Fermiology and superconductivity studies on the non-tetrachalcogenafulvalene structured organic superconductor beta-(BDA-TTP)_2SbF_6

The quantum oscillatory effect and superconductivity in a non-tetrachalcogenafulvalene (TCF) structure based organic superconductor beta-(BDA-TTP)_2SbF_6 are studied. Here the Shubnikov-de Haas effect (SdH) and angular dependent magnetoresistance oscillations (AMRO) are observed. The oscillation frequency associated with a cylindrical Fermi surface is found to be about 4050 tesla, which is also verified by the tunnel diode oscillator (TDO) measurement. The upper critical field Hc2 measurement in a tilted magnetic field and the TDO measurement in the mixed state reveal a highly anisotropic superconducting nature in this material. We compared physical properties of beta-(BDA-TTP)_2SbF_6 with typical TCF structure based quasi two-dimensional organic conductors. A notable feature of beta-(BDA-TTP)_2SbF_6 superconductor is a large value of effective cyclotron mass m_c^*=12.4+/1.1 m_e, which is the largest yet found in an organic superconductor. A possible origin of the enhanced effective mass and its relation to the superconductivity are briefly discussed.Comment: 8 pages, 10 figure

Non-human TRIM5 variants enhance recognition of HIV-1-infected cells by CD8+ T cells

Tripartite motif-containing protein 5 (TRIM5) restricts human immunodeficiency virus type-1 (HIV-1) in a species-specific manner by uncoating viral particles while activating early innate responses. Although the contribution of TRIM5 proteins to cellular immunity has not yet been studied, their interactions with the incoming viral capsid and the cellular proteasome led us to hypothesize a role for them. Here, we investigate whether the expression of two non-human TRIM5 orthologs, rhesus TRIM5α (RhT5) and TRIM-cyclophilin A (TCyp), both of which are potent restrictors of HIV-1, could enhance immune recognition of infected cells by CD8+ T cells. We illustrate how TRIM5 restriction improves CD8+ T cell-mediated HIV-1 inhibition. Moreover, when TRIM5 activity was blocked by the non-immunosuppressive analog of cyclosporin A, SmBz-CsA, we found a significant reduction in CD107a/MIP1β expression in HIV-1-specific CD8+ T cells. This finding underscores the direct link between TRIM5 restriction and activation of CD8+ T-cell responses. Interestingly, cells expressing RhT5 induced stronger CD8+ T-cell responses through the specific recognition of the HIV-1 capsid by the immune system. The underlying mechanism of this process may involve TRIM5-specific capsid recruitment to cellular proteasomes and increase peptide availability for loading and presentation of HLA class I antigens. In summary, we identified a novel function for non-human TRIM5 variants in cellular immunity. We hypothesise that TRIM5 can couple innate viral sensing and CD8+ T-cell activation to increase species barriers against retrovirus infection. IMPORTANCE: New therapeutics to tackle HIV-1 infection should aim to combine rapid innate viral sensing and cellular immune recognition. Such strategies could prevent seeding of the viral reservoir and the immune damage that occurs during acute infection. The non-human TRIM5 variants, rhesus TRIM5α (RhT5) and TRIM-cyclophilin A (TCyp), are attractive candidates owing to their potency in sensing HIV-1 and blocking its activity. Here, we show that expression of RhT5 and TCyp in HIV-1-infected cells improves CD8+ T cell-mediated inhibition through the direct activation of HIV-1-specific CD8+ T-cell responses. We found that the potency in CD8+ activation was stronger for RhT5 variants and capsid-specific CD8+ T-cells in a mechanism that relies on TRIM5-dependent particle recruitment to cellular proteasomes. This novel mechanism couples innate viral sensing with cellular immunity in a single protein and could be exploited to develop innovative therapeutics for control of HIV-1 infection

How to summarise and report written qualitative data from patients: a method for use in cancer support care

