MICU1 regulation of mitochondrial Ca(2+) uptake dictates survival and tissue regeneration.

Mitochondrial Ca(2+) uptake through the recently discovered Mitochondrial Calcium Uniporter (MCU) is controlled by its gatekeeper Mitochondrial Calcium Uptake 1 (MICU1). However, the physiological and pathological role of MICU1 remains unclear. Here we show that MICU1 is vital for adaptation to postnatal life and for tissue repair after injury. MICU1 knockout is perinatally lethal in mice without causing gross anatomical defects. We used liver regeneration after partial hepatectomy as a physiological stress response model. Upon MICU1 loss, early priming is unaffected, but the pro-inflammatory phase does not resolve and liver regeneration fails, with impaired cell cycle entry and extensive necrosis. Ca(2+) overload-induced mitochondrial permeability transition pore (PTP) opening is accelerated in MICU1-deficient hepatocytes. PTP inhibition prevents necrosis and rescues regeneration. Thus, our study identifies an unanticipated dependence of liver regeneration on MICU1 and highlights the importance of regulating MCU under stress conditions when the risk of Ca(2+) overload is elevated

RVFV Infection in Goats by Different Routes of Inoculation

Rift Valley fever virus (RVFV) is a zoonotic arbovirus of the Phenuiviridae family. Infection causes abortions in pregnant animals, high mortality in neonate animals, and mild to severe symptoms in both people and animals. There is currently an ongoing effort to produce safe and efficacious veterinary vaccines against RVFV in livestock to protect against both primary infection in animals and zoonotic infections in people. To test the efficacy of these vaccines, it is essential to have a reliable challenge model in relevant target species, including ruminants. We evaluated two goat breeds (Nubian and LaMancha), three routes of inoculation (intranasal, mosquito-primed subcutaneous, and subcutaneous) using an infectious dose of 107 pfu/mL, a virus strain from the 2006⁻2007 Kenyan/Sudan outbreak and compared the effect of using virus stocks produced in either mammalian or mosquito cells. Our results demonstrated that the highest and longest viremia titers were achieved in Nubian goats. The Nubian breed was also efficient at producing clinical signs, consistent viremia (peak viremia: 1.2 × 103⁻1.0 × 105 pfu/mL serum), nasal and oral shedding of viral RNA (1.5 × 101⁻8 × 106 genome copies/swab), a systemic infection of tissues, and robust antibody responses regardless of the inoculation route. The Nubian goat breed and a needle-free intranasal inoculation technique could both be utilized in future vaccine and challenge studies. These studies are important for preventing the spread and outbreak of zoonotic viruses like RVFV and are supported by the Canadian-led BSL4ZNet network

Systematic review of hypertension and diabetes burden, risk factors, and interventions for prevention and control in Malawi

Recent studies have found an increasing burden of noncommunicable diseases in sub-Saharan Africa. A compressive search of PubMed, Medline, EMBASE, and the World Health Organization Global Health Library databases was undertaken to identify studies reporting on the prevalence, risk factors, and interventions for hypertension and diabetes in Malawi. The findings from 23 included studies revealed a high burden of hypertension and diabetes in Malawi, with estimates ranging from 15.8% to 32.9% and from 2.4% to 5.6%, respectively. Associated risk factors included old age, tobacco smoking, excessive alcohol consumption, obesity, physical inactivity, high salt and sugar intake, low fruit and vegetable intake, high body mass index, and high waist-to-hip ratio. Certain antiretroviral therapy regimens were also associated with increased diabetes and hypertension risk in human immunodeficiency virus patient populations. Nationwide, the quality of clinical care was generally limited and demonstrated a need for innovative and targeted interventions to prevent, control, and treat noncommunicable diseases in Malawi