bluuebunny/crossref_metadata_2025 huggingface dataset:
OS IMPACTOS DA IMPLANTAÇÃO DO REGISTRO DE PONTO BIOMÉTRICO NAS HORAS EXTRAS EM UMA EMPRESA DO SETOR SUCROENERGÉTICO
Authors: Simedo Arnaldo José , Simedo Mariana Bárbara Lopes
Published: March 2021

O avanço tecnológico tem possibilitado a melhoria constante de processos nas organizações, por meio de otimização de tempo, redução de custos, maior segurança, entre outros. Cada vez mais, o reconhecimento biométrico está presente no cotidiano das pessoas, seja em seus smartphones, caixas eletrônicos, aeroportos e, mais recentemente, nas urnas eletrônicas. Em meio a esse contexto, o presente trabalho buscou analisar como a implantação do ponto biométrico pode influenciar na quantidade de horas extras registradas. Para tanto, foi realizada uma pesquisa descritiva de caráter quantitativo, tendo como instrumento de coleta de dados a análise documental. Foram avaliados os relatórios de hora extra e adicional noturno dos 54 meses anteriores e 54 meses posteriores à introdução do projeto. Os resultados indicaram que, após a adoção da nova tecnologia, houve redução na quantidade de horas extras e adicional noturno, além do aumento das horas falta, o que ocasionou redução de custo com a folha de pagamento. Concluiu-se que a tecnologia biométrica foi responsável pela redução de 55.825 horas extras em um período de 54 meses, gerando para a empresa uma economia estimada de R$426.327,00.
PANDEMIC OF COVID-19 IN INDONESIA: SOCIAL POLITICS PERSPECTIVE (Pandemi Covid-19 di Indonesia: Perspektif Sosial Politik)
Authors: Lestari Shindy Diah Ayu
Published: March 2021

In the second half of the twentieth century, global security issues have quickly transformed into what is defined nowadays as non-traditional security issues and the latest of such non-traditional security problem has emerged recently as the recent Covid-19 pandemic impacted the whole world on an unprecedented scale. Indonesia, as the fourth most populated country with 267 million people, face an extraordinary challenge and therefore it is interesting to see and to learn how the situation developed, what the Government of Indonesia did, included what the Government should do, not only from the healthcare point of view, but also from other perspectives such as social and political. Using the problems arising during the pandemic in Indonesia as a non-traditional security issue, the present work aims to assess the difficulties faced by the country in order to establish a set of short and long term plans that should be addressed in order to improve the preparedness and to correct the current flaws generating difficulties to develop an optimal response. Governmental decisions and communication should be clear and follow a solid strategy to ensure population awareness. Law enforcement should strictly emphasize on the dangerousness of Covid-19. Coordination between central and local governments should be efficient and involve experts and respected figures. Not only healthcare but also economic, social and political issues need to be planned and projected during and after pandemic and the lessons taken during this pandemic should be used to build solid and better foundations for future development of the Republic of Indonesia.
Fed-Batch mcl- Polyhydroxyalkanoates Production in Pseudomonas putida KT2440 and ΔphaZ Mutant on Biodiesel-Derived Crude Glycerol
Authors: Borrero-de Acuña José Manuel , Rohde Manfred , Saldias Cesar , Poblete-Castro Ignacio
Published: March 2021

Crude glycerol has emerged as a suitable feedstock for the biotechnological production of various industrial chemicals given its high surplus catalyzed by the biodiesel industry.Pseudomonasbacteria metabolize the polyol into several biopolymers, including alginate and medium-chain-length poly(3-hydroxyalkanoates) (mcl-PHAs). AlthoughP. putidais a suited platform to derive these polyoxoesters from crude glycerol, the attained concentrations in batch and fed-batch cultures are still low. In this study, we employedP. putidaKT2440 and the hyper-PHA producer ΔphaZmutant in two different fed-batch modes to synthesizemcl-PHAs from raw glycerol. Initially, the cells grew in a batch phase (μmax0.21 h–1) for 22 h followed by a carbon-limiting exponential feeding, where the specific growth rate was set at 0.1 (h–1), resulting in a cell dry weight (CDW) of nearly 50 (g L–1) at 40 h cultivation. During the PHA production stage, we supplied the substrate at a constant rate of 50 (g h–1), where the KT2440 and the ΔphaZproduced 9.7 and 12.7 gPHA L–1, respectively, after 60 h cultivation. We next evaluated the PHA production ability of theP. putidastrains using a DO-stat approach under nitrogen depletion. Citric acid was the main by-product secreted by the cells, accumulating in the culture broth up to 48 (g L–1) under nitrogen limitation. The mutant ΔphaZamassed 38.9% of the CDW asmcl-PHA and exhibited a specific PHA volumetric productivity of 0.34 (g L–1h–1), 48% higher than the parental KT2440 under the same growth conditions. The biosynthesizedmcl-PHAs had average molecular weights ranging from 460 to 505 KDa and a polydispersity index (PDI) of 2.4–2.6. Here, we demonstrated that the DO-stat feeding approach in high cell density cultures enables the high yield production ofmcl-PHA inP. putidastrains using the industrial crude glycerol, where the fed-batch process selection is essential to exploit the superior biopolymer production hallmarks of engineered bacterial strains.
lncRNA Gm16410 Mediates PM2.5-Induced Macrophage Activation via PI3K/AKT Pathway
Authors: Xu Jingbin , Xu Henggui , Ma Kexin , Wang Yue , Niu Ben , Zhang Li , Li Fasheng
Published: March 2021

