Clusterin (CLU) is considered one of the most important roles for pathogenesis of Alzheimer’s Disease (AD). The early genome-wide association studies (GWAS) identified the CLU rs11136000 polymorphism is significantly associated with AD in Caucasian. However, the subsequent studies are unable to replicate these findings in different populations. Although two independent meta-analyses show evidence to support significant association in Asian and Caucasian populations by integrating the data from 18 and 25 related GWAS studies, respectively, many of the following 18 studies also reported the inconsistent results. Moreover, there are six missed and a misclassified GWAS studies in the two meta-analyses. Therefore, we suspected that the small-scale and incompletion or heterogeneity of the samples maybe lead to different results of these studies. In this study, large-scale samples from 50 related GWAS studies (28,464 AD cases and 45,784 controls) were selected afresh from seven authoritative sources to reevaluate the effect of rs11136000 polymorphism to AD risk. Similarly, we identified that the minor allele variant of rs11136000 significantly decrease AD risk in Caucasian ethnicity using the allele, dominant and recessive model. Different from the results of the previous studies, however, the results showed a negligible or no association in Asian and Chinese populations. Collectively, our analysis suggests that, for Asian and Chinese populations, the variant of rs11136000 may be irrelevant to AD risk. We believe that these findings can help to improve the understanding of the AD’s pathogenesis.
In karst rocky desertification areas, bryophytes coexist with algae, bacteria, and fungi on exposed calcareous rocks to form a bryophyte crust, which plays an irreplaceable role in the restoration of karst degraded ecosystems. We investigated the biodiversity of crust bryophytes in karst rocky desertification areas from Guizhou Province, China. A total of 145 species in 22 families and 56 genera were identified. According to frequency and coverage, seven candidate dominant mosses were screened out, and five drought-resistant indexes of them were measured. Hypnum leptothallum, Racopilum cuspidigerum, and Hyophila involuta have high drought adaptability. We explored the interactions between two dominant mosses (H. leptothallum, H. involuta) and the structure of microbial communities in three karst rocky desertification types. Microbial diversity and function analysis showed that both moss species and karst rocky desertification types affect microbial communities. Moss species much more strongly affected the diversity and changed the community composition of these microbial groups. Bacteria were more sensitive in the microbiome as their communities changed strongly between mosses and drought resistance factors. Moreover, several species of fungi and bacteria could be significantly associated with three drought-resistant indexes: Pro (free proline content), SOD (superoxide dismutase activity), and POD (peroxidase activity), which were closely related to the drought adaptability of mosses. Our results enforced the potential role of moss-associated microbes that are important components involved in the related biological processes when bryophytes adapted to arid habitats, or as one kind of promoters in the distribution pattern of early mosses succession in karst rocky desertification areas.
Fluorescent stapled peptides are important chemical tools for detecting intracellular distribution, protein-protein interactions, and localization of target proteins. These peptides are usually labeled with bulky sized fluorophores through reactive functional groups, which may alter the physical properties and biological activities of peptides. Herein, au nique strategy is developed for synthesizing new stapled peptides with built-in fluorescence. The stapled peptides were prepared throughR h-catalyzed C(sp 2)ÀHo lefination in tryptophan (Trp) residues by using pyridine/pyrimi-dine as the directing groups under mild conditions. This methodd isplays good regioselectivity and high efficiency. Furthermore, as ap roof of concept for its biological applications, stapled peptides without additional fluorophore 9a and 9b were constructed for ac ell imaging study.T hese peptides displayed strongb inding affinity toward integrin avb3i nA 549 cells by cell imaging experiments. Notably they demonstrated even better anticancer activity than commercial antagonist cyclic (RGDfK). The methodw ill provide robust tools for the peptidemacrocyclization field.
The Hirsutella genus is very special asexually-reproducing pathogens of insects by reduced sporulation, host specificity and spores covered by a thick mucilage layer. However, the ecological function of conidial mucilage remains elusive. In this study, the possible ecological role of conidial mucilage from the entomopathogenic fungus Hirsutella satumaensis was functionally investigated through tolerance, adherence and insect bioassays involving aerial conidia (AC) and mucilage-free conidia (MFC). Measurements of hydrophobicity using microbial adhesion to hydrocarbons (MATH) indicated that mucilage is main contributor to the surface hydrophobicity of AC. When subjected in tolerance assays to extreme temperatures, high chemical pressure, extended exposure to ultraviolet radiation and cold stress, AC produced more colonies, exhibited higher conidiation and germination percentages than those of MFC. In adhesion assays, MFC displayed an approximately 40% reduction in adherence to locust, dragonfly cuticle and onion epidermis when washed with 0.05% Tween 20. Similarly, Galleria mellonella and Plutella xylostella larvae infected with mucilage-producing AC experienced a relatively higher mortality rate. Our findings suggest that mucilage is critical to the ecological adaptability of H. satumaensis, where it plays positive roles on maintenance of spore surface hydrophobicity, enhancement of spore resistance to extreme environments and strengthening of spore adhesion and host pathogenicity.
