Dynamics and mechanisms of clonal expansion of HIV-1-infected cells in a humanized mouse model.

Combination anti-retroviral therapy (cART) has drastically improved the clinical outcome of HIV-1 infection. Nonetheless, despite effective cART, HIV-1 persists indefinitely in infected individuals. Clonal expansion of HIV-1-infected cells in peripheral blood has been reported recently. cART is effective in stopping the retroviral replication cycle, but not in inhibiting clonal expansion of the infected host cells. Thus, the proliferation of HIV-1-infected cells may play a role in viral persistence, but little is known about the kinetics of the generation, the tissue distribution or the underlying mechanism of clonal expansion in vivo. Here we analyzed the clonality of HIV-1-infected cells using high-throughput integration site analysis in a hematopoietic stem cell-transplanted humanized mouse model. Clonally expanded, HIV-1-infected cells were detectable at two weeks post infection, their abundance increased with time, and certain clones were present in multiple organs. Expansion of HIV-1-infected clones was significantly more frequent when the provirus was integrated near host genes in specific gene ontological classes, including cell activation and chromatin regulation. These results identify potential drivers of clonal expansion of HIV-1-infected cells in vivo

Off-line studies of the laser ionization of yttrium at the IGISOL facility

A laser ion source is under development at the IGISOL facility, Jyvaskyla, in order to address deficiencies in the ion guide technique. The key elements of interest are those of a refractory nature, whose isotopes and isomers are widely studied using both laser spectroscopic and high precision mass measurement techniques. Yttrium has been the first element of choice for the new laser ion source. In this work we present a new coupled dye-Ti:Sapphire laser scheme and give a detailed discussion of the results obtained from laser ionization of yttrium atoms produced in an ion guide via joule heating of a filament. The importance of not only gas purity, but indeed the baseline vacuum pressure in the environment outside the ion guide is discussed in light of the fast gas phase chemistry seen in the yttrium system. A single laser shot model is introduced and is compared to the experimental data in order to extract the level of impurities within the gas cell.Comment: 18 pages submitted to NIM

Highly Strengthened Superconducting Magnet for a 40 T Compact Hybrid Magnet(Magnet Technology)

A 16 T outer superconducting magnet for a 40 T compact hybrid magnet is investigated. A highly strengthened superconducting magnet with a 360 mm room temperature bore can be made using newly developed (Nb, Ti)_3Sn wires with Cu-Al_2O_3 reinforcing stabilizer. The coil weight is outstandingly reduced by as much as 70 %

Beta-Arrestin Functionally Regulates the Non-Bleaching Pigment Parapinopsin in Lamprey Pineal

The light response of vertebrate visual cells is achieved by light-sensing proteins such as opsin-based pigments as well as signal transduction proteins, including visual arrestin. Previous studies have indicated that the pineal pigment parapinopsin has evolutionally and physiologically important characteristics. Parapinopsin is phylogenetically related to vertebrate visual pigments. However, unlike the photoproduct of the visual pigment rhodopsin, which is unstable, dissociating from its chromophore and bleaching, the parapinopsin photoproduct is stable and does not release its chromophore. Here, we investigated arrestin, which regulates parapinopsin signaling, in the lamprey pineal organ, where parapinopsin and rhodopsin are localized to distinct photoreceptor cells. We found that beta-arrestin, which binds to stimulated G protein-coupled receptors (GPCRs) other than opsin-based pigments, was localized to parapinopsin-containing cells. This result stands in contrast to the localization of visual arrestin in rhodopsin-containing cells. Beta-arrestin bound to cultured cell membranes containing parapinopsin light-dependently and translocated to the outer segments of pineal parapinopsin-containing cells, suggesting that beta-arrestin binds to parapinopsin to arrest parapinopsin signaling. Interestingly, beta-arrestin colocalized with parapinopsin in the granules of the parapinopsin-expressing cell bodies under light illumination. Because beta-arrestin, which is a mediator of clathrin-mediated GPCR internalization, also served as a mediator of parapinopsin internalization in cultured cells, these results suggest that the granules were generated light-dependently by beta-arrestin-mediated internalization of parapinopsins from the outer segments. Therefore, our findings imply that beta-arrestin-mediated internalization is responsible for eliminating the stable photoproduct and restoring cell conditions to the original dark state. Taken together with a previous finding that the bleaching pigment evolved from a non-bleaching pigment, vertebrate visual arrestin may have evolved from a “beta-like” arrestin by losing its clathrin-binding domain and its function as an internalization mediator. Such changes would have followed the evolution of vertebrate visual pigments, which generate unstable photoproducts that independently decay by chromophore dissociation

The association of pain with suicidal ideation and suicide attempts with depressive symptoms among adults aged ≥50 years from low- and middle-income countries

