Refractory Disseminated Coccidioidomycosis and Mycobacteriosis in Interferon‐γ Receptor 1 Deficiency

Severe coccidioidomycosis is rare, and specific genetic susceptibility to the disease remains unidentified. We describe a patient with disseminated recalcitrant coccidioidomycosis with autosomal dominant interferon-gamma receptor 1 deficiency caused by a heterozygous IFNGR1 818del4 mutation. Therefore, the interleukin-12/interferon-gamma axis appears to be critical for control of coccidioidomycosis.

HIV/AIDS, Undernutrition, and Food Insecurity

Despite tremendous advances in care for human immunodeficiency virus (HIV) infection and increased funding for treatment, morbidity and mortality due to HIV/AIDS in developing countries remains unacceptably high. A major contributing factor is that >800 million people remain chronically undernourished globally, and the HIV epidemic largely overlaps with populations already experiencing low diet quality and quantity. Here, we present an updated review of the relationship between HIV infection, nutritional deficiencies, and food insecurity and consider efforts to interrupt this cycle at a programmatic level. As HIV infection progresses, it causes a catabolic state and increased susceptibility to other infections, which are compounded by a lack of caloric and other nutrient intake, leading to progressive worsening of malnutrition. Despite calls from national and international organizations to integrate HIV and nutritional programs, data are lacking on how such programs can be effectively implemented in resource-poor settings, on the optimum content and duration of nutritional support, and on ideal target recipients.

Heritable Factors Play a Major Role in Determining Host Responses toWuchereria bancroftiInfection in an Isolated South Pacific Island Population

It is increasingly recognized that host genetic factors may play an important role in determining the outcome of filarial infections. To test this hypothesis in bancroftian lymphatic filariasis, pedigree data were collected twice during an 18-year period from an isolated Polynesian population living on a Pacific island where lymphatic filariasis is endemic.

Mechanisms Influencing the Timing and Success of Reproductive Migration in a Capital Breeding Semelparous Fish Species, the Sockeye Salmon

Two populations of homing sockeye salmon (Oncorhynchus nerka; Adams and Chilko) were intercepted in the marine approaches around the northern and southern ends of Vancouver Island (British Columbia, Canada) en route to a natal river. More than 500 salmon were nonlethally biopsied for blood plasma, gill filament tips, and gross somatic energy (GSE) and were released with either acoustic or radio transmitters. At the time of capture, GSE, body length, and circulating testosterone ([T]) differed between populations, differences that reflected known life-history variations. Within-population analyses showed that in Adams sockeye salmon, plasma glucose ([glu]), lactate ([lactate]), and ion concentrations were higher in the northern approach than in the southern approach, suggesting that the former was more stressful. GSE, [T], and gill Na(+),K(+)-ATPase activities also differed between the two locales, and each varied significantly with Julian date, suggesting seasonality. Despite these relative geographic differences, the timing of river entry and the ability to reach spawning areas were strongly correlated with energetic, reproductive, and osmoregulatory state. Salmon that delayed river entry and reached spawning areas had relatively high GSE and low [T] and gill ATPase. In contrast, salmon that entered the river directly but that ultimately failed to reach spawning areas had lower GSE and higher [T] and gill ATPase, and they also swam at significantly faster rates (failed fish approximately 20.0 km d(-1) vs. successful fish approximately 15.5 km d(-1)). Physiologically, salmon that did not enter the river at all but that presumably died in the marine environment exhibited high stress (plasma [glu] and [lactate]) and ionoregulatory measures (plasma [Na(+)], [Cl(-)], osmolality).

Macrophysiology: A Conceptual Reunification

Widespread recognition of the importance of biological studies at large spatial and temporal scales, particularly in the face of many of the most pressing issues facing humanity, has fueled the argument that there is a need to reinvigorate such studies in physiological ecology through the establishment of a macrophysiology. Following a period when the fields of ecology and physiological ecology had been regarded as largely synonymous, studies of this kind were relatively commonplace in the first half of the twentieth century. However, such large-scale work subsequently became rather scarce as physiological studies concentrated on the biochemical and molecular mechanisms underlying the capacities and tolerances of species. In some sense, macrophysiology is thus an attempt at a conceptual reunification. In this article, we provide a conceptual framework for the continued development of macrophysiology. We subdivide this framework into three major components: the establishment of macrophysiological patterns, determining the form of those patterns (the very general ways in which they are shaped), and understanding the mechanisms that give rise to them. We suggest ways in which each of these components could be developed usefully.

Reply to Antonucci et al

A Human Domain Antibody and LewisbGlycoconjugate That Inhibit Binding ofHelicobacter pylorito LewisbReceptor and Adhesion to Human Gastric Epithelium

Increasing antibiotic resistance has prompted development of alternative approaches to antimicrobial therapy, including blocking microbial adhesion to host receptors. The BabA adhesin of Helicobacter pylori binds to fucosylated blood group antigens, such as the Lewis(b) antigens in human primate gastric mucosa. We have isolated a human domain antibody specific for BabA that inhibits binding of BabA to Lewis(b) and prevents adhesion of H. pylori to human gastric epithelium. In addition, Lewis(b) oligosaccharides covalently linked to poly-D-lysine inhibited BabA binding to Le(b). The poly-D-lysine-Le(b) hexasaccharide and an Le(b) human serum albumin conjugate not only inhibited adherence of H. pylori to gastric epithelium but also displaced adherent bacteria when added to human stomach sections. Combinations of Le(b) and sialyl Le(x) or domain antibody 25 and sialyl Le(x) acted synergistically. Domain antibody 25 inhibitor may have potential for prophylactic use and, in combination with Le(b) glycoconjugates, therapeutic use in treatment of drug-resistant H. pylori infection.

Microbiology and Aging: Clinical Manifestations Microbiology and Aging Edited by Steven Percival Towata, NJ: Humana Press, 2009. 334 pp. $169.00 (hardcover).

Trends in Multidrug Treatment Failure and Subsequent Mortality among Antiretroviral Therapy–Experienced Patients with HIV Infection in North America

Although combination antiretroviral therapy continues to evolve, with potentially more effective options emerging each year, the ability of therapy to prevent multiple regimen failure and mortality in clinical practice remains poorly defined.

Insect Rate‐Temperature Relationships: Environmental Variation and the Metabolic Theory of Ecology

Much of the recent discussion concerning the form and underlying mechanistic basis of metabolic rate-temperature and development rate-temperature relationships has been precipitated by the development of the metabolic theory of ecology (MTE). Empirical tests of the theory's fundamental equation are an essential component of establishing its validity. Here, we test the temperature component of the fundamental equation of the MTE as it applies to metabolic rate and development rate, using insects as model organisms. Specifically, we test (i) whether mean activation energies, E, approximate the 0.65 eV value proposed by the proponents of the MTE and whether the range of values is tightly constrained between 0.6 and 0.7 eV, as they have argued; (ii) whether phylogenetic signal is apparent in the rate-temperature relationships; (iii) whether the slopes of the rate-temperature relationships show consistent, directional variation associated with environmental variables; and (iv) whether intra- and interspecific rate-temperature relationships differ significantly. Because the majority of activation energy values fell outside the predicted range and rate-temperature relationships showed consistent directional variation correlated with large-scale climatic variation, we conclude that data from insects provide only limited support for the MTE. In consequence, we consider alternative explanations for variation in rate-temperature relationships.