Higher alcohol intake may modify the association between mammographic density and breast cancer: An analysis of three case-control studies

Alcohol consumption and mammographic density are established risk factors for breast cancer. This study examined whether the association of mammographic density with breast cancer varies by alcohol intake. Mammographic density was assessed in digitized images for 1207 cases and 1663 controls from three populations (Japan, Hawaii, California) using a computer-assisted method. Associations were estimated by logistic regression. When comparing ever to never drinking, mean density was similar and consumption was not associated with breast cancer risk. However, within the Hawaii/Japan subset, women consuming >1 drink/day had a non-significantly elevated relative risk compared to never drinkers. Also in the Hawaii/Japan population, alcohol intake only modified the association between mammographic density and breast cancer in women consuming >1 drink/day (p(interaction)=0.05) with significant risk estimates of 3.65 and 6.58 for the 2nd and 3rd density tertiles as compared to 1.57 and 1.61 for never drinkers in Hawaii/Japan. Although these findings suggest a stronger association between mammographic density and breast cancer risk for alcohol consumers, the small number of cases requires caution in interpreting the results.     

An acidic oligopeptide displayed on AAV2 improves axial muscle tropism after systemic delivery

Background

Countrywide 5.9 million, 0-11 Month old children are immunized annually by EPI (Expended Program on Immunization) against 8 vaccine preventable diseases including measles and so on. Unfortunately the basic immunity centers are not uniform throughout the country. Each center provides services to about 27000 people which is inadequate. The purpose of this study was to explore the development of EPI Pakistan in terms of immunization of measles.

Methods

Nucleotide sequences were analyzed by neighbor joining method (bootstrap test) using Bio- edit and MEGA-5 software to find evolutionary relationship between wild type measles strain and vaccine strain (Edmonston strain) used in Pakistan. For statistical analysis of data SPSS 16 was used.

Results

Currently 1.3 vaccinators are working at each U C (union council) which according to national EPI policy should be at least 2. About 56% and 44% children of age 0-11 months did not received second dose of measles in the last two years respectively. Out of these 4231 cases which were reported last year, 1370 have received their first dose of measles vaccine.

Conclusion

Seroconversion and seroprevalence study of the vaccine and field strain of measles virus is needed to confirm whether its failure is due to service unavailability or vaccine in-affectivity.     

Epidemiology and potential land-sea transfer of enteric bacteria from terrestrial to marine species in the Monterey Bay Region of California

Marine mammals are at risk for infection by fecal-associated zoonotic pathogens when they swim and feed in polluted nearshore marine waters. Because of their tendency to consume 25-30% of their body weight per day in coastal filter-feeding invertebrates, southern sea otters (Enhydra lutris nereis) can act as sentinels of marine ecosystem health in California. Feces from domestic and wildlife species were tested to determine prevalence, potential virulence, and diversity of selected opportunistic enteric bacterial pathogens in the Monterey Bay region. We hypothesized that if sea otters are sentinels of coastal health, and fecal pollution flows from land to sea, then sea otters and terrestrial animals might share the same enteric bacterial species and strains. Twenty-eight percent of fecal samples tested during 2007-2010 were positive for one or more potential pathogens. Campylobacter spp. were isolated most frequently, with an overall prevalence of 11%, followed by Vibrio cholerae (9%), Salmonella spp. (6%), V. parahaemolyticus (5%), and V. alginolyticus (3%). Sea otters were found positive for all target bacteria, exhibiting similar prevalences for Campylobacter and Salmonella spp. but greater prevalences for Vibrio spp. when compared to terrestrial animals. Fifteen Salmonella serotypes were detected, 11 of which were isolated from opossums. This is the first report of sea otter infection by S. enterica Heidelberg, a serotype also associated with human clinical disease. Similar strains of S. enterica Typhimurium were identified in otters, opossums, and gulls, suggesting the possibility of land-sea transfer of enteric bacterial pathogens from terrestrial sources to sea otters.     

Cathepsin B controls the persistence of memory CD8+ T lymphocytes

The persistence of memory T lymphocytes confers lifelong protection from pathogens. Memory T cells survive and undergo homeostatic proliferation (HSP) in the absence of Ag, although the cell-intrinsic mechanisms by which cytokines drive the HSP of memory T cells are not well understood. In this study we report that lysosome stability limits the long-term maintenance of memory CD8(+) T cell populations. Serine protease inhibitor (Spi) 2A, an anti-apoptotic cytosolic cathepsin inhibitor, is induced by both IL-15 and IL-7. Mice deficient in Spi2A developed fewer memory phenotype CD44(hi)CD8(+) T cells with age, which underwent reduced HSP in the bone marrow. Spi2A was also required for the maintenance of central memory CD8(+) T cell populations after acute infection with lymphocytic choriomeningitis virus. Spi2A-deficient Ag-specific CD8(+) T cell populations declined more than wild-type competitors after viral infection, and they were eroded further after successive infections. Spi2A protected memory cells from lysosomal breakdown by inhibiting cathepsin B. The impaired maintenance of Spi2A-deficient memory CD8(+) T cells was rescued by concomitant cathepsin B deficiency, demonstrating that cathepsin B was a physiological target of Spi2A in memory CD8(+) T cell survival. Our findings support a model in which protection from lysosomal rupture through cytokine-induced expression of Spi2A determines the long-term persistence of memory CD8(+) T cells.     

