Role of brain c‐Jun N‐terminal kinase 2 in the control of the insulin receptor and its relationship with cognitive performance in a high‐fat diet pre‐clinical model

Insulin resistance has negative consequences on the physiological functioning of the nervous system. The appearance of type 3 diabetes in the brain leads to the development of the sporadic form of Alzheimer's disease. The c‐Jun N‐terminal kinases (JNK), a subfamily of the Mitogen Activated Protein Kinases, are enzymes composed by three different isoforms with differential modulatory activity against the insulin receptor (IR) and its substrate. This research focused on understanding the regulatory role of JNK2 on the IR, as well as study the effect of a high‐fat diet (HFD) in the brain. Our observations determined how JNK2 ablation did not induce compensatory responses in the expression of the other isoforms but led to an increase in JNKs total activity. HFD‐fed animals also showed an increased activity profile of the JNKs. These animals also displayed endoplasmic reticulum stress and up‐regulation of the protein tyrosine phosphatase 1B (PTP1B) and the suppressor of cytokine signalling 3 protein. Consequently, a reduction in insulin sensitivity was detected and it is correlated with a decrease on the signalling of the IR. Moreover, cognitive impairment was observed in all groups but only wild‐type genotype animals fed with HFD showed neuroinflammatory responses. In conclusion, HFD and JNK2 absence cause alterations in normal cognitive activity by altering the signalling of the IR. These affectations are related to the appearance of endoplasmic reticulum stress and an increase in the levels of inhibitory proteins like PTP1B and suppressor of cytokine signalling 3 protein.

     

Spectral analysis discerns pattern and feedback in natural‐ and anthropogenic‐disturbed boreal black spruce forests

The two major disturbance types of boreal black spruce forest in north–central Quebec, Canada – natural disturbance by wildfire and anthropogenic disturbance by harvest – may affect processes of recovery differently and leave distinct post‐disturbance soil and vegetation spatial patterns. We tested whether 1) spatial patterns of physico‐chemical soil organic layer properties, black spruce diameter and density, and understory ericaceous shrub cover, differ between these two principal disturbance types; 2) operations associated with forest harvest result in distinct, regular spatial patterns of these same variables related to presence of machine trails; and 3) ericaceous shrub presence is a potential factor contributing to the legacy of spatial patterns after harvest. We explored these patterns on black spruce‐feathermoss forest stands, including fire‐origin stands (18 and 98 years) and stands originating from harvest (16 and 62 years) in central Quebec, Canada. We used two spatial analysis methods, spectral analysis and principal component analysis in the frequency domain, to characterize and relate spatial patterns of these soil and vegetation variables, measured along 50‐m transects on each site. Spatial patterns of distribution of soil and vegetation variables were different on the burned and the harvested forest sites. Wildfire gave rise to spatial patterns in soil and vegetation variables at multiple scales, reflecting the complexity generated by variable burn intensity. Patterns following forest harvest were mainly related to the regular structure defined by trails created by logging operations. In contrast to burned sites, ericaceous shrub patterns on harvested sites were strongly associated with spatial arrangements of spruce diameter and density, promoting absence of canopy closure and persistence of trails. Moreover, different spatial signatures did not converge in the long‐term (62–98 years) between the two disturbance types. The divergence in spatial structure between natural and anthropogenic disturbances has implications for ecosystem structure and function in the longer term.     

Water abstraction impacts stream ecosystem functioning via wetted‐channel contraction

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Mannose receptor-mediated endothelial cell activation contributes to B16 melanoma cell adhesion and metastasis in liver

The role of mannose receptors from hepatic sinusoidal endothelium (HSE) in liver colonization by B16 melanoma (B16M) cells was studied. The expression of high mannose-type oligosaccharides on the surface of B16M cells was enhanced by in vitro treatment with 1-deoximannojirimycin (1-DMM). There was a significant (P < 0.01) enhancement of hepatic metastasis when B16M cells were 1-DMM-treated before being intrasplenically injected into C57BL/6J mice. Intraperitoneal administration of 5 mg/kg recombinant human interleukin-1 receptor antagonist (rHuIL-1Ra) inhibited the 1-DMM-induced enhancement of metastasis. Expression of high mannose-type oligosaccharides on the surface of 1-DMM-treated B16M cells and their in vitro adhesion to the HSE was significantly correlated (R = 0.82). The addition of either 100 μg/ml mannan or paraformaldehyde (PFA)-fixed 1-DMM-treated B16M cells to cultured HSE for a period of 12 h significantly (P < 0.01) increased the release of IL-1β from the HSE compared to that liberated by the HSE incubated with either basal medium or PFA-fixed untreated B16M cells. The same HSE treatments also significantly (P < 0.01) increased the degree of adhesion of other B16M cells to HSE, being abrogated by anti-mouse vascular cell adhesion molecule-1 (VCAM-1) antibodies. The conditioned media from HSE cultures, activated by PFA-fixed, 1-DMM-treated B16M cells significantly (P < 0.01) increased B16M cell proliferation when compared to conditioned media from HSE cultures incubated with PFA-fixed, untreated B16M cells. Thus, 1-DMM treatment of B16M cells enhanced the development of hepatic metastasis by IL-1-dependent mechanisms. The mechanism is consistent with in vitro mannose receptor-mediated melanoma cell attachment to the HSE, which subsequently upregulates IL-1β release, VCAM-1-dependent adherence, and melanoma growth factor(s) release by HSE. J. Cell. Physiol. 174:322–330, 1998. © 1998 Wiley-Liss, Inc.     

