Magnetic and Metal-Insulator Transitions in beta-Na0.5CoO2 and gamma-K0.5CoO2 -NMR and Neutron Diffraction Studies-

Co-oxides beta-Na0.5CoO2 and gamma-K0.5CoO2 have been prepared by the Na de-intercalation from alpha-NaCoO2 and by the floating-zone method, respectively. It has been found that successive phase transitions take place at temperatures Tc1 and Tc2 in both systems. The appearance of the internal magnetic field at Tc1 with decreasing temperature T indicates that the antiferromagnetic order exists at T < Tc1, as in gamma-Na0.5CoO2. For beta-Na0.5CoO2, the transition temperatures and the NMR parameters determined from the data taken for magnetically ordered state are similar to those of gamma-Na0.5CoO2, indicating that the difference of the stacking ways of the CoO2 layers between these systems do not significantly affect their physical properties. For gamma-K0.5CoO2, the quantitative difference of the physical quantities are found from those of beta- and gamma-Na0.5CoO2. The difference between the values of Tci (i = 1 and 2) of these systems might be explained by considering the distance between CoO2 layers.Comment: 8 pages, 14 figures, 1 Tabl

Fermi surface and quasiparticle dynamics of Na(x)CoO2 {x=0.7} investigated by Angle-Resolved Photoemission Spectroscopy

We present an angle-resolved photoemission study of Na0.7CoO2, the host cobaltate of the NaxCoO2.yH2O series. Our results show a large hexagonal-like hole-type Fermi surface, an extremely narrow strongly renormalized quasiparticle band and a small Fermi velocity. Along the Gamma to M high symmetry line, the quasiparticle band crosses the Fermi level from M toward Gamma consistent with a negative sign of effective single-particle hopping (t ): t is estimated to be about 8 meV which is on the order of exchange coupling J in this system. This suggests that t ~ J ~ 10 meV is an important energy scale in the system. Quasiparticles are well defined only in the T-linear resistivity regime. Small single particle hopping and unconventional quasiparticle dynamics may have implications for understanding the unusual behavior of this new class of compounds.Comment: Revised text, Added Figs, Submitted to PR

Interferon regulatory factor 8-deficiency determines massive neutrophil recruitment but T cell defect in fast growing granulomas during tuberculosis

Following Mycobacterium tuberculosis (Mtb) infection, immune cell recruitment in lungs is pivotal in establishing protective immunity through granuloma formation and neogenesis of lymphoid structures (LS). Interferon regulatory factor-8 (IRF-8) plays an important role in host defense against Mtb, although the mechanisms driving anti-mycobacterial immunity remain unclear. In this study, IRF-8 deficient mice (IRF-8−/−) were aerogenously infected with a low-dose Mtb Erdman virulent strain and the course of infection was compared with that induced in wild-type (WT-B6) counterparts. Tuberculosis (TB) progression was examined in both groups using pathological, microbiological and immunological parameters. Following Mtb exposure, the bacterial load in lungs and spleens progressed comparably in the two groups for two weeks, after which IRF-8−/− mice developed a fatal acute TB whereas in WT-B6 the disease reached a chronic stage. In lungs of IRF-8−/−, uncontrolled growth of pulmonary granulomas and impaired development of LS were observed, associated with unbalanced homeostatic chemokines, progressive loss of infiltrating T lymphocytes and massive prevalence of neutrophils at late infection stages. Our data define IRF-8 as an essential factor for the maintenance of proper immune cell recruitment in granulomas and LS required to restrain Mtb infection. Moreover, IRF-8−/− mice, relying on a common human and mouse genetic mutation linked to susceptibility/severity of mycobacterial diseases, represent a valuable model of acute TB for comparative studies with chronically-infected congenic WT-B6 for dissecting protective and pathological immune reactions

The global syndemic of metabolic diseases in the young adult population: a consortium from the Global Burden of Disease 2000-2019

