1,721,084 research outputs found
Advances in understanding the functions of native GlyT1 and GlyT2 neuronal glycine transporters
No full textA narrative review of genetic alterations in primary thyroid epithelial cancer
No full textThyroid carcinoma is the most frequent endocrine neoplasia. Different types of thyroid carcinoma are described: well-differentiated papillary thyroid carcinoma (PTC), poorly differentiated thyroid carcinoma (PDTC), follicular thyroid carcinoma (FTC), anaplastic thyroid carcinoma (ATC), and medullary thyroid carcinoma (MTC). MTC is inherited as an autosomal dominant trait in 25% of cases. The genetic landscape of thyroid carcinoma has been largely deciphered. In PTC, genetic alterations have been found in about 95% of tumors: BRAF mutations and RET rearrangements are the main genetic alterations. BRAF and RAS mutations have been confirmed to play an important role also in PDTC and ATC, together with TP53 mutations that are fundamental in tumor progression. It has also been clearly demonstrated that telomerase reverse transcriptase (TERT) promoter mutations and TP53 mutations are present with a high-frequency in more advanced tumors, frequently associated with other mutations, and their presence, especially if simultaneous, is a signature of aggressiveness. In MTC, next-generation sequencing confirmed that mutations in the RET gene are the most common molecular events followed by H-RAS and K-RAS mutations. The comprehensive knowledge of the genetic events responsible for thyroid tumorigenesis is important to better predict the biological behavior and better plan the therapeutic strategy for specific treatment of the malignancy based on its molecular profile
Release of [3H]GABA evoked by high affinity GABA uptake through GAT1 transporters occurs by homoexchange and through GAT1-independent, Ca2+ mediated mechanisms
No full text
High-affinity GABA uptake by neuronal GAT1 transporters provokes release of [3H]GABA by homoexchange and through GAT1-independent Ca(2+)-mediated mechanisms
No full textHigh-affinity uptake of GABA into nerve terminals may have functions other than recapture of the neurotransmitter. Synaptosomes purified from mouse cerebellum were prelabelled with [3H]GABA and then superfused with GABA and drugs selective for some presynaptic targets. Influx of GABA through
GAT1 transporters stimulated efflux of [3H]GABA in a concentration-dependent manner (EC50 ~ 3 mM).
The efflux of the transmitter occurred in part by GAT1 reversal through the so called homoexchange. The ion fluxes (particularly Naþ influx) accompanying GABA uptake triggered intraterminal Ca2þ signals through both plasmalemmal Naþ/Ca2þ exchangers, sensitive to KB-R7943 or to ifenprodil and mitochondrial Naþ/Ca2þ exchangers, sensitive to CGP37157. These Ca2þ signals likely facilitated GABA release from nerve terminals via niflumic acid- and NPPB-sensitive anion channels. The results show that GABA, at concentrations corresponding to the high-affinity uptake, can evoke GABA release which occurs in part by the expected GAT1-mediated homoexchange, while the transporter-independent component of the GABA uptake-evoked GABA release takes place by hitherto unsuspected mechanisms which include Naþ/Ca2þ exchangers and anion channels. The significance of the novel function of the GABA high-affinituptake here identified deserves further multidisciplinary investigation
endocrine neoplasia type 2 syndromes (MEN 2): results froma the ItameN network analysis on the prevalence of differente genotypes and phenotypes
No full textMultiple endocrine neoplasia type 2 (MEN 2) is a genetic disease characterized by medullary thyroid carcinoma (MTC) associated (MEN 2A and 2B) or not familial MTC (FMTC) with other endocrine neoplasia due to germline RET gene mutations. The prevalence of these rare genetic diseases and their corresponding RET mutations are unknown due to the small size of the study population.
METHODS:
We collected data on germline RET mutations of 250 families with hereditary MTC followed in 20 different Italian centres.
RESULTS AND CONCLUSIONS:
The most frequent RET amino acid substitution was Val804Met (19.6%) followed by Cys634Arg (13.6%). A total of 40 different germline RET mutations were present. Six families (2.4%) were negative for germline RET mutations. The comparison of the prevalence of RET germline mutations in the present study with those published by other European studies showed a higher prevalence of Val804Met and Ser891Ala mutations and a lower prevalence of Leu790Phe and Tyr791Phe (P<0.0001). A statistically significant higher prevalence of mutations affecting non-cysteine codons was also found (P<0.0001). Furthermore, the phenotype data collection showed an unexpected higher prevalence of FMTC (57.6%) with respect to other MEN 2 syndromes (34% MEN 2A and 6.8% of MEN 2B). In conclusion, we observed a statistically significant different pattern of RET mutations in Italian MEN 2 families with respect to other European studies and a higher prevalence of FMTC phenotype. The different ethnic origins of the patients and the particular attention given to analysing apparently sporadic MTC for RET germline mutations may explain these findings
Corrigendum to ?Colocalization of neurotransmitter transporters on the plasma membrane of the same nerve terminal may reflect cotransmission? [Brain Res. Bull. 127 (2016) 100?110] (S0361923016302155) (10.1016/j.brainresbull.2016.08.013)
No full textThere is increasing evidence for the neuronal coexistence of classical transmitters. Implications in favor of cotransmission have often been represented by the identification, in the same neuron, of the putative cotransmitters, their synthetic enzymes and/or their vesicular transporters. In contrast, coexpression of neurotransmitter transporters on the plasma membrane of the same nerve terminal, although a potentially important indication for cotransmission, has received poor attention. We here used preparations of isolated nerve endings to functionally identify transporters coexpressed on the plasma membrane of the same terminal, in order to verify if such transporter coexpression indeed exists in neuronal systems in which cotransmission has already been established or reasonably suspected through other technical approaches. We could observe that functional transporters for glycine and glutamate are coexpressed on nerve terminals in the cerebellum; transporters for dopamine and GABA coexist on striatal terminals; transporters for glycine and GABA, previously found to coexist as cotransmission markers on nerve terminals of spinal cord and cerebellum, are not coexpressed in neocortex and hippocampus, where cotransmission has not been proposed to occur; transporters for GABA, glycine and glutamate are colocalized on nerve terminals of the spinal cord. Confocal microscopy experiments were performed to substantiate functional data, highlighting the presence of the co-existing transporters under study on MAP-2 positive synaptosomes. It is concluded that investigating the colocalization of functional neurotransmitter transporters on the plasma membrane of nerve terminals can provide useful information on the possibility of cotransmission
Colocalization of neurotransmitter transporters on the plasma membrane of the same nerve terminal may reflect cotransmission.
No full text
- …