Stable triazolylphosphonate analogues of phosphohistidine

Histidine-phosphorylated proteins and the corresponding kinases are important components of bacterial and eukaryotic cell-signalling pathways, and are therefore potential drug targets. The study of these biomolecules has been hampered by the lability of the phosphoramidate functional group in the phosphohistidines and the lack of generic antibodies. Herein, the design and concise synthesis of stable triazolylphosphonate analogues of N1- and N3-phosphohistidine, and derivatives suitable for bioconjugation, are described.     

Combined effects of two ocean change stressors, warming and acidification, on fertilization and early development of the Antarctic echinoid Sterechinus neumayeri

The effects of concurrent ocean warming and acidification on Antarctic marine benthos warrant investigation as little is known about potential synergies between these climate change stressors. We examined the interactive effects of warming and acidification on fertilization and embryonic development of the ecologically important sea urchin Sterechinus neumayeri reared from fertilization in elevated temperature (+1.5°C and 3°C) and decreased pH (?0.3 and ?0.5 pH units) treatments. Fertilization using gametes from multiple males and females, to represent populations of spawners, was resilient to acidification at ambient temperature (0°C). At elevated temperatures, there was a negative interactive effect of temperature and pH on percentage of fertilization (11% reduction at 3°C). For cleavage stage embryos, there was a significant, but small reduction (6%) in the percentage of normal embryos at pH 7.5. For blastulae, a 10–11% decrease in normal development occurred in the +3°C treatments across all pH levels. Our results highlight the importance of considering the impacts of both temperature and pH in assessing the life history response of S. neumayeri in a changing polar ocean. While fertilization and development to the blastula stage were robust to levels of temperature and pH change predicted over coming decades, deleterious interactive effects were evident between these stressors at levels projected to occur by 2100 and beyond.     

Development of leaf shape

Variation among vascular plants in the initiation and patterning of leaves results in a diverse array of leaf shape, including the strap-like leaf of many grasses and the broad lamina of most eudicots. Recent findings highlight the importance of interactions between the shoot apical meristem (SAM) and developing leaf primordia in axis specification and the establishment of leaf shape. Global regulators of epigenetic states have been implicated in these interactions and may play a role in distinguishing founder cells and stem cells within the SAM.     

Dispatch. Animal communication: what makes a dog able to understand its master?

The dog has a special relationship with humans, going beyond that of other domestic animals. Recent evidence suggests this comes from domestication rather than wolf behaviour, perhaps involving something as simple as a change in natural looking behaviour.     

Biomarkers of Whale Shark Health: A Metabolomic Approach

In a search for biomarkers of health in whale sharks and as exploration of metabolomics as a modern tool for understanding animal physiology, the metabolite composition of serum in six whale sharks (Rhincodon typus) from an aquarium collection was explored using ¹H nuclear magnetic resonance (NMR) spectroscopy and direct analysis in real time (DART) mass spectrometry (MS). Principal components analysis (PCA) of spectral data showed that individual animals could be resolved based on the metabolite composition of their serum and that two unhealthy individuals could be discriminated from the remaining healthy animals. The major difference between healthy and unhealthy individuals was the concentration of homarine, here reported for the first time in an elasmobranch, which was present at substantially lower concentrations in unhealthy whale sharks, suggesting that this metabolite may be a useful biomarker of health status in this species. The function(s) of homarine in sharks remain uncertain but it likely plays a significant role as an osmolyte. The presence of trimethylamine oxide (TMAO), another well-known protective osmolyte of elasmobranchs, at 0.1–0.3 mol L⁻¹ was also confirmed using both NMR and MS. Twenty-three additional potential biomarkers were identified based on significant differences in the frequency of their occurrence between samples from healthy and unhealthy animals, as detected by DART MS. Overall, NMR and MS provided complementary data that showed that metabolomics is a useful approach for biomarker prospecting in poorly studied species like elasmobranchs.     

GPR54-Dependent Stimulation of Luteinizing Hormone Secretion by Neurokinin B in Prepubertal Rats

Kisspeptin, neurokinin B (NKB) and dynorphin A (Dyn) are coexpressed within KNDy neurons that project from the hypothalamic arcuate nucleus (ARC) to GnRH neurons and numerous other hypothalamic targets. Each of the KNDy neuropeptides has been implicated in regulating pulsatile GnRH/LH secretion. In isolation, kisspeptin is generally known to stimulate, and Dyn to inhibit LH secretion. However, the NKB analog, senktide, has variously been reported to inhibit, stimulate or have no effect on LH secretion. In prepubertal mice, rats and monkeys, senktide stimulates LH secretion. Furthermore, in the monkey this effect is dependent on kisspeptin signaling through its receptor, GPR54. The present study tested the hypotheses that the stimulatory effects of NKB on LH secretion in intact rats are mediated by kisspeptin/GPR54 signaling and are independent of a Dyn tone. To test this, ovarian-intact prepubertal rats were subjected to frequent automated blood sampling before and after intracerebroventricular injections of KNDy neuropeptide analogs. Senktide robustly induced single LH pulses, while neither the GPR54 antagonist, Kp-234, nor the Dyn agonist and antagonist ({"type":"entrez-nucleotide","attrs":{"text":"U50488","term_id":"1277101","term_text":"U50488"}}U50488 and nor-BNI, respectively) had an effect on basal LH levels. However, Kp-234 potently blocked the senktide-induced LH pulses. Modulation of the Dyn tone by {"type":"entrez-nucleotide","attrs":{"text":"U50488","term_id":"1277101","term_text":"U50488"}}U50488 or nor-BNI did not affect the senktide-induced LH pulses. These data demonstrate that the stimulatory effect of NKB on LH secretion in intact female rats is dependent upon kisspeptin/GPR54 signaling, but not on Dyn signaling.