Comprehensive transcriptomic analysis of Tibetan Schizothoracinae fish Gymnocypris przewalskii reveals how it adapts to a high altitude aquatic life.

BACKGROUND: Understanding the genetic basis of adaptation to high altitude life is of paramount importance for preserving and managing genetic diversity in highland animals. This objective has been addressed mainly in terrestrial fauna but rarely in aquatic animals. Tibetan Schizothoracinae fish is the ideal model system in evolutionary biology, carrying key insights into evolutionary genetics of speciation and adaptation at high altitude. Gymnocypris przewalskii is the newly formed Schizothoracinae fish species in the Tibetan Plateau, inhabits chronic cold, extreme saline and alkaline aquatic environment in Lake Qinghai, thus evolving the unique genomic signatures to adapt extremely severe environments. RESULTS: To characterize its genomic features, we assembled de novo transcriptome of G. przewalskii from Lake Qinghai. Intriguingly, by comparative genomic analyses of G. przewalskii and 8 other fish species, we identified potential expansions in gene families related to energy metabolism, transport and developmental functions, possibly underlying the adaptation to these environmental stresses. Through comprehensive molecular evolution analyses, we found that sets of genes controlling mitochondrion, ion homoeostasis, acid-base balance and innate immunity show significant signals of positive selection. Compared to previous studies on highland fishes, we failed to identify any positively selected genes related to hypoxia response. CONCLUSIONS: Our findings provide comprehensive insights into the genetic basis of teleost fish that underlie their adaptation to extreme high altitude aquatic life on the Tibetan Plateau.

[Analysis of clinicopathological features and prognosis between alpha-fetoprotein negative and positive hepatocellular carcinoma patients after R0 radical hepatectomy].

OBJECTIVE: To investigate the differences between clinicopathological features and prognosis of alpha-fetoprotein (AFP) negative (AFP < 20 ng/ml) and positive (AFP ≥ 20 ng/ml) hepatocellular carcinoma (HCC) patients. METHODS: Clinicopathological data of 142 AFP-negative and 109 AFP-positive HCC patients who underwent RO radical hepatectomy in the Cancer Hospital of Chinese Academy of Medical Sciences between January 2006 and December 2011 were retrospectively reviewed and analyzed in this study. RESULTS: Compared with the AFP-negative patients, a higher female to male sex ratio, the later Barcelona Clinic Liver Cancer ( BCLC) stage, more liver capsule invasion and poorer Edmondson-Steiner grade were in the AFP-positive cases (P < 0.05 for all). Furthermore, the 1-, 3-, and 5- year overall survival rates were 94.4%, 82.4% and 61.0% in the AFP-negative group and 87.2%, 61.1% and 40.2%, respectively, in the AFP-positive group (P < 0.001). The multivariate analysis with Cox's proportional hazards model showed that AFP status, tumor size and Edmondson-Steiner grade are independent risk factors for survival of all the patients (P < 0.05) , and large tumor and Edmondson-Steiner grades III/IV are independent risk factors for worse survival in AFP-negative patients (P < 0.05). However, large tumor diameter was proved to be an independent risk factor leading to poor prognosis of AFP-positive cases (P < 0.05). CONCLUSION: High levels of AFP indicate that the tumors are more malignant and with unfavorable prognosis.

[Peripheral nervous impairment in a patient with methylmalonic aciduria combined with hyperhomocysteinemia].

Methylmalonic aciduria combined homocysteinemia can cause multisystemic damages, mainly involving central nervous system, while the peripheral nerves are rarely impaired. A 10-year-old boy complained of weakness of both lower extremities for 1 month. His past history showed mildly delay of intelligence as well as motor development. He had proteinuria when he was 3 years old and was diagnosed as epilepsy, which was controlled by sodium valproate when he was 8 years 6 months old. His physical examination showed attenuated bilateral knee jerk reflex, while the bilateral achilles tendon reflex was absent; the examination of sensation was normal and the bilateral Babinski sign was positive. The electromyography indicated injury of peripheral nerves. The elevated levels of urine methylmalonic aciduria and plasma homocysteinemia were consistent with the diagnosis of methylmalonic aciduria combined homocysteinemia. The pathogenic gene was confirmed as MMACHC, on which two pathogenic mutations (c.365A>T and c.609G>A) were detected. cblC defect was confirmed. He was treated by vitamin B12, calcium folinate, L-carnitine and betaine supplementation, and significant improvement was observed after 6 months. According to this case, we suggest that urinary organic acid analysis and plasma homocysteine should be performed in patients with unknown peripheral neuropathy, especially combined with multisystemic damages.Early diagnosis and treatment are important to improve the prognosis.

Whole-brain monosynaptic outputs and presynaptic inputs of GABAergic neurons in the vestibular nuclei complex of mice.

GABAergic neurons in the vestibular nuclei (VN) participate in multiple vital vestibular sensory processing allowing for the maintenance and rehabilitation of vestibular functions. However, although the important role of GABA in the central vestibular system has been widely reported, the underlying neural circuits between VN GABAergic neurons and other brain functional regions remain elusive, which limits the further study of the underlying mechanism. Hence, it is necessary to elucidate neural connectivity based on outputs and inputs of GABAergic neurons in the VN. This study employed a modified rabies virus retrograde tracing vector and cre-dependent adeno-associated viruses (AAVs) anterograde tracing vector, combined with a transgenic VGAT-IRES-Cre mice, to map the inputs and outputs of VN GABAergic neurons in the whole brain. We found that 51 discrete brain regions received projections from VN GABAergic neurons in the whole brain, and there were 77 upstream nuclei innervating GABAergic neurons in the VN. These nuclei were mainly located in four brain regions, including the medulla, pons, midbrain, and cerebellum. Among them, VN GABAergic neurons established neural circuits with some functional nuclei in the whole brain, especially regulating balance maintenance, emotion control, pain processing, sleep and circadian rhythm regulation, and fluid homeostasis. Therefore, this study deepens a comprehensive understanding of the whole-brain neural connectivity of VN, providing the neuroanatomical information for further research on the neural mechanism of the co-morbidities with vestibular dysfunction.