Space Availability in Confined Sheep during Pregnancy,Effects in Movement Patterns and Use of Space

Space availability is essential to grant the welfare of animals. To determine the effect of space availability on movement and space use in pregnant ewes (Ovis aries), 54 individuals were studied during the last 11 weeks of gestation. Three treatments were tested (1, 2, and 3 m²/ewe; 6 ewes/group). Ewes'' positions were collected for 15 minutes using continuous scan samplings two days/week. Total and net distance, net/total distance ratio, maximum and minimum step length, movement activity, angular dispersion, nearest, furthest and mean neighbour distance, peripheral location ratio, and corrected peripheral location ratio were calculated. Restriction in space availability resulted in smaller total travelled distance, net to total distance ratio, maximum step length, and angular dispersion but higher movement activity at 1 m²/ewe as compared to 2 and 3 m²/ewe (P<0.01). On the other hand, nearest and furthest neighbour distances increased from 1 to 3 m²/ewe (P<0.001). Largest total distance, maximum and minimum step length, and movement activity, as well as lowest net/total distance ratio and angular dispersion were observed during the first weeks (P<0.05) while inter-individual distances increased through gestation. Results indicate that movement patterns and space use in ewes were clearly restricted by limitations of space availability to 1 m²/ewe. This reflected in shorter, more sinuous trajectories composed of shorter steps, lower inter-individual distances and higher movement activity potentially linked with higher restlessness levels. On the contrary, differences between 2 and 3 m²/ewe, for most variables indicate that increasing space availability from 2 to 3 m²/ewe would appear to have limited benefits, reflected mostly in a further increment in the inter-individual distances among group members. No major variations in spatial requirements were detected through gestation, except for slight increments in inter-individual distances and an initial adaptation period, with ewes being restless and highly motivated to explore their new environment.     

Vitamin C transporter gene (SLC23A1 and SLC23A2) polymorphisms, plasma vitamin C levels, and gastric cancer risk in the EPIC cohort

Vitamin C is known to protect mucosal tissues from oxidative stress and inhibit nitrosamine formation in the stomach. High consumption of fruits, particularly citrus, and higher circulating vitamin C concentrations may be inversely associated with gastric cancer (GC) risk. We investigated 20 polymorphisms in vitamin C transporter genes SCL23A1 and SCL23A2 and GC risk in 365 cases and 1,284 controls nested within the European Prospective Investigation into Cancer and Nutrition cohort. We also evaluated the association between these polymorphisms and baseline plasma vitamin C levels in a subset of participants. Four SNPs were predictors of plasma vitamin C levels (SLC23A1 rs11950646 and rs33972313; SLC23A2 rs6053005 and rs6133175) in multivariable linear regression models. One SNP (SLC23A2 rs6116569) was associated with GC risk, in particular non-cardia GC (OR = 1.63, 95 % CI = 1.11–2.39, based on 178 non-cardia cases), but this association was attenuated when plasma vitamin C was included in the logistic regression model. Haplotype analysis of SLC23A1 yielded no associations with GC. In SLC23A2, one haplotype was associated with both overall and non-cardia GC, another haplotype was associated with GC overall, and a third was associated with intestinal-type GC. Common variants in SLC23A1 and SLC23A2 may influence plasma vitamin C concentration independent of dietary intake, and variation in SLC23A2 may influence GC risk. Additional prospective studies in large populations and consortia are recommended. Investigation of variation in vitamin C transporter genes may shed light on the preventative properties of vitamin C in gastric carcinogenesis.     

A novel mitochondrial outer membrane protein, MOMA-1, that affects cristae morphology in Caenorhabditis elegans

Three proteins with similar effects on mitochondrial morphology were identified in an RNA interference (RNAi) screen for mitochondrial abnormalities in Caenorhabditis elegans. One of these is the novel mitochondrial outer membrane protein MOMA-1. The second is the CHCHD3 homologue, CHCH-3, a small intermembrane space protein that may act as a chaperone. The third is a mitofilin homologue, IMMT-1. Mitofilins are inner membrane proteins that control the shapes of cristae. RNAi or mutations in each of these genes change the relatively constant diameters of mitochondria into highly variable diameters, ranging from thin tubes to localized swellings. Neither growth nor brood size of the moma-1, chch-3, or immt-1 single mutants is affected, suggesting that their metabolic functions are normal. However, growth of moma-1 or immt-1 mutants on chch-3(RNAi) leads to withered gonads, a lack of mitochondrial staining, and a dramatic reduction in fecundity, while moma-1; immt-1 double mutants are indistinguishable from single mutants. Mutations in moma-1 and immt-1 also have similar effects on cristae morphology. We conclude that MOMA-1 and IMMT-1 act in the same pathway. It is likely that the observed effects on mitochondrial diameter are an indirect effect of disrupting cristae morphology.