Complete Genome Sequence Analysis of Nocardia brasiliensis HUJEG-1 Reveals a Saprobic Lifestyle and the Genes Needed for Human Pathogenesis

Nocardia brasiliensis is an important etiologic agent of mycetoma. These bacteria live as a saprobe in soil or organic material and enter the tissue via minor trauma. Mycetoma is characterized by tumefaction and the production of fistula and abscesses, with no spontaneous cure. By using mass sequencing, we determined the complete genomic nucleotide sequence of the bacteria. According to our data, the genome is a circular chromosome 9,436,348-bp long with 68% G+C content that encodes 8,414 proteins. We observed orthologs for virulence factors, a higher number of genes involved in lipid biosynthesis and catabolism, and gene clusters for the synthesis of bioactive compounds, such as antibiotics, terpenes, and polyketides. An in silico analysis of the sequence supports the conclusion that the bacteria acquired diverse genes by horizontal transfer from other soil bacteria, even from eukaryotic organisms. The genome composition reflects the evolution of bacteria via the acquisition of a large amount of DNA, which allows it to survive in new ecological niches, including humans

CyberKnife Robotic-Assisted Stereotactic Radiosurgery for Advanced Stages of Ciliochoroidal Uveal Melanoma. Preliminary Results in Mexico

Objective: The objective of this study was to report the early results of CyberKnife® (CK®) stereotactic radiosurgery in advanced stages of ciliochoroidal (CBCh) melanoma in Mexican patients. Methods: A retrospective review of charts was performed to analyze the outcomes of patients who underwent CK® (Accuray Inc, Sunnyvale, CA, United States). Results: Four patients with CBCh melanoma were treated under this protocol. The mean age was 53.2 ± 5.3 years (range, 47-60). Median of follow-up was 9.5 ± 3.1 months (range, 5-12). Mean tumor diameter was 13.49 mm, mean thickness, 11.74 mm, and mean gross tumor volume was 1251.97 mm3. Tumors were dome- (50%) and mushroom-shaped (50%) in medium-to-large sizes. Three patients had T3b tumors, and one had a T4d tumor at the early tumor staging according to the American Joint Committee on Cancer. A mean dose of 2763 ± 181.3 cGy was prescribed to the 90% isodose line. All patients achieved local tumor control after single-session radiosurgery at the latest follow-up. One patient presented with acute toxicity (extensive serous retinal detachment associated with radiation induced tumor vasculopathy) that was promptly managed. None of the patients required secondary enucleation. Conclusions: CK® appears to be an effective therapy for medium to large-sized CBCh melanoma. A prospective comparative study with longer follow-up is needed to confirm these findings and to evaluate long-term morbidity

Evidence of spatial clustering of childhood acute lymphoblastic leukemia cases in Greater Mexico City: report from the Mexican Inter-Institutional Group for the identification of the causes of childhood leukemia

BackgroundA heterogeneous geographic distribution of childhood acute lymphoblastic leukemia (ALL) cases has been described, possibly, related to the presence of different environmental factors. The aim of the present study was to explore the geographical distribution of childhood ALL cases in Greater Mexico City (GMC).MethodsA population-based case-control study was conducted. Children <18 years old, newly diagnosed with ALL and residents of GMC were included. Controls were patients without leukemia recruited from second-level public hospitals, frequency-matched by sex, age, and health institution with the cases. The residence address where the patients lived during the last year before diagnosis (cases) or the interview (controls) was used for geolocation. Kulldorff’s spatial scan statistic was used to detect spatial clusters (SCs). Relative risks (RR), associated p-value and number of cases included for each cluster were obtained.ResultsA total of 1054 cases with ALL were analyzed. Of these, 408 (38.7%) were distributed across eight SCs detected. A relative risk of 1.61 (p<0.0001) was observed for the main cluster. Similar results were noted for the remaining seven ones. Additionally, a proximity between SCs, electrical installations and petrochemical facilities was observed.ConclusionsThe identification of SCs in certain regions of GMC suggest the possible role of environmental factors in the etiology of childhood ALL

Genome annotation of a Saccharomyces sp. lager brewer's yeast

The genome of lager brewer's yeast is a hybrid, with Saccharomyces eubayanus and Saccharomyces cerevisiae as sub-genomes. Due to their specific use in the beer industry, relatively little information is available. The genome of brewing yeast was sequenced and annotated in this study. We obtained a genome size of 22.7 Mbp that consisted of 133 scaffolds, with 65 scaffolds larger than 10 kbp. With respect to the annotation, 9939 genes were obtained, and when they were submitted to a local alignment, we found that 53.93% of these genes corresponded to S. cerevisiae, while another 42.86% originated from S. eubayanus. Our results confirm that our strain is a hybrid of at least two different genomes

Bioassay-Guided Isolation and Identification of Cytotoxic Compounds from <em>Gymnosperma</em> <em>glutinosum</em> Leaves

