Liberty, Equality and Fairness: A Study of Citizen Participation in Federal Agency Rulemaking

This study examines individual-level citizen participation in the notice and comment component of federal agency rulemaking. It focuses on characteristics of individual participants ascertained through a survey mailed to 400 actual commenters. Survey data is used to evaluate the representativeness of these participants to the general public. Also, the compatible of citizen participation in rulemaking with the democratic ideals of liberty, equality, and fairness is evaluated, along with potential consequences of proposed reforms

Lack of clinical AIDS in SIV-infected sooty mangabeys with significant CD4+ T cell loss is associated with double-negative T cells

SIV infection of natural host species such as sooty mangabeys results in high viral replication without clinical signs of simian AIDS. Studying such infections is useful for identifying immunologic parameters that lead to AIDS in HIV-infected patients. Here we have demonstrated that acute, SIV-induced CD4+ T cell depletion in sooty mangabeys does not result in immune dysfunction and progression to simian AIDS and that a population of CD3 +CD4-CD8- T cells (double-negative T cells) partially compensates for CD4+ T cell function in these animals. Passaging plasma from an SIV-infected sooty mangabey with very few CD4 + T cells to SIV-negative animals resulted in rapid loss of CD4 + T cells. Nonetheless, all sooty mangabeys generated SIV-specific antibody and T cell responses and maintained normal levels of plasma lipopolysaccharide. Moreover, all CD4- low sooty mangabeys elicited a de novo immune response following influenza vaccination. Such preserved immune responses as well as the low levels of immune activation observed in these animals were associated with the presence of double-negative T cells capable of producing Th1, Th2, and Th17 cytokines. These studies indicate that SIV-infected sooty mangabeys do not appear to rely entirely on CD4+ T cells to maintain immunity and identify double-negative T cells as a potential subset of cells capable of performing CD4+ T cell-like helper functions upon SIV-induced CD4+ T cell depletion in this species

Decadal-scale hotspot methane ebullition within lakes following abrupt permafrost thaw

Thermokarst lakes accelerate deep permafrost thaw and the mobilization of previously frozen soil organic carbon. This leads to microbial decomposition and large releases of carbon dioxide (CO2) and methane (CH4) that enhance climate warming. However, the time scale of permafrost-carbon emissions following thaw is not well known but is important for understanding how abrupt permafrost thaw impacts climate feedback. We combined field measurements and radiocarbon dating of CH4 ebullition with (a) an assessment of lake area changes delineated from high-resolution (1–2.5 m) optical imagery and (b) geophysical measurements of thaw bulbs (taliks) to determine the spatiotemporal dynamics of hotspot-seep CH4 ebullition in interior Alaska thermokarst lakes. Hotspot seeps are characterized as point-sources of high ebullition that release 14C-depleted CH4 from deep (up to tens of meters) within lake thaw bulbs year-round. Thermokarst lakes, initiated by a variety of factors, doubled in number and increased 37.5% in area from 1949 to 2009 as climate warmed. Approximately 80% of contemporary CH4 hotspot seeps were associated with this recent thermokarst activity, occurring where 60 years of abrupt thaw took place as a result of new and expanded lake areas. Hotspot occurrence diminished with distance from thermokarst lake margins. We attribute older 14C ages of CH4 released from hotspot seeps in older, expanding thermokarst lakes (14CCH4 20 079 ± 1227 years BP, mean ± standard error (s.e.m.) years) to deeper taliks (thaw bulbs) compared to younger 14CCH4 in new lakes (14CCH4 8526 ± 741 years BP) with shallower taliks. We find that smaller, non-hotspot ebullition seeps have younger 14C ages (expanding lakes 7473 ± 1762 years; new lakes 4742 ± 803 years) and that their emissions span a larger historic range. These observations provide a first-order constraint on the magnitude and decadal-scale duration of CH4-hotspot seep emissions following formation of thermokarst lakes as climate warms

CD4saurus Rex &HIVelociraptor vs. development of clinically useful immunological markers: a Jurassic tale of frozen evolution

One of the most neglected areas of everyday clinical practice for HIV physicians is unexpectedly represented by CD4 T cell counts when used as an aid to clinical decisions. All who care for HIV patients believe that CD4+ T cell counts are a reliable method to evaluate a patient immune status. There is however a fatalistic acceptance that besides its general usefulness, CD4+ T cell counts have relevant clincal and immunological limits. Shortcomings of CD4 counts appear in certain clinical scenarios including identification of immunological nonresponders, subsequent development of cancer on antiretroviral teatment, failure on tretment simplification. Historical and recently described parameters might be better suited to advise management of patients at certain times during their disease history. Immunogenotypic parameters and innate immune parameters that define progression as well as immune parameters associated with immune recovery are available and have not been introduced into validation processes in larger trials. The scientific and clinical community needs an effort in stimulating clinical evolution of immunological tests beyond "CD4saurus Rex" introducing new parameters in the clinical arena after appropriate validatio

