Using functional genomics to decipher the complexity of microbial pathogenicity

From the first identification of bacteria as a causative agent of disease, researchers have been developing methods and techniques to understand their pathogenic processes. For decades, this work has been limited to looking at a small number of genetically manipulatable isolates in in vitro assays or animal models of infection. Despite these limitations such work has facilitated the development of successful therapeutic strategies, most notably vaccines that target specific virulence-related features. There are however many antimicrobial resistant pathogens for which vaccination strategies have not worked, as we simply do not know enough about how they cause disease. We are however at the dawn of a new era in the study of microbial pathogenicity, where large collections of bacteria isolated directly from human infections can be sequenced and assayed to identify the bacterial features that affect disease severity in humans. Here, we describe our attempt to perform such a study focussed on the major human pathogen Staphylococcus aureus, which demonstrates the step changes such approaches can make to understanding microbial pathogenicity

Large Numbers of Matings Give Female Field Crickets a Direct Benefit but not a Genetic Benefit

Female crickets can potentially gain both direct and indirect benefits from mating multiple times with different males. Most studies have only examined the effects of small numbers of matings, although female crickets are capable of mating many times. The goal of this paper is to examine the direct and indirect benefits of mating large numbers of times for female reproductive success. In a previous experiment, female Gryllus vocalis were found to gain diminishing direct benefits from mating large numbers of times. In this study I attempt to determine whether mating large numbers of times yields similar diminishing returns on female indirect benefits. Virgin female Gryllus vocalis crickets were assigned to mate five, ten or 15 times with either the same or different males. Females that mated more times gained direct benefits in terms of laying more eggs and more fertilized eggs. Females that mated with different males rather than mating repeatedly with the same male did not have higher offspring hatching success, a result that is contrary to other published results comparing female reproductive success with repeated versus different partners. These results suggest that females that mate large numbers of times fail to gain additional genetic benefits from doing so

Depth refuge and the impacts of SCUBA spearfishing on coral reef fishes

In recent decades, spearfishing with SCUBA has emerged as an efficient method for targeting reef fish in deeper waters. However, deeper waters are increasingly recognised as a potential source of refuge that may help sustain fishery resources. We used a combination of historical catch data over a 20-year time period and fishery-independent surveys to investigate the effects of SCUBA spearfishing on coral reef fish populations in the southern Mariana Islands. Two jurisdictions were studied; Guam, where SCUBA spearfishing is practiced, and the nearby Commonwealth of Northern Mariana Islands (CNMI), where SCUBA spearfishing has been banned since 2003. Fishery-independent data were collected using baited remote underwater stereo-video systems (stereo-BRUVs) stratified by depth, marine protected area status and jurisdiction. Herbivores (primary consumers) dominated spearfishing catches, with parrotfish (scarines) and surgeonfish/unicornfish (acanthurids) the main groups harvested. However, the large, endangered humphead wrasse (Cheilinus undulatus) was the main species by weight landed by SCUBA spearfishers. SCUBA spearfishing was associated with declining size of scarines over time and catches shifting from a dominance of large parrotfishes to a mixed assemblage with increasing proportions of acanthurids. Comparisons between Guam and the nearby CNMI revealed differences in the assemblage of fished species and also greater size of scarines and acanthurids in deep water where SCUBA fishing is banned. These results suggest that SCUBA spearfishing impacts reef fish populations and that the restriction of this fishing method will ensure refuge for fish populations in deeper waters. We recommend a ban on SCUBA spearfishing to preserve or aid the recovery of large, functionally important coral reef species and to improve the sustainability of coral reef fisheries

Health Journalism Internships: A Social Marketing Strategy to Address Health Disparities

The USA seeks to eliminate health disparities by stimulating the rapid uptake of health-promoting behaviors within disadvantaged communities. A health journalism internship incorporates social marketing strategies to increase communities' access to cancer information, while helping the interns who are recruited from underrepresented communities gain admission to top graduate schools. Interns are taught basic health journalism skills that enable them to create immediate streams of cancer-related press releases for submission to community newspapers. Interns are charged with the social responsibility of continuing this dissemination process throughout their careers. Intermediate outcomes are measured as mediators of distal behavioral change goals

Does Reduced IGF-1R Signaling in Igf1r+/− Mice Alter Aging?

Mutations in insulin/IGF-1 signaling pathway have been shown to lead to increased longevity in various invertebrate models. Therefore, the effect of the haplo- insufficiency of the IGF-1 receptor (Igf1r+/−) on longevity/aging was evaluated in C57Bl/6 mice using rigorous criteria where lifespan and end-of-life pathology were measured under optimal husbandry conditions using large sample sizes. Igf1r+/− mice exhibited reductions in IGF-1 receptor levels and the activation of Akt by IGF-1, with no compensatory increases in serum IGF-1 or tissue IGF-1 mRNA levels, indicating that the Igf1r+/− mice show reduced IGF-1 signaling. Aged male, but not female Igf1r+/− mice were glucose intolerant, and both genders developed insulin resistance as they aged. Female, but not male Igf1r+/− mice survived longer than wild type mice after lethal paraquat and diquat exposure, and female Igf1r+/− mice also exhibited less diquat-induced liver damage. However, no significant difference between the lifespans of the male Igf1r+/− and wild type mice was observed; and the mean lifespan of the Igf1r+/− females was increased only slightly (less than 5%) compared to wild type mice. A comprehensive pathological analysis showed no significant difference in end-of-life pathological lesions between the Igf1r+/− and wild type mice. These data show that the Igf1r+/− mouse is not a model of increased longevity and delayed aging as predicted by invertebrate models with mutations in the insulin/IGF-1 signaling pathway

