Search

Diabetes mellitus (DM) is a metabolic disorder associated with serious liver complications. As a metabolic chronic disease, DM is very common in the elderly. Recent studies suggest ameliorating effects of vitamin D on metabolic and oxidative stress in the liver tissue in an experimental model of DM. The aim of this study was to investigate the expression of vitamin D receptors (VDRs) and 1α-hydroxylase, the key enzyme for the production of active vitamin D form (calcitriol) in the liver during long-term diabetes mellitus type 1 (DM1) in aging rats. We performed immunohistochemical analysis of liver expression of 1α-hydroxylase and VDRs during aging in long-term streptozotocin-induced DM1. 1α-Hydroxylase was identified in the monocyte/macrophage system of the liver. In addition to the nuclear expression, we also observed the expression of VDR in membranes of lipid droplets within hepatocytes. Aging and long-term DM1 resulted in significant increases in the number of 1α-hydroxylase immunoreactive cells, as well as the percentage of strongly positive VDR hepatocytes. In conclusion, the liver has the capacity for active vitamin D synthesis in its monocyte/macrophage system that is substantially increased in aging and long-term diabetes mellitus. These conditions are also characterized by significant increases in vitamin D receptor expression in hepatocytes. The present study suggests that VDR signaling system could be a potential target in prevention of liver complications caused by diabetes and aging. [ABSTRACT FROM AUTHOR]

Collectins and ficolins are multimeric proteins present in various tissues and are actively involved in innate immune responses. In chickens, six different collagenous lectins have been characterized so far: mannose-binding lectin (MBL), surfactant protein A (SP-A), collectin 10 (COLEC10), collectin 11 (COLEC11), collectin 12 (COLEC12), lung lectin (LL) and one ficolin (FCN). However, the structural and functional features of the chicken collectins and ficolin are still not fully understood. Therefore, the aims of this study were: (i) to make an overview of the genetic structure and function of chicken collectins and the ficolin, (ii) to investigate the variation in the chicken collectins and the ficolin gene in different chicken populations, and (iii) to assess the presence of MBL gene variants in different chicken populations. We performed comparative genomic analysis using publically available data. The obtained results showed that collectins and ficolins have conserved protein sequences and gene structure across all vertebrate groups and this is especially notable for COLEC10, COLEC11 and COLEC12. For the purpose of studying the genetic variation, 179 animals from 14 populations were genotyped using 31 SNPs covering five genomic regions. The obtained results revealed low level of heterozygosity in the collagenous lectins except for the COLEC12 gene and the LL – SPA – MBL region compared to heterozygosity at neutral microsatellite markers. In addition, the MBL gene variants were assessed in different chicken populations based on the polymorphisms in the promoter region. We observed 10 previously identified MBL variants with A2/A8 and A4 as the most frequent alleles. [ABSTRACT FROM AUTHOR]

It is well documented that spin density wave (SDW) in (TMTSF)2PF6 undergoes another phase transition at T*≈4 K, though the nature of the new low temperature phase is controversial. We have shown recently that the new phase is well described in terms of unconventional SDW (USDW) which modifies the quasi-particle spectrum dramatically. In this paper, we show that the same model describes consistently the Hall resistivity observed in (TMTSF)2PF6. [Copyright &y& Elsevier]

Abstract: The quasi-one-dimensional cuprates (La,Y,Sr,Ca)14Cu24O41, consisting of spin-chains and spin-ladders, have attracted much attention, mainly because they represent the first superconducting copper oxide with a non-square lattice. Theoretically, in isolated hole-doped two-leg ladders, superconductivity is tightly associated with the spin gap, although in competition with a charge-density wave (CDW). Indeed, both the gapped spin-liquid and CDW states have been established in the doped spin-ladders of , however the relevance of these objects to electronic properties and superconductivity is still subject of intensive discussion. In this treatise, an appreciable set of experimental data is reviewed, which has been acquired in recent years, indicating a variety of magnetic and charge arrangements found in the chains and ladders of underdoped (La,Y) y (S,Ca)14−y Cu24O41 and fully doped . Based on these data, phase diagrams are constructed for the chains of underdoped systems (as a function of La, Y-substitution), as well as for the chains and ladders of the fully doped ones (as a function of Ca-substitution). We try to reconcile contradictory results concerning the charge dynamics in the ladders, like the hole redistribution between ladders and chains, collective modes and pseudogap, field-dependent transport and the temperature scales and doping levels at which the two-dimensional CDW develops in the ladder planes. The remaining open issues are clearly extracted. In the discussion the experimental results are contrasted with theoretical predictions, which allows us to conclude with two important remarks concerning the nature of the competing CDW and superconducting ground states. A density wave in ladders, characterized by a sinusoidal charge modulation, belongs to the class of broken symmetry patterns, which is theoretically predicted for strongly correlated low-dimensional electron systems; however its precise texture and nature is still an open issue. As for superconductivity, the presence of the spin gap in the normal state points towards d-wave symmetry and magnetic origin of the attractive interaction. However, there is a finite density of mobile quasi-particles that appears for high Ca contents and increases with pressure, concomitantly with increased two-dimensionality and metallicity. For this reason the superconductivity in the doped ladders of which occurs under high pressure cannot simply be a stabilization of the d-wave superconductivity expected for a pure single ladder system. [Copyright &y& Elsevier]

