of COVID-19 coagulopathy.
Features of Neutrophils From Atopic and Non-Atopic Elite Endurance Runners
Authors: Zambonatto Raquel Freitas , Teixeira Renata Nakata , Poma Sarah de Oliveira , da Silva Eliane Borges , de Almeida Mariana Mendes , Leite Gerson dos Santos , dos Santos Cesar Miguel Momesso , Alves Heloisa Helena de Oliveira , Gorjão Renata , Pithon-Curi Tania Cristina , Carvalho Celso R. F. , Curi Rui , Levada-Pires Adriana Cristina
Published: June 2021

We collected peripheral blood from thirty-nine elite male endurance runners at rest (24 hours after the last exercise session) and used the Allergy Questionnaire for Athletes score and plasma specific IgE level to separate them into atopic and non-atopic athletes. Neutrophils obtained from atopic and non-atopic athletes were subsequently stimulatedin vitrowith fMLP (N-formyl-methionyl-leucyl-phenylalanine), LPS (lipopolysaccharide), or PMA (phorbol 12-myristate 13-acetate). Neutrophils from non-atopic runners responded appropriately to LPS, as evidenced by the production of pro (IL-8, TNF-α, and IL-6) and anti-inflammatory (IL-10) cytokines. Neutrophils from atopic elite runners exhibited lower responses to LPS stimulus as indicated by no increase in IL-1β, TNF-α, and IL-6 production. Neutrophils from non-atopic and atopic runners responded similarly to fMLP stimulation, indicating that migration function remained unaltered. Both groups were unresponsive to PMA induced reactive oxygen species (ROS) production. Training hours and training volume were not associated with neutrophil IgE receptor gene expression or any evaluated neutrophil function. Since non-atopic runners normally responded to LPS stimulation, the reduced neutrophil response to the stimuli was most likely due to the atopic state and not exercise training. The findings reported are of clinical relevance because atopic runners exhibit a constant decline in competition performance and are more susceptible to invading microorganisms.
A 2-Dose AERAS-402 Regimen Boosts CD8+ Polyfunctionality in HIV-Negative, BCG-Vaccinated Recipients
Authors: Sivakumaran Dhanasekaran , Blatner Gretta , Bakken Rasmus , Hokey David , Ritz Christian , Jenum Synne , Grewal Harleen M. S.
Published: June 2021

Despite the widespread use of BCG, tuberculosis (TB) remains a global threat. Existing vaccine candidates in clinical trials are designed to replace or boost BCG which does not provide satisfying long-term protection. AERAS-402 is a replication-deficient Ad35 vaccine encoding a fusion protein of the M. tuberculosis (Mtb) antigens 85A, 85B, and TB10.4. The present phase I trial assessed the safety and immunogenicity of AERAS-402 in participants living in India – a highly TB-endemic area. Healthy male participants aged 18–45 years with a negative QuantiFERON-TB Gold in-tube test (QFT) were recruited. Enrolled participants (n=12) were randomized 2:1 to receive two intramuscular injections of either AERAS-402 (3 x 1010viral particles [vp]); (n=8) or placebo (n=4) on study days 0 and 28. Safety and immunogenicity parameters were evaluated for up to 182 days post the second injection. Immunogenicity was assessed by a flow cytometry-based intracellular cytokine staining (ICS) assay and transcriptional profiling. The latter was examined using dual-color-Reverse-Transcriptase-Multiplex-Ligation-dependent-Probe-Amplification (dc-RT MLPA) assay. AERAS-402 was well tolerated, and no vaccine-related serious adverse events were recorded. The vaccine-induced CD8+ T-cell responses were dominated by cells co-expressing IFN-γ, TNF-α, and IL-2 (“polyfunctional” cells) and were more robust than CD4+ T-cell responses. Five genes (CXCL10, GNLY, IFI35, IL1BandPTPRCv2) were differentially expressed between the AERAS-402-group and the placebo group, suggesting vaccine-induced responses. Further, compared to pre-vaccination, three genes (CLEC7A, PTPRCv1andTAGAP)were consistently up-regulated following two doses of vaccination in the AERAS-402-group. No safety concerns were observed for AERAS-402 in healthy Indian adult males. The vaccine-induced predominantly polyfunctional CD8+T cells in response to Ag85B, humoral immunity, and altered gene expression profiles in peripheral blood mononuclear cells (PBMCs) indicative of activation of various immunologically relevant biological pathways.
Prebiotic Inulin and Sodium Butyrate Attenuate Obesity-Induced Intestinal Barrier Dysfunction by Induction of Antimicrobial Peptides
Authors: Beisner Julia , Filipe Rosa Louisa , Kaden-Volynets Valentina , Stolzer Iris , Günther Claudia , Bischoff Stephan C.
Published: June 2021

