Placental 5-methylcytosine and 5-hydroxymethylcytosine patterns associate with size at birth

Altered placental function as a consequence of aberrant imprinted gene expression may be one mechanism mediating the association between low birth weight and increased cardiometabolic disease risk. Imprinted gene expression is regulated by epigenetic mechanisms, particularly DNA methylation (5mC) at differentially methylated regions (DMRs). While 5-hydroxymethylcytosine (5hmC) is also present at DMRs, many techniques do not distinguish between 5mC and 5hmC. Using human placental samples, we show that the expression of the imprinted gene CDKN1C associates with birth weight. Using specific techniques to map 5mC and 5hmC at DMRs controlling the expression of CDKN1C and the imprinted gene IGF2, we show that 5mC enrichment at KvDMR and DMR0, and 5hmC enrichment within the H19 gene body, associate positively with birth weight. Importantly, the presence of 5hmC at imprinted DMRs may complicate the interpretation of DNA methylation studies in placenta; future studies should consider using techniques that distinguish between, and permit quantification of, both modifications.     

Treatment of W. bancrofti (Wb) in HIV/Wb Coinfections in South India

BackgroundThe disease course of human immunodeficiency virus (HIV) is often altered by existing or newly acquired coincident infections.Conclusions/SignificanceWe were unable to find a significant effect of W. bancrofti infection or its treatment on HIV clinical course or surrogate markers of HIV disease progression though we recognized that our study was limited by the smaller than predicted sample size and by the use of ART in half of the patients. Treatment of W. bancrofti coinfection in HIV positive subjects (as is usual in mass drug administration campaigns) did not represent an increased risk to the subjects, and should therefore be considered for PLWHA living in W. bancrofti endemic areas.

Trial Registration

ClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT00344279","term_id":"NCT00344279"}}NCT00344279     

Trace Element Studies on Tinospora cordifolia (Menispermaceae), Ocimum sanctum (Lamiaceae), Moringa oleifera (Moringaceae), and Phyllanthus niruri (Euphorbiaceae) Using PIXE

Traditionally, Tinospora cordifolia (Willd.) Hook. F. & Thomson (Menispermaceae), Ocimum sanctum L. (Lamiaceae), Moringa oleifera Lam. (Moringaceae), and Phyllanthus niruri L. (Euphorbiaceae) are some of the commonly used medicinal plants in India for curing ailments ranging from common cold, skin diseases, and dental infections to major disorders like diabetes, hypertension, jaundice, rheumatism, etc. To understand and correlate their medicinal use, trace element studies on the aqueous extract of these medicinal plants have been carried out using particle-induced X-ray emission technique. A 2-MeV proton beam was used to identify and characterize major and minor elements namely Cl, K, Ca, Ti, Cr, Mn, Fe, Co, Ni, Cu, Zn, Br, and Sr in them. Results have revealed that these elements are present in varying concentrations in the selected plants. Notable results include very high concentrations of Cl, K, and Ca in all the leaf samples, appreciable levels of Mn in all plants, high Zn content in T. cordifolia, and the aqueous extract of Moringa leaves compared to others and relative higher concentrations of Cr in all the plants.     

Extramedullary hematopoiesis in a case of benign mixed mammary tumor in a female dog: cytological and histopathological assessment

Backgroud  

Extramedullary hematopoiesis (EMH) is defined as the presence of hematopoietic stem cells such as erythroid and myeloid lineage plus megakaryocytes in extramedullary sites like liver, spleen and lymph nodes and is usually associated with either bone marrow or hematological disorders. Mammary EMH is a rare condition either in human and veterinary medicine and can be associated with benign mixed mammary tumors, similarly to that described in this case.     

G protein beta gamma subunit interaction with the dynein light-chain component Tctex-1 regulates neurite outgrowth

Tctex-1, a light-chain component of the cytoplasmic dynein motor complex, can function independently of dynein to regulate multiple steps in neuronal development. However, how dynein-associated and dynein-free pools of Tctex-1 are maintained in the cell is not known. Tctex-1 was recently identified as a Gbetagamma-binding protein and shown to be identical to the receptor-independent activator of G protein signaling AGS2. We propose a novel role for the interaction of Gbetagamma with Tctex-1 in neurite outgrowth. Ectopic expression of either Tctex-1 or Gbetagamma promotes neurite outgrowth whereas interfering with their function inhibits neuritogenesis. Using embryonic mouse brain extracts, we demonstrate an endogenous Gbetagamma-Tctex-1 complex and show that Gbetagamma co-segregates with dynein-free fractions of Tctex-1. Furthermore, Gbeta competes with the dynein intermediate chain for binding to Tctex-1, regulating assembly of Tctex-1 into the dynein motor complex. We propose that Tctex-1 is a novel effector of Gbetagamma, and that Gbetagamma-Tctex-1 complex plays a key role in the dynein-independent function of Tctex-1 in regulating neurite outgrowth in primary hippocampal neurons, most likely by modulating actin and microtubule dynamics.     