Fibrodysplasia ossificans progressiva (FOP) is a rare hereditary disease caused by a mutation in the intracellular domain of the activin A receptor type I and is characterized by episodes (flare-ups) of progressive heterotopic endochondral ossification (HO) in the soft tissues. The mutation alone is not sufficient for the occurrence of HO since flare-ups are triggered by inflammation and activation of the innate immune system. A number of cellular and humoral mediators have been implicated in animal and in vitro models. Observations in humans support the inflammatory nature of the condition, but data on the involved mediators are variable. We hypothesize that for induction of flare-ups in patients with FOP increase in at least one of the pro-inflammatory cytokines is both essential and sufficient to trigger the entire process of the inflammatory cells influx resulting in the novel ectopic bone formation and we suggest that C-C motif ligand 5 (CCL5), a pro-inflammatory chemokine also known as Regulated on activation, normal T-cell expressed and secreted (RANTES), might be the key candidate. CCL5 is a chemoattractant for all cellular types implicated in HO and is produced by the cells of the tissue microenvironment at the sites of HO as well as by the pro-inflammatory cellular mediators. CCL5 induces ossification in cultured human pluripotent mesenchymal cells (hMSCs) and in the primary culture of monocytes from FOP patients (but not from their healthy relatives), stimulation with lipopolysaccharide induces CCL5 expression. Finally, in a pilot study we used a panel of 23 cytokines and chemokines to screen the plasma samples of three subjects: a female patient with FOP during a flare-up; a female patient with hyperostosis corticalis generalisata (van Buchem disease), another rare disease characterized by excessive bone formation at the sites where it regularly occurs that does not include inflammatory events; and a healthy woman without bone disorders. There appeared a rather clear-cut signal of a 2-fold higher level of CCL5 in the FOP patient vs. the healthy subject and the van Buchem patient. Evaluation of the hypothesis would require an international prospective study, with main motivation being the lack of a conclusive treatment as the major unmet need in FOP. A treatment targeting CCL5 receptor already exists and is used in HIV-infected patients. [ABSTRACT FROM AUTHOR]

We report the temperature and magnetic field dependence of transport properties in epitaxial films of the manganite La 1− x Ca x MnO 3 in the overdoped region of the phase diagram for x > 0.5, where a charge–ordered (CO) and an antiferromagnetic (AF) phase are present. Resistivity, magnetoresistance and angular dependence of magnetoresistance were measured in the temperature interval 4.2K < T < 300K, for three concentrations x = 0.52,0.58 and 0.75 and in magnetic fields up to 5 T. The semiconductor/insulator–like behavior in zero field was observed in the entire temperature range for all three concentrations x and the electric conduction, at lower temperatures, in the CO state obeys 3D Mott's variable-range hopping model. A huge negative magnetoresistance for x = 0.52 and x = 0.58, a metal–insulator transition for B > 3 T for x = 0.52 and the presence of anisotropy in magnetoresistance for x = 0.52 and x = 0.58 show the fingerprints of colossal magnetoresistance (CMR) behavior implying the existence of ferromagnetic (FM) clusters. The declining influence of the FM clusters in the CO/AF part of the phase diagram with increasing x contributes to a possible explanation that a phase coexistence is the origin of the CMR phenomenon. [ABSTRACT FROM AUTHOR]