PM2.5 refers to atmospheric particulate matters with a diameter of less than 2.5 μm. The deposit of PM2.5 in lung cells can cause oxidative stress, leading to changes in macrophage polarity, which can subsequently cause pulmonary inflammation. Long-chain non-coding RNA (lncRNA) is a class of transcripts that regulate biological processes through multiple mechanisms. However, the role of lncRNA in PM2.5-induced lung inflammation has not been established. In this study, the biological effects and associated mechanism of lncRNA in PM2.5-induced change in macrophage polarity were investigated. The lncRNA-mediated PM2.5-induced macrophage inflammation and lung inflammation-associated injury were also determined. Mice were exposed to chronic levels of PM2.5, and changes in the expression of lncRNA in the lung were measured by lncRNA microarray. lncRNAs that showed significant changes in expression in response to PM2.5 were identified. lncRNA showing the biggest change was subjected to further analysis to determine its functional roles and mechanisms with respect to macrophage activation. The result showed that a significant reduction in expression of one lncRNA, identified as lncGm16410, was observed in the lung of mice and RAW264.7 cells following exposure to PM2.5. lncGm16410 suppressed PM2.5-induced macrophage activation via the SRC protein-mediated PI3K/AKT signaling pathway. PM2.5 promoted lung inflammation by downregulating the expression of lncGm16410, enhancing the activation of macrophages. Thus, lncGm16410 might provide new insight into the prevention of PM2.5 injury.
LHPP-Mediated Histidine Dephosphorylation Suppresses the Self-Renewal of Mouse Embryonic Stem Cells
Authors: Xia Rong Mu , Yao Dong Bo , Cai Xue Min , Xu Xiu Qin
Published: March 2021

Self-renewal of embryonic stem cells (ESCs) is orchestrated by a vast number of genes at the transcriptional and translational levels. However, the molecular mechanisms of post-translational regulatory factors in ESC self-renewal remain unclear. Histidine phosphorylation, also known as hidden phosphorylation, cannot be detected by conventional experimental methods. A recent study defined phospholysine phosphohistidine inorganic pyrophosphate phosphatase (LHPP) as a histidine phosphatase, which regulates various biological behaviors in cells via histidine dephosphorylation. In this study, the doxycycline (DOX)-induced hLHPP-overexpressing mouse ESCs and mouse LHPP silenced mESCs were constructed. Quantitative polymerase chain reaction (qPCR), western blotting analysis, immunofluorescence, Flow cytometry, colony formation assays, alkaline phosphatase (AP) and bromodeoxyuridine (Brdu) staining were performed. We found that the histidine phosphorylation level was strikingly reduced following LHPP overexpression. Besides, the expression of Oct4 and Lefty1, indispensable genes in the process of ESCs self-renewal, was significantly down-regulated, while markers related to the differentiation were markedly elevated. Moreover, LHPP-mediated histidine dephosphorylation induced G0/G1 phase arrest in mESCs, suggesting LHPP was implicated in cell proliferation and cell cycle. Conversely, silencing of Lhpp promoted the self-renewal of mESCs and reversed the RA induced increased expression of genes associated with differentiation. Mechanistically, our findings suggested that the enzymatic active site of LHPP was the cysteine residue at position 226, not 53. LHPP-mediated histidine dephosphorylation lowered the expression levels of β-catenin and the cell cycle-related genes CDK4 and CyclinD1, while it up-regulated the cell cycle suppressor genes P21 and P27. Taken together, our findings reveal that LHPP-mediated histidine dephosphorylation plays a role in the self-renewal of ESCs. LHPP-mediated histidine dephosphorylation inhibited the self-renewal of ESCs by negatively regulating the Wnt/β-catenin pathway and downstream cell cycle-related genes, providing a new perspective and regulatory target for ESCs self-renewal.
The Role of p21-Activated Kinases in Cancer and Beyond: Where Are We Heading?
Authors: Liu Hui , Liu Kangdong , Dong Zigang
Published: March 2021

The p21-activated kinases (PAKs), downstream effectors of Ras-related Rho GTPase Cdc42 and Rac, are serine/threonine kinases. Biologically, PAKs participate in various cellular processes, including growth, apoptosis, mitosis, immune response, motility, inflammation, and gene expression, making PAKs the nexus of several pathogenic and oncogenic signaling pathways. PAKs were proved to play critical roles in human diseases, including cancer, infectious diseases, neurological disorders, diabetes, pancreatic acinar diseases, and cardiac disorders. In this review, we systematically discuss the structure, function, alteration, and molecular mechanisms of PAKs that are involved in the pathogenic and oncogenic effects, as well as PAK inhibitors, which may be developed and deployed in cancer therapy, anti-viral infection, and other diseases. Furthermore, we highlight the critical questions of PAKs in future research, which provide an opportunity to offer input and guidance on new directions for PAKs in pathogenic, oncogenic, and drug discovery research.
Galectin-14 Promotes Trophoblast Migration and Invasion by Upregulating the Expression of MMP-9 and N-Cadherin
Authors: Wang Miaomiao , Xu Yuqing , Wang Peng , Xu Yanfei , Jin Pengzhen , Wu Zaigui , Qian Yeqing , Bai Long , Dong Minyue
Published: March 2021

