bluuebunny/crossref_metadata_2025 huggingface dataset:
Halobacterium salinarum and Haloferax volcanii Comparative Transcriptomics Reveals Conserved Transcriptional Processing Sites
Authors: Ibrahim Amr Galal Abd El-Raheem , Vêncio Ricardo Z. N. , Lorenzetti Alan P. R. , Koide Tie
Published: June 2021

Post-transcriptional processing of messenger RNA is an important regulatory strategy that allows relatively fast responses to changes in environmental conditions. In halophile systems biology, the protein perspective of this problem (i.e., ribonucleases which implement the cleavages) is generally more studied than the RNA perspective (i.e., processing sites). In the present in silico work, we mapped genome-wide transcriptional processing sites (TPS) in two halophilic model organisms, Halobacterium salinarum NRC-1 and Haloferax volcanii DS2. TPS were established by reanalysis of publicly available differential RNA-seq (dRNA-seq) data, searching for non-primary (monophosphorylated RNAs) enrichment. We found 2093 TPS in 43% of H. salinarum genes and 3515 TPS in 49% of H. volcanii chromosomal genes. Of the 244 conserved TPS sites found, the majority were located around start and stop codons of orthologous genes. Specific genes are highlighted when discussing antisense, ribosome and insertion sequence associated TPS. Examples include the cell division gene ftsZ2, whose differential processing signal along growth was detected and correlated with post-transcriptional regulation, and biogenesis of sense overlapping transcripts associated with IS200/IS605. We hereby present the comparative, transcriptomics-based processing site maps with a companion browsing interface.
Mechanical Influence of Inherited Folds in Thrust Development: A Case Study from the Variscan Fold-and-Thrust Belt in SW Sardinia (Italy)
Authors: Cocco Fabrizio , Funedda Antonio
Published: June 2021

Fold-and-thrust belts have a high variability of structural styles, whose investigation provides continuous updates of the predictive models that try to better approximate the geometries recognized in the field. The majority of studies are focused on the geometry and development of folds and thrust surfaces and the amount of displacement, taking into account the role played by the involved stratigraphic succession assumed as a layer cake. We present a case study from the external zone of the Variscan fold-and-thrust belt in SW Sardinia, where it was possible to investigate the lateral and vertical variations of the mechanical properties of the involved succession, how they related to previous folding, control thrust geometry, and kinematics. In this case, the superposition of two fold systems acted as a buttress that induced extensive back-thrusting. We found that there is a close connection between the attitude of the bedding and the geometry of back thrust surfaces, shear strength during thrust propagation, and variation in the shortening amount, depending on which part of the folds were cut across. The folding-related mechanical anisotropy also seems to have induced a ductile deformation in the footwall of back-thrusts. Although the case study considers the development of back-thrust, the relations between thrust and not-layer cake geometries could also be applied to fore-thrust development.
Study of Organic Matter of Unconventional Reservoirs by IR Spectroscopy and IR Microscopy
Authors: Tanykova Natalya , Petrova Yuliya , Kostina Julia , Kozlova Elena , Leushina Evgenia , Spasennykh Mikhail
Published: June 2021

The study of organic matter content and composition in source rocks using the methods of organic geochemistry is an important part of unconventional reservoir characterization. The aim of this work was the structural group analysis of organic matter directly in the source rock in combination with a quantitative assessment and surface distribution analysis of the rock sample by FTIR spectroscopy and FTIR microscopy. We have developed new experimental procedures for semi-quantitative assessment of the organic matter content, composition and distribution in the source rocks and applied these procedures for the study of the samples from the Bazhenov shale formation (West Siberia, Russia). The results have been verified using the data from the study of organic matter obtained by Rock-Eval pyrolysis and differential thermal analysis. The obtained results demonstrate the prospects of FTIR spectroscopy and FTIR microscopy application for non-destructive and express analysis of the chemical structure and distribution of organic matter in rocks.
Proof of Concept of Novel Visuo-Spatial-Motor Fall Prevention Training for Old People
Authors: Koppelaar Henk , Kordestani-Moghadam Parastou , Kouhkani Sareh , Irandoust Farnoosh , Segers Gijs , de Haas Lonneke , Bantje Thijmen , van Warmerdam Martin
Published: June 2021

Falls in the geriatric population are one of the most important causes of disabilities in this age group. Its consequences impose a great deal of economic burden on health and insurance systems. This study was conducted by a multidisciplinary team with the aim of evaluating the effect of visuo-spatial-motor training for the prevention of falls in older adults. The subjects consisted of 31 volunteers aged 60 to 92 years who were studied in three groups: (1) A group under standard physical training, (2) a group under visuo-spatial-motor interventions, and (3) a control group (without any intervention). The results of the study showed that visual-spatial motor exercises significantly reduced the risk of falls of the subjects.
Running Pace Percentile Values for Brazilian Non-Professional Road Runners
Authors: Thuany Mabliny , Knechtle Beat , Hill Lee , Rosemann Thomas , Gomes Thayse Natacha
Published: June 2021

