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11.
Matteo Zurlo Francesco Nicoli Davide Proietto Beatrice Dallan Cristina Zuccato Lucia Carmela Cosenza Jessica Gasparello Chiara Papi Elisabetta d'Aversa Monica Borgatti Chiara Scapoli Alessia Finotti Roberto Gambari 《Journal of cellular and molecular medicine》2023,27(3):353-364
Inhibitors of the mammalian target of rapamycin (mTOR) have been proposed to improve vaccine responses, especially in the elderly. Accordingly, testing mTOR inhibitors (such as Sirolimus) and other geroprotective drugs might be considered a key strategy to improve overall health resilience of aged populations. In this respect, Sirolimus (also known as rapamycin) is of great interest, in consideration of the fact that it is extensively used in routine therapy and in clinical studies for the treatment of several diseases. Recently, Sirolimus has been considered in laboratory and clinical studies aimed to find novel protocols for the therapy of hemoglobinopathies (e.g. β-Thalassemia). The objective of the present study was to analyse the activity of CD4+ and CD8+ T cells in β-Thalassemia patients treated with Sirolimus, taking advantages from the availability of cellular samples of the NCT03877809 clinical trial. The approach was to verify IFN-γ releases following stimulation of peripheral blood mononuclear cells (PBMCs) to stimulatory CEF and CEFTA peptide pools, stimulatory for CD4+ and CD8+ T cells, respectively. The main results of the present study are that treatment of β-Thalassemia patients with Sirolimus has a positive impact on the biological activity and number of memory CD4+ and CD8+ T cells releasing IFN-γ following stimulation with antigenic stimuli present in immunological memory. These data are to our knowledge novel and in our opinion of interest, in consideration of the fact that β-Thalassemia patients are considered prone to immune deficiency. 相似文献
12.
Margherita Sosio Giuseppe Amati Carmela Cappellano Edoardo Sarubbi Federica Monti Stefano Donadio 《Molecular microbiology》1996,22(1):43-51
SecA protein, the ATPase promoting translocation of proteins across the Escherichia coli inner membrane, contains two ATP-binding domains that differ greatly in their affinity for bound nucleotide. In order to define more precisely the location of the high-affinity nucleotide-binding site, oligonucleotide-directed mutagenesis was used to introduce cysteine residues into the SecA sequence, and a cysteine-specific cleavage reagent was employed to generate defined peptides of SecA protein after photocross-linking with [α-32P]-ATP. This analysis revealed that the nucleotide was cross-linked between amino acid residues 75 and 97 of SecA protein. The biochemical function of the high affinity ATP-binding domain was explored by subcellular fractionation studies which demonstrated that SecA proteins defective in this region were found almost exclusively in their integral membrane form, while SecA proteins with defects in the low-affinity ATP-domain showed a normal distribution of cytosolic, peripheral and integral membrane forms. Interestingly, the SecA51(Ts) protein that has a Leu to Pro substitution at amino acid residue 43 bound ATP with high affinity, but its fractionation pattern and translocation ATPase activity were similar to those of proteins with defects in the high-affinity ATP-binding site. These results delimit more precisely the high-affinity ATP-binding domain of SecA, indicate the importance of the early amino-terminal region of SecA protein in the functioning of this domain, and demonstrate the role of this domain in regulating penetration of SecA protein into the inner membrane. Our results lead to a simple model for the regulation of a cycle of SecA insertion into, and de-insertion from, the inner membrane by the activity of the high-affinity ATP-binding domain. 相似文献
13.
Summary The expression and distribution of S-100 protein and type IV collagen was studied immunohistochemically in sympathetic neuroblasts
from the paravertebral region to the adrenal glands in human embryos and fetuses ranging from 7 to 12 weeks gestational age.
Prom 7 weeks gestational age, S-100 protein was detected in round or oval cells mingling with sympathetic neuroblasts, and
in spindle-shaped cells forming a continuous layer around them. The latter S-100 protein-positive cells were found in contact
with the Schwann cells of nerve fibres entering the groups of sympathetic neuroblasts. Staining for type IV collagen showed
that all groups of sympathetic neuroblasts were surrounded by a continuous basement membrane. By examining serial sections
stained for type IV collagen and S-100 protein, a continuous basement membrane was found along the distribution pattern of
the peripheral S-100 protein-positive spindle cells. The morphology of these cells, and their relationships with Schwann cells
and with the basement membrane of the sympathetic neuroblasts, indicated that they were Schwann-like cells probably capable
of synthesizing a continuous basement membrane separating the neuroblasts from the adjacent tissues. In contrast, the round
or oval S-100 protein-positive cells, in contact with the sympathetic neuroblasts and not associated with nerve fibres, were
considered as sustentacular or sustentacular precursor cells. At week 7 gestational age, the peri-adrenal sympathetic neuroblasts
and their sustentacular and Schwann-like cells started to invade the adrenal glands and mingled with the adrenal cortical
cells. These findings suggest the extra-adrenal origin of the sustentacular cells in embryonic and fetal adrenal glands. 相似文献
14.
A Casino M Cipollaro A M Guerrini G Mastrocinque A Spena V Scarlato 《Nucleic acids research》1981,9(6):1499-1518
A Fortran computer algorithm has been used to analyze the nucleotide sequence of several structural genes. The analysis performed on both coding and complementary DNA strands shows that whereas open reading frames shorter than 100 codons are randomly distributed on both DNA strands, open reading frames longer than 100 codons ("virtual genes") are significantly more frequent on the complementary DNA strand than on the coding one. These "virtual genes" were further investigated by looking at intron sequences, splicing points, signal sequences and by analyzing gene mutations. On the basis of this analysis coding and complementary DNA strands of several eukaryotic structural genes cannot be distinguished. In particular we suggest that the complementary DNA strand of the human epsilon-globin gene might indeed code for a protein. 相似文献
15.