Galectin-14 is specifically expressed in placental trophoblasts, and its expression is reduced in trophoblasts retrieved from the cervix of women destined to develop early pregnancy loss. However, the roles of galectin-14 in regulating trophoblasts and in the pathogenesis of pregnancy complication have never been investigated. In the current research, we aimed to investigate the roles of galectin-14 in the regulation of trophoblasts. Tissues of the placenta and villi were collected. Primary trophoblasts and human trophoblast cell line HTR-8/SVneo were used. Western blotting and RT-PCR were used to quantify gene expression. The siRNA-mediated galectin-14 knockdown and lentivirus-mediated overexpression were performed to manipulate the gene expression in trophoblasts. Transwell migration and invasion assays were used to evaluate cell migration and invasion capacity. Gelatin zymography was used to determine the gelatinase activity. Galectin-14 was significantly decreased in the villi of early pregnancy loss and the placenta of preeclampsia. Knockdown of galectin-14 in primary trophoblasts inhibited cell migration and invasion, downregulated the expression of matrix metalloproteinase (MMP)-9 and N-cadherin, the activity of MMP-9, and decreased the phosphorylation of Akt. Meanwhile, the overexpression of galectin-14 in HTR-8/SVneo promoted cell migration and invasion, upregulated the expression of MMP-9 and N-cadherin, the activity of MMP-9, and increased the phosphorylation of Akt. Increased Akt phosphorylation promoted cell migration and invasion and upregulated the expression and activity of MMP-9, while decreased Akt phosphorylation inhibited cell migration and invasion and downregulated the expression and activity of MMP-9. Thus, galectin-14 promotes trophoblast migration and invasion by enhancing the expression of MMP-9 and N-cadherin through Akt phosphorylation. The dysregulation of galectin-14 is involved in the pathogenesis of early pregnancy loss and preeclampsia.
The Immunomodulatory Capacity of Induced Pluripotent Stem Cells in the Post-stroke Environment
Authors: Spellicy Samantha E. , Hess David C.
Published: March 2021

Inflammation has proven to be a key contributing factor to the pathogenesis of ischemic and hemorrhagic stroke. This sequential and progressive response, marked by proliferation of resident immune cells and recruitment of peripheral immune populations, results in increased oxidative stress, and neuronal cell death. Therapeutics aimed at quelling various stages of this post-stroke inflammatory response have shown promise recently, one of which being differentiated induced pluripotent stem cells (iPSCs). While direct repopulation of damaged tissues and enhanced neurogenesis are hypothesized to encompass some of the therapeutic potential of iPSCs, recent evidence has demonstrated a substantial paracrine effect on neuroinflammation. Specifically, investigation of iPSCs, iPSC-neural progenitor cells (iPSC-NPCs), and iPSC-neuroepithelial like stem cells (iPSC-lt-NESC) has demonstrated significant immunomodulation of proinflammatory signaling and endogenous inflammatory cell populations, such as microglia. This review aims to examine the mechanisms by which iPSCs mediate neuroinflammation in the post-stroke environment, as well as delineate avenues for further investigation.
Antibodies Against the Plasmodium vivax Apical Membrane Antigen 1 From the Belem Strain Share Common Epitopes Among Other Worldwide Variants
Authors: França Ana Caroline Barbosa , Françoso Kátia Sanches , Marques Rodolfo Ferreira , Trossini Gustavo H. G. , Gomes Renan A. , Póvoa Marinete M. , Cunha Maristela G. , Silveira Eduardo L. V. , Soares Irene S.
Published: March 2021

Malaria is a human parasitic disease distributed in many tropical countries and caused by various Plasmodium species. Plasmodium vivax has the largest geographical distribution of the Plasmodium species and is predominant in the Americas, including Brazil. Only a small number of P. vivax vaccine formulations have successfully reached clinical trials relative to their P. falciparum counterparts. One of the candidate antigens for a blood-stage P. vivax vaccine is apical membrane antigen 1 (PvAMA-1). Due to the worldwide distribution of Plasmodium parasites, a high degree of variability has been detected in this antigen sequence, representing a considerable challenge to the development of a universal vaccine against malaria. In this study, we evaluated how PvAMA-1 polymorphisms influence vaccine-derived immune responses in P. vivax malaria. To this end, we expressed 9 recombinant protein representatives of different PvAMA-1 allelic variants in the yeast Pichia pastoris: Belem, Chesson I, Sal-1, Indonesia XIX, SK0814, TC103, PNG_05_ESP, PNG_62_MU, and PNG_68_MAS. After protein expression and purification, we evaluated the breadth of the immune responses derived from malaria-exposed individuals from the Amazon region. From 611 serum samples of malaria-exposed individuals, 53.68% of them reacted against the PvAMA-1 Belem through ELISA. Positive samples were further tested against recombinant proteins representing the other PvAMA-1 allelic variants. Whereas Sal-1, Chesson I and SK0814 variants were highly recognized by tested serum samples, Indonesia XIX, TC103, PNG_05_ESP, PNG_62_MU, and PNG_68_MAS were only slightly recognized. Moreover, polyclonal sera derived from C57BL/6 mice immunized with the PvAMA-1 Belem protein predominantly recognized Belem, Sal-1, Chesson I, SK0814, and Indonesia XIX through ELISA. Last, ELISA-based competition assays demonstrated that a previous interaction between anti-Belem polyclonal serum and Sal-1, Chesson I, SK0814, or Indonesia XIX proteins could further inhibit antibody binding to the Belem variant. Our human and mouse data suggest the presence of common epitopes or cross-reactivity between Belem, Sal-1, Chesson I, and SK0814 variants. Although the PvAMA-1 Belem variant induces strain-transcendent antibodies, PvAMA-1 variants from Thailand and Papua New Guinea may need to be included in a universal vaccine formulation to achieve protection against P. vivax malaria.
The Role of Intestinal Dysbacteriosis Induced Arachidonic Acid Metabolism Disorder in Inflammaging in Atherosclerosis
Authors: Sun Yingxin , Wu Danbin , Zeng Wenyun , Chen Yefei , Guo Maojuan , Lu Bin , Li Huhu , Sun Chun , Yang Lin , Jiang Xijuan , Gao Qing
Published: March 2021

Background

Aging induced chronic systemic inflammatory response is an important risk factor for atherosclerosis (AS) development; however, the detailed mechanism is yet to be elucidated.