Background: The purpose of this study was to establish sex-specific percentile curves and values for the running pace of Brazilian non-professional runners. Methods: The sample comprised 1152 amateur runners aged 18–72 (61.8% males), from the five Brazilian regions. The runners answered an online questionnaire providing information about their biological (sex, age, height, weight) and training (volume and frequency/week, running pace) characteristics. Using 25th, 50th, and 75th percentile, the running pace was computed for women and men by age groups and by running distances (5 km, 10 km, 21 km, and 42 km). Sex- and age-specific percentile curves (10th, 25th, 50th, 75th, and 90th) were created through the Lambda Mu Sigma method. Results: For all ages and distance, men performed better than women, and a decrease in the performance was observed across age groups. Among male runners, the beginning of their thirties and the end of their forties seem to be the moments where they observed substantial improvements in running pace; among female runners, this improvement phase was observed to be more pronounced toward the end of their forties. Conclusions: Percentile values of running pace could help coaches during training programs and runners to better understand “how well” they are comparing against their peers.
Habitability, Resilience, and Satisfaction in Mexican Homes to COVID-19 Pandemic
Authors: Jaimes Torres Maribel , Aguilera Portillo Mónica , Cuerdo-Vilches Teresa , Oteiza Ignacio , Navas-Martín Miguel Ángel
Published: June 2021

Following the 2020 confinement due to the COVID-19 pandemic, housing has become the only safe place and this has exposed inequity in habitability. This research on the reality of confined households and the perception of their homes in the Mexican republic is based on a mixed participatory study, combining quantitative and qualitative approaches. The online questionnaire consisted of 58 questions in the quantitative approximation. The qualitative part required the provision of an image of the workspace, with testimonies and personal reflections. During the lockdown, all participants saw an increase in overall energy consumption; more than half reported not being in thermal comfort; and a third declared deficiencies in noise insulation. Regarding the perception of the telework/tele-study space, we found the following categories: bedrooms, living/dining rooms, studies and others. In addition, respondents had often adapted the workspace for both individual and shared use. In general, the households were satisfied with the size of their houses but would like landscaped spaces or better views outside. Confinement made housing the protective element against the pandemic. The consequences will have an effect globally, so new architectural design paradigms need to be rethought.
Assessment of Maximal Aerobic Capacity in Ski Mountaineering: A Laboratory-Based Study
Authors: Menz Verena , Niedermeier Martin , Stehle Rainer , Mugele Hendrik , Faulhaber Martin
Published: June 2021

This study aims to evaluate the agreement in maximum oxygen consumption (V˙O2max) between a running protocol and a ski mountaineering (SKIMO) protocol. Eighteen (eleven males, seven females) ski mountaineers (age: 25 ± 3 years) participated in the study. V˙O2max, maximum heart rate (HRmax), and maximum blood lactate concentration (BLAmax) were determined in an incremental uphill running test and an incremental SKIMO-equipment-specific test. V˙O2max did not differ between the SKIMO and uphill running protocols (p = 0.927; mean difference –0.07 ± 3.3 mL/min/kg), nor did HRmax (p = 0.587, mean difference –0.7 ± 5.1 bpm). A significant correlation was found between V˙O2max SKIMO and V˙O2max running (p ≤ 0.001; ICC = 0.862 (95% CI: 0.670−0.946)). The coefficient of variation was 4.4% (95% CI: 3.3−6.5). BLAmax was significantly lower for SKIMO compared to running (12.0 ± 14.1%; p = 0.002). This study demonstrates that V˙O2max determined with a traditional uphill running protocol demonstrates good agreement with an equipment-specific SKIMO protocol.
LGB Tobacco Control: Do Health Belief Model Constructs Predict Tobacco Use Intentions Differently between LGB and Heterosexual Individuals?
Authors: Li Yachao , Yang Bo , Chen Bryan
Published: June 2021

This research includes two studies testing whether the Health Belief Model (HBM) constructs predict tobacco use intentions differently between heterosexual and lesbian, gay, and bisexual (LGB) people. Focusing on cigarette smoking, Study 1 (n = 1808 U.S. adult current smokers) found that the perceived health threat and perceived benefits of smoking differently predicted intentions to continue smoking between heterosexual and LGB smokers. The perceived health threat of smoking had a weaker negative relationship and perceived benefits of smoking had a stronger positive relationship with smoking intentions among LGB smokers than heterosexual smokers. Focusing on vaping, Study 2 (n = 2801 U.S. adults) found that the perceived health threat and perceived barriers of vaping differentially predicted vaping intentions between heterosexual and LGB individuals. The perceived health threat of vaping only negatively predicted vaping intentions among heterosexual people. Perceived barriers to vaping had a stronger negative relationship with intentions to vape among LGB people than among heterosexual people. Our finding suggests that compared to perceptions of tobacco-related health consequences (perceived heath threat), behavioral perceptions (perceived benefits and barriers) may have stronger impacts on tobacco use intentions among LGB people. Thus, efforts focusing on reducing tobacco-related disparities among the LGB community should address perceived benefits and barriers of tobacco use.
How Do Failed Entrepreneurs Cope with Their Prior Failure When They Seek Subsequent Re-Entry into Serial Entrepreneurship? Failed Entrepreneurs’ Optimism and Defensive Pessimism and Coping Humor as a Moderator
Authors: Hwang Kumju , Choi Jinsook
Published: June 2021