Defects in the mucosal barrier have been associated with metabolic diseases such as obesity and non-alcoholic fatty liver disease (NAFLD). Mice fed a Western-style diet (WSD) develop obesity and are characterized by a diet-induced intestinal barrier dysfunction, bacterial endotoxin translocation and subsequent liver steatosis. To examine whether inulin or sodium butyrate could improve gut barrier dysfunction, C57BL/6 mice were fed a control diet or a WSD ± fructose supplemented with either 10% inulin or 5% sodium butyrate for 12 weeks respectively. Inulin and sodium butyrate attenuated hepatosteatitis in the WSD-induced obesity mouse model by reducing weight gain, liver weight, plasma and hepatic triglyceride level. Furthermore, supplementation with inulin or sodium butyrate induced expression of Paneth cell α-defensins and matrix metalloproteinase-7 (MMP7), which was impaired by the WSD and particularly the fructose-added WSD. Effects on antimicrobial peptide function in the ileum were accompanied by induction of β-defensin-1 and tight junction genes in the colon resulting in improved intestinal permeability and endotoxemia. Organoid culture of small intestinal crypts revealed that the short chain fatty acids (SCFA) butyrate, propionate and acetate, fermentation products of inulin, induce Paneth cell α-defensin expression in vitro, and that histone deacetylation and STAT3 might play a role in butyrate-mediated induction of α-defensins. In summary, inulin and sodium butyrate attenuate diet-induced barrier dysfunction and induce expression of Paneth cell antimicrobials. The administration of prebiotic fiber or sodium butyrate could be an interesting therapeutic approach to improve diet-induced obesity.
Targeting Future Pandemics, a Case for De Novo Purine Synthesis and Basic Research
Authors: Mazzarino Randall C.
Published: June 2021

We are currently experiencing a deadly novel viral pandemic with no efficacious, readily available anti-viral therapies to SARS-CoV-2. Viruses will hijack host cellular machinery, including metabolic processes. Here, I provide theory and evidence for targeting the host de novo purine synthetic pathway for broad spectrum anti-viral drug development as well as the pursuit of basic science to mitigate the risks of future novel viral outbreaks.
Modeling Seasonal Distribution of Irrawaddy Dolphins (Orcaella brevirostris) in a Transnational Important Marine Mammal Area
Authors: Verutes Gregory M. , Tubbs Sarah E. , Selmes Nick , Clark Darren R. , Walker Peter , Clements Oliver
Published: June 2021

Fishing activities continue to decimate populations of marine mammals, fish, and their habitats in the coastal waters of the Kep Archipelago, a cluster of tropical islands on the Cambodia-Vietnam border. In 2019, the area was recognized as an Important Marine Mammal Area, largely owing to the significant presence of Irrawaddy dolphins (Orcaella brevirostris). Understanding habitat preferences and distribution aids in the identification of areas to target for monitoring and conservation, which is particularly challenging in data-limited nations of Southeast Asia. Here, we test the hypothesis that accurate seasonal habitat models, relying on environmental data and species occurrences alone, can be used to describe the ecological processes governing abundance for the resident dolphin population of the Kep Archipelago, Cambodia. Leveraging two years of species and oceanographic data—depth, slope, distance to shore and rivers, sea surface temperature, and chlorophyll-a concentration—we built temporally stratified models to estimate distribution and infer seasonal habitat importance. Overall, Irrawaddy dolphins of Kep displayed habitat preferences similar to other populations, and were predominately encountered in three situations: (1) water depths ranging from 3.0 to 5.3 m, (2) surface water temperatures of 27–32°C, and (3) in close proximity to offshore islands (< 7.5 km). With respect to seasonality, statistical tests detected significant differences for all environment variables considered except seafloor slope. Four predictor sets, each with a unique combination of variables, were used to map seasonal variation in dolphin habitat suitability. Models with highest variable importance scores were water depth, pre- and during monsoon season (61–62%), and sea surface temperature, post-monsoon (71%), which suggests that greater freshwater flow during the wet season may alter primary productivity and dolphin prey abundance. Importantly, findings show the majority of areas with highest habitat suitability are not currently surveyed for dolphins and located outside Kep’s Marine Fisheries Management Area. This research confirms the need to expand monitoring to new areas where high-impact fisheries and other human activities operate. Baseline knowledge on dolphin distribution can guide regional conservation efforts by taking into account the seasonality of the species and support the design of tailored management strategies that address transboundary threats to an Important Marine Mammal Area.
Fish Scales and Their Biomimetic Applications
Authors: Yaseen Asim Asghar , Waqar Taha , Khan Muhammad Azhar Ali , Asad Muhammad , Djavanroodi Faramarz
Published: June 2021

