The inhibition of trypsin, plasmin, and thrombin by benzyl 4-guanidinobenzoate and 4′-nitrobenzyl 4-guanidinobenzoate

AbstractThe inhibition of the enzymes trypsin, plasmin, and thrombin by benzyl 4-guanidinobenzoate and 4′-nitrobenzyl 4-guanidinobenzoate is caused by acylation of the active site. Second order rate constants were determined

Field experiments on individual adaptation of the spider crab Inachus phalangium to its sea anemone host Anemonia viridis in the northern Adriatic Sea

We studied the adaptation of the spider crab Inachus phalangium (Fabricius, 1755) to one of its sea anemone host species, Anemonia viridis (Forsskål, 1775) in the coastal region of Rovinj, Croatia. Similar to other brachyuran species, Inachus spp. generally lives within the anemone to obtain protection from possible predators. Using removal and reintroduction experiments, this study investigates the protection mechanism and shows a loss of adaptation after a period of 10 days when the crabs are taken out of their host and kept solitary. Thirty-nine anemones from two different trial sites were marked individually and the inhabiting crabs were isolated to be released back into their individual hosts later. The reactions of the anemones were closely observed and characterized to determine the respective state of crab adaptation. As 35 out of 39 individuals provoked a defense /attack reaction of the anemone, it is concluded that the crabs possessed some sort of non-permanent protection mechanism that was lost during the test run (chi-square test, p < 0.00014). All tested crabs re-inhabited their host anemones within a maximum of 20 minutes after they had been reintroduced and stung by the anemones. Therefore, habituation to the host’s defense / attack mechanism is acquired individually and not genetically inherent to the species. The results are compared to adaptation and protection data on other decapod crustaceans and some anemonefishes

Social evaluation at a distance – facets of stereotype content about student groups in higher distance education

In the academic domain, belonging to a negatively stereotyped group can impair performance and peer relationships. In higher distance education, stereotypes may be particularly influential as face-to-face contact is limited and non-traditional students who are at risk of being stereotyped are overrepresented. Still, research on stereotypes in higher distance education is sparse. The current research addresses this gap by investigating the Big Two of social perception (warmth, competence) and subordinate facets (friendliness, morality, assertiveness, ability, conscientiousness) in the context of higher distance education. It tests a) how well models with warmth/competence or the facets fit the data, b) whether stereotypes in higher distance education depend on the student group, and c) how the Big Two and subordinate facets predict intergroup emotions and behavioral intentions in higher distance education. An online survey with N = 626 students (74% female) of a large distance university showed that a measurement model with four facets (i.e., friendliness, morality, ability, conscientiousness) reveals adequate model fit for 12 student groups. Perceived stereotypes were positive for female students, older students, and students with children. However, migrant as well as younger students were perceived negatively. Across groups, stereotype content facets predicted intergroup emotions and behavioral intentions of facilitation or harm. Implications for the influence of negative stereotypes in higher distance education are discussed

Pharmacological manipulation of L-carnitine transport into L6 cells with stable overexpression of human OCTN2

Abstract.: The high-affinity Na+-dependent carnitine transporter OCTN2 (SLC22A5) has a high renal expression and reabsorbs most filtered carnitine. To gain more insight into substrate specificity of OCTN2, we overexpressed hOCTN2 in L6 cells and characterized the structural requirements of substances acting as human OCTN2 (hOCTN2) inhibitors. A 1905-bp fragment containing the hOCTN2 complete coding sequence was introduced into the pWpiresGFP vector, and L6 cells were stably transduced using a lentiviral system. The transduced L6 cells revealed increased expression of hOCTN2 on the mRNA, protein and functional levels. Structural requirements for hOCTN2 inhibition were predicted in silico and investigated in vitro. Essential structural requirements for OCTN2 inhibition include a constantly positively charged nitrogen atom and a carboxyl, nitrile or ester group connected by a 2-4-atom linker. Our cell system is suitable for studying in vitro interactions with OCTN2, which can subsequently be investigated in viv

The value of different resistance parameters in distinguishing biopsy-proved dysfunction of renal allografts

