Population Structure among Mycobacterium tuberculosis Isolates from Pulmonary Tuberculosis Patients in Colombia

Background

Phylogeographic composition of M. tuberculosis populations reveals associations between lineages and human populations that might have implications for the development of strategies to control the disease. In Latin America, lineage 4 or the Euro-American, is predominant with considerable variations among and within countries. In Colombia, although few studies from specific localities have revealed differences in M. tuberculosis populations, there are still areas of the country where this information is lacking, as is a comparison of Colombian isolates with those from the rest of the world.

Principal Findings

A total of 414 M. tuberculosis isolates from adult pulmonary tuberculosis cases from three Colombian states were studied. Isolates were genotyped using IS6110-restriction fragment length polymorphism (RFLP), spoligotyping, and 24-locus Mycobacterial interspersed repetitive units variable number tandem repeats (MIRU-VNTRs). SIT42 (LAM9) and SIT62 (H1) represented 53.3% of isolates, followed by 8.21% SIT50 (H3), 5.07% SIT53 (T1), and 3.14% SIT727 (H1). Composite spoligotyping and 24-locus MIRU- VNTR minimum spanning tree analysis suggest a recent expansion of SIT42 and SIT62 evolved originally from SIT53 (T1). The proportion of Haarlem sublineage (44.3%) was significantly higher than that in neighboring countries. Associations were found between M. tuberculosis MDR and SIT45 (H1), as well as HIV-positive serology with SIT727 (H1) and SIT53 (T1).

Conclusions

This study showed the population structure of M. tuberculosis in several regions from Colombia with a dominance of the LAM and Haarlem sublineages, particularly in two major urban settings (Medellín and Cali). Dominant spoligotypes were LAM9 (SIT 42) and Haarlem (SIT62). The proportion of the Haarlem sublineage was higher in Colombia compared to that in neighboring countries, suggesting particular conditions of co-evolution with the corresponding human population that favor the success of this sublineage.     

Human Cytomegalovirus Tegument Protein pp65 Is Detected in All Intra- and Extra-Axial Brain Tumours Independent of the Tumour Type or Grade

Human cytomegalovirus (HCMV) has been indicated being a significant oncomodulator. Recent reports have suggested that an antiviral treatment alters the outcome of a glioblastoma. We analysed the performance of commercial HCMV-antibodies applying the immunohistochemical (IHC) methods on brain sample obtained from a subject with a verified HCMV infection, on samples obtained from 14 control subjects, and on a tissue microarray block containing cores of various brain tumours. Based on these trials, we selected the best performing antibody and analysed a cohort of 417 extra- and intra-axial brain tumours such as gliomas, medulloblastomas, primary diffuse large B-cell lymphomas, and meningiomas. HCMV protein pp65 immunoreactivity was observed in all types of tumours analysed, and the IHC expression did not depend on the patient''s age, gender, tumour type, or grade. The labelling pattern observed in the tumours differed from the labelling pattern observed in the tissue with an active HCMV infection. The HCMV protein was expressed in up to 90% of all the tumours investigated. Our results are in accordance with previous reports regarding the HCMV protein expression in glioblastomas and medulloblastomas. In addition, the HCMV protein expression was seen in primary brain lymphomas, low-grade gliomas, and in meningiomas. Our results indicate that the HCMV protein pp65 expression is common in intra- and extra-axial brain tumours. Thus, the assessment of the HCMV expression in tumours of various origins and pathologically altered tissue in conditions such as inflammation, infection, and even degeneration should certainly be facilitated.     

Prognostic Value of Acute Kidney Injury after Cardiac Surgery according to Kidney Disease: Improving Global Outcomes Definition and Staging (KDIGO) Criteria

Objectives

The definition of acute renal failure has been recently reviewed, and the term acute kidney injury (AKI) was proposed to cover the entire spectrum of the syndrome, ranging from small changes in renal function markers to dialysis needs. This study was aimed to evaluate the incidence, morbidity and mortality associated with AKI (based on KDIGO criteria) in patients after cardiac surgery (coronary artery bypass grafting or cardiac valve surgery) and to determine the value of this feature as a predictor of hospital mortality (30 days).

Methods

From January 2003 to June 2013, a total of 2,804 patients underwent cardiac surgery in our service. Cox proportional hazard models were used to determine the association between the development of AKI and 30-day mortality.

