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1.
We have isolated the delta-globin gene of the New-World spider monkey,
Ateles geoffroyi, and compared its nucleotide sequence with those of other
primate delta- and beta-globin genes. Among primate delta-globin genes, the
rate of nonsynonymous substitutions is much less than the rate of
synonymous substitutions. This suggests that primate delta- globin genes
may remain under evolutionary conservation, perhaps because hemoglobin A2
has an as yet unknown physiological importance.
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2.
3.
To determine whether D-penicillamine, known to reduce fibrosis in irradiated rat lung (W. F. Ward, A. Shih - Hoellwarth , and R. D. Tuttle , Radiology 146, 533-537, 1983), also ameliorates radiation injury in the pulmonary endothelium, we measured angiotensin-converting enzyme (ACE) activity, plasminogen activator (PLA) activity, and prostacyclin (PGI2) production in the lungs of penicillamine-treated (10 mg/day, po, continuous after irradiation) and untreated rats from 2 weeks to 6 months after a single dose of 25 Gy of 60Co gamma rays to the right hemithorax. Both ACE and PLA activity in the irradiated right lung of untreated rats decreased dramatically between the 1st and 2nd months after exposure, then reached a plateau through 6 months at approximately 25 and 50% of the normal level, respectively. For the first 2 months after irradiation, penicillamine-treated animals exhibited significantly (P less than 0.05) higher activities of both ACE and PLA than did untreated rats. From 3 to 6 months after irradiation, however, the only significant drug effect on these enzymes was a 25% increase in PLA activity at 6 months. PGI2 production by the irradiated lung of untreated rats increased continuously, and at 6 months was approximately 10 times higher than normal. Penicillamine significantly (P less than 0.05) reduced this hypersecretion, and at 6 months after irradiation, PGI2 production by the lungs of drug-treated rats was only half that of untreated animals. In contrast, the drug had no significant effect on enzyme activities in the lungs of sham-irradiated rats. Thus the antifibrotic agent D-penicillamine delays the onset of radiation-induced enzyme dysfunction in the pulmonary endothelium. In addition at 6 months after irradiation, the lungs of penicillamine-treated rats exhibit 25% more PLA activity and only half as severe a hypersecretion of PGI2 as do the lungs of untreated animals. The drug is most effective in ameliorating endothelial damage during the first 2 months after irradiation, preceding the development of interstitial fibrosis. However, the effect of this penicillamine regimen on pulmonary endothelial function is not as large as its effect on collagen accumulation in irradiated rat lung. 相似文献
4.
Matteo Molteni Davide Magatti Barbara Cardinali Mattia Rocco Fabio Ferri 《Biophysical journal》2013,104(5):1160-1169
The average pore size ξ0 of filamentous networks assembled from biological macromolecules is one of the most important physical parameters affecting their biological functions. Modern optical methods, such as confocal microscopy, can noninvasively image such networks, but extracting a quantitative estimate of ξ0 is a nontrivial task. We present here a fast and simple method based on a two-dimensional bubble approach, which works by analyzing one by one the (thresholded) images of a series of three-dimensional thin data stacks. No skeletonization or reconstruction of the full geometry of the entire network is required. The method was validated by using many isotropic in silico generated networks of different structures, morphologies, and concentrations. For each type of network, the method provides accurate estimates (a few percent) of the average and the standard deviation of the three-dimensional distribution of the pore sizes, defined as the diameters of the largest spheres that can be fit into the pore zones of the entire gel volume. When applied to the analysis of real confocal microscopy images taken on fibrin gels, the method provides an estimate of ξ0 consistent with results from elastic light scattering data. 相似文献
5.
