Comparison of CIDR-based protocols to synchronize estrus in beef heifers

Estrus synchronization and artificial insemination (AI) are reproductive management techniques that allow beef producers to enhance the reproductive efficiency and genetic composition of their cow herd. However, U.S. beef producers have been reluctant to adopt these reproductive management tools, largely due to time and labor. Recent research to synchronize estrus, therefore, has focused on the development of estrus synchronization protocols that facilitate fixed-time AI (FTAI). Although protocols have been developed that allow the successful use of FTAI in beef cows, the same degree of success in beef heifers has not been realized. Additionally, no published research has focused on characterizing the physiological responses to long- and short-term CIDR-based protocols in beef heifers. Experiment 1 evaluated ovulatory response to GnRH and synchrony of estrus and ovulation after PGF2[alpha] (PG) in beef heifers. The CIDR Select and Select Synch + CIDR protocols were evaluated among estrous cycling and prepubertal beef heifers and the CIDR-PG and Select Synch protocols were evaluated among estrous cycling beef heifers. A reduced variance for the intervals to estrus and ovulation was detected for estrous cycling heifers treated with the CIDR Select protocol in comparison to the other 3 treatments. The combined results of the estrous cycling and prepubertal heifers revealed an increased ovulatory response to GnRH for heifers treated with the CIDR Select protocol compared to the Select Synch + CIDR protocol, which ultimately resulted in a reduced variance for interval to estrus and ovulation after PG. Furthermore, no differences within treatment were detected in the variance for interval to estrus or ovulation among estrous cycling and prepubertal heifers treated with the CIDR Select protocol. These results suggest that the CIDR Select protocol may facilitate FTAI more effectively in mixed groups of estrous cycling and prepubertal beef heifers. Experiments 2 and 3 evaluated modifications to the CIDR Select protocol. Estrous cycling beef heifers were used in Exp. 2. The hypothesis tested was that reducing the interval from CIDR removal to GnRH administration by 2 d would facilitate an improvement in the synchrony of estrus after PG. Although a larger number of heifers that were assigned to the 28 d protocol were on d 5 and 6 at the time GnRH was administered, response to GnRH was not improved and synchrony of estrus was not enhanced following PG. In Exp. 3, a second modification to the CIDR Select protocol was evaluated using estrous cycling and prepubertal beef heifers. The hypotheses tested were: 1) reducing the interval from CIDR removal to GnRH may facilitate an improvement in the synchrony of estrus after PG, and 2) the addition of GnRH following CIDR removal is required to improve the synchrony of estrus after PG. Although no difference in estrous response was detected, mean intervals to estrus and variance for interval to estrus differed based on the interaction of treatment length, GnRH, and estrous cyclicity status. The results from Exp. 3 clearly suggest that further evaluation of long-term CIDR-based protocols is required

ER Stress-Induced eIF2-alpha Phosphorylation Underlies Sensitivity of Striatal Neurons to Pathogenic Huntingtin

A hallmark of Huntington's disease is the pronounced sensitivity of striatal neurons to polyglutamine-expanded huntingtin expression. Here we show that cultured striatal cells and murine brain striatum have remarkably low levels of phosphorylation of translation initiation factor eIF2 alpha, a stress-induced process that interferes with general protein synthesis and also induces differential translation of pro-apoptotic factors. EIF2 alpha phosphorylation was elevated in a striatal cell line stably expressing pathogenic huntingtin, as well as in brain sections of Huntington's disease model mice. Pathogenic huntingtin caused endoplasmic reticulum (ER) stress and increased eIF2 alpha phosphorylation by increasing the activity of PKR-like ER-localized eIF2 alpha kinase (PERK). Importantly, striatal neurons exhibited special sensitivity to ER stress-inducing agents, which was potentiated by pathogenic huntingtin. We could strongly reduce huntingtin toxicity by inhibiting PERK. Therefore, alteration of protein homeostasis and eIF2 alpha phosphorylation status by pathogenic huntingtin appears to be an important cause of striatal cell death. A dephosphorylated state of eIF2 alpha has been linked to cognition, which suggests that the effect of pathogenic huntingtin might also be a source of the early cognitive impairment seen in patients

Post-treatment control or treated controllers? Viral remission in treated and untreated primary HIV infection