Entrepreneurial failure is prevalent, and particularly when the COVID−19 crisis exacerbates the economic recession, it becomes even more prevalent. Entrepreneurs experience an intensive emotional crisis when their ventures fail, and this deleterious impact, including stress and emotional pain, may prevent failed entrepreneurs (FEs) from restarting; hence, how they cope with failure has received increased attention in recent years. However, most of the extant literature focuses on success rather than failure, and there is very limited literature on how FEs cope with the psychological and emotional crisis caused by failure. This study focuses on FEs’ use of optimism and defensive pessimism as coping strategies within the mental simulation theory with respect to their re-entry intentions. It examines the impact of career ambition and public self-awareness on optimism, of the fear of failure (FoF) and self-doubt, on defensive pessimism, and of coping humor as a moderator. We used structural equation modeling to analyze the data of 277 Korean FEs who have actual entrepreneurial failure experiences and actively prepared for their re-entry. The results show that career ambitions and public self-awareness have an impact on optimism, and FoF and self-doubt lead to defensive pessimism. Coping humor also has a moderating effect on the path from defensive pessimism to the intention to re-enter. This study advances the literature on coping mechanisms that FEs employ to manage the negative impact of failure and prepare for their subsequent re-entry. Its theoretical model, based on the mental simulation theory combined with social comparison theory, provides a possible integrative framework that includes both the pervasively held view of entrepreneurs’ optimism related to overconfidence and their defensive pessimism related to their vulnerability due to their ventures’ failure. Thus, this study makes theoretical contributions to the literature of entrepreneurial failure, as well as practical implications for policymakers and educators who assist FEs in successfully coping with entrepreneurial failure and re-entry.
A Cost-Benefit Analysis of the COVID-19 Asymptomatic Mass Testing Strategy in the North Metropolitan Area of Barcelona
Authors: López Seguí Francesc , Estrada Cuxart Oriol , Mitjà i Villar Oriol , Hernández Guillamet Guillem , Prat Gil Núria , Maria Bonet Josep , Isnard Blanchar Mar , Moreno Millan Nemesio , Blanco Ignacio , Vilar Capella Marc , Català Sabaté Martí , Aran Solé Anna , Argimon Pallàs Josep Maria , Clotet Bonaventura , Ara del Rey Jordi
Published: June 2021

Background: The epidemiological situation generated by COVID-19 has highlighted the importance of applying non-pharmacological measures in the management of the epidemic. Mass screening of the asymptomatic general population has been established as a priority strategy by carrying out diagnostic tests to detect possible cases, isolate contacts, cut transmission chains and thus limit the spread of the virus. Objective: To evaluate the economic impact of mass COVID-19 screenings of an asymptomatic population during the first and second wave of the epidemic in Catalonia, Spain. Methodology: Cost-Benefit Analysis based on the estimated total costs of mass screening versus health gains and associated health costs avoided. Results: Excluding the value of monetized health, the Benefit-Cost ratio was estimated at 0.45, a low value that would seem to advise against mass screening policies. However, if monetized health is included, the ratio is close to 1.20, reversing the interpretation. In other words, the monetization of health is the critical element that tips the scales in favour of the desirability of screening. Results show that the interventions with the highest return are those that maximize the percentage of positives detected. Conclusion: Efficient management of resources for the policy of mass screening in asymptomatic populations can generate high social returns. The positivity rate critically determines its desirability. Likewise, precocity in the detection of cases will cut more transmissions in the chain of contagion and increase the economic return of these interventions. Maximizing the value of resources depends on screening strategies being accompanied by contact-tracing and specific in their focus, targeting, for example, high-risk subpopulations with the highest rate of expected positives.
Adipose-Derived Stem Cells and Their Derived Microvesicles Ameliorate Detrusor Overactivity Secondary to Bilateral Partial Iliac Arterial Occlusion-Induced Bladder Ischemia
Authors: Chiang Bing-Juin , Liao Chun-Hou , Mao Su-Han , Chien Chiang-Ting
Published: June 2021

(1) Background: We established a new bladder ischemia rat model through bilateral partial iliac arterial occlusion (BPAO) and investigated the therapeutic effect of adipose-derived stem cells (ADSCs) and ADSC-derived microvesicles (MVs); (2) Methods: The study included four groups: (1) sham, (2) BPAO, (3) BPAO + ADSCs, and (4) BPAO + ADSC-derived MVs. Female Wistar rats with BPAO were injected with ADSCs or ADSC-derived MVs through the femoral artery. Doppler flowmetry and real-time laser speckle contrast imaging were performed to quantify blood flow in the common iliac arteries and bladder microcirculation. A 24-h behavior study and transcystometrogram were conducted after 2 weeks. Bladder histology, immunostaining, and lipid peroxidation assay were performed. The expressions of P2X2, P2X3, M2, and M3 receptors and nerve growth factor (NGF) were evaluated; (3) Results: BPAO significantly reduced bladder microcirculation, intercontraction interval (ICI), and bladder volume and increased the amplitude of nonvoiding contraction, neutrophil infiltration, and malondialdehyde and NGF levels. ADSCs and ADSC-derived MVs significantly ameliorated these effects. The results of Western blot showed that the BPAO group exhibited the highest expression of M3 and P2X2 receptors. ADSCs significantly attenuated the expressions of M2 and P2X2 receptors. ADSC-derived MVs significantly attenuated the expressions of M3 and P2X2 receptors; (4) Conclusions: ADSCs and ADSC-derived MVs ameliorated the adverse effects of BPAO including bladder overactivity, bladder ischemia, and oxidative stress. Inflammation, muscarinic signaling, purinergic signaling, and NGF might be involved in the therapeutic mechanism.
Clinicopathologic and Prognostic Association of GRP94 Expression in Colorectal Cancer with Synchronous and Metachronous Metastases
Authors: Yun Sumi , Lee Sukmook , Lee Ho-Young , Oh Hyeon Jeong , Kwak Yoonjin , Lee Hye Seung
Published: June 2021