Wang C Youssef J Saran B Rothberg PG Cunningham ML Molteni A Badr M 《Molecular and cellular biochemistry》1999,201(1-2):25-32
Rotenone decreases the incidence of hepatocellular carcinoma and lowers rates of hepatocellular proliferation. In an effort to delineate mechanisms involved, the in vivo effect of rotenone on liver mitochondrial metabolism, apoptotic machinery as well as elements of the hepatic signal transduction pathways were investigated. Mitochondria from livers of male B6C3F1 mice fed a standard diet containing 600 ppm rotenone for 7 days were uncoupled or inhibited when succinate or glutamate plus malate were used as the substrate, respectively. These livers also showed a significant increase in apoptosis compared with control livers. Furthermore, rotenone increased the expression of c-myc mRNA to 5-fold of control values within 3 days, an effect which was still observed (3-fold) after 7 days. Levels of p53 mRNA were also increased 3-fold after 1 day, but declined to control levels by 7 days. Rotenone also caused a transient, yet marked increase in liver particulate glyceraldehyde phosphate dehydrogenase (GAPDH) protein expression, while it did not alter the expression of the cytosolic form of the enzyme. Conversely, mRNA of the proto-oncogene H-ras showed a decline of 35% after 3 days of rotenone treatment, and remained diminished for the duration of the experiment. These data suggest that rotenone may act as an anticancer agent by diminishing mitochondrial bioenergetics which prevents basal hepatocyte proliferation and lowers the threshold for liver cells with DNA damage to undergo apoptosis. 相似文献
6.
3D structure of Sulfolobus solfataricus carboxypeptidase developed by molecular modeling is confirmed by site-directed mutagenesis and small angle X-ray scattering
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Occhipinti E Martelli PL Spinozzi F Corsi F Formantici C Molteni L Amenitsch H Mariani P Tortora P Casadio R 《Biophysical journal》2003,85(2):1165-1175
Sulfolobus solfataricus carboxypeptidase (CPSso) is a thermostable zinc-metalloenzyme with a M(r) of 43,000. Taking into account the experimentally determined zinc content of one ion per subunit, we developed two alternative 3D models, starting from the available structures of Thermoactinomyces vulgaris carboxypeptidase (Model A) and Pseudomonas carboxypeptidase G2 (Model B). The former enzyme is monomeric and has one metal ion in the active site, while the latter is dimeric and has two bound zinc ions. The two models were computed by exploiting the structural alignment of the one zinc- with the two zinc-containing active sites of the two templates, and with a threading procedure. Both computed structures resembled the respective template, with only one bound zinc with tetrahedric coordination in the active site. With these models, two different quaternary structures can be modeled: one using Model A with a hexameric symmetry, the other from Model B with a tetrameric symmetry. Mutagenesis experiments directed toward the residues putatively involved in metal chelation in either of the models disproved Model A and supported Model B, in which the metal-binding site comprises His(108), Asp(109), and His(168). We also identified Glu(142) as the acidic residue interacting with the water molecule occupying the fourth chelation site. Furthermore, the overall fold and the oligomeric structure of the molecule was validated by small angle x-ray scattering (SAXS). An ab initio original approach was used to reconstruct the shape of the CPSso in solution from the experimental curves. The results clearly support a tetrameric structure. The Monte Carlo method was then used to compare the crystallographic coordinates of the possible quaternary structures for CPSso with the SAXS profiles. The fitting procedure showed that only the model built using the Pseudomonas carboxypeptidase G2 structure as a template fitted the experimental data. 相似文献
7.
