2-methoxyestradiol,an endogenous metabolite of 17b-estradiol,inhibits adipocyte proliferation

The effects of 2-methoxyestradiol (2ME), a naturally occurring mammalian metabolite of 17 -estradiol, on adipocyte growth has been investigated in mouse brown adipose tissue precursor cells developed in primary culture. 2ME inhibits brown adipocyte proliferation in a dose-response manner (IC50 = 1.7 × 10-6 M for DNA synthesis), with much higher potency than its hormone precursor 17-estradiol, and cells acquire the typical differentiated morphology - more round with a higher content of triglycerides. 2ME causes similar effects in the immortal brown adipocyte tumor-derived hibernoma cell line HIB 1B and the immortal 3T3-F442A white adipocyte line. These findings suggest a possible role for 2ME in adipocyte proliferation, and probably in the differentiation process, entering the cells in the adipogenic program.     

Complementation and regulatory interaction between two cloned fimbrial gene clusters of Escherichia coli strain KS71

Summary Complementation experiments with cloned DNA fragments encoding either the KS71A, the KS71B or the KS71C fimbriae of the pyelonephritogenic Escherichia coli strain KS71 were used to localise the P-fimbrillin genes and to demonstrate regulatory interactions between the cloned genes. The structural genes of the KS71A and KS71B fimbriae were located within a common 1.1 kilobase pair ClaI-SmaI fragment, and it was shown that the gene clusters for these fimbriae could complement each other in trans. The gene cluster encoding the KS71C fimbriae did not complement for the other KS71 fimbriae. A DNA fragment, located near the KS71A fimbrillin gene, was found to enhance the production of the KS71B fimbriae in trans.     

Chemokine Receptor Ccr6 Deficiency Alters Hepatic Inflammatory Cell Recruitment and Promotes Liver Inflammation and Fibrosis

Chronic liver diseases are characterized by a sustained inflammatory response in which chemokines and chemokine-receptors orchestrate inflammatory cell recruitment. In this study we investigated the role of the chemokine receptor CCR6 in acute and chronic liver injury. In the absence of liver injury Ccr6 ^-/- mice presented a higher number of hepatic macrophages and increased expression of pro-inflammatory cytokines and M1 markers Tnf-α, Il6 and Mcp1. Inflammation and cell recruitment were increased after carbon tetrachloride-induced acute liver injury in Ccr6 ^-/- mice. Moreover, chronic liver injury by carbon tetrachloride in Ccr6 ^-/- mice was associated with enhanced inflammation and fibrosis, altered macrophage recruitment, enhanced CD4⁺ cells and a reduction in Th17 (CD4⁺IL17⁺) and mature dendritic (MHCII⁺CD11c⁺) cells recruitment. Clodronate depletion of macrophages in Ccr6 ^-/- mice resulted in a reduction of hepatic pro-inflammatory and pro-fibrogenic markers in the absence and after liver injury. Finally, increased CCR6 hepatic expression in patients with alcoholic hepatitis was found to correlate with liver expression of CCL20 and severity of liver disease. In conclusion, CCR6 deficiency affects hepatic inflammatory cell recruitment resulting in the promotion of hepatic inflammation and fibrosis.     

Mixtures with grass litter may hasten shrub litter decomposition after shrub encroachment into mountain grasslands

Aims

Shrub encroachment in mesic grasslands alters the identity and quality of litters entering the system. As litter from shrubs and grasses can differ in their quality, this can lead to differences in litter decomposition by the direct effect of quality, but also to litter interaction during decomposition. The objective of this study was to examine the occurrence of non-additive effects of litter mixtures on the decomposition rates of legume shrub litter (poor in P) or conifer shrub litter (poor in N) and grass litter.

Methods

In addition to single litter type litterbags for the three species, we mixed litters of each pair of possible combinations to determine the influence of each species on mass loss. Litterbags were placed in the field and collected after 1, 6, 8, 12 and 24 months. In each collection, litter of each species remaining in mixed bags was separated, dry weighed and analyzed for C, N and P.

