Zhou, X.-m. | Search bioRxiv

bioRxiv2020

Inhibitory effects of Akt on neuronal FoxO4 activation after subarachnoid hemorrhage in vivo and in vitro

Secondary brain injury following subarachnoid hemorrhage (SAH) is the critical contributor to the mortality of SAH patients. The underlying mechanisms are poorly understood. In this study, we utilized a mice model of SAH to investigate whether FoxO4 is related to the brain injury after SAH and identified its upstream regulator Akt. Experimental SAH was induced in adult male mice by prechiasmatic cistern injection. Brain FoxO4 protein levels in cytoplasm and nucleaus were examined in the sham-operated controls, and in mice 1h, 6h, 12h, 24h, 3d, and 5d after SAH induction. The Akt inhibitor LY294002 was administered by intracerebroventricular infusion to determine its effects on FoxO4. Moreover, the expression of FoxO4 was also investigated in neurons incubated with hemoglobin in vitro, which was also dertermined after inhibition of Akt. FoxO4 protein expression in the nuclei increased remarkably after SAH. The Akt inhibitor LY294002 induced more FoxO4 nuclear localization after SAH in vivo and in vitro. Our results suggest the activation of FoxO4 after SAH and which was inhibited by the increased phosphorylated Akt (p-Akt).

neuroscience↗

bioRxiv2018

Timing and causes of the distribution pattern of Oncomelania hupensis estimated by molecular and geologic data

AbstractAs the only intermediate host of Schistosoma japonicum, Oncomelania hupensis plays an irreplaceable role in the prevalence of schistosomiasis japonica. Several living subspecies of Oncomelania hupensis are found in Asia, especially in China, Japan,the Philippines, and Sulawesi of Indonesia. The existing geographical distribution pattern of O. hupensis has been influenced by geological events. This study used existing mitochondrial gene data for O. hupensis in the GenBank database and the molecular clock method to estimate the divergence time of each subspecies of O. hupensis. For the first time, the timing and causes of the distribution pattern of the different O. hupensis subspecies were studied by combining molecular data with data on geologic events. The results showed that the uplift and isolation of the Qinghai-Tibet Plateau caused Oncomelania hupensis robertsoni to differentiate 4.76 Ma(Million anniversary), while Oncomelania hupensis guangxiensis was affected by the third Himalayan orogenic movement, differentiating 1.10 Ma. Oncomelania hupensis nosophora was influenced by the formation of the Yonaguni Strait and diverged 1.43 Ma. Influenced by ice ages and interglacial periods, Oncomelania hupensis tangi and Oncomelania hupensis formosana diverged 0.57 Ma. The link of the ancient Yangtze River promoted the spread of O. hupensis to the middle and lower reaches of the Yangtze River, and the developed water network facilitated gene exchange among Oncomelania hupensis hupensis in the area. Eventually, 0.62 Ma, O. h. hupensis differentiated.\n\nAuthor summaryPhylogenetic analysis of Pomatiopsidae species showed that Oncomelania was isolated from other genera and clustered independently in phylogenetic trees. Further analysis of the species Oncomelania hupensis and its subspecies was performed. The snail species O. hupensis has multiple subspecies that exhibit certain differences. These subspecies are distributed across Asia, from Chinas Yunnan Province in the west to Japan in the east and south to the Philippines and Indonesia. In addition, the subspecies are widespread in the middle and lower reaches of the Yangtze River in China, and the distribution ranges of the different subspecies do not overlap. The formation of this distribution pattern of each subspecies of O. hupensis has a profound impact on the prevalence of Schistosoma japonicum. Therefore, the authors analyzed molecular data and geological historical events to investigate the timing and causes of the distribution pattern of each subspecies of O. hupensis.

evolutionary biology↗