EcoHIV infection of mice establishes latent viral reservoirs in T cells and active viral reservoirs in macrophages that are sufficient for induction of neurocognitive impairment

Suppression of HIV replication by antiretroviral therapy (ART) or host immunity can prevent AIDS but not other HIV-associated conditions including neurocognitive impairment (HIV-NCI). Pathogenesis in HIV-suppressed individuals has been attributed to reservoirs of latent-inducible virus in resting CD4+ T cells. Macrophages are persistently infected with HIV but their role as HIV reservoirs in vivo has not been fully explored. Here we show that infection of conventional mice with chimeric HIV, EcoHIV, reproduces physiological conditions for development of disease in people on ART including immunocompetence, stable suppression of HIV replication, persistence of integrated, replication-competent HIV in T cells and macrophages, and manifestation of learning and memory deficits in behavioral tests, termed here murine HIV-NCI. EcoHIV established latent reservoirs in CD4+ T lymphocytes in chronically-infected mice but could be induced by epigenetic modulators ex vivo and in mice. In contrast, macrophages expressed EcoHIV constitutively in mice for up to 16 months; murine leukemia virus (MLV), the donor of gp80 envelope in EcoHIV, did not infect macrophages. Both EcoHIV and MLV were found in brain tissue of infected mice but only EcoHIV induced NCI. Murine HIV-NCI was prevented by antiretroviral prophylaxis but once established neither persistent EcoHIV infection in mice nor NCI could be reversed by long-acting antiretroviral therapy. EcoHIV-infected, athymic mice were more permissive to virus replication in macrophages than were wild-type mice, suffered cognitive dysfunction, as well as increased numbers of monocytes and macrophages infiltrating the brain. Our results suggest an important role of HIV expressing macrophages in HIV neuropathogenesis in hosts with suppressed HIV replication

Short-term auditory priming in freely-moving mice

Summary: Priming, a change in the mental processing of a stimulus as a result of prior encounter with a related stimulus, has been observed repeatedly and studied extensively in humans. Yet currently, there is no behavioral model of short-term priming in lab animals, precluding research on the neurobiological basis of priming. Here, we describe an auditory discrimination paradigm for studying response priming in freely moving mice. We find a priming effect in success rate in all mice tested on the task. In contrast, we do not find a priming effect in response times. Compared to non-primed discrimination trials, the addition of incongruent prime stimuli reduces success rate more than congruent prime stimuli, suggesting a cognitive mechanism based on differential interference. The results establish the short-term priming phenomenon in rodents, and the paradigm opens the door to studying the cellular-network basis of priming

Between privacy and security: the factors that drive intentions to use cyber-security applications

Installing security applications is a common way to protect against malicious apps, phishing emails, and other threats in mobile operating systems. While these applications can provide essential security protections, they also tend to access large amounts of people's sensitive information. Therefore, individuals need to evaluate the trade-off between the security features and the privacy invasion when deciding on which protection mechanisms to use. In this paper, we examine factors affecting the willingness to install mobile security applications by taking into account the invasion levels and security features of cyber-security applications. To this end, we propose a visual language that depicts the coverage of different security features as well as privacy intrusiveness levels. Our user study (n=300) shows that users assessing security applications find their trade-off balance in highly secure apps with a medium level of privacy invasion. The results indicate that a low privacy invasion might signal that the security application provides less security. We discuss these findings in the context of understanding the trade-off between privacy and security

Uterine Foxl2 regulates the adherence of the Trophectoderm cells to the endometrial epithelium

Abstract Background Forkhead Transcription Factor L2 (FOXL2) is a member of the forkhead family with important roles in reproduction. Recent studies showed that FOXL2 is expressed in human and bovine endometrium and that its levels fluctuate during pregnancy. In this study, we aimed at evaluating the expression and function of FOXL2 in embryo implantation. Methods Mouse uteri at different days of pregnancy were isolated and analyzed for the expression and localization of FOXL2. A lentiviral strategy was further employed to either knockdown or overexpress FOXL2 in non-receptive human endometrial AN3-CA cells and in receptive Ishikawa cells, respectively. These genetically modified cells were compared to cells infected with a control lentivirus to determine the function of FOXL2 in trophectoderm cells adherence to Endometrial Epithelium was associated with the expression of genes known to be involved in acquisition of uterine receptivity. Results We report that FOXL2 is expressed in both, the luminal epithelium and the myometrium of the mouse uterus and that its expression declines prior to implantation. We found that endometrial cells expressing low FOXL2 levels, either endogenous or genetically manipulated, were associated with a higher attachment rate of mouse blastocysts or human Jeg3 spheroids and mouse blastocysts. In accordance, low-FOXL2 levels were associated with changes in the expression level of components of the Wnt/Fzd and apoptotic pathways, both of which are involved in uterine receptivity. Furthermore, FOXL2 expression was inversely correlated with G-protein signaling protein 2 (Rgs2) and cytokine expression. Conclusions These results suggest that FOXL2 interferes with embryo attachment. Better understanding of the function of FOXL2 in the uterus would possibly suggest novel strategies for treatment of infertility attributed to repeated implantation failure