Patients with advanced colorectal cancer (CRC) with distant metastases have a poor prognosis. We evaluated the clinicopathological relevance of GRP94 expression in these cases. The immunohistochemical expression of GRP94 was studied in 189 CRC patients with synchronous (SM; n = 123) and metachronous metastases (MM; n = 66), using tissue microarray; the association between GRP94 expression, outcome, and tumor-infiltrating lymphocytes (TILs) was also evaluated. GRP94 was expressed in 64.6% (122/189) patients with CRC; GRP94 positivity was found in 67.5% and 59.1% patients with SM and MM, respectively. In the SM group, high GRP94 expression was more common in patients with a higher density of CD4+ TILs (p = 0.002), unlike in the MM group. Survival analysis showed that patients with GRP94 positivity had significantly favorable survival (p = 0.030); after multivariate analysis, GRP94 only served as an independent prognostic factor (p = 0.034; hazard ratio, 0.581; 95% confidence interval, 0.351–0.961) in the SM group. GRP94 expression was detected in 49.4% of metastatic sites and showed significant heterogeneity between primary and metastatic lesions (p = 0.012). GRP94 is widely expressed in CRC with distant metastases; its expression was associated with favorable prognosis in the SM group, unlike in the MM group.
Characterization of Glycosphingolipids in the Human Parathyroid and Thyroid Glands
Authors: Säljö Karin , Thornell Anders , Jin Chunsheng , Stålberg Peter , Norlén Olov , Teneberg Susann
Published: June 2021

As part of a systematic investigation of the glycosphingolipids in human tissues, acid and non-acid glycosphingolipids from human thyroid and parathyroid glands were isolated and characterized with mass spectrometry and binding of carbohydrate-recognizing ligands, with a focus on complex compounds. The glycosphingolipid patterns of the human parathyroid and thyroid glands were very similar. The major acid glycosphingolipids were sulfatide and the gangliosides GM3, GD3, GD1a, GD1b, GT1b and Neu5Ac-neolactotetraosylceramide, and the major non-acid glycosphingolipids were globotriaosylceramide and globoside. We also found neolactotetra- and neolactohexaosylceramide, the x2 glycosphingolipid, and complex glycosphingolipids with terminal blood group O and A determinants in both tissues. A glycosphingolipid with blood group Leb determinant was identified in the thyroid gland, and the parathyroid sample had a glycosphingolipid with terminal blood group B determinant. Immunohistochemistry demonstrated the expression of blood group A antigens in both the thyroid and parathyroid glands. A weak cytoplasmatic expression of the GD1a ganglioside was present in the thyroid, while the parathyroid gland had a strong GD1a expression on the cell surface. Thus, the glycosylation of human thyroid and parathyroid glands is more complex than previously appreciated. Our findings provide a platform for further studies of alterations of cell surface glycosphingolipids in thyroid and parathyroid cancers.
Myeloid-Derived Suppressor Cells Gain Suppressive Function during Neonatal Bacterial Sepsis
Authors: Vance Jordan K. , Rawson Travis W. , Povroznik Jessica M. , Brundage Kathleen M. , Robinson Cory M.
Published: June 2021

Neonates are at an increased risk of an infectious disease. This is consistent with an increased abundance of myeloid-derived suppressor cells (MDSCs) compared with older children and adults. Using a murine model of neonatal bacterial sepsis, we demonstrate that MDSCs modulate their activity during an infection to enhance immune suppressive functions. A gene expression analysis shows that MDSCs increased NOS2, Arg-1 and IL-27p28 expression in vitro and in vivo in response to Escherichia coli O1:K1:H7 and this is regulated at the level of the gene expression. Changes in the effector gene expression are consistent with increased enzymatic activity and cytokine secretion. The neonatal MDSCs express toll-like receptor (TLR) 2, 4 and 5 capable of recognizing pathogen-associated molecular patterns (PAMPS) on E. coli. However, a variable level of effector expression was achieved in response to LPS, peptidoglycan or flagellin. Individual bacterial PAMPs did not stimulate the expression of Arg-l and IL-27p28 equivalently to E. coli. However, the upregulation of NOS2 was achieved in response to LPS, peptidoglycan and flagella. The increased immune suppressive profile translated to an enhanced suppression of CD4+ T cell proliferation. Collectively, these findings increase our understanding of the dynamic nature of MDSC activity and suggest that these cells abundant in early life can acquire activity during an infection that suppresses protective immunity.
Seleno-Functionalization of Quercetin Improves the Non-Covalent Inhibition of Mpro and Its Antiviral Activity in Cells against SARS-CoV-2
Authors: Mangiavacchi Francesca , Botwina Pawel , Menichetti Elena , Bagnoli Luana , Rosati Ornelio , Marini Francesca , Fonseca Sérgio F. , Abenante Laura , Alves Diego , Dabrowska Agnieszka , Kula-Pacurar Anna , Ortega-Alarcon David , Jimenez-Alesanco Ana , Ceballos-Laita Laura , Vega Sonia , Rizzuti Bruno , Abian Olga , Lenardão Eder J. , Velazquez-Campoy Adrian , Pyrc Krzysztof , Sancineto Luca , Santi Claudio
Published: June 2021

