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Domestic yaks (Bos grunniens) provide meat and other necessities for Tibetans living at high altitude on the Qinghai-Tibetan Plateau and in adjacent regions. Comparison between yak and the closely related low-altitude cattle (Bos taurus) is informative in studying animal adaptation to high altitude. Here, we present the draft genome sequence of a female domestic yak generated using Illumina-based technology at 65-fold coverage. Genomic comparisons between yak and cattle identify an expansion in yak of gene families related to sensory perception and energy metabolism, as well as an enrichment of protein domains involved in sensing the extracellular environment and hypoxic stress. Positively selected and rapidly evolving genes in the yak lineage are also found to be significantly enriched in functional categories and pathways related to hypoxia and nutrition metabolism. These findings may have important implications for understanding adaptation to high altitude in other animal species and for hypoxia-related diseases in humans.

Our data suggest a myocardial protective effect of ALDH2 against I/R injury possibly through detoxification of toxic aldehyde and a differential regulation of autophagy through AMPK- and Akt-mTOR signalling during ischaemia and reperfusion, respectively.

Obesity poses a severe threat to human health, including the increased prevalence of hypertension, insulin resistance, diabetes mellitus, cancer, inflammation, sleep apnoea and other chronic diseases. Current therapies focus mainly on suppressing caloric intake, but the efficacy of this approach remains poor. A better understanding of the pathophysiology of obesity will be essential for the management of obesity and its complications. Knowledge gained over the past three decades regarding the aetiological mechanisms underpinning obesity has provided a framework that emphasizes energy imbalance and neurohormonal dysregulation, which are tightly regulated by autophagy. Accordingly, there is an emerging interest in the role of autophagy, a conserved homeostatic process for cellular quality control through the disposal and recycling of cellular components, in the maintenance of cellular homeostasis and organ function by selectively ridding cells of potentially toxic proteins, lipids and organelles. Indeed, defects in autophagy homeostasis are implicated in metabolic disorders, including obesity, insulin resistance, diabetes mellitus and atherosclerosis. In this Review, the alterations in autophagy that occur in response to nutrient stress, and how these changes alter the course of obesogenesis and obesity-related complications, are discussed. The potential of pharmacological modulation of autophagy for the management of obesity is also addressed.

The molecular features of necroptosis in cardiac ischemia-reperfusion (IR) injury have been extensively explored. However, there have been no studies investigating the physiological regulatory mechanisms of melatonin acting on necroptosis in cardiac IR injury. This study was designed to determine the role of necroptosis in microvascular IR injury, and investigate the contribution of melatonin in repressing necroptosis and preventing IR-mediated endothelial system collapse. Our results demonstrated that Ripk3 was primarily activated by IR injury and consequently aggravated endothelial necroptosis, microvessel barrier dysfunction, capillary hyperpermeability, the inflammation response, microcirculatory vasospasms, and microvascular perfusion defects. However, administration of melatonin prevented Ripk3 activation and provided a pro-survival advantage for the endothelial system in the context of cardiac IR injury, similar to the results obtained via genetic ablation of Ripk3. Functional investigations clearly illustrated that activated Ripk3 upregulated PGAM5 expression, and the latter increased CypD phosphorylation, which obligated endothelial cells to undergo necroptosis via augmenting mPTP (mitochondrial permeability transition pore) opening. Interestingly, melatonin supplementation suppressed mPTP opening and interrupted endothelial necroptosis via blocking the Ripk3-PGAM5-CypD signal pathways. Taken together, our studies identified the Ripk3-PGAM5-CypD-mPTP axis as a new pathway responsible for reperfusion-mediated microvascular damage via initiating endothelial necroptosis. In contrast, melatonin treatment inhibited the Ripk3-PGAM5-CypD-mPTP cascade and thus reduced cellular necroptosis, conferring a protective advantage to the endothelial system in IR stress. These findings establish a new paradigm in microvascular IR injury and update the concept for cell death management handled by melatonin under the burden of reperfusion attack.

Diabetic cardiomyopathy (DCM) is often associated with suppressed cardiac autophagy, mitochondrial structural and functional impairment. Sirtuin-3 (Sirt3) has been reported to play a crucial role in mitochondrial homeostasis and confers a protective role against the onset and development of DCM although the precise mechanism(s) remains elusive. Here we hypothesized that Sirt3 exerts cardioprotection against DCM by activating Parkin-mediated mitophagy, en route to preserved mitochondrial homeostasis and suppressed cardiomyocyte apoptosis. Adult male wild-type (WT) and Sirt3 knockout (Sirt3KO) mice were treated with streptozotocin (STZ) or vehicle for 3months prior to assessment of echocardiographic property, interstitial fibrosis, cardiomyocyte apoptosis, mitochondrial morphology, cardiac autophagy and cell signaling molecules. Our findings revealed that STZ-induced diabetes mellitus prompted cardiac dysfunction, interstitial fibrosis, cardiomyocyte apoptosis and mitochondrial injury, accompanied with suppressed autophagy and mitophagy, the effects of which were aggravated by Sirt3KO. To the contrary, Sirt3 overexpression in vitro activated autophagy and mitophagy, inhibited mitochondrial injury and cardiomyocyte apoptosis, the effects of which were attenuated by autophagy inhibition using 3-MA. Moreover, deacetylation of Foxo3A and expression of Parkin were decreased by Sirt3KO, while these effects were facilitated by Sirt3OE in diabetic and high glucose settings. Taken together, our data suggested that suppressed Sirt3-Foxo3A-Parkin signaling mediated downregulation of mitophagy may play a vital role in the development of diabetic cardiomyopathy. This article is part of a Special Issue entitled: Genetic and epigenetic control of heart failure edited by Dr. Jun Ren & Yingmei Zhang.

Mosquitoes are insects of the Diptera, Nematocera, and Culicidae families, some species of which are important disease vectors. Identifying mosquito species based on morphological characteristics is difficult, particularly the identification of specimens collected in the field as part of disease surveillance programs. Because of this difficulty, we constructed DNA barcodes of the cytochrome c oxidase subunit 1, the COI gene, for the more common mosquito species in China, including the major disease vectors. A total of 404 mosquito specimens were collected and assigned to 15 genera and 122 species and subspecies on the basis of morphological characteristics. Individuals of the same species grouped closely together in a Neighborhood-Joining tree based on COI sequence similarity, regardless of collection site. COI gene sequence divergence was approximately 30 times higher for species in the same genus than for members of the same species. Divergence in over 98% of congeneric species ranged from 2.3% to 21.8%, whereas divergence in conspecific individuals ranged from 0% to 1.67%. Cryptic species may be common and a few pseudogenes were detected.