Results

With respect to shrub litter decomposing alone, mass loss of shrub litter when mixed with grass showed a 9–10 % increase in decomposition rate for conifer and a 3 % increase for legume litter. These litter mixture effects varied with time and they were detected after a decomposition period of 1 year in legume litter and of 2 years in conifer litter.

Conclusions

Grass litter hastened conifer and legume litter decomposition in leaf litter mixtures, at least during the first stages of the process. The potential consequences of this result to alter litter accumulation patterns and thus carbon sequestration rates after shrub encroachment into grasslands will depend on whether the observed trends are maintained in the advanced decomposition stages.     

IL-1 beta breaks tolerance through expansion of CD25+ effector T cells

IL-1 is a key proinflammatory driver of several autoimmune diseases including juvenile inflammatory arthritis, diseases with mutations in the NALP/cryopyrin complex and Crohn's disease, and is genetically or clinically associated with many others. IL-1 is a pleiotropic proinflammatory cytokine; however the mechanisms by which increased IL-1 signaling promotes autoreactive T cell activity are not clear. Here we show that autoimmune-prone NOD and IL-1 receptor antagonist-deficient C57BL/6 mice both produce high levels of IL-1, which drives autoreactive effector cell expansion. IL-1beta drives proliferation and cytokine production by CD4(+)CD25(+)FoxP3(-) effector/memory T cells, attenuates CD4(+)CD25(+)FoxP3(+) regulatory T cell function, and allows escape of CD4(+)CD25(-) autoreactive effectors from suppression. Thus, inflammation or constitutive overexpression of IL-1beta in a genetically predisposed host can promote autoreactive effector T cell expansion and function, which attenuates the ability of regulatory T cells to maintain tolerance to self.     

Rheology of passive and adhesion-activated neutrophils probed by atomic force microscopy

The rheology of neutrophils in their passive and activated states plays a key role in determining their function in response to inflammatory stimuli. Atomic force microscopy was used to study neutrophil rheology by measuring the complex shear modulus G*(omega) of passive nonadhered rat neutrophils on poly(HEMA) and neutrophils activated through adhesion to glass. G*(omega) was measured over three frequency decades (0.1-102.4 Hz) by indenting the cells 500 nm with a spherical tip and then applying a 50-nm amplitude multi-frequency signal. G*(omega) of both passive and adhered neutrophils increased as a power law with frequency, with a coupling between elastic (G') and loss (G') moduli. For passive neutrophils at 1.6 Hz, G' = 380 +/- 121 Pa, whereas G' was fourfold smaller and the power law coefficient was of x = 1.184. Adhered neutrophils were over twofold stiffer with a lower slope (x = 1.148). This behavior was adequately described by the power law structural damping model but not by liquid droplet and Kelvin models. The increase in stiffness with frequency may modulate neutrophil transit, arrest, and transmigration in vascular microcirculation.     

TRPV1+ sensory neurons control beta cell stress and islet inflammation in autoimmune diabetes

In type 1 diabetes, T cell-mediated death of pancreatic beta cells produces insulin deficiency. However, what attracts or restricts broadly autoreactive lymphocyte pools to the pancreas remains unclear. We report that TRPV1(+) pancreatic sensory neurons control islet inflammation and insulin resistance. Eliminating these neurons in diabetes-prone NOD mice prevents insulitis and diabetes, despite systemic persistence of pathogenic T cell pools. Insulin resistance and beta cell stress of prediabetic NOD mice are prevented when TRPV1(+) neurons are eliminated. TRPV1(NOD), localized to the Idd4.1 diabetes-risk locus, is a hypofunctional mutant, mediating depressed neurogenic inflammation. Delivering the neuropeptide substance P by intra-arterial injection into the NOD pancreas reverses abnormal insulin resistance, insulitis, and diabetes for weeks. Concordantly, insulin sensitivity is enhanced in trpv1(-/-) mice, whereas insulitis/diabetes-resistant NODxB6Idd4-congenic mice, carrying wild-type TRPV1, show restored TRPV1 function and insulin sensitivity. Our data uncover a fundamental role for insulin-responsive TRPV1(+) sensory neurons in beta cell function and diabetes pathoetiology.     

