A novel DNA-binding motif in prostate tumor overexpressed-1 (PTOV1) required for the expression of ALDH1A1 and CCNG2 in cancer cells

PTOV1 is a transcription and translation regulator and a promoter of cancer progression. Its overexpression in prostate cancer induces transcription of drug resistance and self-renewal genes, and docetaxel resistance. Here we studied PTOV1 ability to directly activate the transcription of ALDH1A1 and CCNG2 by binding to specific promoter sequences. Chromatin immunoprecipitation and electrophoretic mobility shift assays identified a DNA-binding motif inside the PTOV-A domain with similarities to known AT-hooks that specifically interacts with ALDH1A1 and CCNG2 promoters. Mutation of this AT-hook-like sequence significantly decreased the expression of ALDH1A1 and CCNG2 promoted by PTOV1. Immunohistochemistry revealed the association of PTOV1 with mitotic chromosomes in high grade prostate, colon, bladder, and breast carcinomas. Overexpression of PTOV1, ALDH1A1, and CCNG2 significantly correlated with poor prognosis in prostate carcinomas and with shorter relapse-free survival in colon carcinoma. The previously described interaction with translation complexes and its direct binding to ALDH1A1 and CCNG2 promoters found here reveal the PTOV1 capacity to modulate the expression of critical genes at multiple levels in aggressive cancers. Remarkably, the AT-hook motifs in PTOV1 open possibilities for selective targeting its nuclear and/or cytoplasmic activities

Wavelength tuning of fiber lasers using multimode interference effects

We report on a novel scheme to fabricate a simple, cheap, and compact tunable fiber laser. The tuning is realized by splicing a piece of single-mode fiber to one end of an active double-clad fiber, while the other end of the single-mode fiber is spliced to a 15 mm long section of 105/125 multimode fiber. The fluorescence signal entering into the multimode fiber will be reproduced as single images at periodic intervals along the propagation direction of the fiber. The length of the multimode fiber is chosen to be slightly shorter than the first re-imaging point, such that the signal coming out from the single mode fiber is obtained in free space, where a broadband mirror retroreflects the fluorescence signal. Since the position of the re-imaging point is wavelength dependent, different wavelengths will be imaged at different positions. Therefore, wavelength tuning is easily obtained by adjusting the distance between the broadband mirror and the multimode fiber facet end. Using this principle, the tunable fiber laser revealed a tunability of 8 nm, ranging from 1088-1097 nm, and an output power of 500 mW. The simplicity of the setup makes this a very cost-effective tunable fiber laser

Sensitization of retinoids and corticoids to epigenetic drugs in MYC-activated lung cancers by antitumor reprogramming

Components of the SWI/SNF chromatin remodeling complex, including BRG1 (also SMARCA4), are inactivated in cancer. Among other functions, SWI/SNF orchestrates the response to retinoid acid (RA) and glucocorticoids (GC) involving downregulation of MYC. The epigenetic drugs SAHA and azacytidine, as well as RA and GC, are currently being used to treat some malignancies but their therapeutic potential in lung cancer is not well established. Here we aimed to determine the possible therapeutic effects of azacytidine and SAHA (A/S) alone or in combination with GC plus RA (GC/RA) in lung cancers with either BRG1 inactivation or MYC amplification. In vitro, responses to GC/RA treatment were more effective in MYC-amplified cells. These effects were mediated by BRG1 and involved a reprogramming towards prodifferentiation gene expression signatures and downregulation of MYC. In MYC-amplified cells, administration of GC/RA enhanced the cell growth inhibitory effects of A/S which, in turn, accentuated the prodifferentiation features promoted by GC/RA. Finally, these treatments improved overall survival of mice orthotopically implanted with MYC-amplified, but not BRG1-mutant, cells and reduced tumor cell viability and proliferation. We propose that the combination of epigenetic treatments with retinoids and corticoids of MYC-driven lung tumors constitute a strategy for therapeutic intervention in this otherwise incurable disease

Epidemiological and transmissibility analysis of influenza A(H1N1)v in a southern hemisphere setting: Peru

We present a preliminary analysis of 1,771 confirmed cases of influenza A(H1N1)v reported in Peru by 17 July including the frequency of the clinical characteristics, the spatial and age distribution of the cases and the estimate of the transmission potential. Age-specific frequency of cases was highest among school age children and young adults, with the lowest frequency of cases among seniors, a pattern that is consistent with reports from other countries. Estimates of the reproduction number lie in the range of 1.2 to 1.7, which is broadly consistent with previous estimates for this pandemic in other regions. Validation of these estimates will be possible as additional data become available

Cyclin-Dependent Kinase Inhibitor p21 Controls Adult Neural Stem Cell Expansion by Regulating Sox2 Gene Expression