The development of new antiviral drugs against SARS-CoV-2 is a valuable long-term strategy to protect the global population from the COVID-19 pandemic complementary to the vaccination. Considering this, the viral main protease (Mpro) is among the most promising molecular targets in light of its importance during the viral replication cycle. The natural flavonoid quercetin 1 has been recently reported to be a potent Mpro inhibitor in vitro, and we explored the effect produced by the introduction of organoselenium functionalities in this scaffold. In particular, we report here a new synthetic method to prepare previously inaccessible C-8 seleno-quercetin derivatives. By screening a small library of flavonols and flavone derivatives, we observed that some compounds inhibit the protease activity in vitro. For the first time, we demonstrate that quercetin (1) and 8-(p-tolylselenyl)quercetin (2d) block SARS-CoV-2 replication in infected cells at non-toxic concentrations, with an IC50 of 192 μM and 8 μM, respectively. Based on docking experiments driven by experimental evidence, we propose a non-covalent mechanism for Mpro inhibition in which a hydrogen bond between the selenium atom and Gln189 residue in the catalytic pocket could explain the higher Mpro activity of 2d and, as a result, its better antiviral profile.
Differences in the Relative Abundance of ProBDNF and Mature BDNF in A549 and H1299 Human Lung Cancer Cell Media
Authors: Dorandish Sadaf , Atali Sarah , Ray Ravel , Al Khashali Hind , Coleman Kai-Ling , Guthrie Jeffrey , Heyl Deborah , Evans Hedeel Guy
Published: June 2021

Brain-derived neurotrophic factor (BDNF), a member of the neurotrophin family, has been linked to several human malignancies and shown to promote tumorigenesis. The purpose of this study was to explore the relative abundance of pro-brain-derived neurotrophic factor (proBDNF) and mature BDNF (mBDNF) in A549 (p53 wild-type) and H1299 (p53-null) lung cancer cell media. Higher levels of proBDNF were detected in the media of A549 cells than in H1299 cell media. Using inhibitors, we found that the levels of proBDNF and mBDNF in the media are likely regulated by PI3K, AKT, and NFκB. However, the largest change in these levels resulted from MMP2/9 inhibition. Blocking p53 function in A549 cells resulted in increased mBDNF and decreased proBDNF, suggesting a role for p53 in regulating these levels. The ratio of proBDNF/mBDNF was not affected by MMP2 knockdown but increased in the media of both cell lines upon knockdown of MMP9. Downregulation of either MMP2 or MMP9 by siRNA showed that MMP9 siRNA treatment of either A549 or H1299 cells resulted in decreased cell viability and increased apoptosis, an effect diminished upon the same treatment with proBDNF immunodepleted media, suggesting that MMP9 regulates the cytotoxic effects induced by proBDNF in lung cancer cells.
Identification of 13 Guanidinobenzoyl- or Aminidinobenzoyl-Containing Drugs to Potentially Inhibit TMPRSS2 for COVID-19 Treatment
Authors: Huang Xiaoqiang , Pearce Robin , Omenn Gilbert S. , Zhang Yang
Published: June 2021

Positively charged groups that mimic arginine or lysine in a natural substrate of trypsin are necessary for drugs to inhibit the trypsin-like serine protease TMPRSS2 that is involved in the viral entry and spread of coronaviruses, including SARS-CoV-2. Based on this assumption, we identified a set of 13 approved or clinically investigational drugs with positively charged guanidinobenzoyl and/or aminidinobenzoyl groups, including the experimentally verified TMPRSS2 inhibitors Camostat and Nafamostat. Molecular docking using the C-I-TASSER-predicted TMPRSS2 catalytic domain model suggested that the guanidinobenzoyl or aminidinobenzoyl group in all the drugs could form putative salt bridge interactions with the side-chain carboxyl group of Asp435 located in the S1 pocket of TMPRSS2. Molecular dynamics simulations further revealed the high stability of the putative salt bridge interactions over long-time (100 ns) simulations. The molecular mechanics/generalized Born surface area-binding free energy assessment and per-residue energy decomposition analysis also supported the strong binding interactions between TMPRSS2 and the proposed drugs. These results suggest that the proposed compounds, in addition to Camostat and Nafamostat, could be effective TMPRSS2 inhibitors for COVID-19 treatment by occupying the S1 pocket with the hallmark positively charged groups.
Anti-Inflammatory Therapy for Atherosclerosis: Focusing on Cytokines
Authors: Poznyak Anastasia V. , Bharadwaj Dwaipayan , Prasad Gauri , Grechko Andrey V. , Sazonova Margarita A. , Orekhov Alexander N.
Published: June 2021