Biomaterials are evolving quite rapidly over the last decade. Many applications have been considered toward their involvement in saving lives in the line of duty for law enforcement agencies and military operations. This article discusses recent work on the role of biomaterials that can be considered as a competitive alternative to composites, being used against ballistic impacts. The fish-scaled biomaterials are focused on in this paper, highlighting their excellent mechanical properties and structural configurations. In its natural environment, the scale provides fishes with an armor plating, which is significantly effective in their survival against attacks of predator and the impact inflicted from sharp teeth. These bioinspired materials, if engineered properly, can provide an excellent alternative to current Kevlar® type armors, which are significantly heavier and can cause fatigue to the human body over long-term usage. The investigated materials can provide effective alternatives to heavier and expensive materials currently used in different industrial applications. Additionally, some recent development in the usage of fish scales as a biomaterial and its applications in rapid prototyping techniques are presented. Finally, this review provides useful information to researchers in developing and processing cost-effective biomaterials.
First Symptoms of Primary Progressive Aphasia and Alzheimer's Disease in Brazilian Individuals
Authors: dos Reis Talita Gallas , Machado Thais Helena , Caramelli Paulo , Scornavacca Francisco , Fernandez Liana Lisboa , Beber Bárbara Costa
Published: June 2021

Background: Primary Progressive Aphasia (PPA) is characterized by progressive language impairment due to focal degeneration of brain areas related to linguistic processing. The detection and differential diagnosis of PPA can be difficult with clinical features that may overlap with features of other neurological conditions, such as Alzheimer's disease (AD). The scientific production on PPA in Latin American patients is still scarce. This study investigated the first symptoms in a Brazilian sample of patients with PPA in comparison with AD patients.

Method: We compared the first symptoms reported by caregivers of people with PPA (n = 20; semantic variant n = 8, non-fluent variant n = 7, logopenic variant n = 3, and unclassified cases n = 2) and AD (n = 16). Data were collected through the application of a structured questionnaire that was presented in an interview format to the caregiver who knew the patient best.

Results: Anomia, paraphasias and motor speech difficulties were the first symptoms capable of differentiating patients with PPA from those with AD, while memory was exclusive of AD. Among the PPA variants, anomia was the initial symptom associated with the semantic variant, while motor speech difficulties were associated with the non-fluent variant. The results are discussed considering the unique cultural and sociodemographic characteristics of this studied population.

Conclusion: This study demonstrated that some of the initial symptoms of PPA patients may be unique to clinical variants of PPA and of AD, and their investigation may be useful for the early and differential diagnosis of this population.
Perception of Social Odor and Gender-Related Differences Investigated Through the Use of Transfer Entropy and Embodied Medium
Authors: Invitto Sara , Keshmiri Soheil , Mazzatenta Andrea , Grasso Alberto , Romano Daniele , Bona Fabio , Shiomi Masahiro , Sumioka Hidenobu , Ishiguro Hiroshi
Published: June 2021