16.
The genetic defect in multiple endocrine neoplasia type 2A maps next to the centromere of chromosome 10 总被引:12,自引:6,他引:6
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Jingshi Wu Nancy L. Carson Shirley Myers Andrew J. Pakstis Judith R. Kidd Carmela M. Castiglione Linda Anderson L. Suzanne Hoyle Myron Genel Maurice Verdy Charles E. Jackson Nancy E. Simpson Kenneth K. Kidd 《American journal of human genetics》1990,46(3):624-630
Multiple endocrine neoplasia type 2A (MEN2A) is a rare cancer syndrome that is inherited in an apparently autosomal dominant fashion. Previous linkage studies had assigned the MEN2A locus to chromosome 10 in the pericentromeric region. We recently have described several new easily scorable RFLPs for the chromosome 10-specific alpha satellite DNA (the D10Z1) locus that is known, on the basis of previous in situ hybridization experiments, to lie at the centromere. We report here tight linkage between MEN2A and D10Z1, as demonstrated by a maximum lod score of 12.02 at the recombination frequency of zero (1-lod-unit support interval 0-4 cM), indicating that the genetic defect in MEN2A lies in the immediate vicinity of the centromere. By means of a set of ordered polymorphic DNA markers from the pericentromeric region, multipoint as well as pairwise linkage analyses place the MEN2A locus at the middle of a small region (approximately 11 cM) bracketing the centromere with FNRB (at 10p11.2) and RBP3 (at 10q11.2) on either side, providing further support for the centromeric location of the MEN2A locus. Marked sex difference in recombination frequencies exists in this pericentromeric region: significantly (P less than .01) more female than male crossovers were observed across all of the adjacent intervals D10S24-FNRB, FNRB-D10Z1, and D10Z1-RBP3. However, a sex difference was not seen in the 7-cM interval from RBP3 to D10S5, suggesting that large variation in the sex difference in recombination can occur over small chromosomal regions.(ABSTRACT TRUNCATED AT 250 WORDS) 相似文献
17.
Douglas L. Currell Bernice Law Michael Stevens Paul Murata Carmela Ioppolo Filippo Martini 《Biochemical and biophysical research communications》1981,102(1):348-354
Human hemoglobin reacts with 4-Isothiocyanatobenzene sulfonic acid at the four amino groups of the N-terminal valines. The modified protein shows a decreased oxygen affinity over a wide pH range, a reduced alkaline Bohr effect, decreased co-operativity, and a reduced effect of inositol hexasulfate on the oxygen affinity. 相似文献
18.
Girolamo A. Vitello Francesco Calì Mirella Vinci Carmela Scuderi Francesca LEpiscopo Antonino Musumeci Sebastiano A. Musumeci Antonio G. Nicotera 《Journal of musculoskeletal & neuronal interactions》2020,20(4):610
Spinal muscular atrophy (SMA) refers to a group of genetic neuromuscular disorders affecting lower motor neurons causative of numerous phenotypes. To date, according to the age of onset, maximum muscular activity achieved, and life expectation four types of SMA are recognized, all caused by mutations in the SMN1 gene with SMN2 copy number influencing disease severity. Herein, we describe the case of a 31-year-old young male with normal psychomotor development who has experienced fatigue, cramps, and muscle fasciculations in the lower limbs for a period of 2 months. Based on electrophysiological and clinical findings we performed SMA genetic, clinical exome and RNA expression of candidate genes which led us to suggest SMN1-SMN2 genes [(2+0) and (0+0)] combination as possibly being implicated in the phenotype. 相似文献
19.
Isidoro Olmeda Patricia Casino Robert E. Collins Ramón Sendra Sara Callejón Juanjo Huesa Alexei S. Soares Sergi Ferrer Isabel Pardo 《Microbial biotechnology》2021,14(3):1026-1043
Prokaryotic laccases are emergent biocatalysts. However, they have not been broadly found and characterized in bacterial organisms, especially in lactic acid bacteria. Recently, a prokaryotic laccase from the lactic acid bacterium Pediococcus acidilactici 5930, which can degrade biogenic amines, was discovered. Thus, our study aimed to shed light on laccases from lactic acid bacteria focusing on two Pediococcus laccases, P. acidilactici 5930 and Pediococcus pentosaceus 4816, which have provided valuable information on their biochemical activities on redox mediators and biogenic amines. Both laccases are able to oxidize canonical substrates as ABTS, ferrocyanide and 2,6-DMP, and non-conventional substrates as biogenic amines. With ABTS as a substrate, they prefer an acidic environment and show sigmoidal kinetic activity, and are rather thermostable. Moreover, this study has provided the first structural view of two lactic acid bacteria laccases, revealing new structural features not seen before in other well-studied laccases, but which seem characteristic for this group of bacteria. We believe that understanding the role of laccases in lactic acid bacteria will have an impact on their biotechnological applications and provide a framework for the development of engineered lactic acid bacteria with enhanced properties. 相似文献
20.
Melania Manco Maria Rita Spreghini Rosa Luciano Cecilia Pensini Rita Wietrzycowska Sforza Carmela Rustico Marco Cappa Giuseppe Stefano Morino 《PloS one》2013,8(7)