A novel phosphatidylinositol manno-oligosaccharide (dPIM-8) from Gordonia sputi

The deacylated phosphatidylinositol manno-oligosaccharides (dPIMs) from the glycosyl phosphatidylinositol (GPI) carbohydrate antigen anchor of Gordonia sputi were the known 2,6-di-O-alpha-mannopyranosyl-myo-inositol glycerophosphate (dPIM-2) and the illustrated novel compound (dPIM-8), which could not be separated from dPIM-7 and dPIM-6, these three compounds being present in the mixture in the molar ratios 1.0:0.65:0.4. dPIM-8 is an analogue of dPIM-2 (and also of dPIM-7 and dPIM-6) in having alpha-mannopyranose and an alpha-mannopyranosyl linked heptasaccharide bonded to O-2 and O-6, respectively, of the inositol. The dPIM-8 species has not been found previously. [structure: see text]     

The ubiquitin isopeptidase UBPY regulates endosomal ubiquitin dynamics and is essential for receptor down-regulation

UBPY is a ubiquitin-specific protease that can deubiquitinate monoubiquitinated receptor tyrosine kinases, as well as process Lys-48- and Lys-63-linked polyubiquitin to lower denomination forms in vitro. Catalytically inactive UBPY localizes to endosomes, which accumulate ubiquitinated proteins. We have explored the sequelae of short interfering RNA-mediated knockdown of UBPY. Global levels of ubiquitinated protein increase and ubiquitin accumulates on endosomes, although free ubiquitin levels are unchanged. UBPY-depleted cells have more and larger multivesicular endosomal structures that are frequently associated through extended contact areas, characterized by regularly spaced, electron-dense, bridging profiles. Degradation of acutely stimulated receptor tyrosine kinases, epidermal growth factor receptor and Met, is strongly inhibited in UBPY knockdown cells suggesting that UBPY function is essential for growth factor receptor down-regulation. In contrast, stability of the UBPY binding partner STAM is dramatically compromised in UBPY knockdown cells. The cellular functions of UBPY are complex but clearly distinct from those of the Lys-63-ubiquitin-specific protease, AMSH, with which it shares a binding site on the SH3 domain of STAM.     

Estimating the influence of population density and dispersal behavior on the ability to detect and monitor Agrilus planipennis (Coleoptera: Buprestidae) populations

Emerald ash borer, Agrilus planipennis Fairmaire (Coleoptera: Buprestidae), a phloem-feeding pest of ash (Fraxinus spp.) trees native to Asia, was first discovered in North America in 2002. Since then, A. planipennis has been found in 15 states and two Canadian provinces and has killed tens of millions of ash trees. Understanding the probability of detecting and accurately delineating low density populations of A. planipennis is a key component of effective management strategies. Here we approach this issue by 1) quantifying the efficiency of sampling nongirdled ash trees to detect new infestations of A. planipennis under varying population densities and 2) evaluating the likelihood of accurately determining the localized spread of discrete A. planipennis infestations. To estimate the probability a sampled tree would be detected as infested across a gradient of A. planipennis densities, we used A. planipennis larval density estimates collected during intensive surveys conducted in three recently infested sites with known origins. Results indicated the probability of detecting low density populations by sampling nongirdled trees was very low, even when detection tools were assumed to have three-fold higher detection probabilities than nongirdled trees. Using these results and an A. planipennis spread model, we explored the expected accuracy with which the spatial extent of an A. planipennis population could be determined. Model simulations indicated a poor ability to delineate the extent of the distribution of localized A. planipennis populations, particularly when a small proportion of the population was assumed to have a higher propensity for dispersal.     

Plume characteristics and dynamics of UV and IR laser-desorbed oligonucleotides

Laser desorption of dye-tagged oligonucleotides was studied using laser-induced fluorescence imaging. Desorption with ultra violet (UV) and infra-red (IR) lasers resulted in forward directed plumes of molecules. In the case of UV desorption, the initial shot desorbed approximately seven-fold more material than subsequent shots. In contrast, the initial shot in IR desorption resulted in the ejection of less material compared to subsequent shots and these plumes had a component directed along the path of the laser. Thermal equilibrium of the molecules in the plume was achieved after approximately 25 μs with a spread in molecular temperature which was described by a modified Maxwell-Boltzmann equation.     