Goals of work: Determination of key themes to aid the analysis of qualitative data collected at three cancer support centres in England, using the Measure Yourself Concerns and Wellbeing (MYCaW) questionnaire. Patients and methods: People with cancer who use complementary therapies experience and value a wide range of treatment effects, yet tools are urgently required to quantitatively measure these outcomes. MYCAW is an individualised questionnaire used in cancer support centres providing complementary therapies, scoring 'concerns or problems' and 'wellbeing' and collects qualitative data about other major events in a patient's life and what has been most important to the patient. Content analysis on 782 MYCaW questionnaires from people at these cancer support centres was carried out. The "concerns", "other things going on in their life" and "important aspects of centre" were thematically categorised, externally validated by a focus group and the inter-rater reliability calculated. Main results: Clinical information from a cancer patient's perspective was collected that is not measured on standard quality of life questionnaires; furthermore some themes acknowledge the multifaceted aspects of CAM provision, rather than information only relating to the therapeutic intervention. Categories for qualitative MYCaW analysis have been established providing a tool for future research and/or service delivery improvement within cancer support centres such as these. Conclusions: The established themes provide a framework to aid analysis of qualitative aspects of complementary therapy care for people with cancer, improving our understanding of how the patient’s cancer experience can be aided by complementary therapies in specialized cancer centres

Altered striatal endocannabinoid signaling in a transgenic mouse model of spinocerebellar ataxia type-3

Spinocerebellar ataxia type-3 (SCA-3) is the most prevalent autosomal dominant inherited ataxia. We recently found that the endocannabinoid system is altered in the post-mortem cerebellum of SCA-3 patients, and similar results were also found in the cerebellar and brainstem nuclei of a SCA-3 transgenic mouse model. Given that the neuropathology of SCA-3 is not restricted to these two brain regions but rather, it is also evident in other structures (e.g., the basal ganglia), we studied the possible changes to endocannabinoid signaling in the striatum of these transgenic mice. SCA-3 mutant mice suffer defects in motor coordination, balance and they have an abnormal gait, reflecting a cerebellar/brainstem neuropathology. However, they also show dystonia-like behavior (limb clasping) that may be related to the malfunction/deterioration of specific neurons in the striatum. Indeed, we found a loss of striatal projecting neurons in SCA-3 mutant mice, accompanied by a reduction in glial glutamate transporters that could potentially aggravate excitotoxic damage. In terms of endocannabinoid signaling, no changes in CB2 receptors were evident, yet an important reduction in CB1 receptors was detected by qPCR and immunostaining. The reduction in CB1 receptors was presumed to occur in striatal afferent and efferent neurons, also potentially aggravating excitotoxicity. We also measured the endocannabinoid lipids in the striatum and despite a marked increase in the FAAH enzyme in this area, no overall changes in these lipids were found. Collectively, these studies confirm that the striatal endocannabinoid system is altered in SCA-3 mutant mice, adding to the equivalent changes found in other strongly affected CNS structures in this type of ataxia (i.e.: the cerebellum and brainstem). These data open the way to search for drugs that might correct these changes.Funding: This study has been supported: (i) by MICINN (SAF2009-11847 and SAF2015-68580-C2-1-R), CIBERNED (CB06/05/0089) and “Fundación Eugenio Rodríguez Pascual”, to JFR; (ii) by the Research and Education Component of the Advancing a Healthier Wisconsin Endowment at the Medical College of Wisconsin, to CJH; and (iii) by Fundação para a Ciência e Tecnologia through the project POCI-01-0145-FEDER-016818 (PTDC/NEU-NMC/3648/2014) and co-financed by the Portuguese North Regional Operational Program (ON.2 – O Novo Norte) under the National Strategic Reference Framework (QREN), through the European Regional Development Fund (FEDER), to PM. Carmen Rodríguez-Cueto was a predoctoral fellow supported by FPI Program-Ministry of Science. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.info:eu-repo/semantics/publishedVersio

Percutaneous treatment with Mitraclip for functional mitral regurgitation: medium-term follow up according to left ventricular function

