Genetic ablation of glutaredoxin-1 causes enhanced resolution of airways hyperresponsiveness and mucus metaplasia in mice with allergic airways disease

Protein-S-glutathionylation (PSSG) is an oxidative modification of reactive cysteines that has emerged as an important player in pathophysiological processes. Under physiological conditions, the thiol transferase, glutaredoxin-1 (Glrx1) catalyses deglutathionylation. Although we previously demonstrated that Glrx1 expression is increased in mice with allergic inflammation, the impact of Glrx1/PSSG in the development of allergic airways disease remains unknown. In the present study we examined the impact of genetic ablation of Glrx1 in the pathogenesis of allergic inflammation and airway hyperresponsiveness (AHR) in mice. Glrx1(-/-) or WT mice were subjected to the antigen, ovalbumin (OVA), and parameters of allergic airways disease were evaluated 48 h after three challenges, and 48 h or 7 days after six challenges with aerosolized antigen. Although no clear increases in PSSG were observed in WT mice in response to OVA, marked increases were detected in lung tissue of mice lacking Glrx1 48 h following six antigen challenges. Inflammation and expression of proinflammatory mediators were decreased in Glrx1(-/-) mice, dependent on the time of analysis. WT and Glrx1(-/-) mice demonstrated comparable increases in AHR 48 h after three or six challenges with OVA. However, 7 days postcessation of six challenges, parameters of AHR in Glrx1(-/-) mice were resolved to control levels, accompanied by marked decreases in mucus metaplasia and expression of Muc5AC and GOB5. These results demonstrate that the Glrx1/S-glutathionylation redox status in mice is a critical regulator of AHR, suggesting that avenues to increase S-glutathionylation of specific target proteins may be beneficial to attenuate AHR.     

The passionvine mealybug,Planococcus minor (Maskell) (Hemiptera: Pseudococcidae), and its natural enemies in the cocoa agroecosystem in Trinidad

Planococcus minor (Maskell) is native to South Asia, but it is also present in several Neotropical locations including the island of Trinidad in the southern Caribbean. The mealybug poses a serious threat to uninfested countries in this region as well as the mainland U.S. As part of an effort to gather much needed information on P. minor, 33 cocoa (Theobroma cacao L.) field sites on the island were surveyed in 2006 with a view to assess the occurrence and pest status of the mealybug. P. minor was identified from 20 field sites, indicating that it was well distributed across the island on this crop, which appeared to be a reliable indicator host plant. Infestation levels were generally low and populations were sparsely distributed across the field sites categorized into three habitat types. The following year, nine field sites were surveyed for natural enemies of P. minor using laboratory-infested potatoes in sentinel traps. Species from four insect orders and six families were collected and identified. The major predators belonged to the families Cecidomyiidae and Coccinellidae. Two primary parasitoids, Leptomastix dactylopii Howard (Encyrtidae) and Coccidoxenoides perminutus (Girault) (=Pauridia peregrina Timberlake, =Coccidoxenoides peregrinus (Timberlake)) (Encyrtidae), were reared from different mealybug stages, along with several hyperparasitoids. The primary parasitoids were probably introduced fortuitously. These diverse natural enemies were recovered throughout the sampling period from the different habitat types. The identification of key natural enemies associated with P. minor has important implications for the implementation of biological control in newly infested areas.     

Septin ring size scaling and dynamics require the coiled-coil region of Shs1p

Septins are conserved GTP-binding proteins that assemble into heteromeric complexes that form filaments and higher-order structures in cells. What directs filament assembly, determines the size of higher-order septin structures, and governs septin dynamics is still not well understood. We previously identified two kinases essential for septin ring assembly in the filamentous fungus Ashbya gossypii and demonstrate here that the septin Shs1p is multiphosphorylated at the C-terminus of the protein near the predicted coiled-coil domain. Expression of the nonphosphorylatable allele shs1-9A does not mimic the loss of the kinase nor does complete truncation of the Shs1p C-terminus. Surprisingly, however, loss of the C-terminus or the predicted coiled-coil domain of Shs1p generates expanded zones of septin assemblies and ectopic septin fibers, as well as aberrant cell morphology. The expanded structures form coincident with ring assembly and are heteromeric. Interestingly, while septin recruitment to convex membranes is increased, septin localization is diminished at concave membranes in these mutants. Additionally, the loss of the coiled-coil leads to increased mobility of Shs1p. These data indicate the coiled-coil of Shs1p is an important negative regulator of septin ring size and mobility, and its absence may make septin assembly sensitive to local membrane curvature.     