Atherosclerosis is a well-known global health problem. Despite the high prevalence of the disease, numerous aspects of pathogenesis remain unclear. Subsequently, there are still no cure or adequate preventive measures available. Atherogenesis is now considered a complex interplay between lipid metabolism alterations, oxidative stress, and inflammation. Inflammation in atherogenesis involves cellular elements of both innate (such as macrophages and monocytes) and adaptive immunity (such as B-cells and T-cells), as well as various cytokines cascades. Because inflammation is, in general, a well-investigated therapeutic target, and strategies for controlling inflammation have been successfully used to combat a number of other diseases, inflammation seems to be the preferred target for the treatment of atherosclerosis as well. In this review, we summarized data on targeting the most studied inflammatory molecular targets, CRP, IL-1β, IL-6, IFN-γ, and TNF-α. Studies in animal models have shown the efficacy of anti-inflammatory therapy, while clinical studies revealed the incompetence of existing data, which blocks the development of an effective atheroprotective drug. However, all data on cytokine targeting give evidence that anti-inflammatory therapy can be a part of a complex treatment.
Complementary Contribution of Wild Bumblebees and Managed Honeybee to the Pollination Niche of an Introduced Blueberry Crop
Authors: Miñarro Marcos , García Daniel
Published: June 2021

The entomophilous pollination niche (abundance, phenotypic traits, foraging behaviours and environmental tolerances of insect pollinators) helps to understand and better manage crop pollination. We apply this niche approach to assess how an entomophilous crop (blueberry, Vaccinium ashei) can be expanded into new territories (i.e., northern Spain) far from their original area of domestication (North America). Insect visits to blueberry flowers were monitored in a plantation on 12 different days, at 8 different times during day and covering various weather conditions. Abundance, visitation rate, pollen gathering behaviour, and frequency of inter-plant and inter-row movements were recorded. The pollinator assemblage was basically composed of one managed honeybee species (50.8% of visits) and three native bumblebee species (48.3%). There was a marked pattern of seasonal segregation throughout bloom, with bumblebees dominating the early bloom and honeybee the late bloom. Pollinators also segregated along gradients of daily temperature and relative humidity. Finally, the two pollinator types differed in foraging behaviour, with bumblebees having a visitation rate double that of honeybee, collecting pollen more frequently and changing plant and row more frequently. The spatio-temporal and functional complementarity between honeybee and bumblebees suggested here encourages the consideration of an integrated crop pollination strategy for blueberries, based on the concurrence of both wild and managed bees.
A History of Heart Failure Is an Independent Risk Factor for Death in Patients Admitted with Coronavirus 19 Disease
Authors: Castagna Francesco , Kataria Rachna , Madan Shivank , Ali Syed Zain , Diab Karim , Leyton Christopher , Arfaras-Melainis Angelos , Kim Paul , Giorgi Federico M. , Vukelic Sasa , Saeed Omar , Patel Snehal R. , Sims Daniel B. , Jorde Ulrich P.
Published: June 2021

Aims: The association between cardiovascular diseases, such as coronary artery disease and hypertension, and worse outcomes in COVID-19 patients has been previously demonstrated. However, the effect of a prior diagnosis of heart failure (HF) with reduced or preserved left ventricular ejection fraction on COVID-19 outcomes has not yet been established. Methods and Results: We retrospectively studied all adult patients with COVID-19 admitted to our institution from March 1st to 2nd May 2020. Patients were grouped based on the presence or absence of HF. We used competing events survival models to examine the association between HF and death, need for intubation, or need for dialysis during hospitalization. Of 4043 patients admitted with COVID-19, 335 patients (8.3%) had a prior diagnosis of HF. Patients with HF were older, had lower body mass index, and a significantly higher burden of co-morbidities compared to patients without HF, yet the two groups presented to the hospital with similar clinical severity and similar markers of systemic inflammation. Patients with HF had a higher cumulative in-hospital mortality compared to patients without HF (49.0% vs. 27.2%, p < 0.001) that remained statistically significant (HR = 1.383, p = 0.001) after adjustment for age, body mass index, and comorbidities, as well as after propensity score matching (HR = 1.528, p = 0.001). Notably, no differences in mortality, need for mechanical ventilation, or renal replacement therapy were observed among HF patients with preserved or reduced ejection fraction. Conclusions: The presence of HF is a risk factor of death, substantially increasing in-hospital mortality in patients admitted with COVID-19.
Hepatitis B Virus Infection in Pregnancy: Immunological Response, Natural Course and Pregnancy Outcomes
Authors: Sirilert Sirinart , Tongsong Theera
Published: June 2021

This review aimed to provide an update on the impact of pregnancy on the natural course of hepatitis B virus (HBV) infection and also on the impact of HBV infection on adverse pregnancy outcomes, including mother-to-child transmission (MTCT). For the literature review, original research articles, review articles, and guidelines were narratively reviewed and comprehensively validated. The databases of PubMed, EMBASE, and CINAHL were carefully searched for articles in English on topics related to HBV infection, pregnancy, and vertical transmission from 1960 to May 2021. Immunological changes during pregnancy such as suppression of Th1 response and induction of Th2 immunity lead to an impaired immune reaction to HBV and stimulate viral activity along with the reduction of CD8 T cells to escape immune detection. The impact of pregnancy on the natural course of chronic HBV infection seems to be minimal, while pregnancy can increase morbidity and mortality in the case of advanced HBV hepatitis or cirrhosis. Importantly, hepatitis flare or alanine aminotransferase (ALT) flare can occur during pregnancy and is more common during the postpartum period due to the interaction between HBV and the immune response. Interestingly, the impact of HBV infection on adverse pregnancy outcomes is more serious than ever thought. Updated evidence indicates that pregnancies with chronic HBV infection increase the risk of preterm birth and gestational diabetes, especially in cases of positive hepatitis e antigen (HBeAg).
Management of Kidney Failure in Patients with Diabetes Mellitus: What Are the Best Options?
Authors: Buades Juan M. , Craver Lourdes , Del Pino Maria Dolores , Prieto-Velasco Mario , Ruiz Juan C. , Salgueira Mercedes , de Sequera Patricia , Vega Nicanor
Published: June 2021