In the adult brain, continual neurogenesis of olfactory neurons is sustained by the existence of neural stem cells (NSCs) in the subependymal niche. Elimination of the cyclin-dependent kinase inhibitor 1A (p21) leads to premature exhaustion of the subependymal NSC pool, suggesting a relationship between cell cycle control and long-term self-renewal, but the molecular mechanisms underlying NSC maintenance by p21 remain unexplored. Here we identify a function of p21 in the direct regulation of the expression of pluripotency factor Sox2, a key regulator of the specification and maintenance of neural progenitors. We observe that p21 directly binds a Sox2 enhancer and negatively regulates Sox2 expression in NSCs. Augmented levels of Sox2 in p21 null cells induce replicative stress and a DNA damage response that leads to cell growth arrest mediated by increased levels of p19(Arf) and p53. Our results show a regulation of NSC expansion driven by a p21/Sox2/p53 axis

Características hematológicas y bioquímicas en pacientes con y sin diabetes mellitus tipo 2 (DM2) sometidos a hemodiálisis durante un año de seguimiento

Objective: To report if there are hematologic and biochemical differences among patients with and without type 2 diabetes mellitus (T2DM) undergoing hemodialysis (HD). Materials and methods: An observational, retrospective, cohort study of patients treated in the Renal Health Program at the Centro de Prevención de Enfermedad Renal S.A.C. (CENPER) in Lima, Peru. The hematologic and biochemical parameters of 3 patients with T2DM and 3 patients without T2DM undergoing HD were compared. Results: Significant differences (p < 0.05) were found in the lymphocyte percentage, lymphocyte/monocyte ratio (LMR), hemoglobin and hematocrit concentration (lower in diabetic patients), monocyte percentage, and neutrophil/ lymphocyte ratio (NLR) (higher in diabetic patients). In the biochemical parameters, the only significant difference was found in the glutamic-oxaloacetic transaminase (GOT) value, which was higher in the diabetic patients compared with the non-diabetic patients (p < 0.005). Conclusions: Diabetes is an important factor linked to inflammation, anemia, lymphopenia and monocytosis in patients undergoing HD. The LMR was the most powerful marker of inflammation in this patient series. Larger-scale studies are required to verify this evidence.Objetivo: Reportar si existen diferencias hematológicas y bioquímicas entre los pacientes con y sin diabetes mellitus tipo 2 (DM2) bajo tratamiento de hemodiálisis (HD). Materiales y métodos: Estudio observacional de cohorte retrospectiva de pacientes atendidos por el Programa de Salud renal en el Centro de Prevención de Enfermedad Renal S.A.C (CENPER) de Lima, Perú. Se compararon los parámetros hematológicos y bioquímicos de 3 pacientes con DM2 y 3 pacientes sin DM2 sometidos a HD. Resultados: Se encontraron diferencias significativas (p<0,05) en el porcentaje de linfocitos, el cociente linfocito/ monocito (LMR), la concentración de hemoglobina y hematocrito (menor en pacientes diabéticos), en el porcentaje de monocitos y en el cociente neutrófilo/ linfocitos (NLR) (mayor en pacientes diabéticos). En los parámetros bioquímicos solo se encontró diferencia significativa en la transaminasa TGO que está más elevada en pacientes diabéticos comparados con pacientes no diabéticos (p<0.005). Conclusiones: Diabetes es un factor importante asociado con inflamación, anemia, linfopenia y monocitosis en pacientes sometidos a HD. LMR fue el marcador más potente de inflamación en esta serie de pacientes. Estudios a mayor escala son requeridos para corroborar esta evidencia

microRNA Expression and Its Association With Disability and Brain Atrophy in Multiple Sclerosis Patients Treated With Glatiramer Acetate.

Background: MicroRNAs are small non-coding RNA that regulate gene expression at a post-transcriptional level affecting several cellular processes including inflammation, neurodegeneration and remyelination. Different patterns of miRNAs expression have been demonstrated in multiple sclerosis compared to controls, as well as in different courses of the disease. For these reason they have been postulated as promising biomarkers candidates in multiple sclerosis. Objective: To correlate serum microRNAs profile expression with disability, cognitive functioning and brain volume in patients with remitting-relapsing multiple sclerosis. Methods: Cross-sectional study in relapsing-remitting multiple sclerosis patients treated with glatiramer acetate. Disability was measured with Expanded Disability Status Scale (EDSS) and cognitive function was studied with Symbol Digit Modalities Test (SDMT). Brain volume was analyzed with automatic software NeuroQuant® . Results: We found an association between miR.146a.5p (rs:0.434, p=0.03) and miR.9.5p (rs:0.516, p=0.028) with EDSS; and miR-146a.5p (rs:-0.476, p=0.016) and miR-126.3p (rs:-0.528, p=0.007) with SDMT. Regarding to the brain volume, miR.9.5p correlated with thalamus (rs:-0.545, p=0.036); miR.200c.3p with pallidum (rs:-0.68, p=0.002) and cerebellum (rs:-0.472, p=0.048); miR-138.5p with amygdala (rs:0.73, p=0.016) and pallidum (rs:0.64, p=0.048); and miR-223.3p with caudate (rs:0.46, p=0.04). Conclusions: These data support the hypothesis of microRNA as potential biomarkers in this disease. More studies are needed to validate these results and to better understand the role of microRNAs in the pathogenesis, monitoring and therapeutic response of multiple sclerosis.post-print1410 K