Elicitation of simian immunodeficiency virus-specific cytotoxic T lymphocytes in mucosal compartments of rhesus monkeys by systemic vaccination

Since most human immunodeficiency virus (HIV) infections are initiated following mucosal exposure to the virus, the anatomic containment or abortion of an HIV infection is likely to require vaccine-elicited cellular immune responses in those mucosal sites. Studying vaccine-elicited mucosal immune responses has been problematic because of the difficulties associated with sampling T lymphocytes from those anatomic compartments. In the present study, we demonstrate that mucosal cytotoxic T lymphocytes (CTL) specific for simian immunodeficiency virus (SIV) and simian HIV can be reproducibly sampled from intestinal mucosal tissue of rhesus monkeys obtained under endoscopic guidance. These lymphocytes recognize peptide-major histocompatibility complex class I complexes and express gamma interferon on exposure to peptide antigen. Interestingly, systemic immunization of monkeys with plasmid DNA immunogens followed by live recombinant attenuated poxviruses or adenoviruses with genes deleted elicits high-frequency SIV-specific CTL responses in these mucosal tissues. These studies therefore suggest that systemic delivery of potent HIV immunogens may suffice to elicit substantial mucosal CTL responses.     

Identification of an endocrine disrupting agent from corn with mitogenic activity

A mitogenic agent in corncob bedding and fresh corn products disrupts sexual behavior and estrous cyclicity in rats. The mitogenic activity resides in an isomeric mixture of linoleic acid derivatives with a tetrahydrofuran ring and two hydroxyl groups (THF-diols) that include 9, (12)-oxy-10,13-dihydroxystearic acid and 10, (13)-oxy-9,12-dihydroxystearic acid. Synthetic THF-diols stimulated breast cancer cell proliferation in vitro and disrupted the estrous cycle in female rats at oral doses of approximately 0.30 mg/kg body weight/day. Exposure to THF-diols may disrupt endocrine function in experimental animals at doses approximately 200 times lower than classical phytoestrogens, promote proliferation of breast or prostate cancer, and adversely affect human health.     

Interaction between the small-nuclear-RNA cap hypermethylase and the spinal muscular atrophy protein,survival of motor neuron

The biogenesis of spliceosomal small nuclear ribonucleoproteins (snRNPs) requires the cytoplasmic assembly of the Sm-core complex, followed by the hypermethylation of the small nuclear RNA (snRNA) 5′ cap. Both the Sm-core complex and the snRNA trimethylguanosine cap are required for the efficient nuclear import of snRNPs. Here, we show that trimethylguanosine synthase 1 (TGS1), the human homologue of the yeast snRNA cap hypermethylase, interacts directly with the survival of motor neuron (SMN) protein. Both proteins are similarly distributed, localizing in the cytoplasm and in nuclear Cajal bodies. The interaction between TGS1 and SMN is disrupted by a mutation in SMN that mimics the predominant isoform of the protein that is expressed in patients with the neurodegenerative disease, spinal muscular atrophy. These data indicate that, in addition to its function in cytoplasmic Sm-core assembly, the SMN protein also functions in the recruitment of the snRNA cap hypermethylase.     

Spag17 Deficiency Results in Skeletal Malformations and Bone Abnormalities

Height is the result of many growth and development processes. Most of the genes associated with height are known to play a role in skeletal development. Single-nucleotide polymorphisms in the SPAG17 gene have been associated with human height. However, it is not clear how this gene influences linear growth. Here we show that a targeted mutation in Spag17 leads to skeletal malformations. Hind limb length in mutants was significantly shorter than in wild-type mice. Studies revealed differences in maturation of femur and tibia suggesting alterations in limb patterning. Morphometric studies showed increased bone formation evidenced by increased trabecular bone area and the ratio of bone area to total area, leading to reductions in the ratio of marrow area/total area in the femur. Micro-CTs and von Kossa staining demonstrated increased mineral in the femur. Moreover, osteocalcin and osterix were more highly expressed in mutant mice than in wild-type mice femurs. These data suggest that femur bone shortening may be due to premature ossification. On the other hand, tibias appear to be shorter due to a delay in cartilage and bone development. Morphometric studies showed reduction in growth plate and bone formation. These defects did not affect bone mineralization, although the volume of primary bone and levels of osteocalcin and osterix were higher. Other skeletal malformations were observed including fused sternebrae, reduced mineralization in the skull, medial and metacarpal phalanges. Primary cilia from chondrocytes, osteoblasts, and embryonic fibroblasts (MEFs) isolated from knockout mice were shorter and fewer cells had primary cilia in comparison to cells from wild-type mice. In addition, Spag17 knockdown in wild-type MEFs by Spag17 siRNA duplex reproduced the shorter primary cilia phenotype. Our findings disclosed unexpected functions for Spag17 in the regulation of skeletal growth and mineralization, perhaps because of its role in primary cilia of chondrocytes and osteoblasts.     

Psychosocial Factors of Antenatal Anxiety and Depression in Pakistan: Is Social Support a Mediator?

Introduction

Pregnancy is generally viewed as a time of fulfillment and joy; however, for many women it can be a stressful event. In South Asia it is associated with cultural stigmas revolving around gender discrimination, abnormal births and genetic abnormalities.