Diabetic kidney disease (DKD) is the most frequent cause of kidney failure (KF). There are large variations in the incidence rates of kidney replacement therapy (KRT). Late referral to nephrology services has been associated with an increased risk of adverse outcomes. In many countries, when patients reach severely reduced glomerular filtration rate (GFR), they are managed by multidisciplinary teams led by nephrologists. In these clinics, efforts will continue to halt chronic kidney disease (CKD) progression and to prevent cardiovascular mortality and morbidity. In patients with diabetes and severely reduced GFR and KF, treating hyperglycemia is a challenge, since some drugs are contraindicated and most of them require dose adjustments. Even more, a decision-making process will help in deciding whether the patient would prefer comprehensive conservative care or KRT. On many occasions, this decision will be conditioned by diabetes mellitus itself. Effective education should cover the necessary information for the patient and family to answer these questions: 1. Should I go for KRT or not? 2. If the answer is KRT, dialysis and/or transplantation? 3. Dialysis at home or in center? 4. If dialysis at home, peritoneal dialysis or home hemodialysis? 5. If transplantation is desired, discuss the options of whether the donation would be from a living or deceased donor. This review addresses the determinant factors with an impact on DKD, aiming to shed light on the specific needs that arise in the management and recommendations on how to achieve a comprehensive approach to the diabetic patient with chronic kidney disease.
Maternal Systemic Lupus Erythematosus (SLE) High Risk for Preterm Delivery and Not for Long-Term Neurological Morbidity of the Offspring
Authors: Davidov Dora , Sheiner Eyal , Wainstock Tamar , Miodownik Shayna , Pariente Gali
Published: June 2021

Objective: Pregnancies of women with systemic lupus erythematosus (SLE) are associated with preterm delivery. As preterm delivery is associated with long-term neurological morbidity, we opted to evaluate the long-term neurologic outcomes of offspring born to mothers with SLE regardless of gestational age. Methods: Perinatal outcomes and long-term neurological disease of children of women with and without SLE during pregnancy were evaluated. Children of women with and without SLE were followed until 18 years of age for neurological diseases. Generalized estimating equation (GEE) models were used to assess perinatal outcomes. To compare cumulative neurological morbidity incidence a Kaplan–Meier survival curve was used, and a Cox proportional hazards model was used to control for confounders. Result: A total of 243,682 deliveries were included, of which 100 (0.041%) were of women with SLE. Using a GEE model, maternal SLE was noted as an independent risk factor for preterm delivery. The cumulative incidence of long-term neurological disease was not found to be significantly higher when using the Kaplan Meier survival curves and maternal SLE was not found to be associated with long-term neurological disease of the offspring when a Cox model was used. Conclusion: Despite the association of SLE with preterm delivery, no difference in long-term neurological disease was found among children of women with or without SLE.
Evaluating Impact Damage of Flat Composite Plate for Surrogate Bird-Strike Testing of Aeroengine Fan Blade
Authors: Sun Youchao , Zhang Yuemei , Zhou Yadong , Zhang Haitao , Zeng Haijun , Yang Kun
Published: June 2021

Bird-strike failure of fan blades is one of the basic challenges for the safety of aircraft engines. Simplified flat blade-like plates are always used for damage mechanism study of composite laminates. One undesirable issue is the failure at the root of clamped flat plates under high-velocity impact. For this purpose, two different strategies were exploited to obtain desirable impact damage distributions, namely the impact location and the boundary condition. Numerical models of the simplified flat blade-like plate and the bird projectile were constructed by using finite element method (FEM) and smoothed particle hydrodynamics (SPH) approaches. The impact damage distributions were comparatively investigated in detail. The numerical results show that changing the boundary condition is the most effective way to obtain preferable impact damages for further failure analysis of real fan blades. Present results will be useful to the future surrogate experimental design of simplified bird-strike testing.
Extreme Meteorological Events in a Coastal Lagoon Ecosystem: The Ria de Aveiro Lagoon (Portugal) Case Study
Authors: Lopes José Fortes , Lopes Carina Lurdes , Dias João Miguel
Published: June 2021

