Complete genome sequence of the bacterium Ketogulonicigenium vulgare Y25

Ketogulonicigenium vulgare is characterized by the efficient production of 2KGA from L-sorbose. Ketogulonicigenium vulgare Y25 is known as a 2-keto-L-gulonic acid-producing strain in the vitamin C industry. Here we report the finished, annotated genome sequence of Ketogulonicigenium vulgare Y25.     

1.42A crystal structure of mini-IGF-1(2): an analysis of the disulfide isomerization property and receptor binding property of IGF-1 based on the three-dimensional structure

Insulin and insulin-like growth factor 1 (IGF-1) share a homologous sequence, a similar three-dimensional structure and weakly overlapping biological activity, but IGF-1 folds into two thermodynamically stable disulfide isomers, while insulin folds into one unique stable tertiary structure. This is a very interesting phenomenon in which one amino acid sequence encodes two three-dimensional structures, and its molecular mechanism has remained unclear for a long time. In this study, the crystal structure of mini-IGF-1(2), a disulfide isomer of an artificial analog of IGF-1, was solved by the SAD/SIRAS method using our in-house X-ray source. Evidence was found in the structure showing that the intra-A-chain/domain disulfide bond of some molecules was broken; thus, it was proposed that disulfide isomerization begins with the breakdown of this disulfide bond. Furthermore, based on the structural comparison of IGF-1 and insulin, a new assumption was made that in insulin the several hydrogen bonds formed between the N-terminal region of the B-chain and the intra-A-chain disulfide region of the A-chain are the main reason for the stability of the intra-A-chain disulfide bond and for the prevention of disulfide isomerization, while Phe B1 and His B5 are very important for the formation of these hydrogen bonds. Moreover, the receptor binding property of IGF-1 was analyzed in detail based on the structural comparison of mini-IGF-1(2), native IGF-1, and small mini-IGF-1.     

Structures and magnetic properties of mono-doped fullerenes C59Xn and C59X(6mn)m (X=Bm,N+, P+, As+, Si): isoelectronic analogues of C60 and C60(6m)

Structures of mono-doped fullerenes, C59Xn and C59X(6mn)m (X=Bm, N+, P+, As+, Si), the isoelectronic analogues to C60 and C606m with 60 and 66 pi-electrons, have been investigated at the B3LYP/6-31G* level of density functional theory. On the basis of the computed nucleus independent chemical shifts (NICS) at the cage center and also at the center of individual rings as magnetic criteria, heterofullerenes with 60 pi-electrons are as aromatic as the parent C60, while those with 66 pi-electrons are much less aromatic than C606m. The very distinct endohedral chemical shifts of the 66 pi-electron systems may be useful to identify the heterofullerenes through their endohedral 3He NMR chemical shifts.     

Ageing related thyroid deficiency increases brain-targeted transport of liver-derived ApoE4-laden exosomes leading to cognitive impairment

Alzheimer’s disease (AD) is the prevalent cause of dementia in the ageing world population. Apolipoprotein E4 (ApoE4) allele is the key genetic risk factor for AD, although the mechanisms linking ApoE4 with neurocognitive impairments and aberrant metabolism remains to be fully characterised. We discovered a significant increase in the ApoE4 content of serum exosomes in old healthy subjects and AD patients carrying ApoE4 allele as compared with healthy adults. Elevated exosomal ApoE4 demonstrated significant inverse correlation with serum level of thyroid hormones and cognitive function. We analysed effects of ApoE4-containing peripheral exosomes on neural cells and neurological outputs in aged or thyroidectomised young mice. Ageing-associated hypothyroidism as well as acute thyroidectomy augmented transport of liver-derived ApoE4 reach exosomes into the brain, where ApoE4 activated nucleotide-binding oligomerisation domain-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome by increasing cholesterol level in neural cells. This, in turn, affected cognition, locomotion and mood. Our study reveals pathological potential of exosomes-mediated relocation of ApoE4 from the periphery to the brain, this process can represent potential therapeutic target.Subject terms: Cognitive neuroscience, Alzheimer''s disease, Cellular neuroscience     

Nitrate increases cisplatin chemosensitivity of oral squamous cell carcinoma via REDD1/AKT signaling pathway

Although cisplatin is one of the chemotherapeutics most frequently used in oral squamous cell carcinoma (OSCC) treatment,it exerts multiple side effects and poo...     

The Roles of Hypoxia-Inducible Factors in Regulating Neural Stem Cells Migration to Glioma Stem Cells and Determinating Their Fates

The mortality of patients with malignant gliomas remains high despite the advancement in multi-modal therapy including surgery, radio- and chemotherapy. Glioma stem cells (GSCs), sharing some characteristics with normal neural stem cells (NSCs), contribute to the cellular origin for primary gliomas and the recurrence of malignant gliomas after current conventional therapy. Accordingly, targeting GSCs proves to be a promising avenue of therapeutic intervention. The specific tropism of NSCs to GSCs provides a novel platform for targeted delivery of therapeutic agents. Tropism and mobilization of NSCs are enhanced by hypoxia through upregulating chemotactic cytokines and activating several signaling pathways. Moreover, hypoxia-inducible factors (HIFs) produced under hypoxic microenvironment of the stem cell niche play critical roles in the growth and stemness phenotypes regulation of both NSCs and GSCs. However, the definite cellular and molecular mechanisms of HIFs involvement in the process remain obscure. In this review, we focus on the pivotal roles of HIFs in migration of NSCs to GSCs and potential roles of HIFs in dictating the fates of migrated NSCs and targeted GSCs.     

Relationships between musk extraction, social rank and tail-rubbing in male Alpine musk deer, Moschus sifanicus

Musk deer (Moschus spp.) are small, solitary forest ruminants well-known for the musk secreted by adult males. Because of illegal hunting and habitat degradation and loss, the five species of musk deer are classified as endangered. Musk deer farming has been a positive example of ex situ conservation, maintaining deer numbers whilst sustaining musk production. This study was conducted at the Xinglongshan Musk Deer Farm in Gansu Province in northwest China, and was designed to explore the relationships among musk extraction, fighting ability and social rank in captive, male alpine musk deer (Moschus sifanicus). Results showed that musk production was related to a male’s rank in the dominance hierarchy. Males in the middle rank of the dominance hierarchy tended to produce more musk than deer of higher and lower ranks. This is due to the time-energy budgeting patterns and captive stress of males with different status in the dominance hierarchy. That is, high-ranking males need to budget more time and energy to maintain their higher rank, while low-ranking males are exposed to more aggression from higher-ranking individuals, thus limiting their access to resources such as food and shelter. Accordingly, high-ranking and low-ranking males endured more stress than middle-ranking males, negatively affecting their annual musk production. Supporting the correlation between musk production and the frequency of tail-rubbing behavior was not significant, average musk extraction could not be predicted based on the frequency of tail-rubbing alone. Status in the dominance hierarchy, however, was positively correlated with tail-rubbing frequency, with males of higher rank tending to tail-rub more frequently. Conflict winners tended to initiate tail-rubbing after the conflict; tail-rubbing accounted for 83.33% of the post-conflict behavior expressed by the winner. Tail-rubbing was one of the behavioral rewards of winning a conflict and was also related to releasing aggression; not solely for scent marking territory and trails. Based on the results of this study, there was no direct relationship between musk production and captive males’ status in the dominance hierarchy (and, therefore, in the intensity of aggression displayed). If the sole aim of musk deer farms is to domesticate musk deer for maximum production of musk, we suggest that highly aggressive males be removed from the population. Musk production will remain unchanged, however, aggression level and intensity of fighting could be lessened thus reducing farming costs.