In Vivo validation of a bioinformatics based tool to identify reduced replication capacity in HIV-1.

Although antiretroviral drug resistance is common in treated HIV infected individuals, it is not a consistent indicator of HIV morbidity and mortality. To the contrary, HIV resistance-associated mutations may lead to changes in viral fitness that are beneficial to infected individuals. Using a bioinformatics-based model to assess the effects of numerous drug resistance mutations, we determined that the D30N mutation in HIV-1 protease had the largest decrease in replication capacity among known protease resistance mutations. To test this in silico result in an in vivo environment, we constructed several drug-resistant mutant HIV-1 strains and compared their relative fitness utilizing the SCID-hu mouse model. We found HIV-1 containing the D30N mutation had a significant defect in vivo, showing impaired replication kinetics and a decreased ability to deplete CD4+ thymocytes, compared to the wild-type or virus without the D30N mutation. In comparison, virus containing the M184V mutation in reverse transcriptase, which shows decreased replication capacity in vitro, did not have an effect on viral fitness in vivo. Thus, in this study we have verified an in silico bioinformatics result with a biological assessment to identify a unique mutation in HIV-1 that has a significant fitness defect in vivo

Investigation of the Prevalence of Learning Disabilities Within the Home-School Population of Southwest Michigan

Problem. The special education needs of home-school children have rarely been studied. This research utilizes the homeschool population of Southwest Michigan to investigate the incidence of learning disabilities (LD) within this group. At the same time, it is possible to investigate some of the criticisms of the learning disability field of study. Method. Two hundred ninety-eight home-school children in southwest Michigan were assessed for LD using the Michigan State Board of Education definitional criteria. Achievement was assessed by use of the Wide Range Achievement Test, third revision. Ability was measured with the Wechsler Intelligence Scale for Children, third revision. A discrepancy of 18 standard score points was used to determine possible LD. Subjects were then examined for the presence of other factors that would explain the learning problems of subjects having a severe discrepancy between ability and achievement. Results. Of the sample group, 3.7% were found to exhibit learning problems that could not be explained by other than a diagnosis of LD. A significant relationship was found between levels of teacher involvement and the presence of learning problems. Conclusions. A lower prevalence of LD is found within the home-school population when compared with Board of Education figures of public school prevalence rates. However, this difference was not statistically significant. The concept of LD is problematic from the standpoint of definition and assessment and might better be conceived as Learning Difficulty Syndrome. Learning problems appear related to teacher involvement

Validation of the SCID-hu Thy/Liv mouse model with four classes of licensed antiretrovirals.

BackgroundThe SCID-hu Thy/Liv mouse model of HIV-1 infection is a useful platform for the preclinical evaluation of antiviral efficacy in vivo. We performed this study to validate the model with representatives of all four classes of licensed antiretrovirals.Methodology/principal findingsEndpoint analyses for quantification of Thy/Liv implant viral load included ELISA for cell-associated p24, branched DNA assay for HIV-1 RNA, and detection of infected thymocytes by intracellular staining for Gag-p24. Antiviral protection from HIV-1-mediated thymocyte depletion was assessed by multicolor flow cytometric analysis of thymocyte subpopulations based on surface expression of CD3, CD4, and CD8. These mice can be productively infected with molecular clones of HIV-1 (e.g., the X4 clone NL4-3) as well as with primary R5 and R5X4 isolates. To determine whether results in this model are concordant with those found in humans, we performed direct comparisons of two drugs in the same class, each of which has known potency and dosing levels in humans. Here we show that second-generation antiretrovirals were, as expected, more potent than their first-generation predecessors: emtricitabine was more potent than lamivudine, efavirenz was more potent than nevirapine, and atazanavir was more potent than indinavir. After interspecies pharmacodynamic scaling, the dose ranges found to inhibit viral replication in the SCID-hu Thy/Liv mouse were similar to those used in humans. Moreover, HIV-1 replication in these mice was genetically stable; treatment of the mice with lamivudine did not result in the M184V substitution in reverse transcriptase, and the multidrug-resistant NY index case HIV-1 retained its drug-resistance substitutions.ConclusionGiven the fidelity of such comparisons, we conclude that this highly reproducible mouse model is likely to predict clinical antiviral efficacy in humans