Plasma proteome dynamics: analysis of lipoproteins and acute phase response proteins with 2H2O metabolic labeling

Understanding the pathologies related to the regulation of protein metabolism requires methods for studying the kinetics of individual proteins. We developed a (2)H(2)O metabolic labeling technique and software for protein kinetic studies in free living organisms. This approach for proteome dynamic studies requires the measurement of total body water enrichments by GC-MS, isotopic distribution of the tryptic peptide by LC-MS/MS, and estimation of the asymptotical number of deuterium incorporated into a peptide by software. We applied this technique to measure the synthesis rates of several plasma lipoproteins and acute phase response proteins in rats. Samples were collected at different time points, and proteins were separated by a gradient gel electrophoresis. (2)H labeling of tryptic peptides was analyzed by ion trap tandem mass spectrometry (LTQ MS/MS) for measurement of the fractional synthesis rates of plasma proteins. The high sensitivity of LTQ MS in zoom scan mode in combination with (2)H label amplification in proteolytic peptides allows detection of the changes in plasma protein synthesis related to animal nutritional status. Our results demonstrate that fasting has divergent effects on the rate of synthesis of plasma proteins, increasing synthesis of ApoB 100 but decreasing formation of albumin and fibrinogen. We conclude that this technique can effectively measure the synthesis of plasma proteins and can be used to study the regulation of protein homeostasis under physiological and pathological conditions.     

Regulation of DNA glycosylases and their role in limiting disease

This review will present a current understanding of mechanisms for the initiation of base excision repair (BER) of oxidatively-induced DNA damage and the biological consequences of deficiencies in these enzymes in mouse model systems and human populations.     

Religious cognition down-regulates sexually selected,characteristically male behaviors in men,but not in women

Men are typically stronger, riskier, “showier,” and more impulsive than women. According to sexual selection theory, such behaviors may have enhanced reproductive fitness for ancestral human males. However, such behaviors are facultative, and the mechanisms that cause them respond to social and environmental cues that indicate whether outlays of strength, risk-taking, showing off, or impulsivity are likely to lead to payoffs in any given instance. Recent research based on the Reproductive Religiosity Model suggests that, in contemporary Western societies, religious beliefs and institutions are differentially espoused and promulgated by restricted sexual strategists (whose reproductive strategies focus on high fertility, monogamy, and high parental care) to limit the exercise of unrestricted sexuality, which threatens the viability of restricted sexual strategies (e.g., by reducing paternity certainty and male parental investment). On this basis, we hypothesized that experimental manipulations of religious cognition would reduce men's impulsivity and motivation to demonstrate their physical prowess. Supporting this hypothesis, three experiments revealed that priming participants with religious concepts (i.e., participants wrote essays about religion, read an essay supporting the existence of an afterlife, or were implicitly exposed to religious words) reduced men's (but not women's) impulsivity with money and their physical endurance on a hand grip task. The primes affected men's behaviors irrespectively of men's scores on a self-report measure of religious commitment.     

Formaldehyde-induced genome instability is suppressed by an XPF-dependent pathway

Formaldehyde is a reactive chemical that is commonly used in the production of industrial, laboratory, household, and cosmetic products. The causal association between formaldehyde exposure and increased incidence of cancer led the International Agency for Research on Cancer to classify formaldehyde as a carcinogen. Formaldehyde-induced DNA-protein crosslinks (DPCs) elicit responses involving nucleotide excision repair (NER) and homologous recombination (HR) repair pathways; however, little is known about the cellular and genetic changes that subsequently lead to formaldehyde-induced genotoxic and cytotoxic effects. Herein, investigations of genes that modulate the cytotoxic effects of formaldehyde exposure revealed that of five NER-deficient Chinese Hamster Ovary (CHO) cell lines tested, XPF- and ERCC1-deficient cells were most sensitive to formaldehyde treatment as compared to wild-type cells. Cell cycle analyses revealed that formaldehyde-treated XPF-deficient cells exhibited an immediate G2/M arrest that was associated with altered cell ploidy and apoptosis. Additionally, an elevated number of DNA double-strand breaks (DSBs), chromosomal breaks and radial formation were also observed in XPF-deficient cells following formaldehyde treatment. Formaldehyde-induced DSBs occurred in a replication-dependent, but an XPF-independent manner. However, delayed DSB repair was observed in the absence of XPF function. Collectively, our findings highlight the role of an XPF-dependent pathway in mitigating the sensitivity to formaldehyde-induced DNA damage as evidenced by the increased genomic instability and reduced cell viability in an XPF-deficient background. In addition, centrosome and microtubule abnormalities, as well as enlarged nuclei, caused by formaldehyde exposure are demonstrated in a repair-proficient cell line.