IFITM Proteins Restrict Antibody-Dependent Enhancement of Dengue Virus Infection

Interferon-inducible transmembrane (IFITM) proteins restrict the entry processes of several pathogenic viruses, including the flaviviruses West Nile virus and dengue virus (DENV). DENV infects cells directly or via antibody-dependent enhancement (ADE) in Fc-receptor-bearing cells, a process thought to contribute to severe disease in a secondary infection. Here we investigated whether ADE-mediated DENV infection bypasses IFITM-mediated restriction or whether IFITM proteins can be protective in a secondary infection. We observed that IFITM proteins restricted ADE-mediated and direct infection with comparable efficiencies in a myelogenous leukemia cell line. Our data suggest that IFITM proteins can contribute to control of secondary DENV infections

Overexpression of Akt1 Enhances Adipogenesis and Leads to Lipoma Formation in Zebrafish

<div><h3>Background</h3><p>Obesity is a complex, multifactorial disorder influenced by the interaction of genetic, epigenetic, and environmental factors. Obesity increases the risk of contracting many chronic diseases or metabolic syndrome. Researchers have established several mammalian models of obesity to study its underlying mechanism. However, a lower vertebrate model for conveniently performing drug screening against obesity remains elusive. The specific aim of this study was to create a zebrafish obesity model by over expressing the insulin signaling hub of the <em>Akt1</em> gene.</p> <h3>Methodology/Principal Findings</h3><p><em>Skin oncogenic transformation screening shows that a stable zebrafish transgenic of Tg(krt4Hsa.myrAkt1</em>)^cy18 displays severely obese phenotypes at the adult stage. In Tg(<em>krt4:Hsa.myrAkt1</em>)^cy18, the expression of exogenous human constitutively active Akt1 (myrAkt1) can activate endogenous downstream targets of mTOR, GSK-3α/β, and 70S6K. During the embryonic to larval transitory phase, the specific over expression of myrAkt1 in skin can promote hypertrophic and hyperplastic growth. From 21 hour post-fertilization (hpf) onwards, myrAkt1 transgene was ectopically expressed in several mesenchymal derived tissues. This may be the result of the integration position effect. Tg(<em>krt4:Hsa.myrAkt1</em>)^cy18 caused a rapid increase of body weight, hyperplastic growth of adipocytes, abnormal accumulation of fat tissues, and blood glucose intolerance at the adult stage. Real-time RT-PCR analysis showed the majority of key genes on regulating adipogenesis, adipocytokine, and inflammation are highly upregulated in Tg(<em>krt4:Hsa.myrAkt1</em>)^cy18. In contrast, the myogenesis- and skeletogenesis-related gene transcripts are significantly downregulated in Tg(<em>krt4:Hsa.myrAkt1</em>)^cy18, suggesting that excess adipocyte differentiation occurs at the expense of other mesenchymal derived tissues.</p> <h3>Conclusion/Significance</h3><p>Collectively, the findings of this study provide direct evidence that Akt1 signaling plays an important role in balancing normal levels of fat tissue in vivo. The obese zebrafish examined in this study could be a new powerful model to screen novel drugs for the treatment of human obesity.</p> </div

Environmental chemical stressors as epigenome modifiers:a new horizon in assessment of toxicological effects

In eukaryotic cells, chromatin transformation from euchromatin into heterochromatin as a means of controlling gene expression and replication has been known as the ?accessibility hypothesis?. The interplay of epigenetic changes including histone modifications, DNA methylation, RNA interference (RNAi) and other functional epigenetic components are intricate. It is believed that these changes are well-programmed, inherited and can be modified by environmental contaminant stressors. Environmentally-driven epigenetic alterations during development, e.g. embryonic, foetal or neonatal stage, may influence disease susceptibility in adulthood. Therefore, understanding how epigenome modifications develop in response to environmental chemicals and, how epigenetic-xenobiotic interactions influence human health will shed new insights into gene-environment interactions in the epidemiology of several diseases including cancer. In this review, we consider studies of chemical modifiers including nutritional and xenobiotic effects on epigenetic components in vitro or in vivo. By examining the most-studied epigenome modifications and how their respective roles are interlinked, we highlight the central role of xenbiotic-modified epigenetic mechanisms. A major requirement will be to study and understand effects following environmentally-relevant exposures. We suggest that the study of epigenetic toxicology will open up new opportunities to devise strategies for the prevention or treatment of at-risk populations

Feasibility and safety of elective laparoscopic total extraperitoneal preperitoneal groin hernia repair in the elderly: a propensity score-matched comparison

Ying-Buh Liu,1 Chih-Chin Yu,1 Chao-Chuan Wu,1,2 Chia-Da Lin,1,2 Shih-Chieh Chueh,3,4 Yao-Chou Tsai1,2 1Department of Surgery, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Taipei, Taiwan; 2Department of Urology, Tzu Chi University, Medical College, Hualien, Taiwan; 3Department of Urology, National Taiwan University Hospital, Taipei, Taiwan; 4Cleveland Clinic, Glickman Urologic and Kidney Institute, Cleveland Clinic Lerner College of Medicine, Cleveland, OH, USA Background: Several studies of hernia registries have revealed that elderly patients have higher perioperative complication rates compared with younger patients. However, the incidence of hernia increases with the aging process. To evaluate the feasibility and safety of laparoscopic hernia repair in elderly patients (&ge;75 years), we conducted a prospective case-matched control study to compare perioperative outcomes between patients older and younger than 75&nbsp;years. Methods: Between September 2008 and July 2015, 572 consecutive patients undergoing endoscopic hernia repair were included in this prospective study. This case-matched control study was matched based on sex, American Society of Anesthesiologists score, and body mass index between patients younger and &ge;75 years. The propensity-score matching of two groups was carried out on a 1:1 basis. Perioperative data were prospectively recorded for all patients including demographic data, operation time, length of hospital stay, narcotic dose, and complications. Results: In the final analysis, 54 patients who were &lt;75 years were extracted to match the 54 patients &ge;75 years. These two groups had similar baseline characteristics excluding age. They also had similar perioperative outcomes in hernia recurrence, metachronous contralateral hernia occurrence, complication rate and chronic pain. The patients &ge;75 years of age had lower requirements for analgesics than those who were &lt;75 years of age (p=0.047). Conclusion: This is the first comparative cohort study investigating the impact of aging in an Asian hernia population. Laparoscopic inguinal hernia repair is feasible and safe for older patients, with comparable perioperative outcomes to patients &lt;75 years. Keywords: inguinal hernia, TEP, age, complicatio