CD8+ Lymphocytes Control Viral Replication in SIVmac239-Infected Rhesus Macaques without Decreasing the Lifespan of Productively Infected Cells

While CD8+ T cells are clearly important in controlling virus replication during HIV and SIV infections, the mechanisms underlying this antiviral effect remain poorly understood. In this study, we assessed the in vivo effect of CD8+ lymphocyte depletion on the lifespan of productively infected cells during chronic SIVmac239 infection of rhesus macaques. We treated two groups of animals that were either CD8+ lymphocyte-depleted or controls with antiretroviral therapy, and used mathematical modeling to assess the lifespan of infected cells either in the presence or absence of CD8+ lymphocytes. We found that, in both early (day 57 post-SIV) and late (day 177 post-SIV) chronic SIV infection, depletion of CD8+ lymphocytes did not result in a measurable increase in the lifespan of either short- or long-lived productively infected cells in vivo. This result indicates that the presence of CD8+ lymphocytes does not result in a noticeably shorter lifespan of productively SIV-infected cells, and thus that direct cell killing is unlikely to be the main mechanism underlying the antiviral effect of CD8+ T cells in SIV-infected macaques with high virus replication

A Novel CCR5 Mutation Common in Sooty Mangabeys Reveals SIVsmm Infection of CCR5-Null Natural Hosts and Efficient Alternative Coreceptor Use In Vivo

In contrast to HIV infection in humans and SIV in macaques, SIV infection of natural hosts including sooty mangabeys (SM) is non-pathogenic despite robust virus replication. We identified a novel SM CCR5 allele containing a two base pair deletion (Δ2) encoding a truncated molecule that is not expressed on the cell surface and does not support SIV entry in vitro. The allele was present at a 26% frequency in a large SM colony, along with 3% for a CCR5Δ24 deletion allele that also abrogates surface expression. Overall, 8% of animals were homozygous for defective CCR5 alleles and 41% were heterozygous. The mutant allele was also present in wild SM in West Africa. CD8+ and CD4+ T cells displayed a gradient of CCR5 expression across genotype groups, which was highly significant for CD8+ cells. Remarkably, the prevalence of natural SIVsmm infection was not significantly different in animals lacking functional CCR5 compared to heterozygous and homozygous wild-type animals. Furthermore, animals lacking functional CCR5 had robust plasma viral loads, which were only modestly lower than wild-type animals. SIVsmm primary isolates infected both homozygous mutant and wild-type PBMC in a CCR5-independent manner in vitro, and Envs from both CCR5-null and wild-type infected animals used CXCR6, GPR15 and GPR1 in addition to CCR5 in transfected cells. These data clearly indicate that SIVsmm relies on CCR5-independent entry pathways in SM that are homozygous for defective CCR5 alleles and, while the extent of alternative coreceptor use in SM with CCR5 wild type alleles is uncertain, strongly suggest that SIVsmm tropism and host cell targeting in vivo is defined by the distribution and use of alternative entry pathways in addition to CCR5. SIVsmm entry through alternative pathways in vivo raises the possibility of novel CCR5-negative target cells that may be more expendable than CCR5+ cells and enable the virus to replicate efficiently without causing disease in the face of extremely restricted CCR5 expression seen in SM and several other natural host species

Long-term change and geospatial patterns of river ice cover and navigability in Southcentral Alaska detected with remote sensing

ABSTRACTPeople who travel on ice-covered rivers to access traditional lands and resources can be profoundly impacted by effects of climate change on river ice seasonality. We used remote sensing, bolstered by citizen science, to assess trends and geospatial patterns of the ice cover in the Copper River Basin of Southcentral Alaska. Our analysis of Landsat imagery from water years (WYs) 1973 to 2021 suggests a severely diminishing season of river ice travel (delayed or incomplete freezeup, early breakup) due to increasing air temperatures. The weekly probability of an adequate ice cover for river crossings declined by an average of 53 percentage points. Ice extent was closely related to accumulated freezing degree days (AFDD). AFDDOct-Apr decreased by 15% since WY 1943, a significant warming trend. We mapped the spatiotemporal variation of ice and open water extent with multispectral and synthetic aperture radar (SAR) imagery (Sentinel-2, Sentinel-1). We identified reaches with more reliable opportunities for winter access and others susceptible to extensive open water, differences related to flow energy and channel form. The results of this study can support local decision making and adaptation in response to rapidly changing river ice conditions, and our approach can be applied elsewhere to document change and improve travel safety