ATP-sensitive potassium channels (KATP) are energy sensors on the plasma membrane. By sensing the intracellular ADP/ATP ratio of β-cells, pancreatic KATP channels control insulin release and regulate metabolism at the whole body level. They are implicated in many metabolic disorders and diseases and are therefore important drug targets. Here, we present three structures of pancreatic KATP channels solved by cryoelectron microscopy (cryo-EM), at resolutions ranging from 4.1 to 4.5 Å. These structures depict the binding site of the antidiabetic drug glibenclamide, indicate how Kir6.2 (inward-rectifying potassium channel 6.2) N-terminus participates in the coupling between the peripheral SUR1 (sulfonylurea receptor 1) subunit and the central Kir6.2 channel, reveal the binding mode of activating nucleotides, and suggest the mechanism of how Mg-ADP binding on nucleotide binding domains (NBDs) drives a conformational change of the SUR1 subunit. 相似文献
Chevrier's field mouse, Apodemus chevrieri Milne-Edwards (Rodentia: Muridae), has been identified as the main wild reservoir of plague in the sylvatic plague focus of Yunnan Province, southwest China. Here, the ectoparasite communities of A. chevrieri and the potential medical and veterinary importance of these ectoparasites are described. A high proportion (66%) of 321 mice were found to be infested with ectoparasites. A total of 81 species of ectoparasite, including 48 species of chigger mite, 25 species of mesostigmatid (gamasid) mite, six species of flea and two species of sucking louse were collected. Most species of ectoparasite were relatively uncommon, but a few were abundant. Within this ectoparasite complex, 16 species have previously been reported to be vectors of human disease agents. Apodemus chevrieri would appear therefore to be a natural reservoir for plague bacilli and epidemic haemorrhagic fever (Korean haemorrhagic fever) viruses. 相似文献
Early diagnosis of sepsis and bacterial infection is imperative as treatment relies on early antibiotic administration. There is a need to develop new biomarkers to detect patients with sepsis and bacterial infection as early as possible, thereby enabling prompt antibiotic treatment and improving the survival rate.
Methods
Fifty-one adult patients with suspected bacterial sepsis on admission to the Emergency Department (ED) of a teaching hospital were included into the study. All relevant cultures and serology tests were performed. Serum levels for Group II Secretory Phospholipase A2 (sPLA2-IIA) and CD64 were subsequently analyzed.
Results and Discussion
Sepsis was confirmed in 42 patients from a total of 51 recruited subjects. Twenty-one patients had culture-confirmed bacterial infections. Both biomarkers were shown to be good in distinguishing sepsis from non-sepsis groups. CD64 and sPLA2-IIA also demonstrated a strong correlation with early sepsis diagnosis in adults. The area under the curve (AUC) of both Receiver Operating Characteristic curves showed that sPLA2-IIA was better than CD64 (AUC = 0.93, 95% confidence interval (CI) = 0.83–0.97 and AUC = 0.88, 95% CI = 0.82–0.99, respectively). The optimum cutoff value was 2.13μg/l for sPLA2-IIA (sensitivity = 91%, specificity = 78%) and 45 antigen bound cell (abc) for CD64 (sensitivity = 81%, specificity = 89%). In diagnosing bacterial infections, sPLA2-IIA showed superiority over CD64 (AUC = 0.97, 95% CI = 0.85–0.96, and AUC = 0.95, 95% CI = 0.93–1.00, respectively). The optimum cutoff value for bacterial infection was 5.63μg/l for sPLA2-IIA (sensitivity = 94%, specificity = 94%) and 46abc for CD64 (sensitivity = 94%, specificity = 83%).
Conclusions
sPLA2-IIA showed superior performance in sepsis and bacterial infection diagnosis compared to CD64. sPLA2-IIA appears to be an excellent biomarker for sepsis screening and for diagnosing bacterial infections, whereas CD64 could be used for screening bacterial infections. Both biomarkers either alone or in combination with other markers may assist in decision making for early antimicrobial administration. We recommend incorporating sPLA2-IIA and CD64 into the diagnostic algorithm of sepsis in ED. 相似文献
Microorganisms play an important role in the growth and development of numerous insect species. The mulberry silkworm, Bombyx mori (Lepidoptera), harbors several bacteria in its midgut aiding the metabolic processes; however, the variability of bacterial spp. present in the midgut and their role(s) in the growth and development of the silkworm are poorly understood. The present work compares the diversity of midgut bacterial communities in silkworms of variable voltinism (Pure Mysore, PM: multivoltine; CSR2: bivoltine and PM × CSR2: crossbreed) through metagenomics. The predominance of Enterococcus (30.30%) followed by Bacillus (16.96%) was observed in PM, whereas Lactobacillus (56.56%) followed by Enterococcus (10.58%) was seen only in CSR2. Interestingly, crossbreed midgut harbored diverse bacterial communities (36.21% Lactobacillus, 25.94% Bacillus, 8.1% Enterococcus, and 18.37% uncultured bacteria). Metagenomic profiles indicate variability in the gut bacterial population in different kinds of silkworms influencing the physiological activities accordingly. The dominant bacteria, particularly lactobacilli, bacilli, and enterococci could be further explored for identifying the potential probiotic consortia based on a literature survey and potential involvement in nutrient absorption, disease/stress tolerance, and improved economic traits.
In the present work, DNA was extrated from 63 skeletal samples recovered at the Neolithic site of San Juan ante Portam Latinam
(SJAPL) (Araba, Basque Country). These samples have proved useful as genetic material for the performance of population studies.
To achieve this it was necessary to overcome the methodological problems arising when working with damaged DNA molecules.
We succeeded in performing an amplification and restriction analysis of the polymorphisms present in the mtDNA. Ninety seven
percent of the samples were classified as belonging to one of the nine mtDNA haplogroups described in Caucasians. This work
shows that restriction analysis is a useful methodological tool to perform reliable population genetic analysis on archaeological
remains. Tha analysis of ancient and modern haplogroup distribution can shed more light on the genetic evolution of human
populations. Moreover, a more exhaustive data on prehistoric populations will allow to build stronger hypothesis on the genetic
relationships among human populations. 相似文献