From perceived parental entrepreneurial passion to technopreneurship intention: The moderating role of perseverance and perceived parental entrepreneurial rewards

In light of significant advancements in both theoretical and practical aspects of technopreneurship, supported by empirical research, there remains an unexplored area within the academic domain pertaining to the impact of perceived parents’ entrepreneurial passion towards a career in technopreneurship and technopreneurship intention among Generation Z students remains unexplored in the academic domain. This study thus aims to examine how perceived parents’ entrepreneurial passion, perceived desirability and perceived feasibility would stimulate attitude towards a career in technopreneurship and technopreneurship intention among Generation Z students in Zimbabwe. It is based on a nomothetic quantitative methodology, where a survey was applied to collect responses from Generation Z university students in the Harare Metropolitan Province of Zimbabwe. Through structural equation modelling, the findings are validated, confirming that perceived parents’ entrepreneurial passion, perceived desirability and perceived feasibility do indeed influence attitudes towards pursuing a career in technopreneurship. The study also discovered that attitude towards a career in technopreneurship has a positive and a significant impact on technopreneurship intention. Moreover, the results support the moderation role of perseverance and perceived parental entrepreneurial rewards on the nexus be�tween attitude towards a career in technopreneurship and technopreneurship intention. Based on the results, the study concludes that perceived parents’ entrepreneurial passion, perceived desirability and perceived feasibility would stimulate attitude towards a career in technopreneurship and technopreneurship intention among Generation Z students

Azithromycin Treatment Alters Gene Expression in Inflammatory, Lipid Metabolism, and Cell Cycle Pathways in Well-Differentiated Human Airway Epithelia

Prolonged macrolide antibiotic therapy at low doses improves clinical outcome in patients affected with diffuse panbronchiolitis and cystic fibrosis. Consensus is building that the therapeutic effects are due to anti-inflammatory, rather than anti-microbial activities, but the mode of action is likely complex. To gain insights into how the macrolide azithromycin (AZT) modulates inflammatory responses in airways, well-differentiated primary cultures of human airway epithelia were exposed to AZT alone, an inflammatory stimulus consisting of soluble factors from cystic fibrosis airways, or AZT followed by the inflammatory stimulus. RNA microarrays were conducted to identify global and specific gene expression changes. Analysis of gene expression changes revealed that the AZT treatment alone altered the gene profile of the cells, primarily by significantly increasing the expression of lipid/cholesterol genes and decreasing the expression of cell cycle/mitosis genes. The increase in cholesterol biosynthetic genes was confirmed by increased filipin staining, an index of free cholesterol, after AZT treatment. AZT also affected genes with inflammatory annotations, but the effect was variable (both up- and down-regulation) and gene specific. AZT pretreatment prevented the up-regulation of some genes, such as MUC5AC and MMP9, triggered by the inflammatory stimulus, but the up-regulation of other inflammatory genes, e.g., cytokines and chemokines, such as interleukin-8, was not affected. On the other hand, HLA genes were increased by AZT. Notably, secreted IL-8 protein levels did not reflect mRNA levels, and were, in fact, higher after AZT pretreatment in cultures exposed to the inflammatory stimulus, suggesting that AZT can affect inflammatory pathways other than by altering gene expression. These findings suggest that the specific effects of AZT on inflamed and non-inflamed airway epithelia are likely relevant to its clinical activity, and their apparent complexity may help explain the diverse immunomodulatory roles of macrolides

Inhibition of mitochondrial function by metformin increases glucose uptake, glycolysis and GDF-15 release from intestinal cells

Funder: BBSRCAbstract: Even though metformin is widely used to treat type2 diabetes, reducing glycaemia and body weight, the mechanisms of action are still elusive. Recent studies have identified the gastrointestinal tract as an important site of action. Here we used intestinal organoids to explore the effects of metformin on intestinal cell physiology. Bulk RNA-sequencing analysis identified changes in hexose metabolism pathways, particularly glycolytic genes. Metformin increased expression of Slc2a1 (GLUT1), decreased expression of Slc2a2 (GLUT2) and Slc5a1 (SGLT1) whilst increasing GLUT-dependent glucose uptake and glycolytic rate as observed by live cell imaging of genetically encoded metabolite sensors and measurement of oxygen consumption and extracellular acidification rates. Metformin caused mitochondrial dysfunction and metformin’s effects on 2D-cultures were phenocopied by treatment with rotenone and antimycin-A, including upregulation of GDF15 expression, previously linked to metformin dependent weight loss. Gene expression changes elicited by metformin were replicated in 3D apical-out organoids and distal small intestines of metformin treated mice. We conclude that metformin affects glucose uptake, glycolysis and GDF-15 secretion, likely downstream of the observed mitochondrial dysfunction. This may explain the effects of metformin on intestinal glucose utilisation and food balance

International genome-wide meta-analysis identifies new primary biliary cirrhosis risk loci and targetable pathogenic pathways.