Spatial patterns of shrub encroachment in neighbouring grassland communities in the Pyrenees: floristic composition heterogeneity drives shrub proliferation rates

We studied the role of floristic composition and associational resistance in shrub dynamics by comparing spatial patterns of shrub cover after prescribed burning in neighbouring grassland communities with different palatability. The study focused on the shrub Cytisus balansae ssp. europaeus (G. López and Jarvis) Muñoz Garmendia. Seven two-dimensional transects (20 × 0.5 m) were established to monitor shrub cover for at least 10 years after prescribed burning. Shrub cover and spatial patterns were assessed in each transect. Floristic similarity between transects and Cytisus associations with different species were estimated. Over an entire transect, shrub cover and shrub scale of pattern and patch size were lowest in the unpalatable Festuca eskia grasslands and highest in F. paniculata grasslands. At short distances, we found negative associations between Cytisus and most of the grasses, except for F. nigrescens and Agrostis capillaris, which showed positive associations with Cytisus. Thus, the effects of associational resistance on shrub encroachment were not as marked as expected, F. eskia grasslands showing the lowest shrub encroachment rates after fire. By contrast, Cytisus was positively associated with the most palatable grasses in the site, namely F. nigrescens and A. capillaris. We conclude that differences in floristic composition drive shrub encroachment rates in these spatially heterogeneous communities.     

Structure and expression of the lignin O-methyltransferase gene from Zea mays L.

The isolation and characterization of cDNA and homologous genomic clones encoding the lignin O-methyltransferase (OMT) from maize is reported. The cDNA clone has been isolated by differential screening of maize root cDNA library. Southern analysis indicates that a single gene codes for this protein. The genomic sequence contains a single 916 bp intron. The deduced protein sequence from DNA shares significant homology with the recently reported lignin-bispecific caffeic acid/5-hydroxyferulic OMTs from alfalfa and aspen. It also shares homology with OMTs from bovine pineal glands and a purple non-sulfur photosynthetic bacterium. The mRNA of this gene is present at different levels in distinct organs of the plant with the highest accumulation detected in the elongation zone of roots. Bacterial extracts from clones containing the maize OMT cDNA show an activity in methylation of caffeic acid to ferulic acid comparable to that existing in the plant extracts. These results indicate that the described gene encodes the caffeic acid 3-O-methyltransferase (COMT) involved in the lignin biosynthesis of maize.     

Counterfactual Reasoning Deficits in Schizophrenia Patients

Background

Counterfactual thinking is a specific type of conditional reasoning that enables the generation of mental simulations of alternatives to past factual events. Although it has been broadly studied in the general population, research on schizophrenia is still scarce. The aim of the current study was to further examine counterfactual reasoning in this illness.

Methods

Forty schizophrenia patients and 40 controls completed a series of tests that assessed the influence of the “causal order effect” on counterfactual thinking, and the ability to generate counterfactual thoughts and counterfactually derive inferences from a hypothetical situation. Socio-demographic and clinical characteristics, as well as neurocognitive variables, were also examined.

Results

Compared to controls, the schizophrenia patients generated fewer counterfactual thoughts when faced with a simulated scenario. The pattern of response when assessing the causality effect of the order was also different between the groups, with the patients being more frequently unable to attribute any ordering of events than the control subjects. Additionally, the schizophrenia patients showed more difficulties when deriving normative counterfactual inferences from hypothetical social situations. None of the counterfactual reasoning measures was associated to any of the cognitive functions or clinical and socio-demographic variables assessed.

Conclusions

A global impairment in counterfactual thinking characterizes schizophrenia patients. Because of the potential impact of such deficits on psychosocial functioning, targeting counterfactual reasoning for improvement might be considered in future treatment approaches.