Extreme weather events (EWEs) represent meteorological hazards for coastal lagoon hydrodynamics, of which intensity and frequency are increasing over the last decades as a consequence of climate changes. The imbalances they generated should affect primarily vulnerable low-lying areas while potentially disturbing the physical balances (salt and water temperature) and, therefore, the ecosystem equilibrium. This study arises from the need to assess the impact of EWEs on the Ria de Aveiro, a lagoon situated in the Portuguese coastal area. Furthermore, it was considered that those events occur under the frame of a future sea-level rise, as predicted by several climate change scenarios. Two EWEs scenarios, a dry and an extremely wet early summer reflecting past situations and likely to occur in the future, were considered to assess the departure from the system baseline functioning. It was used as a biogeochemistry model that simulates the hydrodynamics, as well as the baseline physical and biogeochemistry state variables. The dry summer scenario, corresponding to a significant reduction in the river’s inflow, evidences a shift of the system to a situation under oceanic dominance characterized by colder and saltier water (~18 °C; 34 PSU) than the baseline while lowering the concentration of the nutrients and reducing the phytoplankton population to a low-level limit. Under a wet summer scenario, the lagoon shifted to a brackish and warmer situation (~21 °C, <15 PSU) in a time scale of some tidal periods, driven by the combining effect of the tidal transport and the river’s inflow. Phytoplankton patterns respond to variability on local and short-term scales that reflect physical conditions within the lagoon, inducing nutrient-supported growth. Overall, the results indicate that EWEs generate local and transient changes in physical conditions (namely salinity and water temperature) in response to the characteristic variability of the lagoon’s hydrodynamics associated with a tidal-dominated system. Therefore, in addition to the potential impact of changing physical conditions on the ecosystem, saline intrusion along the lagoon or the transfer of brackish water to the mouth of the system are the main consequences of EWEs, while the main biogeochemistry changes tend to remain moderate.
Role of RIM101 for Sporulation at Alkaline pH in Ashbya gossypii
Authors: Wasserstrom Lisa , Wendland Jürgen
Published: June 2021

Microorganisms need to sense and adapt to fluctuations in the environmental pH. In fungal species, this response is mediated by the conserved pacC/RIM101 pathway. In Aspergillus nidulans, PacC activates alkaline-expressed genes and represses acid-controlled genes in response to alkaline pH and has important functions in regulating growth and conidia formation. In Saccharomyces cerevisiae, the PacC homolog Rim101 is required for adaptation to extracellular pH and to regulate transcription of IME1, the Initiator of MEiosis. S. cerevisiae rim101 mutants are defective in sporulation. In Ashbya gossypii, a filamentous fungus belonging to the family of Saccharomycetaceae, little is known about the role of pH in regulating growth and sporulation. Here, we deleted the AgRIM101 homolog (AFR190C). Our analyses show that Rim101 is important for growth and essential for sporulation at alkaline pH in A. gossypii. Acidic liquid sporulation media were alkalinized by sporulating strains, while the high pH of alkaline media (starting pH = 8.6) was reduced to a pH ~ 7.5 by these strains. However, Agrim101 mutants were unable to sporulate in alkaline media and failed to reduce the initial high pH, while they were capable of sporulation in acidic liquid media in which they increased the pH like the wild type.
Cold Adaptation Strategies and the Potential of Psychrophilic Enzymes from the Antarctic Yeast, Glaciozyma antarctica PI12
Authors: Yusof Nur Athirah , Hashim Noor Haza Fazlin , Bharudin Izwan
Published: June 2021

Psychrophilic organisms possess several adaptive strategies which allow them to sustain life at low temperatures between −20 to 20 °C. Studies on Antarctic psychrophiles are interesting due to the multiple stressors that exist on the permanently cold continent. These organisms produce, among other peculiarities, cold-active enzymes which not only have tremendous biotechnological potential but are valuable models for fundamental research into protein structure and function. Recent innovations in omics technologies such as genomics, transcriptomics, proteomics and metabolomics have contributed a remarkable perspective of the molecular basis underpinning the mechanisms of cold adaptation. This review critically discusses similar and different strategies of cold adaptation in the obligate psychrophilic yeast, Glaciozyma antarctica PI12 at the molecular (genome structure, proteins and enzymes, gene expression) and physiological (antifreeze proteins, membrane fluidity, stress-related proteins) levels. Our extensive studies on G. antarctica have revealed significant insights towards the innate capacity of- and the adaptation strategies employed by this psychrophilic yeast for life in the persistent cold. Furthermore, several cold-active enzymes and proteins with biotechnological potential are also discussed.
Histoplasmosis in Children; HIV/AIDS Not a Major Driver
Authors: Ekeng Bassey E. , Edem Kevin , Amamilo Ikechukwu , Panos Zachary , Denning David W. , Oladele Rita O.
Published: June 2021

The classification of histoplasmosis as an AIDS-defining illness has largely attributed its occurrence in people to the presence of HIV/AIDS especially in Africa. Prior to the advent of the HIV/AIDS epidemic, many cases of histoplasmosis were documented both in the pediatric and adult population. Our review revealed 1461 reported cases of pediatric histoplasmosis globally in the last eight decades (1939–2021). North America (n = 1231) had the highest number of cases, followed by South America (n = 135), Africa (n = 65), Asia (n = 26) and Europe (n = 4). Histoplasmosis was much more common in the non-HIV pediatric population (n = 1418, 97.1%) compared to the HIV population. The non-HIV factors implicated were, childhood malignancies (n = 207), such as leukemias and lymphomas as well as their treatment, lung diseases (n = 7), environmental exposures and toxins (n = 224), autoimmune diseases (n = 12), organ transplants (n = 12), long-term steroid therapy (n = 3), the use of immunosuppressive drugs such as TNF-alpha inhibitors (n = 7) malnutrition (n = 12), histiocytosis (n = 3), hyperimmunoglobulin M and E syndromes (n = 15, 1.2%), pancytopaenias (n = 26), diabetes mellitus (n = 1) and T-cell deficiency (n = 21). Paediatricians should always consider or rule out a diagnosis of histoplasmosis in children presenting with symptoms suggestive of the above clinical conditions.