The data concerning the value of duplex sonography in diagnosing parenchymatous renal allograft dysfunction are controversial. Most early studies did not take into consideration the many factors influencing resistance parameters. We therefore performed a prospective, biopsy-controlled study with exclusion of all known sources of error regarding resistance parameters. Furthermore we investigated the value of a new resistance parameter, the systolic deceleration percentage. Forty-seven duplex sonographic studies were performed on 43 patients (30 male, 13 female, median age 47 years, range 7-70). Fourteen studies were done on normally functioning grafts (control group) an average of 33 days after transplantation. Thirty-three studies were performed on dysfunctional grafts immediately prior to biopsy. Grafts which had been transplanted more than a year previously or with vascular findings or any other clinical or sonographic pathology probably explaining function deterioration were excluded. In all patients, the resistive index (RI), pulsatility index (PI) and systolic deceleration percentage (DP) were calculated in the main renal artery and in the interlobar artery. Of the 33 grafts with dysfunction, nine had vascular rejection (VR), 11 interstitial rejection (IR), 11 cyclosporin A toxicity (CAT) and two other histologies (OR). The mean RI in normal grafts (NO) was 0.71±0.06 in the main artery and 0.68±0.06 in the interlobar artery, in VR 0.86±0.12 and 0.80±0.18, in IR 0.72±0.05 and 0.70±0.07, in CAT 0.67±0.06 and 0.65±0.07 and in OR 0.64±0.07 and 0.60±0.01. For PI, the values were 1.45±0.23 and 1.41±0.28 (NO), 3.5±2.13 and 2.92±2.16 (VR), 1.55±0.26 and 1.46±0.33 (IR), 1.32±0.25 and 1.27±0.26 (CAT) and 1.30±0.34 and 1.13±0.04 (OR). For DP we calculated 28±5% and 29±6% (NO), 43±14% and 36±6% (VR), 29±9% and 27±9% (IR), 31±8% and 32±7% (CAT ) and 32±4% and 28±3% (OR). The sensitivity/specificity for VR with a cutoff mean+2 SD was 0.44/1 for RI, 0.55/0.97 for PI and 0.33/0.89 for DP. It was concluded that:(1) despite the high selection of our patient group, diagnostic accuracy of duplex sonography for diagnosing parenchymatous function disorder in renal allograft remains insufficient; (2) in vascular rejection only, the resistance parameters differ significantly from the values of normal allografts; (3) the higher the cutoff of resistance parameters, the better the specificity and the worse the sensitivity for diagnosing vascular rejection; (4) of all investigated resistance parameters, the RI is the most practical due to a simple measurement techniqu

Early renal transplant dysfunction due to arterial kinking stenosis

The main differential diagnoses of early renal trans-plant dysfunction include ischaemic damage, cyclospo-rin toxicity, and rejection [1]. Rarer causes include bleeding, ureteral obstruction, urinary leak, venou

Adults at high-risk of severe coronavirus disease-2019 (Covid-19) in Brazil

OBJECTIVE: To estimate the proportion and total number of the general adult population who may be at higher risk of severe Covid-19 in Brazil. METHODS: We included 51,770 participants from a nationally representative, household-based health survey (PNS) conducted in Brazil. We estimated the proportion and number of adults (≥ 18 years) at risk of severe Covid-19 by sex, educational level, race/ethnicity, and state based on the presence of one or more of the following risk factors: age ≥ 65 years or medical diagnosis of cardiovascular disease, diabetes, hypertension, chronic respiratory disease, cancer, stroke, chronic kidney disease and moderate to severe asthma, smoking status, and obesity. RESULTS: Adults at risk of severe Covid-19 in Brazil varied from 34.0% (53 million) to 54.5% (86 million) nationwide. Less-educated adults present a 2-fold higher prevalence of risk factors compared to university graduated. We found no differences by sex and race/ethnicity. São Paulo, Rio de Janeiro, Minas Gerais, and Rio Grande do Sul were the most vulnerable states in absolute and relative terms of adults at risk. CONCLUSIONS: Proportion and total number of adults at risk of severe Covid-19 are high in Brazil, with wide variation across states and adult subgroups. These findings should be considered while designing and implementing prevention measures in Brazil. We argue that these results support broad social isolation measures, particularly when testing capacity for SARS-CoV-2 is limited

Expression, regulation and clinical significance of soluble and membrane CD14 receptors in pediatric inflammatory lung diseases

<p>Abstract</p> <p>Background</p> <p>Inflammatory lung diseases are a major morbidity factor in children. Therefore, novel strategies for early detection of inflammatory lung diseases are of high interest. Bacterial lipopolysaccharide (LPS) is recognized via Toll-like receptors and CD14. CD14 exists as a soluble (sCD14) and membrane-associated (mCD14) protein, present on the surface of leukocytes. Previous studies suggest sCD14 as potential marker for inflammatory diseases, but their potential role in pediatric lung diseases remained elusive. Therefore, we examined the expression, regulation and significance of sCD14 and mCD14 in pediatric lung diseases.</p> <p>Methods</p> <p>sCD14 levels were quantified in serum and bronchoalveolar lavage fluid (BALF) of children with infective (pneumonia, cystic fibrosis, CF) and non-infective (asthma) inflammatory lung diseases and healthy control subjects by ELISA. Membrane CD14 expression levels on monocytes in peripheral blood and on alveolar macrophages in BALF were quantified by flow cytometry. <it>In vitro </it>studies were performed to investigate which factors regulate sCD14 release and mCD14 expression.</p> <p>Results</p> <p>sCD14 serum levels were specifically increased in serum of children with pneumonia compared to CF, asthma and control subjects. <it>In vitro</it>, CpG induced the release of sCD14 levels in a protease-independent manner, whereas LPS-mediated mCD14 shedding was prevented by serine protease inhibition.</p> <p>Conclusions</p> <p>This study demonstrates for the first time the expression, regulation and clinical significance of soluble and membrane CD14 receptors in pediatric inflammatory lung diseases and suggests sCD14 as potential marker for pneumonia in children.</p