Sbf/MTMR13 coordinates PI(3)P and Rab21 regulation in endocytic control of cellular remodeling

Cells rely on the coordinated regulation of lipid phosphoinositides and Rab GTPases to define membrane compartment fates along distinct trafficking routes. The family of disease-related myotubularin (MTM) phosphoinositide phosphatases includes catalytically inactive members, or pseudophosphatases, with poorly understood functions. We found that Drosophila MTM pseudophosphatase Sbf coordinates both phosphatidylinositol 3-phosphate (PI(3)P) turnover and Rab21 GTPase activation in an endosomal pathway that controls macrophage remodeling. Sbf dynamically interacts with class II phosphatidylinositol 3-kinase and stably recruits Mtm to promote turnover of a PI(3)P subpool essential for endosomal trafficking. Sbf also functions as a guanine nucleotide exchange factor that promotes Rab21 GTPase activation associated with PI(3)P endosomes. Of importance, Sbf, Mtm, and Rab21 function together, along with Rab11-mediated endosomal trafficking, to control macrophage protrusion formation. This identifies Sbf as a critical coordinator of PI(3)P and Rab21 regulation, which specifies an endosomal pathway and cortical control.     

Case study: Bone mineral density of two elite senior female powerlifters

The purpose of this case study was to examine the bone mineral density (BMD) of 2 women, aged 48 and 54 years, who had engaged in high-intensity resistance training for >30 years each and gained national prominence for their lifting performances. Each subject was measured using a dual x-ray absorptiometry (GE Lunar Prodigy, Fairfield, CT, USA) for both the BMD (grams per centimeter squared) and bone mineral content (grams) of the lumbar spine, dual femur, and total body. The Z and T scores of the 49-year-old subject were significantly higher than either age and gender-matched or peak BMD norms (lumbar spine Z + 2.2, T + 1.8, femoral mean Z + 1.1, T + 0.6, total body Z + 2.4, T + 2.0). The Z and T scores of the 54-year-old mark the largest ever reported in the literature for a Caucasian woman of this age (lumbar spine Z + 2.8, T + 2.2, femoral mean Z + 1.4, T + 1.9, total body Z + 2.6, T + 3.0). Although these results do not prove any causal relationship between long-term high-intensity strength training and elevated BMDs among women, they do raise questions that some type of relationship may exist.     

Tree-hole breeding mosquitoes in Israel

A survey was conducted to evaluate the number of tree-hole breeding mosquito species and their distribution in the six principal woodland types in Israel. Out of approximately 3,000 mature trees examined, only 38 contained holes that retained water for extended periods of time, and breeding mosquitoes were observed in 27 of them. Two specialized tree-hole breeders, Aedes pulchritarsis Rondani and Aedes geniculatus Oliver, were found breeding at several sites in northern Israel, always at locations 500 m above sea level (a.s.l) and with high annual precipitation. Aedes albopictus Skuse which, in Israel, is known as an opportunistic container breeder, was found in this study to have adapted remarkably well to breeding in tree holes and was found in most forest types investigated and in most tree species which had adequate tree holes. Two other species, Culiseta annulata Schrank and Culex pipiens Linnaeus instars, were found in one of the tree holes, but did not survive to reach maturity.     

Sex differences in jealousy: a meta-analytic examination

The theory of evolved sex differences in jealousy predicts sex differences in responses to sexual infidelities and emotional infidelities. Critics have argued that such differences are absent in studies that use continuous measures to assess responses to hypothetical infidelities or in studies that assess responses to real infidelities. These criticisms were tested in two random-effects meta-analyses of 40 published and unpublished papers (providing 209 effect sizes from 47 independent samples) that measured sex differences in jealousy using continuous measures. A significant, theory-supportive sex difference emerged across 45 independent samples using continuous measures of responses to hypothetical infidelities, g*=0.258, 95% confidence interval (CI) [0.188, 0.328], p<.00001. Measured emotion significantly moderated effect size. Effects were strongest when measures assessed distress/upset (g*=0.337) and jealousy (g*=0.309). Other commonly measured negative emotions yielded weaker effects, including hurt (g*=0.161), anger (g*=0.074), and disgust (g*=0.012). Across the 45 independent samples, six significant moderators emerged: random sampling, population type (student vs. nonstudent samples), age, inclusion of a forced-choice question, number of points in the response scale, and year of publication. A significant, theory-supportive effect also emerged across seven studies assessing reactions to actual infidelities, g*=0.234, 95% CI [0.020, 0.448], p=.03. Results demonstrate that the sex difference in jealousy neither is an artifact of response format nor is limited to responses to hypothetical infidelities.     

BRCA1 functions independently of homologous recombination in DNA interstrand crosslink repair

Brca1 is required for DNA repair by homologous recombination (HR) and normal embryonic development. Here we report that deletion of the DNA damage response factor 53BP1 overcomes embryonic lethality in Brca1-nullizygous mice and rescues HR deficiency, as measured by hypersensitivity to polyADP-ribose polymerase (PARP) inhibition. However, Brca1,53BP1 double-deficient cells are hypersensitive to DNA interstrand crosslinks (ICLs), indicating that BRCA1 has an additional role in DNA crosslink repair that is distinct from HR. Disruption of the nonhomologous end-joining (NHEJ) factor, Ku, promotes DNA repair in Brca1-deficient cells; however deletion of either Ku or 53BP1 exacerbates genomic instability in cells lacking FANCD2, a mediator of the Fanconi anemia pathway for ICL repair. BRCA1 therefore has two separate roles in ICL repair that can be modulated by manipulating NHEJ, whereas FANCD2 provides a key activity that cannot be bypassed by ablation of 53BP1 or Ku.