ProSAPs/Shanks are a family of proteins that have a major scaffolding function for components of the postsynaptic density (PSD) of excitatory brain synapses. Members of the family harbor a variety of domains for protein-protein interactions, one of which is a unique PDZ domain that differs significantly from those of other proteins. We have identified a novel binding partner for this PDZ domain, termed ProSAPiP1, that is highly enriched in the PSD and shares significant sequence homology with the PSD protein PSD-Zip70. Both molecules code for a Fez1 domain that can be found in a total of four related proteins. ProSAPiP1 is widely expressed in rat brain and co-localizes with ProSAP2/Shank3 in excitatory spines and synapses. ProSAP2/Shank3 co-immunoprecipitates with ProSAPiP1 but not with PSD-Zip70. Both proteins, however, bind and recruit SPAR to synapses with a central coiled-coil region that harbors a leucine zipper motif. This region is also responsible for homo- and heteromultimerization of ProSAPiP1 and PSD-Zip70. Thus, ProSAPiP1 and PSD-Zip70 are founders of a novel family of scaffolding proteins, the "Fezzins," which adds further complexity to the organization of the PSD protein network. 相似文献
Chemical synapses are asymmetric cell junctions that mediate communication between neurons. Multidomain scaffolding proteins of the Shank family act as major organizing elements of the "postsynaptic density"--that is, the cytoskeletal protein matrix associated with the postsynaptic membrane. A recent study has shown that the C-terminal sterile alpha-motif or "SAM domain" of Shank3 (also known as ProSAP2) can form two-dimensional sheets of helical fibers. Assembly and packaging of these fibers are markedly enhanced by the presence of Zn2+ ions. Zn2+ can be released together with glutamate from synaptic vesicles and can enter the postsynaptic cell through specific ionotropic receptors. Based on these observations, we propose a new model of synaptic plasticity in which Zn2+ influx directly and instantly modulates the structure and function of the postsynaptic density. 相似文献
Reduced precipitation treatments often are used in field experiments to explore the effects of drought on plant productivity and species composition. However, in seasonally snow-covered regions reduced precipitation also reduces snow cover, which can increase soil frost depth, decrease minimum soil temperatures and increase soil freeze–thaw cycles. Therefore, in addition to the effects of reduced precipitation on plants via drought, freezing damage to overwintering plant tissues at or below the soil surface could further affect plant productivity and relative species abundances during the growing season. We examined the effects of both reduced rainfall (via rain-out shelters) and reduced snow cover (via snow removal) at 13 sites globally (primarily grasslands) within the framework of the International Drought Experiment, a coordinated distributed experiment. Plant cover was estimated at the species level, and aboveground biomass was quantified at the functional group level. Among sites, we observed a negative correlation between the snow removal effect on minimum soil temperature and plant biomass production the next growing season. Three sites exhibited significant rain-out shelter effects on plant productivity, but there was no correlation among sites between the rain-out shelter effect on minimum soil moisture and plant biomass. There was no interaction between snow removal and rain-out shelters for plant biomass, although these two factors only exhibited significant effects simultaneously for a single site. Overall, our results reveal that reduced snowfall, when it decreases minimum soil temperatures, can be an important component of the total effect of reduced precipitation on plant productivity. 相似文献
This review describes the current knowledge of the pathogenesis of acute Lyme neuroborreliosis (LNB), from invasion to inflammation of the central nervous system. Borrelia burgdorferi (B.b.) enters the host through a tick bite on the skin and may disseminate from there to secondary organs, including the central nervous system. To achieve this, B.b. first has to evade the hostile immune system. In a second step, the borrelia have to reach the central nervous system and cross the blood-brain barrier. Once in the cerebrospinal fluid (CSF), the spirochetes elicit an inflammatory response. We describe current knowledge about the infiltration of leukocytes into the CSF in LNB. In the final section, we discuss the mechanisms by which the spirochetal infection leads to the observed neural dysfunction. To conclude, we construct a stringent concept of the pathogenesis of LNB. 相似文献
Background: Renal denervation has been proposed as a therapeutic option in patients with resistant hypertension. Circulating blood borne biomarkers might be helpful to identify individuals responding to RDN therapy. MR-proADM is a strong prognostic marker in patients with cardiovascular disease. The aim of this multicenter study was to evaluate the effect of RDN on MR-proADM concentrations.
Methods and results: We measured MR-proADM, BNP, and MR-proANP in 110 patients before and after RDN in a multicenter setting. All patients were followed up after 1 and 6 months by office and ambulatory blood pressure (BP) measurements. The mean office BP decreased from 165/89 to 152/87?mmHg 6 months after RDN (systolic: p?<?0.001; diastolic: ns), the responder-rate was 74%. Intriguingly MR-proADM concentrations increased from 0.66 to 0.69?nmol/L (p?<?0.001) and were significantly associated with reduction of systolic office BP after 6 months in multivariate analyses (coefficient ?0.0018, p?<?0.001). In therapy-responders MR-proADM concentrations showed a significantly higher increase over time (coefficient 0.0105, p?<?0.05), as compared to non-responders. There were no significant differences in BP change for individuals with low and high baseline MR-proADM (BP-Delta low MR-proADM ?23/?4?mmHg vs. high MR-proADM ?24/?5?mmHg). The natriuretic biomarkers BNP and MR-proANP did not change significantly after 6 months. Biomarkers at baseline were not able to predict for therapy-responder.
Conclusion: In patients undergoing RDN, baseline measurements of various biomarkers had no prognostic use for therapy success in this short time follow-up period in a multicenter approach. Intriguingly, MR-proADM showed a significant association with BP reduction after 6 months. 相似文献
Recent results indicate that association mapping in populations from applied plant breeding is a powerful tool to detect QTL
which are of direct relevance for breeding. The focus of this study was to unravel the genetic architecture of six agronomic
traits in sugar beet. To this end, we employed an association mapping approach, based on a very large population of 924 elite
sugar beet lines from applied plant breeding, fingerprinted with 677 single nucleotide polymorphism (SNP) markers covering
the entire genome. We show that in this population linkage disequilibrium decays within a short genetic distance and is sufficient
for the detection of QTL with a large effect size. To increase the QTL detection power and the mapping resolution a much higher
number of SNPs is required. We found that for QTL detection, the mixed model including only the kinship matrix performed best,
even in the presence of a considerable population structure. In genome-wide scans, main effect QTL and epistatic QTL were
detected for all six traits. Our full two-dimensional epistasis scan revealed that for complex traits there appear to be epistatic
master regulators, loci which are involved in a large number of epistatic interactions throughout the genome. 相似文献