9G4+ Antibodies Isolated from HIV-Infected Patients Neutralize HIV-1 and Have Distinct Autoreactivity Profiles

Potent HIV-1 specific broadly neutralizing antibodies (BNA) are uncommon in HIV infected individuals, and have proven hard to elicit by vaccination. Several, isolated monoclonal BNA are polyreactive and also recognize self-antigens, suggesting a breach of immune tolerance in persons living with HIV (PLWH). Persons with systemic lupus erythematosus (SLE) often have elevated levels of autoreactive antibodies encoded by the VH4-34 heavy chain immunoglobulin gene whose protein product can be detected by the 9G4 rat monoclonal antibody. We have recently found that levels of these “9G4+” antibodies are also elevated in PLWH. However, the putative autoreactive nature of these antibodies and the relationship of such reactivities with HIV neutralization have not been investigated. We therefore examined the autoreactivity and HIV neutralization potential of 9G4+ antibodies from PLWH. Results show that 9G4+ antibodies from PLWH bound to recombinant HIV-1 envelope (Env) and neutralized viral infectivity in vitro, whereas 9G4+ antibodies from persons with SLE did not bind to Env and failed to neutralize viral infectivity. In addition, while 9G4+ antibodies from PLWH retained the canonical anti-i reactivity that mediates B cell binding, they did not display other autoreactivities common to SLE 9G4+ antibodies, such as binding to cardiolipin and DNA and had much lower reactivity with apoptotic cells. Taken together, these data indicate that the autoreactivity of 9G4+ antibodies from PLWH is distinct from that of SLE patients, and therefore, their expansion is not due to a general breakdown of B cell tolerance but is instead determined in a more disease-specific manner by self-antigens that become immunogenic in the context of, and possibly due to HIV infection. Further studies of 9G4+ B cells may shed light on the regulation of B cell tolerance and interface between the generation of specific autoreactivities and the induction of antiviral immunity in persons living with HIV.     

Indirect Effects of Impoundment on Migrating Fish: Temperature Gradients in Fish Ladders Slow Dam Passage by Adult Chinook Salmon and Steelhead

Thermal layering in reservoirs upstream from hydroelectric dams can create temperature gradients in fishways used by upstream migrating adults. In the Snake River, Washington, federally-protected adult salmonids (Oncorhynchus spp.) often encounter relatively cool water in dam tailraces and lower ladder sections and warmer water in the upstream portions of ladders. Using radiotelemetry, we examined relationships between fish passage behavior and the temperature difference between the top and bottom of ladders (∆T) at four dams over four years. Some spring Chinook salmon (O. tshawytscha) experienced ∆T ≥ 0.5 °C. Many summer and fall Chinook salmon and summer steelhead (O. mykiss) experienced ∆T ≥ 1.0 °C, and some individuals encountered ΔT > 4.0°C. As ΔT increased, migrants were consistently more likely to move down fish ladders and exit into dam tailraces, resulting in upstream passage delays that ranged from hours to days. Fish body temperatures equilibrated to ladder temperatures and often exceeded 20°C, indicating potential negative physiological and fitness effects. Collectively, the results suggest that gradients in fishway water temperatures present a migration obstacle to many anadromous migrants. Unfavorable temperature gradients may be common at reservoir-fed fish passage facilities, especially those with seasonal thermal layering or stratification. Understanding and managing thermal heterogeneity at such sites may be important for ensuring efficient upstream passage and minimizing stress for migratory, temperature-sensitive species.     

Multifactorial diversity sustains microbial community stability

Maintenance of a high degree of biodiversity in homogeneous environments is poorly understood. A complex cheese starter culture with a long history of use was characterized as a model system to study simple microbial communities. Eight distinct genetic lineages were identified, encompassing two species: Lactococcus lactis and Leuconostoc mesenteroides. The genetic lineages were found to be collections of strains with variable plasmid content and phage sensitivities. Kill-the-winner hypothesis explaining the suppression of the fittest strains by density-dependent phage predation was operational at the strain level. This prevents the eradication of entire genetic lineages from the community during propagation regimes (back-slopping), stabilizing the genetic heterogeneity in the starter culture against environmental uncertainty.     

The Active and the Inactive Form of the hAT1 Receptor Have an Identical Ligand-Binding Environment: An MPA Study on a Constitutively Active Angiotensin II Receptor Mutant

Several models of activation mechanisms were proposed for G protein-coupled receptors (GPCRs), yet no direct methods exist for their elucidation. The availability of constitutively active mutants has given an opportunity to study active receptor conformations within acceptable limits using models such as the angiotensin II type 1 (AT₁)¹ receptor mutant N111G-hAT₁ which displays an important constitutive activity. Recently, by using methionine proximity assay, we showed for the hAT₁ receptor that TMD III, VI, and VII form the ligand-binding pocket of the C-terminal amino acid of an antagonistic AngII analogue. In the present contribution, we investigated whether the same residues would also constitute the ligand-binding contacts in constitutively activated mutant (CAM) receptors. For this purpose, the same Met mutagenesis strategy was carried out on the N111G double mutants. Analysis of 43 receptors mutants in the N111G-hAT₁ series, photolabeled and CNBr digested, showed that there were only subtle structural changes between the wt-receptor and its constitutively active form.     

Genetic portrait of Lisboa immigrant population from Cabo Verde with mitochondrial DNA analysis

Journal of Genetics -     

Homing and straying by anadromous salmonids: a review of mechanisms and rates

There is a long research history addressing olfactory imprinting, natal homing, and non-natal straying by anadromous salmon and trout (Salmonidae). In undisturbed populations, adult straying is a fundamental component of metapopulation biology, facilitating genetic resilience, demographic stability, recolonization, and range expansion into unexploited habitats. Unfortunately, salmonid hatcheries and other human actions worldwide have affected straying in ways that can negatively affect wild populations through competitive interactions, reduced productivity and resiliency, hybridization and domestication effects, and outbreeding depression. Reduced adult straying is therefore an objective for many managed populations. Currently, there is considerable uncertainty about the range of ‘natural’ stray rates and about which mechanisms precipitate straying in either wild or human-influenced fish. Research in several disciplines indicates that adult straying is affected by endocrine physiology and neurological processes in juveniles, incomplete or interrupted imprinting during rearing and emigration, and by complex interactions among adult maturation processes, reproductive behaviors, olfactory memory, environmental conditions during migration, and senescence physiology. Reported salmonid stray rates indicate that the behavior varies among species, among life-history types, and among populations within species. Most strays enter sites near natal areas, but long-distance straying also occurs, especially in hatchery populations that were outplanted or transported as juveniles. A majority of past studies has estimated straying as demographic losses from donor populations, but some have estimated straying into recipient populations. Most recipient-based estimates have substantiated concerns that wild populations are vulnerable to swamping by abundant hatchery and farm-raised strays.