OBJECTIVE(S): An HIV cure will impose aviraemia which is sustained following the withdrawal of antiretroviral therapy (ART). Understanding the efficacy of novel interventions aimed at curing HIV requires characterisation of both natural viral control and the effect of ART on viral control after treatment interruption. DESIGN: Analysis of transient viral control in recent seroconverters in the SPARTAC trial. METHODS: We compared untreated and treated HIV seroconverters (n = 292) and identified periods of control (plasma VL<400 copies/mL for ≥16 weeks off therapy) in 7.9% of ART-naive participants, and in 12.0% overall. HIV DNA was measured by qPCR and HIV-specific CD8 responses were measured by ELISpot. T cell activation and exhaustion were measured by flow cytometry. RESULTS: At baseline, future controllers had lower HIV DNA, lower plasma VLs, higher CD4:CD8 ratios (all p < 0.001), and higher CD4 counts (p < 0.05) than non-controllers. Among controllers, the only difference between the untreated and those who received ART was higher baseline VLs in the latter (p = 0.003), supporting an added ART effect. CONCLUSIONS: Consideration of spontaneous remission in untreated individuals will be critical to avoid overestimating the effect size of new interventions used in HIV cure studies

Role of CD8+ T cells in adult and paediatric HIV infection

Infection with HIV is a continuing global health problem. Antiretroviral therapy effectively suppresses viraemia, but the viral reservoir in latently infected CD4+ T-cells persists for decades and is the main obstacle to HIV eradication. The central role of CD8+ T-cellmediated immune control of natural adult HIV infection has long been established and recent studies suggest that CD8+ T-cells are likely to be crucial in eliminating reactivated reservoirs. However, the questions of what constitutes an effective anti-HIV CD8+ T-cell response and how to induce it therapeutically are outstanding. Moreover, even less is known about the antiviral function of CD8+ T-cells in paediatric HIV infection. Although outnumbered by adult infections, paediatric infection may offer opportunities to achieve HIV cure that could be more widely applicable to cure strategies in adults. Here, I explore the specific aspects of the interplay between host and virus in order to gain a better understanding of the optimal CD8+ T-cell-mediated immune responses. I demonstrate that in contrast to the Gag-specific response that mediates viral control in the context of HLA-B&ast;57, among HLA-B&ast;14-restricted responses, Env-specific cells are more potent than those targeting Gag. This is associated with higher antigen sensitivity and stronger selection pressure in the Env-specific population. I define two broadly distinct phenotypes of HIV non-progression in children. These are characterised by differential protein specificity of the antiviral CD8+ T-cell response but children of both phenotypes demonstrate strong selection pressure exerted on the virus by CD8+ T-cells in the first weeks of life. Next, in the context of the HIV vaccine tested in the Phambili trial, I report an HLA-specific effect of vaccine on disease progression, as a result of altering the natural CD8+ T-cell immunodominance hierarchy. Finally, I demonstrate a new method which allows to selectively deplete human HIV-specific CD8+ T-cell in vitro, and thereby to evaluate the contribution and efficacy of particular CD8+ T-cell specificities to viral inhibition – a critical question to HIV vaccine design and reservoir eradication studies. The work described here adds important insights to our understanding of the HIV-specific CD8+ T-cell responses that are generated from birth through childhood and into adulthood and is relevant to the future studies directed at harnessing the most effective CD8+ T-cell response to achieve HIV cure

Slave cowboys in the cattle lands of southern brazil, 1800-1850

Perhaps the most striking feature of Rio Grande do Sul, Brazil, inthe first part of the nineteenth century was the presence of slave cowboys.Giuseppe Garibaldi, who had fought for many years in RioGrande do Sul alongside the black Ragamuffins in the RagamuffinWar, 1835-1845, considered these recently freed slaves among thefinest busters, ropers, and horse soldiers in all the province, so famousfor its gauchos (1)

The road to Porongos:: haitianismo and artiguismo in the massacre that ended the Farroupilha, 1835-1845

The Porongos defeat over the secessionist rebels on November 14, 1844, militarily and politically solidified the barão de Caxias’ coming victory, which would end the longest rebellion in Brazilian history, the Farroupilha, 1835-1845.  Most of the encounters to come were small, mopping-up and surveillance actions, except for one, at Arroio Grande, just two weeks after Porongos. Suspiciously, the targets of both these assaults were the libertos, slaves the rebels had seized from their provincial loyalist neighbors, and whom they armed and ostensibly freed. Before Porongos, Caxias and the farrapo general Canabarro had arrived at the same conclusion: in order to have peace, conciliation, and a return to Imperial order, the rebels needed proof that their cause was lost. The best and most convenient solution led Caxias and Canabarro to use Black losses to show the war was no longer winnable, and to defang them as a future menace. When Canabarro assembled what was the last great rebel army on the Cerro do Porongos, liberto soldiers comprised its very core.  On that November morning, approximately 35% of Canabarro’s troops were either killed, wounded, or captured. Nearly all those who died or were taken prisoner came from the ranks of the liberto infantry. If the many mysteries swirling around Porongos were stripped away, what would emerge and converge at Porongos were two historical shadows still coursing through the borderlands, hatianismo and artiguismo. These were neither doctrines nor unique to the borderlands, yet together they advised both rebel and Imperial policy, and were implicit in the immediacies of decision-making which determined the libertos’ fate