Objective

To explore the underlying mechanism of how aging aggravates AS advancement.

Methods

A young (five-week-old, YM) and aged group (32-week-old, OM) male apoE-/- mice with a high fat diet were used as models, and age-matched male wild-type C57BL/6J (WT) mice were used as controls. AS lesion size, serum lipid profile, cytokines, and gut microbiota-derived LPS were analyzed after 32 weeks of diet intervention. A correlation analysis between the 16S rRNA sequencing of the feces and serum metabolomics profiles was applied to examine the effect of their interactions on AS.

Results

ApoE-/- mice developed severe atherosclerosis and inflammation in the aorta compared to the WT groups, and aged apoE-/- mice suffered from a more severe AS lesion than their younger counterparts and had low-grade systemic inflammation. Furthermore, increased levels of serum LPS, decreased levels of SCFAs production, as well as dysfunction of the ileal mucosal barrier were detected in aged mice compared with their younger counterparts. There were significant differences in the intestinal flora composition among the four groups, and harmful bacteria such as Lachnospiraceae_FCS020, Ruminococcaceae_UCG-009, Acetatifactor, Lachnoclostridium and Lactobacillus_gasseri were significantly increased in the aged apoE-/- mice compared with the other groups. Concurrently, metabolomics profiling revealed that components involved in the arachidonic acid (AA) metabolic pathway such as 20-HETE, PGF2α, arachidonic acid, and LTB4 were significantly higher in the aged AS group than in the other groups. This suggested that metabolic abnormalities and disorders of intestinal flora occurred in AS mice.

Conclusions

Aging not only altered the gut microbiome community but also substantially disturbed metabolic conditions. Our results confirm that AA metabolism is associated with the imbalance of the intestinal flora in the AS lesions of aged mice. These findings may offer new insights regarding the role of gut flora disorders and its consequent metabolite changed in inflammaging during AS development.
MALDI-TOF MS Biomarker Detection Models to Distinguish RTX Toxin Phenotypes of Moraxella bovoculi Strains Are Enhanced Using Calcium Chloride Supplemented Agar
Authors: Hille Matthew M. , Clawson Michael L. , Dickey Aaron M. , Lowery Justin H. , Loy John Dustin
Published: March 2021

Moraxella bovoculi is the bacterium most often cultured from ocular lesions of cattle with infectious bovine keratoconjunctivitis, also known as bovine pinkeye. Some strains of M. bovoculi contain operons encoding for a repeats-in-toxin (RTX) toxin, which is a known virulence factor of multiple veterinary pathogens. We explored the utility of MALDI-TOF MS and biomarker detection models to classify the presence or absence of an RTX phenotype in M. bovoculi. Ninety strains that had undergone whole genome sequencing were classified by the presence or absence of complete RTX operons and confirmed with a visual assessment of hemolysis on blood agar. Strains were grown on Tryptic Soy Agar (TSA) with 5% sheep blood, TSA with 5% bovine blood that was supplemented with 10% fetal bovine serum, 10 mmol/LCaCl2, or both. The formulations were designed to determine the influence of growth media on toxin production or activity, as calcium ions are required for toxin secretion and activity. Mass spectra were obtained for strains grown on each agar formulation and biomarker models were developed using ClinProTools 3.0 software. The most accurate model was developed using spectra from strains grown on TSA with 5% bovine blood and supplemented with CaCl2, which had a sensitivity and specificity of 93.3% and 73.3%, respectively, regarding RTX phenotype classification. The same biomarker model algorithm developed from strains grown on TSA with 5% sheep blood had a substantially lower sensitivity and specificity of 68.0% and 52.0%, respectively. Our results indicate that MALDI-TOF MS biomarker models can accurately classify strains of M. bovoculi regarding the presence or absence of RTX toxin operons and that agar media modifications improve the accuracy of these models.
Predictive Analysis of the Neutralization Activity in Convalescent Plasmas From COVID-19 Recovered Patients in Zhejiang Province, China, January-March, 2020
Authors: Yuan Yajie , Yu Liang , Jin Zi , Wang Yongjun , Gao Meng , Ding Haojie , Zhuo Xunhui , Zhu Xiao , Gao Fei , Zheng Xiaojun , Ying Guoqing , Xu Xiaowei , Kong Qingming , Lu Shaohong , Lv Hangjun
Published: March 2021

Background

Convalescent plasma (CP) transfusion is considered to be the priority therapeutic option for COVID-19 inpatients when no specific drugs are available for emerging infections. An alternative, simple, and sensitive method is urgently needed for clinical use to detect neutralization activity of the CP to avoid the use of inconvenient micro-neutralization assay.

Method

This study aims to explore optimal index in predicting the COVID-19 CP neutralization activity (neutralizing antibody titers, NAb titers) in an indirect ELISA format. Fifty-seven COVID-19-recovered patients plasma samples were subjected to anti-SARS-CoV-2 RBD, S1, and N protein IgG antibody by indirect ELISA.

Results

ELISA-RBD exhibited high specificity (96.2%) and ELISA-N had high sensitivity (100%); while ELISA-S1 had low sensitivity (86.0%) and specificity (73.1%). Furthermore, ELISA-RBD IgG titers and pseudovirus-based NAb titers correlated significantly, with R2 of 0.2564 (P < 0.0001).