Primary biliary cirrhosis (PBC) is a classical autoimmune liver disease for which effective immunomodulatory therapy is lacking. Here we perform meta-analyses of discovery data sets from genome-wide association studies of European subjects (n=2,764 cases and 10,475 controls) followed by validation genotyping in an independent cohort (n=3,716 cases and 4,261 controls). We discover and validate six previously unknown risk loci for PBC (Pcombined<5 × 10(-8)) and used pathway analysis to identify JAK-STAT/IL12/IL27 signalling and cytokine-cytokine pathways, for which relevant therapies exist

Mortality and pulmonary complications in patients undergoing surgery with perioperative SARS-CoV-2 infection: an international cohort study

Background: The impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on postoperative recovery needs to be understood to inform clinical decision making during and after the COVID-19 pandemic. This study reports 30-day mortality and pulmonary complication rates in patients with perioperative SARS-CoV-2 infection. Methods: This international, multicentre, cohort study at 235 hospitals in 24 countries included all patients undergoing surgery who had SARS-CoV-2 infection confirmed within 7 days before or 30 days after surgery. The primary outcome measure was 30-day postoperative mortality and was assessed in all enrolled patients. The main secondary outcome measure was pulmonary complications, defined as pneumonia, acute respiratory distress syndrome, or unexpected postoperative ventilation. Findings: This analysis includes 1128 patients who had surgery between Jan 1 and March 31, 2020, of whom 835 (74·0%) had emergency surgery and 280 (24·8%) had elective surgery. SARS-CoV-2 infection was confirmed preoperatively in 294 (26·1%) patients. 30-day mortality was 23·8% (268 of 1128). Pulmonary complications occurred in 577 (51·2%) of 1128 patients; 30-day mortality in these patients was 38·0% (219 of 577), accounting for 81·7% (219 of 268) of all deaths. In adjusted analyses, 30-day mortality was associated with male sex (odds ratio 1·75 [95% CI 1·28–2·40], p\textless0·0001), age 70 years or older versus younger than 70 years (2·30 [1·65–3·22], p\textless0·0001), American Society of Anesthesiologists grades 3–5 versus grades 1–2 (2·35 [1·57–3·53], p\textless0·0001), malignant versus benign or obstetric diagnosis (1·55 [1·01–2·39], p=0·046), emergency versus elective surgery (1·67 [1·06–2·63], p=0·026), and major versus minor surgery (1·52 [1·01–2·31], p=0·047). Interpretation: Postoperative pulmonary complications occur in half of patients with perioperative SARS-CoV-2 infection and are associated with high mortality. Thresholds for surgery during the COVID-19 pandemic should be higher than during normal practice, particularly in men aged 70 years and older. Consideration should be given for postponing non-urgent procedures and promoting non-operative treatment to delay or avoid the need for surgery. Funding: National Institute for Health Research (NIHR), Association of Coloproctology of Great Britain and Ireland, Bowel and Cancer Research, Bowel Disease Research Foundation, Association of Upper Gastrointestinal Surgeons, British Association of Surgical Oncology, British Gynaecological Cancer Society, European Society of Coloproctology, NIHR Academy, Sarcoma UK, Vascular Society for Great Britain and Ireland, and Yorkshire Cancer Research

From perceived parental entrepreneurial passion to technopreneurship intention: The moderating role of perseverance and perceived parental entrepreneurial rewards

In light of significant advancements in both theoretical and practical aspects of technopreneurship, supported by empirical research, there remains an unexplored area within the academic domain pertaining to the impact of perceived parents’ entrepreneurial passion towards a career in technopreneurship and technopreneurship intention among Generation Z students remains unexplored in the academic domain. This study thus aims to examine how perceived parents’ entrepreneurial passion, perceived desirability and perceived feasibility would stimulate attitude towards a career in technopreneurship and technopreneurship intention among Generation Z students in Zimbabwe. It is based on a nomothetic quantitative methodology, where a survey was applied to collect responses from Generation Z university students in the Harare Metropolitan Province of Zimbabwe. Through structural equation modelling, the findings are validated, confirming that perceived parents’ entrepreneurial passion, perceived desirability and perceived feasibility do indeed influence attitudes towards pursuing a career in technopreneurship. The study also discovered that attitude towards a career in technopreneurship has a positive and a significant impact on technopreneurship intention. Moreover, the results support the moderation role of perseverance and perceived parental entrepreneurial rewards on the nexus between attitude towards a career in technopreneurship and technopreneurship intention. Based on the results, the study concludes that perceived parents’ entrepreneurial passion, perceived desirability and perceived feasibility would stimulate attitude towards a career in technopreneurship and technopreneurship intention among Generation Z students