Methodology

This cross-sectional study was done at four teaching hospitals in Lahore from February, 2014 to June, 2014. A total of 500 pregnant women seen at hospital obstetrics and gynecology departments were interviewed with a questionnaire consisting of three sections: demographics, the Hospital Anxiety and Depression Scale (HADS) and the Social Provisions Scale (SPS). Pearson’s chi-squared test, bivariate correlations and multiple linear regression were used to analyze associations between the independent variables and scores on the HADS and SPS.

Results

Mean age among the 500 respondents was 27.41 years (5.65). Anxiety levels in participants were categorized as normal (145 women, 29%), borderline (110, 22%) or anxious (245, 49%). Depression levels were categorized as normal (218 women, 43.6%), borderline (123, 24.6%) or depressed (159, 31.8%). Inferential analysis revealed that higher HADS scores were significantly associated with lower scores on the SPS, rural background, history of harassment, abortion, cesarean delivery and unplanned pregnancies (P < .05). Social support (SPS score) mediated the relationship between the total number of children, gender of previous children and HADS score. Women with more daughters were significantly more likely to score higher on the HADS and lower on the SPS, whereas higher numbers of sons were associated with the opposite trends in the scores (P < .05).

Conclusion

Because of the predominantly patriarchal sociocultural context in Pakistan, the predictors of antenatal anxiety and depression may differ from those in developed countries. We therefore suggest that interventions designed and implemented to reduce antenatal anxiety and depression should take into account these unique factors.     

New Insights into Plagiogrammaceae (Bacillariophyta) Based on Multigene Phylogenies and Morphological Characteristics with the Description of a New Genus and Three New Species

Plagiogrammaceae, a poorly described family of diatoms, are common inhabitants of the shallow marine littoral zone, occurring either in the sediments or as epiphytes. Previous molecular phylogenies of the Plagiogrammaceae were inferred but included only up to six genera: Plagiogramma, Dimeregramma, Neofragilaria, Talaroneis, Psammogramma and Psammoneis. In this paper, we describe a new plagiogrammoid genus, Orizaformis, obtained from Bohai Sea (China) and present molecular phylogenies of the family based on three and four genes (nuclear-encoded large and small subunit ribosomal RNAs and chloroplast-encoded rbcL and psbC). Also included in the new phylogenies is Glyphodesmis. The phylogenies suggest that the Plagiogrammaceae is composed of two major clades: one consisting of Talaroneis, Orizaformis and Psammoneis, and the second of Glyphodesmis, Psammogramma, Neofragilaria, Dimeregramma and Plagiogramma. In addition, we describe three new species within established genera: Psammoneis obaidii, which was collected from the Red Sea, Saudi Arabia; and Neofragilaria stilus and Talaroneis biacutifrons from the Mozambique Channel, Indian Ocean, and illustrate two new combination taxa: Neofragilaria anomala and Neofragilaria lineata. Our observations suggest that the biodiversity of the family is strongly needed to be researched, and the phylogenetic analyses provide a useful framework for future studies of Plagiogrammaceae.     

Elderly bioheat modeling: changes in physiology,thermoregulation, and blood flow circulation

A bioheat model for the elderly was developed focusing on blood flow circulatory changes that influence their thermal response in warm and cold environments to predict skin and core temperatures for different segments of the body especially the fingers. The young adult model of Karaki et al. (Int J Therm Sci 67:41–51, 2013) was modified by incorporation of the physiological thermoregulatory and vasomotor changes based on literature observations of physiological changes in the elderly compared to young adults such as lower metabolism and vasoconstriction diminished ability, skin blood flow and its minimum and maximum values, the sweating values, skin fat thickness, as well as the change in threshold parameter related to core or skin temperatures which triggers thermoregulatory action for sweating, maximum dilatation, and maximum constriction. The developed model was validated with published experimental data for elderly exposure to transient and steady hot and cold environments. Predicted finger skin temperature, mean skin temperature, and core temperature were in agreement with published experimental data at a maximum error less than 0.5 °C in the mean skin temperature. The elderly bioheat model showed an increase in finger skin temperature and a decrease in core temperature in cold exposure while it showed a decrease in finger skin temperature and an increase in core temperature in hot exposure.     

A new mathematical model to simulate AVA cold-induced vasodilation reaction to local cooling

The purpose of this work was to integrate a new mathematical model with a bioheat model, based on physiology and first principles, to predict thermoregulatory arterio-venous anastomoses (AVA) and cold-induced vasodilation (CIVD) reaction to local cooling. The transient energy balance equations of body segments constrained by thermoregulatory controls were solved numerically to predict segmental core and skin temperatures, and arterial blood flow for given metabolic rate and environmental conditions. Two similar AVA–CIVD mechanisms were incorporated. The first was activated during drop in local skin temperature (<32 °C). The second mechanism was activated at a minimum finger skin temperature, T _{CIVD, min}, where the AVA flow is dilated and constricted once the skin temperature reached a maximum value. The value of T _CIVD,min was determined empirically from values reported in literature for hand immersions in cold fluid. When compared with published data, the model predicted accurately the onset time of CIVD at 25 min and T _CIVD,min at 10 °C for hand exposure to still air at 0 °C. Good agreement was also obtained between predicted finger skin temperature and experimentally published values for repeated immersion in cold water at environmental conditions of 30, 25, and 20 °C. The CIVD thermal response was found related to core body temperature, finger skin temperature, and initial finger sensible heat loss rate upon exposure to cold fluid. The model captured central and local stimulations of the CIVD and accommodated observed variability reported in literature of onset time of CIVD reaction and T _CIVD,min.