Conclusion

ELISA-RBD could be a substitute for the neutralization assay in resource-limited situations to screen potential plasma donors for further plasma infusion therapy.
Different Lipid Parameters in Predicting Clinical Outcomes in Chinese Statin-Naïve Patients After Coronary Stent Implantation
Authors: Zeng Li , Ye Ziwei , Li Ying , Zhou Yiling , Shi Qingyang , Hu Tao , Fu Minghuan , Wu Caojie , Tian Haoming , Li Sheyu
Published: March 2021

Background: Low-density lipoprotein cholesterol (LDL-C) is a critical surrogate outcome for cardiovascular disease (CVD). Recent observational studies identified different predictive lipid parameters, but these have not been fully validated in the Chinese population. This study aimed to compare the predictive value of lipid parameters for cardiovascular outcomes in Chinese statin-naïve patients who underwent percutaneous coronary intervention (PCI).

Methods: We retrospectively recruited statin-naïve patients who underwent PCI for stable angina and acute coronary syndrome at Sichuan Provincial People's Hospital between 1 January 2016 and 31 December 2017. A follow-up was conducted via outpatient visits or telephone. We divided patients into three groups based on lipid parameter tertiles. We calculated the hazard ratios (HRs) of the highest and lowest tertiles for major adverse cardiovascular events (MACEs) using multivariate Cox proportional hazards regression. We compared the association strength of lipid parameters with MACEs using the HR of non-LDL-C lipid parameters relative to LDL-C.

Results: Among 445 included patients, the highest LDL-C, LDL-C/high-density lipoprotein cholesterol (HDL-C), atherosclerosis index, and non-HDL-C level tertiles were associated with an average increase of 165% (HR 2.65, confidence interval [CI] 1.26 to 5.61; P = 0.01), 324% (HR 4.24, CI 1.89 to 9.52; P < 0.001), 152% (HR 2.52, CI 1.22 to 5.22; P = 0.01), and 125% (HR 2.25, CI 1.09 to 4.64; P = 0.01) in the hazard of composite CVD, respectively. Lipoprotein (a) levels did not show a significant association with the endpoints. Except for LDL-C/HDL-C, different lipid parameter HR ratios were <1.0; none were statistically significant.

Conclusion: Compared with non-LDL-C lipid parameters, LDL-C acts better predictive value for cardiovascular outcomes in general Chinese statin-naïve post-PCI patients.
Insulin Action, Glucose Homeostasis and Free Fatty Acid Metabolism: Insights From a Novel Model
Authors: Stefanovski Darko , Punjabi Naresh M. , Boston Raymond C. , Watanabe Richard M.
Published: March 2021

Glucose and free fatty acids (FFA) are essential nutrients that are both partly regulated by insulin. Impaired insulin secretion and insulin resistance are hallmarks of aberrant glucose disposal, and type 2 diabetes (T2DM). In the current study, a novel model of FFA kinetics is proposed to estimate the role insulin action on FFA lipolysis and oxidation allowing estimation of adipose tissue insulin sensitivity (SIFFA). Twenty-five normal volunteers were recruited for the current study. To participate, volunteers had to be less than 40 years of age and have a body mass index (BMI) < 30 kg/m2, and be free of medical comorbidity. The proposed model of FFA kinetics was used to analyze the data derived from the insulin-modified FSIGT. Mean fractional standard deviations of the parameter estimates were all less than 20%. Standardized residuals of the fit of the model to the FFA temporal data were randomly distributed, with only one estimated point lying outside the 2-standard deviation range, suggesting an acceptable fit of the model to the FFA data. The current study describes a novel one-compartment non-linear model of FFA kinetics during an FSIGT that provides an FFA metabolism insulin sensitivity parameter (SIFFA). Furthermore, the models suggest a new role of glucose as the modulator of FFA disposal. Estimates of SIFFA confirmed previous findings that FFA metabolism is more sensitive to changes in insulin than glucose metabolism. Novel derived indices of insulin sensitivity of FFA (SIFFA) were correlated with minimal model indices. These associations suggest a cooperative rather than competitive interplay between the two primary nutrients (glucose and FFA) and allude to the FFA acting as the buffer, such that glucose homeostasis is maintained.
Central and Peripheral Adiposity Had Different Effect on Disability in Centenarians
Authors: Yang Shanshan , Wang Shengshu , Tai Penggang , Jia Wangping , Han Ke , Liu Miao , He Yao
Published: March 2021

Purpose

To explore the correlations between waist circumference, body mass index, calf circumference (CC), and waist-calf circumference ratio (WCR) and activities of daily living (ADLs) and instrumental activities of daily living (IADLs) in Hainan centenarians.

Patients and Methods

A total of 1,002 Hainan centenarians were selected by full sample household survey. ADLs and IADLs were used to investigate the ability of activity and instrumental activity in daily living. The possible non-linear associations were further analyzed using restricted cubic spline.

Results

After adjusting for demographic characteristics (gender, age, ethnicity, marital status, educational level, and type of residence) and lifestyle (smoking, drinking, and exercise), the odds ratio (OR) of CC (continuous variable) on ADL disability in centenarians was 0.90 (95% CI: 0.85–0.96), while high WCR (continuous variable) was related with high risk of ADL disability (OR=1.73; 95% confidence interval[CI], 1.07–2.80). The ORs of CC and WCR for IADL severe disability were 0.86 (95% CI, 0.82–0.91) and 2.23 (95% CI, 1.52–3.28), respectively.

