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Actinobacillus pleuropneumoniae is a Gram-negative bacterium causing porcine pleuropneumonia and severe economic losses in the global swine industry. The toxic trace element copper is required for many physiological and pathological processes in organisms. However, CopA, one of the most well-characterized P-type ATPases contributing to copper resistance, has not been characterized in A. pleuropneumoniae. We used quantitative PCR analysis to examine expression of the copA gene in A. pleuropneumoniae and investigated sequence conservation among serotypes and other Gram-negative bacteria. Growth characteristics were determined using growth curve analyses and spot dilution assays of the wild-type strain and a △copA mutant. We also used flame atomic absorption spectrophotometry to determine intracellular copper content and examined the virulence of the △copA mutant in a mouse model. The copA expression was induced by copper, and its nucleotide sequence was highly conserved among different serotypes of A. pleuropneumoniae. The amino acid sequence of CopA shared high identity with CopA sequences reported from several Gram-negative bacteria. Furthermore, the △copA mutant exhibited impaired growth and had higher intracellular copper content compared with the wild-type strain when supplemented with copper. The mouse model revealed that CopA had no influence on the virulence of A. pleuropneumoniae. In conclusion, these results demonstrated that CopA is required for resistance of A. pleuropneumoniae to copper and protects A. pleuropneumoniae against copper toxicity via copper efflux.
The interplay between cortical surface thickness (CTh), subcortical volumes (SCV) and disability in patients with relapsing remitting multiple sclerosis (RRMS) is still not clear.
To examine the relationship between CTh, SCV, and disability and investigate differences in CTh, SCV and disability between African Americans (AA) and Caucasian Americans (CA).
Sixty-five RRMS (33AA, 32 CA) participants underwent Expanded Disability Status Scale and Multiple Sclerosis Functional Composite (MSFC) assessments, including timed 25-foot walk (T25FW), nine-hole peg test (9HPT) on dominant (D) and non-dominant hand (ND) and paced auditory serial addition test (PASAT-3). Symbol digit modalities test (SDMT) was also administered. All participants underwent 3T brain MRI. CTh was measured in the Frontal (FA), Parietal (PA), Temporal (TA), Occipital (OA), Cingulate (CA), and Global (GA) cortical surface areas (CSA). SCV measurements included Thalamus (TV), Caudate (CV), Putamen (PV), Pallidum (PaV), Hippocampus (HV), Amyg contributor to disability. Longitudinal, large-scale studies are warranted to confirm our findings.
Differences in CSA CTh reinforce the different disease pathobiology between AA and CA. Regional CTh may represent a useful biomarker related to multi-domain disability only in CA, while in AA DGM injury might be a more important contributor to disability. Longitudinal, large-scale studies are warranted to confirm our findings.
The volume change of multiple sclerosis (MS) lesion is related to its activity and can be used to assess disease progression. Therefore, the purpose of this study was to develop radiomics models for predicting the evolution of unenhanced MS lesions by using different kinds of machine learning algorithms and explore the optimal model.
In this prospective observation, 45 follow-up MR images obtained in 36 patients with MS (mean age 32.53±10.91; 23 women, 13 men) were evaluated. The lesions will be defined as interval activity and interval inactivity, respectively, based on the percentage of enlargement or reduction of the lesion >20% in the follow-up MR images. We extracted radiomic features of lesions on FLAIR images, and used recursive feature elimination (RFE), ReliefF algorithm and least absolute shrinkage and selection operator (LASSO) for feature selection, then three classification models including logistic regression, random forest and support vector machine (SVM) were used to build predictive moredicting the evolution of MS lesions.
The results demonstrated that the radiomics-based machine learning model has potential in predicting the evolution of MS lesions.
The associations between cadmium exposure and chronic kidney disease have rarely been reported in longitudinal studies. In this study, we investigated the associations between the estimated glomerular filtration rate and cadmium exposure in a cross-sectional study in a longitudinal cohort.
In total, 790 subjects (≥35 years of age) living in southeastern China were included at 1998. Cadmium in blood (BCd) and urine (UCd) as well as renal dysfunction biomarkers, urinary N-acetyl-β d-glucosaminidase (UNAG) and albumin (UALB), were determined. selleck products 497 subjects were followed at 2006 and a total of 456 subjects were finally included after excluding subjects that did not have exposure or effects biomarkers. The BCd, UCd, UNAG and UALB were determined using baseline methods. At follow-up, the estimated glomerular filtration rate (eGFR) was computed using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation. Single nucleotide polymorphisms (SNPs) in metallothioneins 1A (MT1A) rs11076161 and MT2A rsct the nomogram. Linear discriminant analysis (LCA) showed that 87.6% of CKD was accurately predicted based on the three factors.
Baseline age, BCd and UALB were associated with follow-up eGFR, and baseline BCd and UALB were predictive factors for incidence of CKD.
Baseline age, BCd and UALB were associated with follow-up eGFR, and baseline BCd and UALB were predictive factors for incidence of CKD.Imidazole and thiadiazole derivatives display an extensive application in pharmaceutical chemistry, and they have been investigated as bioactive molecules for medicinal chemistry purposes. Classical carbonic anhydrase (CA) inhibitors are based on sulfonamide groups, but inhibiting all CA isoforms nonspecifically, thereby causing undesired side effects, is the main drawback of these types of inhibitors. Here we reported an investigation of novel 2,6-disubstituted imidazo[2,1-b][1,3,4]thiadiazole derivatives (9a-k, 10a, and 11a) and 2,5,6-trisubstituted imidazo[2,1-b][1,3,4]thiadiazole derivatives (12a-20a) that do not possess the zinc-binding sulfonamide group for the inhibition of human carbonic anhydrase (hCA, EC 4.2.1.1) I and II isoforms and also of acetylcholinesterase (AChE, EC 3.1.1.7). Imidazo[2,1-b][1,3,4]thiadiazoles demonstrated low nanomolar inhibitory activity against hCA I, hCA II, and AChE (KIs are in the range of 23.44-105.50 nM, 10.32-104.70 nM, and 20.52-54.06 nM, respectively). Besides, compound 9b inhibit hCA I up to 18-fold compared to acetazolamide, while compound 10a has a 5-fold selectivity towards hCA II.
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