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921.
NADP is essential for biosynthetic pathways, energy, and signal transduction. In living organisms, NADP biosynthesis proceeds through the phosphorylation of NAD with a reaction catalyzed by NAD kinase. We expressed, purified, and characterized Bacillus subtilis NAD kinase. This enzyme represents a new member of the inorganic polyphosphate [poly(P)]/ATP NAD kinase subfamily, as it can use poly(P), ATP, or other nucleoside triphosphates as phosphoryl donors. NAD kinase showed marked positive cooperativity for the substrates ATP and poly(P) and was inhibited by its product, NADP, suggesting that the enzyme plays a major regulatory role in NADP biosynthesis. We discovered that quinolinic acid, a central metabolite in NAD(P) biosynthesis, behaved like a strong allosteric activator for the enzyme. Therefore, we propose that NAD kinase is a key enzyme for both NADP metabolism and quinolinic acid metabolism. 相似文献
922.
Resta N Susca FC Di Giacomo MC Stella A Bukvic N Bagnulo R Simone C Guanti G 《Journal of cellular physiology》2006,209(1):67-73
Roberts syndrome (RS) is a rare disorder characterized by tetraphocomelia and several other clinical features. Cells from RS patients exhibit characteristic premature separation of heterochromatic region of many chromosomes and abnormalities in cell cycle. Mutations in the ESCO2 gene have recently been identified in 20 RS families. We performed mutational analysis of the ESCO2 gene in two fetuses diagnosed with RS and their normal parents. In both fetuses, we identified homozygosity for the c. 745_746delGT mutation, while the non-consanguineous parents were both heterozygous for the same mutation. Considering the position of the mutation identified, we carried out qualitative and quantitative real-time ESCO2 cDNA analysis on RNA isolated from CVS-stromal cells in one fetus, amniocytes in the second fetus, and lymphocytes from the heterozygous parents. The results of this analysis showed that despite the presence of a premature termination codon (PTC) 112 nucleotides upstream of the next exon3-exon4 junction, the mutant ESCO2 mRNA was present in both fetuses, albeit at low levels, indicating a partial resistance to nonsense mediated decay (NMD). Interestingly, when cells derived from the two fetuses were treated with an inhibitor of translation, they revealed the presence of tissue and individual variability in NMD efficiency, despite the identical mutational status. The existence of such a variation in the NMD efficiency could explain the broad intrafamilial and interfamilial variability in the clinical presentation of RS patients, and in other genetic diseases where nonsense mutations are responsible for most of the mutation load. Moreover, considering that a mutated full length mRNA was produced in both fetuses, we used Western blot analysis to demonstrate the absence of the ESCO2-truncated protein in cells derived from both fetuses and in a lymphoblastoid cell line derived from the parents. 相似文献
923.
NF1 gene mutations represent the major molecular event underlying neurofibromatosis-Noonan syndrome 总被引:7,自引:0,他引:7 下载免费PDF全文
De Luca A Bottillo I Sarkozy A Carta C Neri C Bellacchio E Schirinzi A Conti E Zampino G Battaglia A Majore S Rinaldi MM Carella M Marino B Pizzuti A Digilio MC Tartaglia M Dallapiccola B 《American journal of human genetics》2005,77(6):1092-1101
Neurofibromatosis type 1 (NF1) demonstrates phenotypic overlap with Noonan syndrome (NS) in some patients, which results in the so-called neurofibromatosis-Noonan syndrome (NFNS). From a genetic point of view, NFNS is a poorly understood condition, and controversy remains as to whether it represents a variable manifestation of either NF1 or NS or is a distinct clinical entity. To answer this question, we screened a cohort with clinically well-characterized NFNS for mutations in the entire coding sequence of the NF1 and PTPN11 genes. Heterozygous NF1 defects were identified in 16 of the 17 unrelated subjects included in the study, which provides evidence that mutations in NF1 represent the major molecular event underlying this condition. Lesions included nonsense mutations, out-of-frame deletions, missense changes, small inframe deletions, and one large multiexon deletion. Remarkably, a high prevalence of inframe defects affecting exons 24 and 25, which encode a portion of the GAP-related domain of the protein, was observed. On the other hand, no defect in PTPN11 was observed, and no lesion affecting exons 11-27 of the NF1 gene was identified in 100 PTPN11 mutation-negative subjects with NS, which provides further evidence that NFNS and NS are genetically distinct disorders. These results support the view that NFNS represents a variant of NF1 and is caused by mutations of the NF1 gene, some of which have been demonstrated to cause classic NF1 in other individuals. 相似文献
924.