Bioassay-guided fractionation of hexane extracts of<em> Gymnosperma glutinosum</em> (Asteraceae) leaves, collected in North Mexico, afforded the known compounds hentriacontane (<strong>1</strong>) and (+)-13<em>S</em>,14<em>R</em>,15-trihydroxy-<em>ent</em>-labd-7-ene (<strong>2</strong>), as well as the new <em>ent</em>-labdane diterpene (−)-13<em>S</em>,14<em>R</em>,15-trihydroxy-7-oxo-<em>ent</em>-labd-8(9)-ene (<strong>3</strong>). In addition, D-glycero-D-galactoheptitol (<strong>4</strong>) was isolated from the methanolic extract of this plant. Their structures were established on the basis of high-field 1D- and 2D NMR methods supported by HR-MS data. The cytotoxic activity was determined by using the <em>in vitro</em> L5178Y-R lymphoma murine model. Hentriacontane (<strong>1</strong>) and the new <em>ent</em>-labdane <strong>3</strong> showed weak cytotoxicity, whereas the <em>ent</em>-labdane <strong>2</strong> showed significant (<em>p</em> < 0.05) and concentration dependent cytotoxicity (up to 78%) against L5178Y-R cells at concentrations ranging from 7.8 to 250 µg/mL

Functional characterization of NK cells in Mexican pediatric patients with acute lymphoblastic leukemia: Report from the Mexican Interinstitutional Group for the Identification of the Causes of Childhood Leukemia.

Acute lymphoblastic leukemia (ALL) is the most common cancer in children around the globe. Mexico City has one of the highest incidence rates of childhood leukemia worldwide with 49.5 cases per million children under the age of 15 which is similar to that reported for Hispanic populations living in the United States. In addition, it has been noted a dismal prognosis in Mexican and Hispanic ALL pediatric population. Although ALL, like cancer in general, has its origins in endogenous, exogenous, and genetic factors, several studies have shown that the immune system also plays a deterministic role in cancer development. Among various elements of the immune system, T lymphocytes and NK cells seem to dominate the immune response against leukemia. The aim of the present study was to perform a phenotypic and functional characterization of NK cells in ALL Mexican children at the moment of diagnosis and before treatment initiation. A case-control study was conducted by the Mexican Interinstitutional Group for the Identification of the Causes of Childhood Leukemia (MIGICCL). 41 cases were incident ALL children younger than 17 years old and residents of Mexico City. 14 controls were children without leukemia, matched by age and sex with cases. NK cell function was evaluated by degranulation assays towards K562 cells and SLAM-associated protein (SAP) expression was measured by intracellular staining. All assays were performed using peripheral blood mononuclear cells from controls and patients. The results indicate that NK mediated cytotoxicity, measured by CD107a degranulation assays in response to K562 cells, was reduced in ALL patients compared to controls. Interestingly, an impaired NK cell killing of target cells was not equally distributed among ALL patients. In contrast to patients classified as high-risk, standard-risk patients did not display a significant reduction in NK cell-mediated cytotoxicity. Moreover, patients presenting a leukocyte count ≥ 50,000xmm3 displayed a reduction in NK-cell mediated cytotoxicity and a reduction in SAP expression, indicating a positive correlation between a reduced SAP expression and an impaired NK cell-mediated citotoxicity. In the present study it was observed that unlike patients with standard-risk, NK cells from children presenting high-risk ALL, harbor an impaired cytotoxicity towards K562 at diagnosis. In addition, NK cell function was observed to be compromised in patients with a leukocyte count ≥50,000xmm3, where also it was noticed a decreased expression of SAP compared to patients with a leukocyte count <50,000xmm3. These data indicate NK cell-mediated cytotoxicity is not equally affected in ALL patients, nevertheless a positive correlation between low SAP expression and decreased NK cell-mediated cytotoxicity was observed in ALL patients with a leukocyte count ≥50,000xmm3. Finally, an abnormal NK cell-mediated cytotoxicity may represent a prognostic factor for high-risk acute lymphoblastic leukemia

Table_1_Evidence of spatial clustering of childhood acute lymphoblastic leukemia cases in Greater Mexico City: report from the Mexican Inter-Institutional Group for the identification of the causes of childhood leukemia.xlsx

BackgroundA heterogeneous geographic distribution of childhood acute lymphoblastic leukemia (ALL) cases has been described, possibly, related to the presence of different environmental factors. The aim of the present study was to explore the geographical distribution of childhood ALL cases in Greater Mexico City (GMC).MethodsA population-based case-control study was conducted. Children ResultsA total of 1054 cases with ALL were analyzed. Of these, 408 (38.7%) were distributed across eight SCs detected. A relative risk of 1.61 (pConclusionsThe identification of SCs in certain regions of GMC suggest the possible role of environmental factors in the etiology of childhood ALL.</p