Background: Functional mitral regurgitation (FMR) is a bad prognosis condition despite optimal medical treatment. Nowadays there is an open debate about the surgical versus percutaneous treatment. The main objective of this study is to evaluate the mid-term follow up clinical outcomes of patients with FMR treated with MitraClip((R)) system, according to their left ventricular ejection fraction (LVEF). Methods: Data was obtained from two experienced centers in transcatheter mitral valve repair (TMVR). All consecutive cases of severe FMR undergoing TMVR in both centers with the same inclusion criteria were included prospectively in this study and followed-up. Periodical follow-ups with clinical and echocardiographic evaluation were scheduled from the baseline procedure, at 3 months and then yearly. Results: From October 2015 to October 2019, a total of 119 patients with FMR at 2 centers in Spain underwent TMVR with the MitraClip((R)) procedure and were included in this study. The mean age was 73.8+/-8.9 years old and 32 patients (26.9%) were female. A 39.5% of cases [47] had a LVEF 30% (group 2). There was a similar distribution in cardiovascular risk factors, age and other diseases. All MitraClip((R)) implantations were elective and procedural success was achieved in 110 patients (92.4%) with a similar distribution between the groups. There were no differences in procedural time and the number of implanted clips. The median follow-up was 22.6 months (IQR, 11.43-34.98 months). The primary combined endpoint occurred in the 41.6% of the global cohort, 57.5% in group 1 and 30.99% in group 2 (P=0.036). LVEF was associated to the main event in the multivariate analysis (HR 2.09, 95% CI: 1.12-3.89; P=0.02). Conclusions: The MitraClip edge-to-edge technique is a safe and effective procedure for the treatment of FMR. In this study, patients with LVEF >30% treated with Mitraclip presented better clinical cardiovascular outcomes than those with a LVEF </=30%. Regardless clinical outcomes, at the end of the follow-up, there was a sustained reduction in MR grades and an important improvement in NYHA functional class

Effect of High-Intensity Interval Training on Body Composition, Cardiorespiratory Fitness, Blood Pressure, and Substrate Utilization During Exercise Among Prehypertensive and Hypertensive Patients With Excessive Adiposity

Indexación: Scopus.Regular exercise training is a recognized lifestyle strategy to lower resting blood pressure (BP), but little is known about substrate metabolism in population with high BP. Thus, the purpose of this study was to investigate the effects of 16-weeks of HIIT on body composition, BP, cardiorespiratory fitness by (Formula presented.) O2max, and substrate utilization during exercise among prehypertensive and hypertensive patients with excessive adiposity. We also aimed to test the potential association between changes in cardiorespiratory fitness, substrate utilization during exercise and BP. Forty-two physically inactive overweight/obese participants participated in 16-weeks of HIIT intervention. The HIIT frequency was three times a week (work ratio 1:2:10, for interval cycling: rest period: repeated times; 80–100% of the maximum heart rate). Groups were distributed based on their baseline BP: HIIT-hypertensive (H-HTN: age 47.7 ± 12.0 years; body mass index [BMI] 30.3 ± 5.5 kg/m2; systolic [SBP]/diastolic BP [DBP] 151.6 ± 10/81.9 ± 4.2 mmHg), HIIT-pre-hypertensive (H-PreHTN: age 37.6 ± 12.0 years; BMI 31.9 ± 5.3 kg/m2; SBP/DBP 134.4 ± 3.2/74.9 ± 7.0 mmHg), and a normotensive control group (H-CG: age 40.7 ± 11.0 years; BMI 29.5 ± 4.2 kg/m2; SBP/DBP 117.0 ± 6.2/72.4 ± 4.1 mmHg). Anthropometry/body composition, BP, and metabolic substrate utilization during exercise (fat [FATox], carbohydrate [CHOox] oxidation, respiratory exchange ratio [RER], and (Formula presented.) O2max), were measured before and after the 16-week HIIT intervention. Adjusted mixed linear models revealed a significant improved in (Formula presented.) O2max were + 3.34 in the H-CG, + 3.63 in the H-PreHTN, and + 5.92 mL⋅kg–1⋅min–1, in the H-HTN group, however, the Time × Group interaction were not significant (p = 0.083). All the exercise types induced similar decreases on SBP (−8.70) in the H-HTN, (−7.14) in the H-CG, and (−5.11) mmHg in the H-PreHTN, as well as DBP levels (−5.43) mmHg in H-CG group (p = 0.032 vs. H-HTN group). At 16-week, no significant correlations were noted for the changes of blood pressure, cardiorespiratory fitness or exercise metabolism substrates outcomes. In conclusion, our results suggest that a 16-week HIIT-intervention improved (Formula presented.) O2max and blood pressure BP, but these changes are independent of substrate utilization during exercise in normotensive and hypertensive participants with excessive adiposity. © Copyright © 2020 Delgado-Floody, Izquierdo, Ramírez-Vélez, Caamaño-Navarrete, Moris, Jerez-Mayorga, Andrade and Álvarez.https://www.frontiersin.org/articles/10.3389/fphys.2020.558910/ful

