Alterations in the activation of corticotropin-releasing factor neurons in the paraventricular nucleus following a single or multiple days of sleep restriction.

Sleep disturbances are common among disorders associated with hypothalamic pituitary-adrenal (HPA) axis dysfunction, such as depression and anxiety. This comorbidity may partly be the result of the intersection between the role of the HPA axis in mediating the stress response and its involvement in sleep-wake cyclicity. Our previous work has shown that following 20 h of sleep restriction, mice show a blunting of the HPA axis in response to an acute stressor. Furthermore, these responses differ in a sex-dependent manner. This study sought to examine the effect of sleep restriction on corticotropin-releasing factor (CRF)-containing neurons in the paraventricular nucleus (PVN) of the hypothalamus. Male and female Crf-IRES-Cre: Ai14 (Tdtomato) reporter mice were sleep restricted for 20 h daily for either a single or three consecutive days using the modified multiple platform method. These mice allowed the visualization of CRF+ neurons throughout the brain. Animals were subjected to acute restraint stress, and their brains were collected to assess PVN neuronal activation via c-Fos immunohistochemistry. Analyses of cell counts revealed an ablation of the restraint-induced increase in both CRF/c-Fos colocalization and overall c-Fos expression in female mice following both a single day and three days of sleep restriction. Males showed an overall decrease in restraint-induced c-Fos levels following a single day of sleep restriction. However, male mice examined after three days of sleep restriction showed a recovery in PVN-CRF and overall PVN neuronal activation. These data suggest the sex dependent dysregulation in CRF function following sleep restriction.

Comparison of Wild Type DNA Sequence of Spike Protein from SARS-CoV-2 with Optimized Sequence on The Induction of Protective Responses Against SARS-Cov-2 Challenge in Mouse Model

COVID-19 caused by SARS-CoV-2 has been spreading worldwide. To date, several vaccine candidates moved into EUA or CA applications. Although DNA vaccine is on phase III clinical trial, it is a promised technology platform with many advantages. Here, we showed that the pGX9501 DNA vaccine encoded the spike full-length protein-induced strong humoral and cellular immune responses in mice with higher neutralizing antibodies, blocking the hACE2-RBD binding against live virus infection in vitro. Importantly, higher levels of IFN-{gamma} expression in CD8+ and CD4+ T cell and specific cytotoxic lymphocyte (CTL) killings effect were also observed in the pGX9501-immunized group. It provided subsequent protection against virus challenges in the hACE2 transgenic mouse model. Overall, pGX9501 was a promising DNA vaccine candidate against COVID-19, inducing strong humoral immunity and cellular immunity that contributed to the vaccines protective effects.

Current Visceral Leishmaniasis Research: A Research Review to Inspire Future Study.

Visceral leishmaniasis (VL), one of the deadliest parasitic diseases in the world, causes more than 50,000 human deaths each year and afflicts millions of people throughout South America, East Africa, South Asia, and Mediterranean Region. In 2015 the World Health Organization classified VL as a neglected tropical disease (NTD), prompting concentrated study of the VL epidemic using mathematical and simulation models. This paper reviews literature related to prevalence and prevention control strategies. More than thirty current research works were reviewed and classified based on VL epidemic study methods, including modeling approaches, control strategies, and simulation techniques since 2013. A summarization of these technical methods, major findings, and contributions from existing works revealed that VL epidemic research efforts must improve in the areas of validating and verifying VL mathematical models with real-world epidemic data. In addition, more dynamic disease control strategies must be explored and advanced simulation techniques must be used to predict VL pandemics.