Fenugreek seeds modulate 1,2-dimethylhydrazine-induced hepatic oxidative stress during colon carcinogenesis

1,2-dimethylhydrazine (DMH) is a colon carcinogen which undergoes oxidative metabolism in the liver. We have investigated the modulatory effect of fenugreek seeds (a spice) on colon tumor incidence as well as hepatic lipid peroxidation (LPO) and antioxidant status during DMH-induced colon carcinogenesis in male Wistar rats. In DMH treated rats, 100% colon tumor incidence was accompanied by enhanced LPO and a decrease in reduced glutathione (GSH) content as well as a fall in glutathione peroxidase (GPx), glutathione S-transferase (GST), superoxide dismutase (SOD) and catalase (CAT) activities. Inclusion of fenugreek seed powder in the diet of DMH treated rats reduced the colon tumor incidence to 16.6%, decreased the LPO and increased the activities of GPx, GST, SOD and CAT in the liver. We report that fenugreek modulates DMH-induced hepatic oxidative stressduring colon cancer     

Forebrain regions associated with postexercise differences in autonomic and cardiovascular function during baroreceptor unloading

The cortical regions representing peripheral autonomic reactions in humans are poorly understood. This study examined whether changes in forebrain activity were associated with the altered physiological responses to lower body negative pressure (LBNP) following a single bout of dynamic exercise (POST-EX). We hypothesized that, compared with the nonexercised condition (NO-EX), POST-EX would elicit greater reductions in stroke volume (SV) and larger increases in heart rate (HR) and muscle sympathetic nerve activity (MSNA) during LBNP (5, 15, and 35 mmHg). Forebrain neural activity (n = 11) was measured using blood oxygen level-dependent (BOLD) functional magnetic resonance imaging. HR, SV, arterial blood pressure (ABP), and MSNA were collected separately. Compared with NO-EX, baseline ABP was reduced, whereas HR and total vascular conductance (TVC) were elevated in POST-EX (P < 0.05). In both conditions, 5 mmHg LBNP did not elicit a change (from baseline) in any physiological parameter. Compared with NO-EX, 35 mmHg LBNP-mediated decreases in SV and TVC produced greater increases in HR and MSNA during POST-EX (P < 0.05). The right posterior insula and dorsal anterior cingulate cortex demonstrated a larger decrease in BOLD at 5 mmHg LBNP but greater BOLD increase at 15 and 35 mmHg LBNP POST-EX vs. NO-EX (P < 0.005). Conversely, the thalamus and ventral medial prefrontal cortex displayed the opposite BOLD activity pattern (i.e., larger increase at 5 mmHg LBNP but greater decrease at 15 and 35 mmHg LBNP POST-EX vs. NO-EX). Our findings suggest that discrete forebrain regions may be involved with the generation of baroreflex-mediated sympathetic and cardiovascular responses elicited by moderate LBNP.     

VSGdb: a database for trypanosome variant surface glycoproteins,a large and diverse family of coiled coil proteins

Background  

Trypanosomes are coated with a variant surface glycoprotein (VSG) that is so densely packed that it physically protects underlying proteins from effectors of the host immune system. Periodically cells expressing a distinct VSG arise in a population and thereby evade immunity. The main structural feature of VSGs are two long α-helices that form a coiled coil, and sets of relatively unstructured loops that are distal to the plasma membrane and contain most or all of the protective epitopes. The primary structure of different VSGs is highly variable, typically displaying only ~20% identity with each other. The genome has nearly 2000 VSG genes, which are located in subtelomeres. Only one VSG gene is expressed at a time, and switching between VSGs primarily involves gene conversion events. The archive of silent VSGs undergoes diversifying evolution rapidly, also involving gene conversion. The VSG family is a paradigm for α helical coiled coil structures, epitope variation and GPI-anchor signals. At the DNA level, the genes are a paradigm for diversifying evolutionary processes and for the role of subtelomeres and recombination mechanisms in generation of diversity in multigene families. To enable ready availability of VSG sequences for addressing these general questions, and trypanosome-specific questions, we have created VSGdb, a database of all known sequences.     

Oxidative stress, tissue remodeling and regression during amphibian metamorphosis

Anuran metamorphosis is characterized by rapid and drastic changes in the body form and function under the influence of thyroid hormones. We evaluated the involvement of reactive oxygen species and antioxidant defenses during intestinal remodeling and tail regression of tadpoles of Xenopus laevis. Oxidative stress resulting from depletion in catalase and reduced glutathione, and simultaneous increase in lipid peroxidation during intestinal remodeling as well as tail regression are probably responsible for cell death and differentiation in these organs. Gene expression data for superoxide dismutase and catalase supports this contention. A dramatic increase in another antioxidant, ascorbic acid content of both these organs during metamorphic climax indicates its multifactor role such as collagen synthesis in intestine and controlled tail regression. These findings suggest that the cellular environment in the intestine and tail becomes progressively more oxidizing during its remodeling and regression respectively.