Abstract Funding Acknowledgements Type of funding sources: None. Background A large proportion of premature deaths are related to metabolic diseases in the young adult population. We examined the global trends and mortality of metabolic diseases using estimates from the Global Burden of Diseases, Injuries and Risk Factors Study (GBD) 2019 in individuals aged below 40 years. Methods From 2000-2019, global estimates of prevalence, deaths, and disability-adjusted life years (DALYs) were described for metabolic diseases (type 2 diabetes mellitus [T2DM], hypertension, non-alcoholic fatty liver disease [NAFLD]). Global estimates were limited to mortality and DALYs for risk factors (hyperlipidemia and obesity). Subgroup analyses were performed based on sex, geographical regions and Socio-Demographic Index (SDI). Age-standardized prevalence, death, and DALYs were presented per 100,000 population with 95% uncertainty intervals (UI). Findings The prevalence for all metabolic diseases increased from 2000-2019, with the most pronounced increase in males and high SDI countries. In 2019, the highest age-standardised death rates were observed in hypertension (133·88 [121·25-155·73]; males, 160·13 [138·91-180·79]; females, 119·66 [102·33-136·86]), followed by obesity (62·59 [39·92-89·13]; males, 66·55 [39·76-97·21]; females, 58·14 [38·53-81·39]), hyperlipidemia (56·51 [41·83-73·62]; males, 67·33 [50·78-86·43]; females, 46·50 [32·70-62·38]), T2DM (18·49 [17·18-19·66]; males, 19·94 [18·50-21·32]; females, 17·30 [15·62-18·70]) and NAFLD (2·09 [1·61-2·60]; males, 2·38 [1·82-3·02]; females, 1·82 [1·41-2·27]). Similarly, obesity (1932·54 [1276·61-2639·74]) had the highest age-standardised DALYs, followed by hypertension (2885·57 [2580·75-3201·05]), hyperlipidemia (1207·15 [975·07-1461·11]), T2DM (801·55 [670·58-954·43]) and NAFLD (53·33 [40·73-68·29]). Mortality rates decreased over time in hyperlipidemia (-60%), hypertension (-47%), NAFLD (-31%) and T2DM (-20%), but not in obesity (107% increase). The highest metabolic-related mortality was observed in the Eastern Mediterranean and low SDI countries. Conclusion The growing prevalence of metabolic diseases, increasing obesity-related mortality trends, and the sex-regional-socioeconomic disparities evident in young adulthood, present the concerning global burden of metabolic diseases now and in the years ahead. </jats:sec

Astrocytes mediate synapse elimination through MEGF10 and MERTK pathways

To achieve its precise neural connectivity, the developing mammalian nervous system undergoes extensive activity-dependent synapse remodeling. Recently microglial cells have been shown to be responsible for a portion of synaptic remodeling, but the remaining mechanisms remain mysterious. Here we report a new role for astrocytes in actively engulfing CNS synapses. This process helps to mediate synapse elimination, requires the Megf10 and Mertk phagocytic pathways, and is strongly dependent on neuronal activity. Developing mice deficient in both astrocyte pathways fail to normally refine their retinogeniculate connections and retain excess functional synapses. Lastly, we show that in the adult mouse brain, astrocytes continuously engulf both excitatory and inhibitory synapses. These studies reveal a novel role for astrocytes in mediating synapse elimination in the developing and adult brain, identify Megf10 and Mertk as critical players in the synapse remodeling underlying neural circuit refinement, and have important implications for understanding learning and memory as well as neurological disease processes

Enhanced Virulence of Chlamydia muridarum Respiratory Infections in the Absence of TLR2 Activation

Chlamydia trachomatis is a common sexually transmitted pathogen and is associated with infant pneumonia. Data from the female mouse model of genital tract chlamydia infection suggests a requirement for TLR2-dependent signaling in the induction of inflammation and oviduct pathology. We hypothesized that the role of TLR2 in moderating mucosal inflammation is site specific. In order to investigate this, we infected mice via the intranasal route with C. muridarum and observed that in the absence of TLR2 activation, mice had more severe disease, higher lung cytokine levels, and an exaggerated influx of neutrophils and T-cells into the lungs. This could not be explained by impaired bacterial clearance as TLR2-deficient mice cleared the infection similar to controls. These data suggest that TLR2 has an anti-inflammatory function in the lung during Chlamydia infection, and that the role of TLR2 in mucosal inflammation varies at different mucosal surfaces

Vessel co-option mediates resistance to anti-angiogenic therapy in liver metastases

The efficacy of angiogenesis inhibitors in cancer is limited by resistance mechanisms that are poorly understood. Notably, instead of through the induction of angiogenesis, tumor vascularization can occur through the nonangiogenic mechanism of vessel co-option. Here we show that vessel co-option is associated with a poor response to the anti-angiogenic agent bevacizumab in patients with colorectal cancer liver metastases. Moreover, we find that vessel co-option is also prevalent in human breast cancer liver metastases, a setting in which results with anti-angiogenic therapy have been disappointing. In preclinical mechanistic studies, we found that cancer cell motility mediated by the actin-related protein 2/3 complex (Arp2/3) is required for vessel co-option in liver metastases in vivo and that, in this setting, combined inhibition of angiogenesis and vessel co-option is more effective than the inhibition of angiogenesis alone. Vessel co-option is therefore a clinically relevant mechanism of resistance to anti-angiogenic therapy and combined inhibition of angiogenesis and vessel co-option might be a warranted therapeutic strategy