Engler MM Engler MB Pierson DM Molteni LB Molteni A 《Experimental biology and medicine (Maywood, N.J.)》2003,228(3):299-307
Previous studies have shown that docosahexaenoic acid (DHA) has an antihypertensive effect in spontaneously hypertensive rats (SHR). To investigate possible mechanisms for this effect, vascular pathology and reactivity were determined in SHR treated with dietary DHA. SHR (7 weeks) were fed a purified diet with either a combination of corn/soybean oils or a DHA-enriched oil for 6 weeks. Histological evaluation of heart tissue, aorta, coronary, and renal arteries was performed. Vascular responses were determined in isolated aortic rings. Contractile responses to agonists, including norepinephrine (10(-9) to 10(-4) M), potassium chloride (5-55 mM), and angiotensin II (5 x 10(-7) M) were assessed. Vasorelaxant responses to acetylcholine (10(-9) to 10 (-4) M), sodium nitroprusside (10(-9) to 10(-6) M), papaverine (10(-5) to 10(-4) M), and methoxyverapamil (D600, 1-100 microM) were determined. DHA-fed SHR had significantly reduced blood pressure (P < 0.001) and vascular wall thicknesses in the coronary, thoracic, and abdominal aorta compared with controls (P < 0.05) Contractile responses to agonists mediated by receptor stimulation and potassium depolarization were not altered in DHA-fed SHR. Endothelial-dependent relaxations to acetylcholine were not altered which suggests endothelial-derived nitric oxide production/release is not affected by dietary DHA. Other mechanisms of vascular relaxation, including intracellular cyclic nucleotides, cGMP, and cAMP were not altered by dietary DHA because aortic relaxant responses to sodium nitroprusside and papaverine were similar in control and DHA-fed SHR. No significant differences were seen in relaxant responses to the calcium channel blocker, D600, or contractile responses to norepinephrine in the absence of extracellular calcium. These results suggest that dietary DHA does not affect mechanisms related to extracellular calcium channels or intracellular calcium mobilization. Moreover, the contractile and vasorelaxant responses are not differentially altered with dietary DHA in this in vivo SHR model. The findings demonstrate that dietary DHA reduces systolic blood pressure and vascular wall thickness in SHR. This may contribute to decrease arterial stiffness and pulse pressure, in addition to the antihypertensive properties of DHA. The antihypertensive properties of DHA are not related to alterations in vascular responses. 相似文献
8.
Iannuzzi L Molteni L Di Meo GP Perucatti A Lorenzi L Incarnato D De Giovanni A Succi G Gustavsson I 《Cytogenetics and cell genetics》2001,94(3-4):225-228
Three hundred and twenty-two (264 males and 58 females), randomly sampled Grey Alpine cattle individuals from Northeastern Italy, were investigated cytogenetically by both conventional chromosome staining and R-banding. Two hundred and eighty-one (87%) individuals had a normal karyotype and 41 (13%) carried chromosomal aberrations such as (a) rob(1;29) in two individuals, (b) rob(26;29) in 36 individuals, (c) XX/XY-chimerism in two individuals, and (d) an abnormally long chromosome in one individual. All these aberrations except (d) have been described before. GBG-, RBG-, CBA-banding and sequential GBG/CBA- and RBG/CBA-banding techniques revealed that the abnormally long chromosome was the result of a reciprocal translocation between chromosomes 1 (q21-->qter) and 5 (q11-->q33), as confirmed also by chromosome painting with human chromosome 3 and 12 probes. The dam of the carrier bull carried the same translocation, while the grandam showed a normal karyotype. Since the sire of the dam was not available for study, no conclusion about the origin of the chromosome translocation could be drawn. The carrier bull was eliminated because of poor fertility. The dam had three other calves, which all were chromosomally normal. On average the dam had to be served 2.5 times (breed average was 1.2) to be in calf. 相似文献
9.
Francesco Cerritelli Gianfranco Pizzolorusso Cinzia Renzetti Vincenzo Cozzolino Marianna D’Orazio Mariacristina Lupacchini Benedetta Marinelli Alessandro Accorsi Chiara Lucci Jenny Lancellotti Silvia Ballabio Carola Castelli Daniela Molteni Roberto Besana Lucia Tubaldi Francesco Paolo Perri Paola Fusilli Carmine D’Incecco Gina Barlafante 《PloS one》2015,10(5)
BackgroundDespite some preliminary evidence, it is still largely unknown whether osteopathic manipulative treatment improves preterm clinical outcomes.ResultsA total of 695 newborns were randomly assigned to either the study group (n= 352) or the control group (n=343). A statistical significant difference was observed between the two groups for the primary outcome (13.8 and 17.5 days for the study and control group respectively, p<0.001, effect size: 0.31). Multivariate analysis showed a reduction of the length of stay of 3.9 days (95% CI -5.5 to -2.3, p<0.001). Furthermore, there were significant reductions with treatment as compared to usual care in cost (difference between study and control group: 1,586.01€; 95% CI 1,087.18 to 6,277.28; p<0.001) but not in daily weight gain. There were no complications associated to the intervention.ConclusionsOsteopathic treatment reduced significantly the number of days of hospitalization and is cost-effective on a large cohort of preterm infants. 相似文献
10.
Alessandro Battaggia Alberto Donzelli Maria Font Davide Molteni Antonio Galvano 《PloS one》2015,10(4)