Opposite Roles of NMDA Receptors in Relapsing and Primary Progressive Multiple Sclerosis

Synaptic transmission and plasticity mediated by NMDA receptors (NMDARs) could modulate the severity of multiple sclerosis (MS). Here the role of NMDARs in MS was first explored in 691 subjects carrying specific allelic variants of the NR1 subunit gene or of the NR2B subunit gene of this glutamate receptor. The analysis was replicated for significant SNPs in an independent sample of 1548 MS subjects. The C allele of rs4880213 was found to be associated with reduced NMDAR-mediated cortical excitability, and with increased probability of having more disability than the CT/TT MS subjects. MS severity was higher in the CC group among relapsing-remitting MS (RR-MS) patients, while primary progressive MS (PP-MS) subjects homozygous for the T allele had more pronounced clinical worsening. Mean time to first relapse, but not to an active MRI scan, was lower in the CC group of RR-MS patients, and the number of subjects with two or more clinical relapses in the first two years of the disease was higher in CC compared to CT/TT group. Furthermore, the percentage of relapses associated with residual disability was lower in subjects carrying the T allele. Lesion load at the MRI was conversely unaffected by the C or T allele of this SNP in RR-MS patients. Axonal and neuronal degeneration at the optical coherence tomography was more severe in the TT group of PP-MS patients, while reduced retinal nerve fiber thickness had less consequences on visual acuity in RR-MS patients bearing the T allele. Finally, the T allele was associated with preserved cognitive abilities at the Rao’s brief repeatable neuropsychological battery in RR-MS. Signaling through glutamate NMDARs enhances both compensatory synaptic plasticity and excitotoxic neurodegeneration, impacting in opposite ways on RR-MS and PP-MS pathophysiological mechanisms.     

Influence of rumen protein degradability on productive and reproductive performance in buffalo cows

The present study aimed to ascertain the influence of crude protein (CP) digestibility in the rumen on the quantity and quality of milk production and reproductive performance, blood (BU) and milk (MU) urea, haematological profile and vaginal mucus urea, ammonia and potassium of buffalo cows. Lactating buffaloes (n = 84), 60 days in milk, were randomly subdivided into Group C (control, n = 42) and Group T (fed a diet supplemented with Aspergillus oryzae, n = 42). In three fistulated buffalo, the diet supplemented with Aspergillus oryzae showed a decrease (P < 0.01) in protein digestibility in the rumen (79.3 vs. 45.9%). No differences were registered in productive performance. Nine buffaloes not in oestrus during the dietary treatment (Groups T1 and C1), 30 days in milk, were used to study the haematological profile and to determine milk urea and ammonia in the vaginal mucus. The animals in Group T1 had higher ammonia values in the blood (P < 0.01) but not in the vaginal mucus than Group C1. A relationship was found between MU and BU. MU was influenced by CP intake and dry matter intake. No differences between the treatments were observed in reproductive performance and the conception rate and calving interval were 37.9% and 41.4% (90 trial-day) and 449 and 419 days respectively in Groups T and C. Reproductive performance was not influenced by high levels of BU nor by blood ammonia levels, although the latter were higher in the group fed the diet supplemented with Aspergillus oryzae.     

Climate change and voltinism of Mythimna sequax: the location and choice of phenological models matter

相似文献   

Diet composition of bigeye tuna (Thunnus obesus) and yellowfin tuna (Thunnus albacares) caught on aggregated schools in the western equatorial Atlantic Ocean

The present study aims to characterize and compare the diet of bigeye and yellowfin tunas caught on aggregated schools in the western equatorial Atlantic Ocean. The samples were collected from January 2011 to June 2016. The tunas were measured on board and the stomachs were removed after evisceration. The stomachs were analyzed regarding their Index of Fullness and the importance of each prey in the diet was estimated by the Index of Relative Importance (IRI). The diet overlap was assessed by the Morisita‐Horn's Index, Non‐Metric Multidimensional Scale (NMDS), and Analysis of Similarity (ANOSIM). The feeding strategy was determined by the Costello's Diagram. The 195 bigeye and 212 yellowfin tunas ranged in fork length from 51 to 137 cm and 43 to 174 cm, respectively. The diet of bigeye tuna was composed of 10 families of fish, three cephalopod families, and four crustacean orders. The diet of yellowfin tuna was composed of 11 families of fish, three cephalopod families, and three crustacean orders. The yellowfin tuna seems to feed upon more abundant prey species near the surface like flying fish, which have the concentration enhanced by the light attractors on the boat, and occasionally on other prey from deeper habitats like lanternfish, squids, and pomfret. Bigeye tuna feed mainly at prey that commonly occurs in deeper habitats like squids, drift fish, lanternfish, and pomfret.     