Results

A total of 1,175 (42%) patients met the diagnostic criteria for AKI based on KDIGO classification during the first 7 postoperative days: 978 (35%) patients met the diagnostic criteria for stage 1 while 100 (4%) patients met the diagnostic criteria for stage 2 and 97 (3%) patients met the diagnostic criteria for stage 3. A total of 63 (2%) patients required dialysis treatment. Overall, the 30-day mortality was 7.1% (2.2%) for patients without AKI and 8.2%, 31% and 55% for patients with AKI at stages 1, 2 and 3, respectively. The KDIGO stage 3 patients who did not require dialysis had a mortality rate of 41%, while the mortality of dialysis patients was 62%. The adjusted Cox regression analysis revealed that AKI based on KDIGO criteria (stages 1–3) was an independent predictor of 30-day mortality (P<0.001 for all. Hazard ratio = 3.35, 11.94 and 24.85).

Conclusion

In the population evaluated in the present study, even slight changes in the renal function based on KDIGO criteria were considered as independent predictors of 30-day mortality after cardiac surgery.     

Aberrant methylation of p16, HIC1, N33, and GSTP1 in tumor epithelium and tumor-associated cells in prostate cancer

The methylation status of p16, HIC1, N33, and GSTP1, which are involved in prostate carcinogenesis, was studied in prostate tissue samples containing neoplasms. Malignant acini, prostatic intraepithelial neoplasia (PIN) and benign prostatic hyperplasia (BPH) foci, and stroma surrounding glandular structures of each type were detected in histological sections, using laser capture microdissection of prostate tissue. High levels of methylation were found in tumor epithelium and adjacent tumor-associated stromal cells. Epigenetic changes in the stroma are indicative of a major role of tumor microenvironment in cancer development and progression. The methylation status of p16, HIC1, N33, and GSTP1 was also assessed in prostate biopsy material and operative tumor samples without laser capture microdissection. The methylation frequencies of all genes in tumor samples were considerably lower than those in microdissected tumor samples (HIC1, 71% vs. 89%; p16, 22% vs. 78%; GSTP1, 32% vs. 100%; and N33, 20% vs. 33%, respectively). It was concluded that laser capture micro-dissection is required in molecular analysis of tumors of this type.     

Functional anthology of intrinsic disorder. 1. Biological processes and functions of proteins with long disordered regions

Identifying relationships between function, amino acid sequence, and protein structure represents a major challenge. In this study, we propose a bioinformatics approach that identifies functional keywords in the Swiss-Prot database that correlate with intrinsic disorder. A statistical evaluation is employed to rank the significance of these correlations. Protein sequence data redundancy and the relationship between protein length and protein structure were taken into consideration to ensure the quality of the statistical inferences. Over 200,000 proteins from the Swiss-Prot database were analyzed using this approach. The predictions of intrinsic disorder were carried out using PONDR VL3E predictor of long disordered regions that achieves an accuracy of above 86%. Overall, out of the 710 Swiss-Prot functional keywords that were each associated with at least 20 proteins, 238 were found to be strongly positively correlated with predicted long intrinsically disordered regions, whereas 302 were strongly negatively correlated with such regions. The remaining 170 keywords were ambiguous without strong positive or negative correlation with the disorder predictions. These functions cover a large variety of biological activities and imply that disordered regions are characterized by a wide functional repertoire. Our results agree well with literature findings, as we were able to find at least one illustrative example of functional disorder or order shown experimentally for the vast majority of keywords showing the strongest positive or negative correlation with intrinsic disorder. This work opens a series of three papers, which enriches the current view of protein structure-function relationships, especially with regards to functionalities of intrinsically disordered proteins, and provides researchers with a novel tool that could be used to improve the understanding of the relationships between protein structure and function. The first paper of the series describes our statistical approach, outlines the major findings, and provides illustrative examples of biological processes and functions positively and negatively correlated with intrinsic disorder.     

RGD Peptide–Albumin Conjugate for Endothelization of Electrospun Materials

Russian Journal of Bioorganic Chemistry - To improve the endothelization of 3D matrices produced by electrospinning we propose adding cyclo(RGDfC) peptide conjugated to human serum albumin (HSA)...