Initiation of combination antiretroviral therapy (cART) reduces inflammation in HIV-infected (HIV+) individuals. Recent studies demonstrated that diffusion MRI based extracellular free water (FW) modeling can be sensitive to neuroinflammation. Here, we investigate the FW in HIV-infection, its temporal evolution, and its association with blood markers, and cognitive scores. Using 96 age-matched participants, we found that FW was significantly elevated in grey and white matter in cART-naïve HIV+ compared to HIV-uninfected (HIV-) individuals at baseline. These increased FW values positively correlated with neurofilament light chain (NfL) and negatively correlated with CD4 counts. FW in grey and white matter, as well as NfL decreased in the HIV+ after 12 weeks of cART treatment. No significant FW differences were noted between the HIV+ and HIV- cohorts at 1 and 2-year follow-up. Results suggest that FW elevation in cART-naïve HIV+ participants is likely due to neuroinflammation. The correlation between FW and NfL, and the improvement in both FW and NfL after 12 weeks of cART treatment further reinforces this conclusion. The longer follow-up at 1 and 2 years suggests that cART helped control neuroinflammation as inferred by FW. Therefore, FW could be used as a biomarker to monitor HIV-associated neuroinflammation.The identification of cell surface markers specific to pancreatic beta cells is important for both the study of islet biology and for investigating the pathophysiology of diseases in which this cell type is lost or damaged. Following analysis of publicly available RNAseq data, we identified specific integrin subunits, integrin αv and integrin β5, that were expressed in beta cells. This finding was further elaborated using immunofluorescence analysis of histological sections derived from donor human pancreas. Despite the broad expression of specific integrin subunits, we found that expression of integrin αvβ5 heterodimers was restricted to beta cells and that this complex persisted in islet remnants of some type 1 diabetic individuals from which insulin expression had been lost. This study identifies αvβ5 heterodimers as a novel cell surface marker of human pancreatic beta cells, a finding that will aid in the identification and characterisation of this important cell type.Hyaluronan synthesis inhibitor 4-methylumbelliferone (4-MU) is a candidate of radiosensitizers which enables both anti-tumour and anti-metastasis effects in X-ray therapy. The curative effects under such 4-MU administration have been investigated in vitro; however, the radiosensitizing mechanisms remain unclear. Here, we investigated the radiosensitizing effects under 4-MU treatment from cell experiments and model estimations. We generated experimental surviving fractions of human fibrosarcoma cells (HT1080) after 4-MU treatment combined with X-ray irradiation. Meanwhilst, we also modelled the pharmacological effects of 4-MU treatment and theoretically analyzed the synergetic effects between 4-MU treatment and X-ray irradiation. The results show that the enhancement of cell killing by 4-MU treatment is the greatest in the intermediate dose range of around 4 Gy, which can be reproduced by considering intercellular communication (so called non-targeted effects) through the model analysis. As supposed to be the involvement of intercellular communication in radiosensitization, the oxidative stress level associated with reactive oxygen species (ROS), which leads to DNA damage induction, is significantly higher by the combination of 4-MU treatment and irradiation than only by X-ray irradiation, and the radiosensitization by 4-MU can be suppressed by the ROS inhibitors. These findings suggest that the synergetic effects between 4-MU treatment and irradiation are predominantly attributed to intercellular communication and provide more efficient tumour control than conventional X-ray therapy.Next Generation Sequencing (NGS) has uncovered hundreds of common and rare genetic variants involved in complex and rare diseases including immune deficiencies in both an autosomal recessive and autosomal dominant pattern. These rare variants however, cannot be classified clinically, and common variants only marginally contribute to disease susceptibility. In this study, we evaluated the multi-gene panel results of Common Variable Immunodeficiency (CVID) patients and argue that rare variants located in different genes play a more prominent role in disease susceptibility and/or etiology. We performed NGS on DNA extracted from the peripheral blood leukocytes from 103 patients using a panel of 19 CVID-related genes CARD11, CD19, CD81, ICOS, CTLA4, CXCR4, GATA2, CR2, IRF2BP2, MOGS, MS4A1, NFKB1, NFKB2, PLCG2, TNFRSF13B, TNFRSF13C, TNFSF12, TRNT1 and TTC37. Detected variants were evaluated and classified based on their impact, pathogenicity classification and population frequency as well as the frequency within our study group. NGS revealed 112 different (a total of 227) variants with under 10% population frequency in 103 patients of which 22(19.6%) were classified as benign, 29(25.9%) were classified as likely benign, 4(3.6%) were classified as likely pathogenic and 2(1.8%) were classified as pathogenic. Moreover, 55(49.1%) of the variants were classified as variants of uncertain significance. We also observed different variant frequencies when compared to population frequency databases. Case-control data is not sufficient to unravel the genetic etiology of immune deficiencies. Thus, it is important to understand the incidence of co-occurrence of two or more rare variants to aid in illuminating their potential roles in the pathogenesis of immune deficiencies.Severe renal ischemia-reperfusion injury (IRI) can lead to acute and chronic kidney dysfunction. Cytoskeletal modifications are among the main effects of this condition. The majority of studies that have contributed to the current understanding of IRI have relied on histological analyses using exogenous probes after the fact. Here we report the successful real-time visualization of actin cytoskeletal alterations in live proximal and distal tubules that arise at the onset of severe IRI. To achieve this, we induced fluorescent actin expression in these segments in rats with hydrodynamic gene delivery (HGD). Using intravital two-photon microscopy we then tracked and quantified endogenous actin dysregulation that occurred by subjecting these animals to 60 min of bilateral renal ischemia. Rapid (by 1-h post-reperfusion) and significant (up to 50%) declines in actin content were observed. The decline in fluorescence within proximal tubules was significantly greater than that observed in distal tubules. read more Actin-based fluorescence was not recovered during the measurement period extending 24 h post-reperfusion.