Evolution of Female Preference for Younger Males

Previous theoretical work has suggested that females should prefer to mate with older males, as older males should have higher fitness than the average fitness of the cohort into which they were born. However, studies in humans and model organisms have shown that as males age, they accumulate deleterious mutations in their germ-line at an ever-increasing rate, thereby reducing the quality of genes passed on to the next generation. Thus, older males may produce relatively poor-quality offspring. To better understand how male age influences female mate preference and offspring quality, we used a genetic algorithm model to study the effect of age-related increases in male genetic load on female mate preference. When we incorporate age-related increases in mutation load in males into our model, we find that females evolve a preference for younger males. Females in this model could determine a male's age, but not his inherited genotype nor his mutation load. Nevertheless, females evolved age-preferences that led them to mate with males that had low mutation loads, but showed no preference for males with respect to their somatic quality. These results suggest that germ-line quality, rather than somatic quality, should be the focus of female preference in good genes models

Transgenerational effects of maternal sexual interactions in seed beetles

Mating often bears large costs to females, especially in species with high levels of sexual conflict over mating rates. Given the direct costs to females associated with multiple mating, which include reductions in lifespan and lifetime reproductive success, past research focused on identifying potential indirect benefits (through increases in offspring fitness) that females may accrue. Far less attention has, however, been devoted to understanding how costs of sexual interactions to females may extend across generations. Hence, little is known about the transgenerational implications of variation in mating rates, or the net consequences of maternal sexual activities across generations. Using the seed beetle, Callosobruchus maculatus, a model system for the study of sexual conflict, we investigate the effects of mating with multiple males versus a single male, and tease apart effects due to sexual harassment and those due to mating per se, over three generations. A multigenerational analysis indicated that females that were exposed to ongoing sexual harassment and who also were permitted to mate with multiple males showed no difference in net fitness compared to females that mated just once without ongoing harassment. Intriguingly, however, females that were continually harassed, but permitted to mate just once, suffered a severe decline in net fitness compared to females that were singly (not harassed) or multiply mated (harassed, but potentially gaining benefits via mating with multiple males). Overall, the enhanced fitness in multiply mated compared to harassed females may indicate that multiple mating confers transgenerational benefits. These benefits may counteract, but do not exceed (i.e., we found no difference between singly and multiply mated females), the large transgenerational costs of harassment. Our study highlights the importance of examining transgenerational effects from an inclusive (looking at both indirect benefits but also costs) perspective, and the need to investigate transgenerational effects across several generations if we are to fully understand the consequences of sexual interactions, sexual conflict evolution, and the interplay of sexual conflict and multi-generational costs and benefits

Systematic Review of Potential Health Risks Posed by Pharmaceutical, Occupational and Consumer Exposures to Metallic and Nanoscale Aluminum, Aluminum Oxides, Aluminum Hydroxide and Its Soluble Salts

Aluminum (Al) is a ubiquitous substance encountered both naturally (as the third most abundant element) and intentionally (used in water, foods, pharmaceuticals, and vaccines); it is also present in ambient and occupational airborne particulates. Existing data underscore the importance of Al physical and chemical forms in relation to its uptake, accumulation, and systemic bioavailability. The present review represents a systematic examination of the peer-reviewed literature on the adverse health effects of Al materials published since a previous critical evaluation compiled by Krewski et al. (2007). Challenges encountered in carrying out the present review reflected the experimental use of different physical and chemical Al forms, different routes of administration, and different target organs in relation to the magnitude, frequency, and duration of exposure. Wide variations in diet can result in Al intakes that are often higher than the World Health Organization provisional tolerable weekly intake (PTWI), which is based on studies with Al citrate. Comparing daily dietary Al exposures on the basis of “total Al”assumes that gastrointestinal bioavailability for all dietary Al forms is equivalent to that for Al citrate, an approach that requires validation. Current occupational exposure limits (OELs) for identical Al substances vary as much as 15-fold. The toxicity of different Al forms depends in large measure on their physical behavior and relative solubility in water. The toxicity of soluble Al forms depends upon the delivered dose of Al+ 3 to target tissues. Trivalent Al reacts with water to produce bidentate superoxide coordination spheres [Al(O2)(H2O4)+ 2 and Al(H2O)6 + 3] that after complexation with O2•−, generate Al superoxides [Al(O2•)](H2O5)]+ 2. Semireduced AlO2• radicals deplete mitochondrial Fe and promote generation of H2O2, O2 • − and OH•. Thus, it is the Al+ 3-induced formation of oxygen radicals that accounts for the oxidative damage that leads to intrinsic apoptosis. In contrast, the toxicity of the insoluble Al oxides depends primarily on their behavior as particulates. Aluminum has been held responsible for human morbidity and mortality, but there is no consistent and convincing evidence to associate the Al found in food and drinking water at the doses and chemical forms presently consumed by people living in North America and Western Europe with increased risk for Alzheimer\u27s disease (AD). Neither is there clear evidence to show use of Al-containing underarm antiperspirants or cosmetics increases the risk of AD or breast cancer. Metallic Al, its oxides, and common Al salts have not been shown to be either genotoxic or carcinogenic. Aluminum exposures during neonatal and pediatric parenteral nutrition (PN) can impair bone mineralization and delay neurological development. Adverse effects to vaccines with Al adjuvants have occurred; however, recent controlled trials found that the immunologic response to certain vaccines with Al adjuvants was no greater, and in some cases less than, that after identical vaccination without Al adjuvants. The scientific literature on the adverse health effects of Al is extensive. Health risk assessments for Al must take into account individual co-factors (e.g., age, renal function, diet, gastric pH). Conclusions from the current review point to the need for refinement of the PTWI, reduction of Al contamination in PN solutions, justification for routine addition of Al to vaccines, and harmonization of OELs for Al substances