Magnetic Resonance Imaging Allows the Evaluation of Tissue Damage and Regeneration in a Mouse Model of Critical Limb Ischemia

Magnetic resonance imaging (MRI) provides non-invasive, repetitive measures in the same individual, allowing the study of a physio-pathological event over time. In this study, we tested the performance of 7 Tesla multi-parametric MRI to monitor the dynamic changes of mouse skeletal muscle injury and regeneration upon acute ischemia induced by femoral artery dissection. T2-mapping (T2 relaxation time), diffusion-tensor imaging (Fractional Anisotropy) and perfusion by Dynamic Contrast-Enhanced MRI (K-trans) were measured and imaging results were correlated with histological morphometric analysis in both Gastrocnemius and Tibialis anterior muscles. We found that tissue damage positively correlated with T2-relaxation time, while myofiber regeneration and capillary density positively correlated with Fractional Anisotropy. Interestingly, K-trans positively correlated with capillary density. Accordingly, repeated MRI measurements between day 1 and day 28 after surgery in ischemic muscles showed that: 1) T2-relaxation time rapidly increased upon ischemia and then gradually declined, returning almost to basal level in the last phases of the regeneration process; 2) Fractional Anisotropy dropped upon ischemic damage induction and then recovered along with muscle regeneration and neoangiogenesis; 3) K-trans reached a minimum upon ischemia, then progressively recovered. Overall, Gastrocnemius and Tibialis anterior muscles displayed similar patterns of MRI parameters dynamic, with more marked responses and less variability in Tibialis anterior. We conclude that MRI provides quantitative information about both tissue damage after ischemia and the subsequent vascular and muscle regeneration, accounting for the differences between subjects and, within the same individual, between different muscles.     

Moniliophthora perniciosa Necrosis- and Ethylene-Inducing Protein 2 (MpNep2) as a Metastable Dimer in Solution: Structural and Functional Implications

Understanding how Nep-like proteins (NLPs) behave during the cell cycle and disease progression of plant pathogenic oomycetes, fungi and bacteria is crucial in light of compelling evidence that these proteins play a role in Witches` Broom Disease (WBD) of Theobroma cacao, one of the most important phytopathological problems to afflict the Southern Hemisphere. The crystal structure of MpNep2, a member of the NLP family and the causal agent of WBD, revealed the key elements for its activity. This protein has the ability to refold after heating and was believed to act as a monomer in solution, in contrast to the related homologs MpNep1 and NPP from the oomyceteous fungus Phytophthora parasitica. Here, we identify and characterize a metastable MpNep2 dimer upon over-expression in Escherichia coli using different biochemical and structural approaches. We found using ultra-fast liquid chromatography that the MpNep2 dimer can be dissociated by heating but not by dilution, oxidation or high ionic strength. Small-angle X-ray scattering revealed a possible tail-to-tail interaction between monomers, and nuclear magnetic resonance measurements identified perturbed residues involved in the putative interface of interaction. We also explored the ability of the MpNep2 monomer to refold after heating or chemical denaturation. We observed that MpNep2 has a low stability and cooperative fold that could be an explanation for its structure and activity recovery after stress. These results can provide new insights into the mechanism for MpNep2′s action in dicot plants during the progression of WBD and may open new avenues for the involvement of NLP- oligomeric species in phytopathological disorders.     

Identification of Key Signaling Molecules Involved in the Activation of the Swelling-Activated Chloride Current in Human Glioblastoma Cells

The swelling-activated chloride current (I _Cl,Vol) is abundantly expressed in glioblastoma (GBM) cells, where it controls cell volume and invasive migration. The transduction pathway mediating I _Cl,Vol activation in GBM cells is, however, poorly understood. By means of pharmacological and electrophysiological approaches, on GL-15 human GBM cells we found that I _Cl,Vol activation by hypotonic swelling required the activity of a U73122-sensitive phospholipase C (PLC). I _Cl,Vol activation could also be induced by the membrane-permeable diacylglycerol (DAG) analog OAG. In contrast, neither calcium (Ca²⁺) chelation by BAPTA-AM nor changes in PKC activity were able to affect I _Cl,Vol activation by hypotonic swelling. We further found that R59022, an inhibitor of diacylglycerol kinase (DGK), reverted I _Cl,Vol activation, suggesting the involvement of phosphatidic acid. In addition, I _Cl,Vol activation required the activity of a EHT1864-sensitive Rac1 small GTPase and the resulting actin polymerization, as I _Cl,Vol activation was prevented by cytochalasin B. We finally show that I _Cl,Vol can be activated by the promigratory fetal calf serum in a PLC- and DGK-dependent manner. This observation is potentially relevant because blood serum can likely come in contact with glioblastoma cells in vivo as a result of the tumor-related partial breakdown of the blood–brain barrier. Given the relevance of I _Cl,Vol in GBM cell volume regulation and invasiveness, the several key signaling molecules found in this study to be involved in the activation of the I _Cl,Vol may represent potential therapeutic targets against this lethal cancer.