Possible Association between Methylphenidate and Mandibular Bone Characteristics Detected by Dental Panoramic Radiograph in Children and Adolescents with ADHD

Some studies have shown that children treated with psychostimulants for attention-deficit hyperactivity disorder (ADHD) have decreased bone mineral density (BMD). Mandibular cortical width (MCW) may be used as a surrogate measure for evaluating BMD. We compared the MCW measured on digital panoramic radiographs (DPR) of 38 children and adolescents with ADHD who were treated with methylphenidate for at least 12 months to the MCW of 58 children and adolescents without ADHD (control). The two groups had a similar mean age (p = 0.3). Mean MCW was significantly lower among children with ADHD compared to those in the control group (2.77 ± 0.33 mm vs. 3.04 ± 0.46 mm, p = 0.004). Additionally, each of the MCW sides were significantly smaller in the group with ADHD compared with the control group. In conclusion, treatment with methylphenidate is associated with low MCW in children and adolescents with ADHD. Analysis of MCW on DPR may help in screening children that are at risk of bone health alterations that may result in low BMD in adulthood. Dentists may be the first to identify bone health abnormalities and should be aware of their role in referring their patients to further follow-up

Heterogenous Canopy in a Lagrangian-Stochastic Dispersion Model for Particulate Matter from Multiple Sources over the Haifa Bay Area

The Haifa Bay area (HBA) is a major metropolitan area in Israel, which consists of high volume transportation routes, major industrial complexes, and the largest international seaport in Israel. These, which lie relatively near densely populated residential areas, result in a multitude of air pollution sources, many of whose emissions are in the form of particulate matter (PM). Previous studies have associated exposure to such PM with adverse health effects. This potential consequence serves as the motivation for this study whose aim is to provide a realistic and detailed three-dimensional concentration field of PM, originating simultaneously from multiple sources. The IIBR in-house Lagrangian stochastic pollutant dispersion model (LSM) is suitable for this endeavor, as it describes the dispersion of a scalar by solving the velocity fluctuations in high Reynolds number flows. Moreover, the LSM was validated in urban field experiments, including in the HBA. However, due to the fact that the multiple urban sources reside within the canopy layer, it was necessary to integrate into the LSM a realistic canopy layer model that depicts the actual effect of the roughness elements’ drag on the flow and turbulent exchange of the urban morphology. This was achieved by an approach which treats the canopy as patches of porous media. The LSM was used to calculate the three-dimensional fields of PM10 and PM2.5 concentrations during the typical conditions of the two workday rush-hour periods. These were compared to three air quality monitoring stations located downstream of the PM sources in the HBA. The LSM predictions for PM2.5 satisfy all acceptance criteria. Regarding the PM10 predictions, the LSM results comply with three out of four acceptance criteria. The analysis of the calculated concentration fields has shown that the PM concentrations up to 105 m AGL exhibit a spatial pattern similar to the ground level. However, it decreases by a factor of two at 45 m AGL, while, at 105 m, the concentration values are close to the background concentrations

Additional file 1: of Uterine Foxl2 regulates the adherence of the Trophectoderm cells to the endometrial epithelium

Figure S1. Embryos attachment to endometrial cells. Mouse blastocysts co-incubated with endometrial cell lines for 48 h (A). Attached embryos that stayed on the plate after the plates were washed and shaken (B). Thin arrows indicate attached embryos, thick arrow indicate unattached embryos. (C) The localization of osteopentin, an adhesion molecule, between the embryo and the endometrial cells. Osteopentin-green, DAPI-blue. (TIFF 2025 kb

Positive and biphasic extracellular waveforms correspond to return currents and axonal spikes

Abstract Multiple biophysical mechanisms may generate non-negative extracellular waveforms during action potentials, but the origin and prevalence of positive spikes and biphasic spikes in the intact brain are unknown. Using extracellular recordings from densely-connected cortical networks in freely-moving mice, we find that a tenth of the waveforms are non-negative. Positive phases of non-negative spikes occur in synchrony or just before wider same-unit negative spikes. Narrow positive spikes occur in isolation in the white matter. Isolated biphasic spikes are narrower than negative spikes, occurring right after spikes of verified inhibitory units. In CA1, units with dominant non-negative spikes exhibit place fields, phase precession, and phase-locking to ripples. Thus, near-somatic narrow positive extracellular potentials correspond to return currents, and isolated non-negative spikes correspond to axonal potentials. Identifying non-negative extracellular waveforms that correspond to non-somatic compartments during spikes can enhance the understanding of physiological and pathological neural mechanisms in intact animals