Maternal and paternal diversity in Xinjiang Kazakh population from China

The ancient silk road of China passed through Xinjiang and facilitated gene exchanges from the East and the West which impacted on the genetic variation and structure of the nomadic Kazakh population residing there. In order to understand the nature of this genetic variation, 151 Xinjiang Kazakh samples were obtained from four main Kazakh groups and were analyzed using mtDNA and Y-chromosome markers. The Xinjiang Kazakh population is heterogeneous, showing the coexistence of matrilineal lineages with different origins. No genetic differentiation of mtDNA is observed among the four different regional Xinjiang Kazakh populations in Xinjiang by AMOVA and Networks. The genetic diversity of Y-STR loci is higher in Xinjiang Kazakhs (0.968 ± 0.014) than the Kazakhs from Kazakhstan (0.629 ± 0.071) and Russia (0.835 ± 0.020). East Eurasians make a more than 50% contribution to the maternal and paternal lineages of Xinjiang Kazakhs. There is more gene flow from West Eurasian into the maternal lineages of Xinjiang Kazakh than to the Kazakhs from Russia and Kazakhstan. Moreover, mtDNA and Y-STR displayed high polymorphism in Xinjiang Kazakhs (the haplotype diversity and power of discrimination were 0.990 ± 0.003, 0.9137 for mtDNA HVS and 0.968 ± 0.014, 0.9489 for Y-STR system, respectively) suggesting they would be very useful and important markers for forensic analysis and population genetic studies.     

Antigenicity of severe fever with thrombocytopenia syndrome virus nucleocapsid protein and its potential application in the virus serodiagnosis

<正>Dear Editor,Severe fever with thrombocytopenia syndrome virus(SFTSV)is a newly identified viral pathogen of the genus Phlebovirus in the family Bunyaviridae(Sun et al.,2012).SFTSV was first identified from patient serum samples in China(Li et al.,2013;Ning et al.,2015).SFTSV can cause a severe hemorrhagic fever-like disease with a reported case fatality rate ranging from 2.5%     

Inter-subunit Cross-linking Suppressed the Dynamic Oligomeric Dissociation of Mycobacterium tuberculosis Hsp16.3 and Reduced Its Chaperone Activity

Small heat shock proteins (sHsps) usually exist as dynamic oligomers and oligomeric dissociation was believed to be a prerequisite for their chaperone activities. The truth of this hypothesis was verified in our present study on Hsp16.3, one member of sHsps from Mycobacterium tuberculosis, mainly by utilizing chemical cross-linking. Analysis using size exclusion chromatography demonstrated that the heat-induced oligomeric dissociation of Hsp16.3 was severely blocked due to highly efficient inter-subunit cross-linkages generated by chemical cross-linking, as well as its chaperone activity being reduced. Further analysis by non-denaturing pore gradient polyacrylamide gel electrophoresis and fluorescence spectrometry revealed that the dynamic oligomeric dissociation/reassociation process of Hsp16.3 at room temperature was suppressed by inter-subunit cross-linkages, accompanied by significantly decreased exposure of hydrophobic surfaces that are usually hidden in oligomers. These findings supported the hypothesis that substrate-binding sites of sHsps are exposed presumably by dissociation of larger oligomers into smaller active oligomers, and therefore such a dissociation process could be adjusted to modulate chaperone activities.     

Monodisperse Hsp16.3 nonamer exhibits dynamic dissociation and reassociation,with the nonamer dissociation prerequisite for chaperone-like activity

Small heat-shock proteins (sHsps) of various origins exist commonly as oligomers and exhibit chaperone-like activities in vitro. Hsp16.3, the sHsp from Mycobacterium tuberculosis, was previously shown to exist as a monodisperse nonamer in solution when analyzed by size-exclusion chromatography and electron cryomicroscropy. This study represents part of our effort to understand the chaperone mechanism of Hsp16.3, focusing on the role of the oligomeric status of the protein. Here, we present evidence to show that the Hsp16.3 nonamer dissociates at elevated temperatures, accompanied by a greatly enhanced chaperone-like activity. Moreover, the chaperone-like activity was increased dramatically when the nonameric structure of Hsp16.3 was disturbed by chemical cross-linking, which impeded the correct reassociation of Hsp16.3 nonamer. These suggest that the dissociation of the nonameric structure is a prerequisite for Hsp16.3 to bind to denaturing substrate proteins. On the other hand, our data obtained by using radiolabeled and non-radiolabeled proteins clearly demonstrated that subunit exchange occurs readily between the Hsp16.3 oligomers, even at a temperature as low as 4 degrees C. In light of all these observations, we propose that Hsp16.3, although it appears to be homogeneous when examined at room temperature, actually undertakes rapid dynamic dissociation/reassociation, with the equilibrium, and thus the chaperone-like activities, regulated mainly by the environmental temperature.     