Swarm Robotics and Java-based Development Tools

Robotics has proven itself to be an important emerging technology. While several commercially-available robotics packages provide a place to begin study, none adapt well to the application of Artificial Intelligence or Swarm Robotics. Our focus is on combining and modifying existing off-the-shelf technologies to augment these kits\u27 capabilities. Our goal is to produce a development suite that includes radio communications, an open source software development package, a mobile chassis capable of independent operation, and the capacity for intra-swarm communication. These tools should enable the production of an intelligent robot capable of coordinating its actions with others of its type. The presentation outlined the initial progress and hurdles, and further detailed the goals of the project

The inositol phosphate pathway as a mediator in the proliferative response of rat calvarial bone cells to cyclical biaxial mechanical strain

Isolated newborn rat calvarial bone cells grown in monolayer on polyurethane membranes in specially constructed culture chambers and subjected to a cyclical biaxial mechanical strain of 0.17% at a frequency of 1 Hz for 30 min demonstrated a 16% increase in DNA synthesis during the subsequent 24 h. The metabolites of the inositol phosphate pathway, shown to be an important second messenger in many cell types, were shown to be elevated using high‐performance liquid chromatography to separate and quantitate the various inositol polyphosphates. Inositol 1,4,5‐trisphosphate, inositol 1,4‐bisphosphate, and inositol 1,3,4,5‐tetrakisphosphate reached peak accumulations after 20 s of mechanical strain. Inositol 1,3,4‐trisphosphate reached a peak accumulation after 2 min, and inositol 1,2,3,4,5,6 phosphate reached a peak accumulation after 60 min of mechanical strain. Neomycin, an inhibitor of phospholipase C, a membrane‐bound enzyme that hydrolyzes phosphatidyl inositol 4,5‐bisphosphate to start the inositol phosphate cascade, completely inhibited accumulation of the above inositol phosphates during mechanical straining of the bone cells. Neomycin also completely abolished the increase in DNA synthesis that was seen after a mechanical strain of 0.17%. It is concluded from this study that the inositol phosphate pathway is activated by mechanical strain in bone cells and that this pathway is an important and primary mediator in the transduction of mechanical strain into cellular proliferation in these cells. Copyright © 1992 Orthopaedic Research Societ

Characterization of exosome-like vesicles released from human tracheobronchial ciliated epithelium: a possible role in innate defense

Airway mucus forms the structural basis of the local innate immune defense mechanism. It is an integrated, active, viscoelastic gel matrix evolved to protect the exposed lung from physical, chemical, and pathological erosion. Exosomes are biologically active vesicles secreted by different cell types including epithelial, hematopoietic, and some tumor cells. They are also present in some biological fluids such as serum, urine, breast milk, and bronchoalveolar lavage fluid. In this study, we demonstrate for the first time that exosome-like vesicles with antiviral properties are present in human tracheobronchial epithelial (HTBE) cell culture secretions. These vesicles have been isolated by differential centrifugation and are characterized further by mass spectrometry, flow cytometry, immunoblotting, electron microscopy, and light-scattering methods. HTBE vesicles exhibited characteristic exosomal size (30–100 nm) and morphology (cup-shaped) with a buoyant density in sucrose of 1.12–1.18 g/ml. Biochemical characterization further revealed typical surface, cytoskeletal, and cytoplasmic proteins characteristic of exosomes, including the multivesicular and late endosomal membrane markers Tsg101 and CD63. The presence of RNA was also observed. The epithelial mucins MUC1, MUC4, and MUC16 also contributed to the vesicles’ structure. Notably, α-2,6-linked sialic acid was associated with these mucin molecules and subsequent functional analysis showed that these vesicles have a neutralizing effect on human influenza virus, which is known to bind sialic acid. Taken together, these findings suggest that airway epithelial cells release exosome-like vesicles and that these structures may be involved in diverse physiological processes in airway biology, including innate mucosal defense.— Kesimer, M., Scull, M., Brighton, B., DeMaria, G., Burns, K., O’Neal, W., Pickles, R. J., Sheehan, J. K. Characterization of exosome-like vesicles released from human tracheobronchial ciliated epithelium: a possible role in innate defense