Daniele Castiglia Alessandro Cestelli Maria Scaturro Tommaso Nastasi Italia Di Liegro 《Neurochemical research》1994,19(12):1531-1537
Two overlapping rat cDNAs, covering a continuous region of 1107 base pairs, have been isolated and sequenced. The clones contain identical open reading frames, encoding a 136 amino acid long polypeptide which exhibits 100% identity to other mammalian H3.3 histone variants. We show that the inserts derive, in particular, from the H3.3B gene. We used these inserts and an insert from an H1° encoding clone, previously described (6), as probes to study the accumulation of mRNAs encoding the corresponding histone replacement variants (namely, H1° and H3.3) during rat brain development. We found that the concentration of both H1° and H3.3B mRNAs decreases from the embryonal day 18 (E18) to the postnatal day 10 (P10), with inverse correlation to protein accumulation.This paper is dedicated to our friend Paolo Carbone who devoted his life to research and teaching in Genetics. We will always remember him for scientific honesty and for his unique qualities of humanity. 相似文献
925.
926.
Giovanni Mantovani Vittorio Gebbia Mario Airoldi Cesare Bumma Paolo Contu Alessandro Bianchi Massimo Ghiani Daniela Dessì Elena Massa Luigi Curreli Biancarosa Lampis Paola Lai Carlo Mulas Antonio Testa Ernesto Proto Gabrio Cadeddu Giorgio Tore 《Cancer immunology, immunotherapy : CII》1998,47(3):149-156
We carried out an open, randomized, phase III, multicenter clinical trial to compare, in neo-adjuvant setting, the clinical
response and toxicity of the combination chemotherapy cisplatin + 5-FU with the same combination plus s.c. recombinant interleukin-2
(rIL-2) in patients with advanced (stage III–IV) head and neck squamous-cell carcinoma (HNSCC). Regimen A was the classical
Al Sarraf treatment: 100 mg/m2 cisplatin i.v. on day 1 plus 1000 mg m−2 day−1 5-FU on days 1–5 as a continuous infusion. Regimen B was the same as regimen A plus 4.5 MIU/day rIL-2 s.c. on days 8–12 and
15–19. Treatment was repeated every 3 weeks for three cycles. A total of 33 patients were enrolled in the study; 30 were evaluable
for toxicity and 28 for response. Seventeen patients were assigned to group A and 16 were assigned to group B. Three patients
(20%) of group A and 4 (31%) of group B had a complete response, 9 patients (60%) of group A and 6 (46%) of group B had a
partial response, with an overall response rate of 12 patients (80%) for group A and 10 patients (77%) for group B. Two patients
(13%) of group A and 3 patients (23%) group B had stable disease; 1 patient (7%) of group A had progressive disease. Thus,
there was not a statistically significant difference in response rate between the two groups and therefore there was no benefit
from the addition of immunotherapy with rIL-2 to the standard chemotherapy. Both regimens were well tolerated. There were
2 toxic deaths (6.7%), 1 from hematological causes in group A and 1 from cardiac causes in group B. Myelosuppression and gastrointestinal
toxicity, mainly nausea/vomiting and stomatitis, were the most frequent toxicities. The calculated number of patients for
the sample has not yet been reached; however, the projection of our present results suggests that it is highly improbable
that a clinically significant difference between the two treatment groups will be observed even if the calculated patient
sample size is achieved.
Received: 9 April 1998 / Accepted: 30 June 1998 相似文献
927.