Objectives: We aimed to examine the relationship of pain with suicidal ideation and suicide attempts with depressive symptoms among adults aged ≥50 years from six low- and middle-income countries (LMICs) (China, Ghana, India, Mexico, Russia, and South Africa). Methods: Cross-sectional, community-based, nationally representative data from the WHO Study on global AGEing and adult health were analyzed. Self-reported information on past 12-month suicidal ideation and suicide attempts among people with depressive symptoms was collected. Pain was assessed with the question “Overall in the last 30 days, how much of bodily aches or pain did you have?” With answer options: “none”, “mild”, “moderate”, “severe/extreme”. Multivariable logistic regression was done to assess associations. Results: Data on 34,129 adults aged ≥50 years (mean [SD] age 62.4 [16.0] years; males 47.9%) were analyzed. Compared to no pain, mild, moderate, and severe/extreme pain were associated with 2.83 (95% CI = 1.51–5.28), 4.01 (95% CI = 2.38–6.76), and 12.26 (95% CI = 6.44–23.36) times higher odds for suicidal ideation. For suicide attempt, only severe/extreme pain was associated with significantly increased odds (OR = 4.68; 95% CI = 1.67–13.08). Conclusions: In this large sample of older adults from multiple LMICs, pain was strongly associated with suicidal thoughts and suicide attempts with depressive symptoms. Future studies should assess whether addressing pain among older people in LMICs may lead to reduction in suicidal thoughts and behaviors

Spin-polarized tunneling of La0.67Sr0.33MnO3/YBa2Cu3O7-d junctions

The transport properties between ferromagnets and high-Tc superconductors are investigated in La0.67Sr0.33MnO3/YBa2Cu3O7-d (LSMO/YBCO)junctions in the geometry of cross-strip lines. The conductance spectra show zero-bias conductance peaks (ZBCP), reflecting the charge transport in the ab-plane. When an external magnetic field is applied to the junctions, the conductance spectra show two notable features, i.e., an increase of background conductance and an asymmetric ZBCP splitting whose amplitude responds nonlinearly to the applied field. It is shown that the magnetic field response are consistent with a theoretical prediction of tunneling spectroscopy when the presence of a ferromagnetic barrier between a spin-polarized ferromagnet and a d-wave superconductor is assumed.Comment: 10 Pages, 7 EPS figures, Submitted to Phys. Rev.

Physical Multimorbidity and Sarcopenia among Adults Aged ≥65 Years in Low- and Middle-Income Countries

Introduction: Physical multimorbidity is plausibly linked to sarcopenia. However, to date, only a few studies exist on this topic, and none have examined this association in low- and middle-income countries (LMICs). Thus, we aimed to investigate the association between multimorbidity and sarcopenia in a sample of older adults from six LMICs (China, Ghana, India, Mexico, Russia, South Africa). Methods: Cross-sectional, community-based data from the WHO Study on Global Ageing and Adult Health (SAGE) were analysed. Sarcopenia was defined as having low skeletal muscle mass (SMM) and weak handgrip strength, while severe sarcopenia was defined as having low SMM, weak handgrip strength, and slow gait speed. A total of 11 physical chronic conditions were assessed and multimorbidity referred to ≥2 chronic conditions. Multivariable logistic regression analysis was conducted. Results: Data on 14,585 adults aged ≥65 years were analysed (mean age 72.6 years, SD 11.5 years; 53.7% females). Adjusted estimates showed that compared to no chronic physical conditions, ≥2 conditions are significantly associated with 1.49 (95% CI = 1.02–2.19) and 2.52 (95% CI = 1.53–4.15) times higher odds for sarcopenia and severe sarcopenia, respectively. Conclusions: In this large sample of older adults from LMICs, physical multimorbidity was significantly associated with sarcopenia and severe sarcopenia. Our study results tentatively suggest that targeting those with multimorbidity may aid in the prevention of sarcopenia, pending future longitudinal research

Lower Limb Muscle Strength and Muscle Mass Are Associated With Incident Symptomatic Knee Osteoarthritis: A Longitudinal Cohort Study

Recent literature suggests that sarcopenia, often represented by low lower limbs muscle mass and strength, can be considered a potential risk factor for knee osteoarthritis (OA), but the available literature is still limited. We therefore aimed to investigate whether sarcopenia is associated with a higher risk of radiographic (ROA) and symptomatic knee OA (SxOA) in a large cohort of North American people in the context of the OA initiative. Sarcopenia at baseline was diagnosed in case of low skeletal muscle mass (i.e., lower skeletal mass index) and poor performance in the chair stands test. The outcomes of interest for this study included ROA (radiographical osteoarthritis) if a knee developed a Kellgren and Lawrence (KL) grade ≥2 at follow-up, and SxOA (symptomatic osteoarthritis) defined as new onset of a combination of painful knee OA. Altogether, 2,492 older participants (mean age: 68.4 years, 61.4% females) were included. At baseline, sarcopenia was present in 6.1% of the population. No significant difference in ROA prevalence was observed between those with and without sarcopenia (p=0.76), whilst people with sarcopenia reported a significant higher prevalence of SxOA (p<0.0001). Using a logistic regression analysis, adjusting for potential confounders at baseline and the diagnosis of sarcopenia during follow-up, sarcopenia was associated with a higher incidence of knee SxOA (odds ratio, OR=2.29; 95%CI [confidence interval]: 1.42-3.71; p=0.001), but not knee ROA (OR=1.48; 95%CI: 0.53-4.10; p=0.45). In conclusion, sarcopenia could be associated with a higher risk of negative knee OA outcomes, in particular symptomatic forms