Conclusion

Central (WCR) and peripheral (CC) adiposity had different effects on disability (ADL and IADL) in centenarians. Even in centenarians, maintaining muscle mass (with higher calf circumference) and avoiding central obesity are of positive significance for the prevention of ADL/IADL disability.
Extending the Spatio-Temporal Applicability of DISPATCH Soil Moisture Downscaling Algorithm: A Study Case Using SMAP, MODIS and Sentinel-3 Data
Authors: Ojha Nitu , Merlin Olivier , Suere Christophe , Escorihuela Maria José
Published: March 2021

DISPATCH is a disaggregation algorithm of the low-resolution soil moisture (SM) estimates derived from passive microwave observations. It provides disaggregated SM data at typically 1 km resolution by using the soil evaporative efficiency (SEE) estimated from optical/thermal data collected around solar noon. DISPATCH is based on the relationship between the evapo-transpiration rate and the surface SM under non-energy-limited conditions and hence is well adapted for semi-arid regions with generally low cloud cover and sparse vegetation. The objective of this paper is to extend the spatio-temporal coverage of DISPATCH data by 1) including more densely vegetated areas and 2) assessing the usefulness of thermal data collected earlier in the morning. Especially, we evaluate the performance of the Temperature Vegetation Dryness Index (TVDI) instead of SEE in the DISPATCH algorithm over vegetated areas (called vegetation-extended DISPATCH) and we quantify the increase in coverage using Sentinel-3 (overpass at around 09:30 am) instead of MODIS (overpass at around 10:30 am and 1:30 pm for Terra and Aqua, respectively) data. In this study, DISPATCH is applied to 36 km resolution Soil Moisture Active and Passive SM data over three 50 km by 50 km areas in Spain and France to assess the effectiveness of the approach over temperate and semi-arid regions. The use of TVDI within DISPATCH increases the coverage of disaggregated images by 9 and 14% over the temperate and semi-arid sites, respectively. Moreover, including the vegetated pixels in the validation areas increases the overall correlation between satellite and in situ SM from 0.36 to 0.43 and from 0.41 to 0.79 for the temperate and semi-arid regions, respectively. The use of Sentinel-3 can increase the spatio-temporal coverage by up to 44% over the considered MODIS tile, while the overlapping disaggregated data sets derived from Sentinel-3 and MODIS land surface temperature data are strongly correlated (around 0.7). Additionally, the correlation between satellite and in situ SM is significantly better for DISPATCH (0.39–0.80) than for the Copernicus Sentinel-1-based (−0.03 to 0.69) and SMAP/S1 (0.37–0.74) product over the three studies (temperate and semi-arid) areas, with an increase in yearly valid retrievals for the vegetation-extended DISPATCH algorithm.
The Role of Membrane-Based Technologies in Environmental Treatment and Reuse of Produced Water
Authors: Zolghadr Ehsan , Firouzjaei Mostafa Dadashi , Amouzandeh Ghoncheh , LeClair Patrick , Elliott Mark
Published: March 2021

Produced water (PW) generation has been increasing recently due to the expansion of fossil fuel extraction and the aging of oil wells worldwide, especially in the United States. The adverse health risks, seismicity, and environmental impacts associated with PW have become a challenging concern. Therefore, there is increased demand for improved PW treatment and reuse management options. There are multiple methods for treating PW; this article focuses on treatment through membrane filtration. Moreover, this mini review aims to summarize statistics on PW abundance and trends in PW generation over time, to briefly call attention to health-related issues, highlight some treatment challenges, and mention the potential purposes for reuse with an emphasis on the United States, the largest generator of PW worldwide.
Promoter Architecture and Transcriptional Regulation of Genes Upregulated in Germination and Coleoptile Elongation of Diverse Rice Genotypes Tolerant to Submergence
Authors: Mohanty Bijayalaxmi
Published: March 2021

Rice has the natural morphological adaptation to germinate and elongate its coleoptile under submerged flooding conditions. The phenotypic deviation associated with the tolerance to submergence at the germination stage could be due to natural variation. However, the molecular basis of this variation is still largely unknown. A comprehensive understanding of gene regulation of different genotypes that have diverse rates of coleoptile elongation can provide significant insights into improved rice varieties. To do so, publicly available transcriptome data of five rice genotypes, which have different lengths of coleoptile elongation under submergence tolerance, were analyzed. The aim was to identify the correlation between promoter architecture, associated with transcriptional and hormonal regulation, in diverse genotype groups of rice that have different rates of coleoptile elongation. This was achieved by identifying the putativecis-elements present in the promoter sequences of genes upregulated in each group of genotypes (tolerant, highly tolerant, and extremely tolerant genotypes). Promoter analysis identified transcription factors (TFs) that are common and unique to each group of genotypes. The candidate TFs that are common in all genotypes are MYB, bZIP, AP2/ERF, ARF, WRKY, ZnF, MADS-box, NAC, AS2, DOF, E2F, ARR-B, and HSF. However, the highly tolerant genotypes interestingly possess binding sites associated with HY5 (bZIP), GBF3, GBF4 and GBF5 (bZIP), DPBF-3 (bZIP), ABF2, ABI5, bHLH, and BES/BZR, in addition to the common TFs. Besides, the extremely tolerant genotypes possess binding sites associated with bHLH TFs such as BEE2, BIM1, BIM3, BM8 and BAM8, and ABF1, in addition to the TFs identified in the tolerant and highly tolerant genotypes. The transcriptional regulation of these TFs could be linked to phenotypic variation in coleoptile elongation in response to submergence tolerance. Moreover, the results indicate a cross-talk between the key TFs and phytohormones such as gibberellic acid, abscisic acid, ethylene, auxin, jasmonic acid, and brassinosteroids, for an altered transcriptional regulation leading to differences in germination and coleoptile elongation under submergence. The information derived from the currentin silicoanalysis can potentially assist in developing new rice breeding targets for direct seeding.
A Real-Time PCR Assay for the Diagnosis of Intestinal Schistosomiasis and Cure Assessment After the Treatment of Individuals With Low Parasite Burden
Authors: Siqueira Liliane Maria Vidal , Senra Carolina , de Oliveira Áureo Almeida , Carneiro Nidia Francisca de Figueiredo , Gomes Luciana Inácia , Rabello Ana , Coelho Paulo Marcos Zech , Oliveira Edward
Published: March 2021