On Graduate Unions and Corporatization

The existence of graduate labor unions is seen as evidence of the changed and changing nature of academic economies over the past two decades. To be exact they are seen as a result of academic capitalism and broad trends towards corporatization (Bousquet, 2008; Lafer, 2003; Rhoads & Rhoades, 2005; Slaughter & Rhoades, 2004) whereby institutions of higher education increasingly engage in market-like behaviors and display “the culture, practices, policies, and workforce strategies more appropriate to corporations” (Steck, 2003, p. 66). This involves adopting “corporate models, cutting costs and seeking profit-making opportunities” resulting in heavy reliance on private funding for research and expanded commercial influence over academic pursuits (Clay, 2008, p. 11) Within the context of changing academic economies and corporate universities scholars see graduate employee unions as a potential source of resistance and progressive change (Bousquet, 2008; Lafer, 2003; Rhoads & Rhoades, 2005)

A Critical View of Graduate Unions

Institutions of higher education increasingly focus on their economic functions and have adopted labor force practices that resemble private businesses. One such strategy is a greater reliance on employing graduate students to perform tasks previously done by faculty. Simultaneously, graduate employees have organized labor unions and pushed for rights and benefits other organized workers have sought. This is a practice that should be of concern to human rights sociologists, lest we neglect to critically reflect on the social relations that our work is embedded within, thereby damaging our abilities to champion the oppressed. This case study examines how graduate labor organizers see their efforts as enabling what they call the corporatization of the university in unintended ways. It adds a new dimension to existing scholarship that depicts graduate labor unions as a counter-force to corporatization and businesslike practices in higher education while arguing that graduate unions are actually participants in these. With this in mind, this paper suggests reasons for human rights sociologists to still support graduate labor union efforts and suggests ways that we can do it without undermining our goal, given the unintended consequences identified by graduate labor organizers

Dysphagia secondary to dermatomyositis treated successfully with intravenous immunoglobulin: a case report

A 46 year old woman presented with a one month history of rash and mylagia. The history, clinical findings and blood tests all supported a diagnosis of dermatomyositis. The patient later developed dysphagia and was successfully treated with intravenous immunoglobulin. Investigations and treatment of dysphagia in the context of dermatomyositis are discussed

Rectal Transmission of Transmitted/Founder HIV-1 Is Efficiently Prevented by Topical 1% Tenofovir in BLT Humanized Mice

Rectal microbicides are being developed to prevent new HIV infections in both men and women. We focused our in vivo preclinical efficacy study on rectally-applied tenofovir. BLT humanized mice (n = 43) were rectally inoculated with either the primary isolate HIV-1(JRCSF) or the MSM-derived transmitted/founder (T/F) virus HIV-1(THRO) within 30 minutes following treatment with topical 1% tenofovir or vehicle. Under our experimental conditions, in the absence of drug treatment we observed 50% and 60% rectal transmission by HIV-1(JRCSF) and HIV-1(THRO), respectively. Topical tenofovir reduced rectal transmission to 8% (1/12; log rank p = 0.03) for HIV-1(JRCSF) and 0% (0/6; log rank p = 0.02) for HIV-1(THRO). This is the first demonstration that any human T/F HIV-1 rectally infects humanized mice and that transmission of the T/F virus can be efficiently blocked by rectally applied 1% tenofovir. These results obtained in BLT mice, along with recent ex vivo, Phase 1 trial and non-human primate reports, provide a critically important step forward in the development of tenofovir-based rectal microbicides

Planting depth and within-field soil variability impacts on corn stand establishment and yield

Seedbed conditions during corn (Zea mays L.) planting can have substantial impact on corn stand establishment and final yield. Planting management decisions are complex due to spatial variability caused by changing soil characteristics such as soil texture or landscape position. Field experiments conducted in central Missouri from 2017 to 2019 assessed the effects of varying corn planting depths on stand establishment and yield. Sites included fine- and coarse-textured alluvial soils, and summit, back, and foot slope positions of Alfisol claypan soil landscapes. On alluvial soil, deep planting (7.6 cm) often had the most uniform and timely emergence. Shallow planting (3.8 cm) had the least uniform emergence and was particularly troublesome on fine-textured soil under warm conditions. Under these conditions, grain yield for one site-year was 2.8 Mg ha–1 less when planting shallow compared with planting deep. On the claypan landscape position study, stand establishment was affected by both warm and cool growing conditions during the emergence period. During warm conditions, deep planting enhanced emergence uniformity and rate (1.1 d less to reach 90% emergence than shallow planting); the opposite was true for cool conditions (3.7 d more). Yield was not affected by planting depth at any of the site-years of the landscape position study. These results indicate that certain soil textures and landscape positions require greater attention to planting depth to achieve optimum stand establishment. Differences could be used in on-the-go planter prescriptions. These findings also demonstrate that despite early establishment differences, stands can often compensate and maintain similar yield