A dual role for the N-terminal region of Mycobacterium tuberculosis Hsp16.3 in self-oligomerization and binding denaturing substrate proteins

The N-terminal regions, which are highly variable in small heat-shock proteins, were found to be structurally disordered in all the 24 subunits of Methanococcus jannaschii Hsp16.5 oligomer and half of the 12 subunits of wheat Hsp16.9 oligomer. The structural and functional roles of the corresponding region (potentially disordered) in Mycobacterium tuberculosis Hsp16.3, existing as nonamers, were investigated in this work. The data demonstrate that the mutant Hsp16.3 protein with 35 N-terminal residues removed (DeltaN35) existed as trimers/dimers rather than as nonamers, failing to bind the hydrophobic probe (1,1'-bi(4-anilino)naphthalene-5,5'-disulfonic acid) and exhibiting no chaperone-like activity. Nevertheless, another mutant protein with the C-terminal extension (of nine residues) removed, although existing predominantly as dimers, exhibited efficient chaperone-like activity even at room temperatures, indicating that pre-existence as nonamers is not a prerequisite for its chaperone-like activity. Meanwhile, the mutant protein with both the N- and C-terminal ends removed fully exists as a dimer lacking any chaperone-like activity. Furthermore, the N-terminal region alone, either as a synthesized peptide or in fusion protein with glutathione S-transferase, was capable of interacting with denaturing proteins. These observations strongly suggest that the N-terminal region of Hsp16.3 is not only involved in self-oligomerization but also contains the critical site for substrate binding. Such a dual role for the N-terminal region would provide an effective mechanism for the small heat-shock protein to modulate its chaperone-like activity through oligomeric dissociation/reassociation. In addition, this study demonstrated that the wild-type protein was able to form heterononamers with DeltaN35 via subunit exchange at a subunit ratio of 2:1. This implies that the 35 N-terminal residues in three of the nine subunits in the wild-type nonamer are not needed for the assembly of nonamers from trimers and are thus probably structurally disordered.     

Astrocyte‐dependent protective effect of quetiapine on GABAergic neuron is associated with the prevention of anxiety‐like behaviors in aging mice after long‐term treatment

Previous studies have demonstrated that quetiapine (QTP) may have neuroprotective properties; however, the underlying mechanisms have not been fully elucidated. In this study, we identified a novel mechanism by which QTP increased the synthesis of ATP in astrocytes and protected GABAergic neurons from aging‐induced death. In 12‐month‐old mice, QTP significantly improved cell number of GABAegic neurons in the cortex and ameliorated anxiety‐like behaviors compared to control group. Complimentary in vitro studies showed that QTP had no direct effect on the survival of aging GABAergic neurons in culture. Astrocyte‐conditioned medium (ACM) pretreated with QTP (ACM_QTP) for 24 h effectively protected GABAergic neurons against aging‐induced spontaneous cell death. It was also found that QTP boosted the synthesis of ATP from cultured astrocytes after 24 h of treatment, which might be responsible for the protective effects on neurons. Consistent with the above findings, a Rhodamine 123 test showed that ACM_QTP, not QTP itself, was able to prevent the decrease in mitochondrial membrane potential in the aging neurons. For the first time, our study has provided evidence that astrocytes may be the conduit through which QTP is able to exert its neuroprotective effects on GABAergic neurons.

     

Isolation and Identification of Three Novel Antioxidant Peptides from the Bactrian Camel Milk Hydrolysates

The aim of this study was isolation and purification of antioxidant peptides from Bactrian camel milk (BCM) hydrolysate. Trypsin, pepsin, alcalase, and pap     

Isolation and Identification of a Novel Antioxidant Peptide from Chickpea (Cicer arietinum L.) Sprout Protein Hydrolysates

International Journal of Peptide Research and Therapeutics - Chickpea (Cicer arietinum L.) is the second most widely cultivated leguminous plant in the world. In this study, the chickpea sprout...