The laboratorial diagnosis of the intestinal schistosomiasis is always performed using Kato-Katz technique. However, this technique presents low sensitivity for diagnosis of individuals with low parasite burden, which constitutes the majority in low endemicity Brazilian locations for the disease. The objective of this study was developed and to validate a real-time PCR assay (qPCR) targeting 121 bp sequence to detect Schistosoma spp. DNA for the diagnosis of intestinal schistosomiasis and a sequence of the human β-actin gene as internal control. Firstly, the qPCR was standardized and next it was evaluated for diagnosis and cure assessment of intestinal schistosomiasis in the resident individuals in Tabuas and Estreito de Miralta, two locations in Brazil endemic for intestinal schistosomiasis. The qPCR assay results were compared with those of the Kato-Katz (KK) test, examining 2 or 24 slides, Saline Gradient (SG) and “reference test” (24 KK slides + SG). The cure assessment was measured by these diagnostic techniques at 30, 90, and 180 days post-treatment. In Tabuas, the positivity rates obtained by the qPCR was 30.4% (45/148) and by “reference test” was of 31.0% (46/148), with no statistical difference (p = 0.91). The presumed cure rates at 30, 90, and 180 days post-treatment were 100, 94.4, and 78.4% by the analysis of 24 KK slides, 100, 94.4, and 78.4% by the SG, and 100, 83.3, and 62.1% by the qPCR assay. In Estreito de Miralta, the positivity obtained by qPCR was 18.3% (26/142) and with “reference test” was 24.6% (35/142), with no statistical difference (p = 0.20). The presumed cure rates were 93.3, 96.9, and 96.5% by the KK, 93.3, 96.9, and 100% by the SG, and 93.3, 93.9, and 96.5% by the qPCR at 30, 90, and 180 days post-treatment, respectively. This study showed that the diagnostic techniques presented different performance in the populations from the two districts (Tabuas and Estreito de Miralta) and reinforces the need of combining techniques to improve diagnosis accuracy, increasing the detection of individuals with low parasite burden. This combination of techniques consists an important strategy for controlling the disease transmission.
The Hygiene Hypothesis – Learning From but Not Living in the Past
Authors: Pfefferle Petra I. , Keber Corinna U. , Cohen Robert M. , Garn Holger
Published: March 2021

Postulated by Strachan more than 30 years ago, the Hygiene Hypothesis has undergone many revisions and adaptations. This review journeys back to the beginnings of the Hygiene Hypothesis and describes the most important landmarks in its development considering the many aspects that have refined and generalized the Hygiene Hypothesis over time. From an epidemiological perspective, the Hygiene Hypothesis advanced to a comprehensive concept expanding beyond the initial focus on allergies. The Hygiene Hypothesis comprise immunological, microbiological and evolutionary aspects. Thus, the original postulate developed into a holistic model that explains the impact of post-modern life-style on humans, who initially evolved in close proximity to a more natural environment. Focusing on diet and the microbiome as the most prominent exogenous influences we describe these discrepancies and the resulting health outcomes and point to potential solutions to reestablish the immunological homeostasis that frequently have been lost in people living in developed societies.
Male Sex Bias in Immune Biomarkers for Tuberculosis
Authors: Bothamley Graham H.
Published: March 2021

Males have a bias toward developing sputum smear-positive pulmonary tuberculosis, whereas other forms of the disease have an equal sex ratio. Immune responses are known to be affected by estrogen and testosterone. Biomarkers may therefore be affected by these hormones, especially between 16 and 45 years of age when the differences are most marked. Using large data sets, we examined whether the male bias was significant in terms of diagnosis or predictive ability for the development of disease in those exposed to tuberculosis. Despite the large numbers, the need to specify homogeneous population groups for analysis affected the statistical power to discount a useful biomarker. In general, males showed higher interferon-gamma responses to TB antigens ESAT-6 and CFP-10, whilst females had stronger tuberculin responses in those with sputum smear- and culture-positive tuberculosis, but smaller responses in those who were screened for tuberculosis and who did not develop disease. Importantly, in contacts of sputum smear-positive pulmonary tuberculosis, more males who did not develop tuberculosis had tuberculin skin tests in the range between 10 and 14 mm, suggesting that sex-specific cut-offs might be better than general cut-off values for determining who should receive preventive treatment. Immunocytochemistry of the tuberculin responses correlated with cell numbers only in females. Total and anti-lipoarabinomannan IgM antibody levels were lower in males, whereas total and anti-BCG IgE antibody levels were higher. Evaluation of biomarkers should take account of the spectrum of tuberculosis and male sex bias for sputum smear-positive pulmonary tuberculosis. These findings improve our understanding of how immune responses contribute to the pathogenesis of infectious tuberculosis as well as suggesting clinical applications of the differences between the sexes.
Inflammasome-Dependent Coagulation Activation in Sepsis
Authors: Wu Runliu , Wang Nian , Comish Paul B. , Tang Daolin , Kang Rui
Published: March 2021