Calabrò Marco Mandelli Laura Crisafulli Concetta Porcelli Stefano Albani Diego Politis Antonis Papadimitriou George N. Di Nicola Marco Janiri Luigi Colombo Roberto Martinotti Giovanni Bellomo Antonello Vieta Eduard Bonassi Stefano Frustaci Alessandra Ducci Giuseppe Landi Stefano Boccia Stefania Serretti Alessandro 《Molecular biology reports》2020,47(1):191-200
Molecular Biology Reports - Serotoninergic system is one of the most important neurotransmission systems investigated in the field of psychiatry. Extensive evidence reveals how alterations of this... 相似文献
928.
Manuela Morleo Simona Brillante Umberto Formisano Luigi Ferrante Fabrizia Carbone Daniela Iaconis Alessandro Palma Viviana Buonomo Angela Serena Maione Paolo Grumati Carmine Settembre Brunella Franco 《The EMBO journal》2021,40(4)
Autophagy is a lysosome‐dependent degradation pathway essential to maintain cellular homeostasis. Therefore, either defective or excessive autophagy may be detrimental for cells and tissues. The past decade was characterized by significant advances in molecular dissection of stimulatory autophagy inputs; however, our understanding of the mechanisms that restrain autophagy is far from complete. Here, we describe a negative feedback mechanism that limits autophagosome biogenesis based on the selective autophagy‐mediated degradation of ATG13, a component of the ULK1 autophagy initiation complex. We demonstrate that the centrosomal protein OFD1 acts as bona fide autophagy receptor for ATG13 via direct interaction with the Atg8/LC3/GABARAP family of proteins. We also show that patients with Oral‐Facial‐Digital type I syndrome, caused by mutations in the OFD1 gene, display excessive autophagy and that genetic inhibition of autophagy in a mouse model of the disease, significantly ameliorates polycystic kidney, a clinical manifestation of the disorder. Collectively, our data report the discovery of an autophagy self‐regulated mechanism and implicate dysregulated autophagy in the pathogenesis of renal cystic disease in mammals. 相似文献
929.
Marc Jubeau Alessandro Sartorio Pier Giulio Marinone Fiorenza Agosti Jacques Van Hoecke Kazunori Nosaka Nicola A Maffiuletti 《Journal of applied physiology》2008,104(1):75-81
This study aimed to compare voluntary and stimulated exercise for changes in muscle strength, growth hormone (GH), blood lactate, and markers of muscle damage. Nine healthy men had two leg press exercise bouts separated by 2 wk. In the first bout, the quadriceps muscles were stimulated by biphasic rectangular pulses (75 Hz, duration 400 mus, on-off ratio 6.25-20 s) with current amplitude being consistently increased throughout 40 contractions at maximal tolerable level. In the second bout, 40 voluntary isometric contractions were performed at the same leg press force output as the first bout. Maximal voluntary isometric strength was measured before and after the bouts, and serum GH and blood lactate concentrations were measured before, during, and after exercise. Serum creatine kinase (CK) activity and muscle soreness were assessed before, immediately after, and 24, 48, and 72 h after exercise. Maximal voluntary strength decreased significantly (P < 0.05) after both bouts, but the magnitude of the decrease was significantly (P < 0.05) greater for the stimulated contractions (-22%) compared with the voluntary contractions (-9%). Increases in serum GH and lactate concentrations were significantly (P < 0.05) larger after the stimulation compared with the voluntary exercise. Increases in serum CK activity and muscle soreness were also significantly (P < 0.05) greater for the stimulation than voluntary exercise. It was concluded that a single bout of electrical stimulation exercise resulted in greater GH response and muscle damage than voluntary exercise. 相似文献
930.
Grazeffe VS Tallarico Lde F Pinheiro Ade S Kawano T Suzuki MF Okazaki K Pereira CA Nakano E 《Mutation research》2008,654(1):58-63
The single cell gel electrophoresis or the comet assay was established in the freshwater snail Biomphalaria glabrata. For detecting DNA damage in circulating hemocytes, adult snails were irradiated with single doses of 2.5, 5, 10 and 20 Gy of (60)Co gamma radiation. Genotoxic effect of ionizing radiation was detected at all doses as a dose-related increase in DNA migration. Comet assay in B. glabrata demonstrated to be a simple, fast and reliable tool in the evaluation of genotoxic effects of environmental mutagens. 相似文献