A novel chemiluminescent probe based on intramolecular cyclization for hydrazine detection in living cells.
BackgroundHirsutella Pat genus, the asexual morphs of the Ophiocordyceps Sung, is globally distributed entomopathogenic fungi, which infect a variety of arthropods, mites and nematodes. The fungal species also have shown potential application in the field of biological control, bio-medicine and food development. Although these fungi are synonymized under Ophiocordyceps, formal taxonomic assignments remain necessary for classification of species in Hirsutella. However, due to the heterogeneity and complexity of Hirsutella genus, more detailed taxonomic and phylogenetic analyses are required to address the following subjects: (1) the relationships between the phialide morphological characteristics and phylogenetic information of Hirsutella with asexual morphs, (2) the origin and evolution of the phialide structure, and (3) host specificity and fungal pathogenicity.ResultsFive typical phialide structures are summarized, in which the variation in phialide characteristics overlaps well with phylogenetic information. A new member of the special twisted neck clade in the Hirsutella-like group, Ophiocordyceps retorta, was reported based on these analyses. The molecular clock calibration analysis based on one fossil record revealed that Hirsutella (asexual morph) species originated from a common ancestor approximately 102 million years ago (Mya) (Early Cretaceous, Lower Albian) and then resolved into two major lineages. One lineage was typically phialidic, which was a larger shape, including H. guyana, H. nodulosa and H. sinensis clades (86.9 Mya, 95% highest posterior density (HPD): 69.1–101.4 Mya). Another main lineage of the phialides was more diversified and smaller than the former, which included H. citriformis and H. thompsonii clades (71.9 Mya, 95% HPD: 41.8–99.6 Mya).ConclusionsOur results showed that certain phialide characteristics of Hirsutella were phylogenetically informative for two groups of taxa. The differentiation of the phialides structures in the major clades demonstrated a clear evolutionary path of Hirsutella (asexual morph) species, which exhibited two trends depending on the host size. Fungi in one of the groups displayed elongated conidiogenous cells with increased complexity of auxiliary structures from the mycelia. The species in another group reduced the volume of phialides and spores, which might be due to an energy-efficient strategy. These results suggested that a common origin allowed for diversification of given clades into separate niches. The distinct parallel evolutionary path combined with the specific phialides structure might result in the host specificity of Hirsutella (asexual morphs). A direct relationship between Hirsutella (asexual morphs) and the Cretaceous–Tertiary extinction was not found, which suggested that the diversity of phialides is more likely to be caused by long-term environmental adaptation and evolution rather than dramatic extinction events. This evolutionary result might correspond to the background of important biological and geological events in the late Creta...
Multiple sclerosis (MS) is a sex-specific autoimmune disease involving central nervous system. Previous studies determined that macrophage migration inhibitory factor (MIF) and its homologue D-dopachrome tautomerase (DDT) sex-specifically affect MS progression. Moreover, other studies reported that rs755622 polymorphism in promoter region of MIF gene is associated with risk of MS and affects the promoter activity to regulate MIF expression in a sex-specific way. Given that MIF and DDT share a part of promoter sequence, we surmise that rs755622 can also regulate DDT expression in a sex-specific way. However, this has not yet been studied. Here, we used five large-scale expression quantitative trait loci (eQTLs) and two RNA-seq datasets from brain and blood to assess the potential influence of rs755622 variant on expression of DDT in different genders by the linear regression and differential expression analysis. The results show that the minor allele frequency of rs755622 and expression of DDT are significantly increased in males for MS subjects and this minor allele variant can significantly upregulate DDT expression for males but not females, which suggests that the regulation of DDT expression level by rs755622 can affect MS progression in males. These findings further support and expand conclusions of previous studies and may help to better understand the mechanisms of MS.
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