Sepsis is a potentially life-threatening, pathological condition caused by a dysregulated host response to infection. Pathologically, systemic inflammation can initiate coagulation activation, leading to organ dysfunction, and ultimately to multiple organ failure and septic death. The inflammasomes are cytosolic multiprotein signaling complexes that control the host response to diverse pathogen-associated molecular patterns (PAMPs) from microorganisms as well as damage-associated molecular patterns (DAMPs) from dead or dying host cells. Recent studies highlight that the activation of canonical and non-canonical inflammasomes not only mediate the maturation and secretion of interleukin-1 (IL1) family cytokines, but also trigger the release of coagulation factor III, tissue factor (F3, best known as TF) in activated macrophages and monocytes. These emerging functions of inflammasomes in immunocoagulation are further positively regulated by stimulator of interferon response cGAMP interactor 1 (STING1, also known as STING or TMEM173, a hub of the innate immune signaling network) and high mobility group box 1 (HMGB1, a nuclear DAMP). This mini-review will discuss the regulation and function of inflammasome-dependent coagulation activation in sepsis.
Activation of Neutrophil Granulocytes by Platelet-Activating Factor Is Impaired During Experimental Sepsis
Authors: Hug Stefan , Bernhard Stefan , Stratmann Alexander Elias Paul , Erber Maike , Wohlgemuth Lisa , Knapp Christiane Leonie , Bauer Jonas Martin , Vidoni Laura , Fauler Michael , Föhr Karl Josef , Radermacher Peter , Hoffmann Andrea , Huber-Lang Markus , Messerer David Alexander Christian
Published: March 2021

Platelet-activating factor (PAF) is an important mediator of the systemic inflammatory response. In the case of sepsis, proper activation and function of neutrophils as the first line of cellular defense are based on a well-balanced physiological response. However, little is known about the role of PAF in cellular changes of neutrophils during sepsis. Therefore, this study investigates the reaction patterns of neutrophils induced by PAF with a focus on membrane potential (MP), intracellular pH, and cellular swelling under physiological and pathophysiological conditions and hypothesizes that the PAF-mediated response of granulocytes is altered during sepsis. The cellular response of granulocytes including MP, intracellular pH, cellular swelling, and other activation markers were analyzed by multiparametric flow cytometry. In addition, the chemotactic activity and the formation of platelet–neutrophil complexes after exposure to PAF were investigated. The changes of the (electro-)physiological response features were translationally verified in a humanex vivowhole blood model of endotoxemia as well as during polymicrobial porcine sepsis. In neutrophils from healthy human donors, PAF elicited a rapid depolarization, an intracellular alkalization, and an increase in cell size in a time- and dose-dependent manner. Mechanistically, the alkalization was dependent on sodium-proton exchanger 1 (NHE1) activity, while the change in cellular shape was sodium flux- but only partially NHE1-dependent. In a pathophysiological altered environment, the PAF-induced response of neutrophils was modulated. Acidifying the extracellular pHin vitroenhanced PAF-mediated depolarization, whereas the increases in cell size and intracellular pH were largely unaffected.Ex vivoexposure of human whole blood to lipopolysaccharide diminished the PAF-induced intracellular alkalization and the change in neutrophil size. During experimental porcine sepsis, depolarization of the MP was significantly impaired. Additionally, there was a trend for increased cellular swelling, whereas intracellular alkalization remained stable. Overall, an impaired (electro-)physiological response of neutrophils to PAF stimulation represents a cellular hallmark of those cells challenged during systemic inflammation. Furthermore, this altered response may be indicative of and causative for the development of neutrophil dysfunction during sepsis.
Monomeric C-Reactive Protein Localized in the Cerebral Tissue of Damaged Vascular Brain Regions Is Associated With Neuro-Inflammation and Neurodegeneration-An Immunohistochemical Study
Authors: Al-Baradie Raid S. , Pu Shuang , Liu Donghui , Zeinolabediny Yasmin , Ferris Glenn , Sanfeli Coral , Corpas Ruben , Garcia-Lara Elisa , Alsagaby Suliman A. , Alshehri Bader M. , Abdel-hadi Ahmed M. , Ahmad Fuzail , Moatari Psalm , Heidari Nima , Slevin Mark
Published: March 2021

Monomeric C-reactive protein (mCRP) is now accepted as having a key role in modulating inflammation and in particular, has been strongly associated with atherosclerotic arterial plaque progression and instability and neuroinflammation after stroke where a build-up of the mCRP protein within the brain parenchyma appears to be connected to vascular damage, neurodegenerative pathophysiology and possibly Alzheimer's Disease (AD) and dementia. Here, using immunohistochemical analysis, we wanted to confirm mCRP localization and overall distribution within a cohort of AD patients showing evidence of previous infarction and then focus on its co-localization with inflammatory active regions in order to provide further evidence of its functional and direct impact. We showed that mCRP was particularly seen in large amounts within brain vessels of all sizes and that the immediate micro-environment surrounding these had become laden with mCRP positive cells and extra cellular matrix. This suggested possible leakage and transport into the local tissue. The mCRP-positive regions were almost always associated with neurodegenerative, damaged tissue as hallmarked by co-positivity with pTau and β-amyloid staining. Where this occurred, cells with the morphology of neurons, macrophages and glia, as well as smaller microvessels became mCRP-positive in regions staining for the inflammatory markers CD68 (macrophage), interleukin-1 beta (IL-1β) and nuclear factor kappa B (NFκB), showing evidence of a perpetuation of inflammation. Positive staining for mCRP was seen even in distant hypothalamic regions. In conclusion, brain injury or inflammatory neurodegenerative processes are strongly associated with mCRP localization within the tissue and given our knowledge of its biological properties, it is likely that this protein plays a direct role in promoting tissue damage and supporting progression of AD after injury.