Association of liver calcitriol (active vitamin D metabolite) catabolism with osteomalacia during prolonged use of certain drugs was reported in several recent studies. To examine whether the increased calcitriol catabolism could be a potential link between ageing/diabetes mellitus (DM) and bone loss, we studied the dynamic of expression of CYP24, the main calcitriol catabolising enzyme in the liver of rats during ageing and a long-term experimental DM1. DM1 model was induced with intraperitoneally injected streptozotocin (STZ) (55 mg/kg). Sprague-Dawley rats were sacrificed 6 and 12 months after the DM1 induction. The immunohistochemical analyses of CYP24 and transforming growth factor β 1 (TGF-β1) expression in the liver were performed. We found that ageing and long-term DM1 resulted in a significantly increased expression of CYP24 in hepatocytes, as well as in non-hepatocyte liver cells (Kupffer cells, hepatic stellate cells and sinusoidal endothelial cells). Ageing and long-term DM1 resulted in an increased expression of TGF-β1 as well. Expression of CYP24 coexisted with the expression of TGF-β1 in all types of hepatic cells. We concluded that liver has the capacity for an active vitamin D catabolism in different populations of liver cells, especially in sinusoidal endothelial cells, through an expression of CYP24. That capacity is substantially increased during ageing and long-term diabetes mellitus. Increased liver calcitriol catabolism could be one of the mechanisms of the bone metabolism impairment related to ageing and diabetes. [ABSTRACT FROM AUTHOR]

We have investigated the long term effects of insulin dependent diabetes mellitus (IDDM) on the fatty acid profile of tissues in aging rats. For this purpose, a rat model for IDDM was established by streptozotocin application. The rats were randomly divided into four groups of 8 animals each: CON 6 (control group sacrificed after 6 months of the experiment), CON 12 (control group sacrificed after 12 months of the experiment), DM 6 (streptozotocin treated and sacrificed after 6 months of diabetes) and DM 12 (streptozotocin treated and sacrificed after 12 months of diabetes). The periods of 6 and 12 months were taken to observe the changes in lipid metabolism for chronic, long-term diabetes. Fatty acid profiles of the liver and skeletal muscle total lipids and phospholipids as well as desaturation indices for ∆6 desaturase (D6D), ∆5 desaturase (∆6D), ∆9 desaturase (∆9D) and de novo lipogenesis index (DNL) were estimated. Additionally the long-term effects (12 months) were tested in the brain, perirenal fat and bone marrow. The fatty acid composition of lipids was altered in IDDM rats in all tested tissues. The desaturation indices revealed the expected significant decrease in ∆9D and ∆5D indices in tested tissues, while indices for ∆6D were not influenced by diabetes. DNL revealed the strong inhibition of de novo lipogenesis in the liver tissue. Values for arachidonic C20:4n6 (arachidonic acid) significantly decreased in liver total lipids in DM 6 and DM 12 groups and in phospholipids in the DM 12 group. Surprisingly, values for C20:4n6 were also significantly lower in the brain tissue in the DM 12 group. Accumulation of C20:4n6 precursors (C18:2n6 and C20:3n6) was visible in all tissues. Docosahexaenoic acid (C22:6n3) significantly decreased in liver total lipids, liver phospholipids and in the brain phospholipids of the DM 12 group. The present results show that age could exacerbate the expected decrease in the liver synthesis of C20:4n6 in IDDM. Moreover, long-term diabetes could impair C22:6n3 synthesis in the liver and muscle, and incorporation of both important fatty acids into brain phospholipids. In conclusion, numerous changes in fatty acid composition are caused by long-term diabetes in aged rats. These changes could be involved in the pathogenesis of senile and diabetes-induced damage. The results could have clinical significance due to the increasing age of diabetic patients. [ABSTRACT FROM AUTHOR]

Spin-dependent thermoelectric transport properties have been experimentally studied on a micro-structured device based on epitaxially grown 75-nm-thick Co 2 Ti 0.6 V 0.4 Sn 0.75 Heusler film with integrated heater and thermometers. The anomalous Nernst coefficient is found to be 0.5 μV/K at 50 K. Thermoelectric power in both longitudinal and transverse directions have been measured with magnetic field rotated in-plane. Asymmetric peaks and valleys are observed at particular in-plane field angle around 25 K. These anomalous peaks show novel magnetic hysteresis due to the interplay between the magnetization and the temperature gradient. These complex behaviors of thermoelectric effect during magnetization reversal still need to be understood. • A microstructured on-chip device of 75-nm-thick Co 2 Ti 0.6 V 0.4 Sn 0.75 Heusler alloy with integrated heater and thermometers. • The anomalous Nernst coefficient reaches 0.5 μV/K at 50 K. • Anomalous peaks with novel magnetic hysteresis in both longitudinal and transverse magnetic-dependent thermopower. [ABSTRACT FROM AUTHOR]