HIV Traffics through a Specialized, Surface-Accessible Intracellular Compartment during trans-Infection of T Cells by Mature Dendritic Cells

In vitro, dendritic cells (DCs) bind and transfer intact, infectious HIV to CD4 T cells without first becoming infected, a process known as trans-infection. trans-infection is accomplished by recruitment of HIV and its receptors to the site of DC–T cell contact and transfer of virions at a structure known as the infectious synapse. In this study, we used fluorescent microscopy to track individual HIV particles trafficking in DCs during virus uptake and trans-infection. Mature DCs rapidly concentrated HIV into an apparently intracellular compartment that lacked markers characteristic of early endosomes, lysosomes, or antigen-processing vesicles. Live cell microscopy demonstrated that the HIV-containing compartment was rapidly polarized toward the infectious synapse after contact with a T cell; however, the bulk of the concentrated virus remained in the DCs after T cell engagement. Individual virions were observed emerging from the compartment and fusing with the T cell membrane at the infectious synapse. The compartmentalized HIV, although engulfed by the cytoplasm, was fully accessible to HIV envelope-specific inhibitors and other membrane-impermeable probes that were delivered to the cell surface. These results demonstrate that HIV resides in an invaginated domain within DCs that is both contiguous with the plasma membrane and distinct from endocytic vesicles. We conclude that HIV virions are routed through this specialized compartment, which allows individual particles to be delivered to T cells during trans-infection

Structural characterization and thermoelectric properties of Br-Doped AgSnm[Sb0.8Bi0.2]Te2+m Systems

Herein, we report the synthesis, structural and microstructural characterization, and thermoelectric properties of AgSnm[Sb0.8Bi0.2]Te2+m and Br-doped telluride systems. These compounds were prepared by solid-state reaction at high temperature. Powder X-ray diffraction data reveal that these samples exhibit crystal structures related to the NaCl-type lattice. The microstructures and morphologies are investigated by scanning electron microscopy, energy-dispersive X-ray spectroscopy (EDS), and high-resolution transmission electron microscopy (HRTEM). Positive values of the Seebeck coefficient (S) indicate that the transport properties are dominated by holes. The S of undoped AgSnm[Sb0.8Bi0.2]Te2+m ranges from +40 to 57 μV·K−1. Br-doped samples with m = 2 show S values of +74 μV·K−1 at RT, and the Seebeck coefficient increases almost linearly with increasing temperature. The total thermal conductivity (κtot) monotonically increases with increasing temperature (10–300 K). The κtot values of undoped AgSnm[Sb0.8Bi0.2]Te2+m are ~1.8 W m−1 K−1 (m = 4) and ~1.0 W m−1 K−1 (m = 2) at 300 K. The electrical conductivity (σ) decreases almost linearly with increasing temperature, indicating metal-like behavior. The ZT value increases as a function of temperature. A maximum ZT value of ~0.07 is achieved at room temperature for the Br-doped phase with m = 4