The perception of putative pheromones or social odors (PPSO) in humans is a widely debated topic because the published results seem ambiguous. Our research aimed to evaluate how cross-modal processing of PPSO and gender voice can affect the behavioral and psychophysiological states of the subject during a listening task with a bodily contact medium, and how these effects could be gender related. Before the experimental session, three embodied media, were exposed to volatilized estratetraenol (Estr), 5α-androst-16-en-3 α-ol (Andr), and Vaseline oil. The experimental session consisted in listening to a story that were transmitted, with a male or female voice, by the communicative medium via a Bluetooth system during a listening task, recorded through 64-active channel electroencephalography (EEG). The sense of co-presence and social presence, elicited by the medium, showed how the established relationship with the medium was gender dependent and modulated by the PPSO. In particular, Andr induced greater responses related to co-presence. The gender of the participants was related to the co-presence desire, where women imagined higher medium co-presence than men. EEG findings seemed to be more responsive to the PPSO–gender voice interaction, than behavioral results. The mismatch between female PPSO and male voice elicited the greatest cortical flow of information. In the case of the Andr–male voice condition, the trained model appeared to assign more relevance to the flow of information to the right frontotemporal regions (involved in odor recognition memory and social behavior). The Estr–male voice condition showed activation of the bilateral frontoparietal network, which is linked to cognitive control, cognitive flexibility, and auditory consciousness. The model appears to distinguish the dissonance condition linked to Andr matched with a female voice: it highlights a flow of information to the right occipital lobe and to the frontal pole. The PPSO could influence the co-presence judgements and EEG response. The results seem suggest that could be an implicit pattern linked to PPSO-related gender differences and gender voice.
Exposure to High Aerial Ammonia Causes Hindgut Dysbiotic Microbiota and Alterations of Microbiota-Derived Metabolites in Growing Pigs
Authors: Tang Shanlong , Zhong Ruqing , Yin Chang , Su Dan , Xie Jingjing , Chen Liang , Liu Lei , Zhang Hongfu
Published: June 2021

Ammonia, an atmospheric pollutant in the air, jeopardizes immune function, and perturbs metabolism, especially lipid metabolism, in human and animals. The roles of intestinal microbiota and its metabolites in maintaining or regulating immune function and metabolism are irreplaceable. Therefore, this study aimed to investigate how aerial ammonia exposure influences hindgut microbiota and its metabolites in a pig model. Twelve growing pigs were treated with or without aerial ammonia (35 mg/m3) for 25 days, and then microbial diversity and microbiota-derived metabolites were measured. The results demonstrated a decreasing trend in leptin (p = 0.0898) and reduced high-density lipoprotein cholesterol (HDL-C, p = 0.0006) in serum after ammonia exposure. Besides, an upward trend in hyocholic acid (HCA), lithocholic acid (LCA), hyodeoxycholic acid (HDCA) (p < 0.1); a downward trend in tauro-deoxycholic acid (TDCA, p < 0.1); and a reduced tauro-HDCA (THDCA, p < 0.05) level were found in the serum bile acid (BA) profiles after ammonia exposure. Ammonia exposure notably raised microbial alpha-diversity with higher Sobs, Shannon, or ACE index in the cecum or colon and the Chao index in the cecum (p < 0.05) and clearly exhibited a distinct microbial cluster in hindgut indicated by principal coordinate analysis (p < 0.01), indicating that ammonia exposure induced alterations of microbial community structure and composition in the hindgut. Further analysis displayed that ammonia exposure increased the number of potentially harmful bacteria, such as Negativibacillus, Alloprevotella, or Lachnospira, and decreased the number of beneficial bacteria, such as Akkermansia or Clostridium_sensu_stricto_1, in the hindgut (FDR < 0.05). Analysis of microbiota-derived metabolites in the hindgut showed that ammonia exposure increased acetate and decreased isobutyrate or isovalerate in the cecum or colon, respectively (p < 0.05). Unlike the alteration of serum BA profiles, cecal BA data showed that high ammonia exposure had a downward trend in cholic acid (CA), HCA, and LCA (p < 0.1); a downward trend in deoxycholic acid (DCA) and HDCA (p < 0.05); and an upward trend in glycol-chenodeoxycholic acid (GCDCA, p < 0.05). Mantel test and correlation analysis revealed associations between microbiota-derived metabolites and ammonia exposure-responsive cecal bacteria. Collectively, the findings illustrated that high ammonia exposure induced the dysbiotic microbiota in the hindgut, thereby affecting the production of microbiota-derived short-chain fatty acids and BAs, which play a pivotal role in the modulation of host systematic metabolism.