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1.
Riccardo E. Marioni Lars Penke Gail Davies Jennifer E. Huffman Caroline Hayward Ian J. Deary 《Proceedings. Biological sciences / The Royal Society》2014,281(1781)
Human cognitive ability shows consistent, positive associations with fitness components across the life-course. Underlying genetic variation should therefore be depleted by selection, which is not observed. Genetic variation in general cognitive ability (intelligence) could be maintained by a mutation–selection balance, with rare variants contributing to its genetic architecture. This study examines the association between the total number of rare stop-gain/loss, splice and missense exonic variants and cognitive ability in childhood and old age in the same individuals. Exome array data were obtained in the Lothian Birth Cohorts of 1921 and 1936 (combined N = 1596). General cognitive ability was assessed at age 11 years and in late life (79 and 70 years, respectively) and was modelled against the total number of stop-gain/loss, splice, and missense exonic variants, with minor allele frequency less than or equal to 0.01, using linear regression adjusted for age and sex. In both cohorts and in both the childhood and late-life models, there were no significant associations between rare variant burden in the exome and cognitive ability that survived correction for multiple testing. Contrary to our a priori hypothesis, we observed no evidence for an association between the total number of rare exonic variants and either childhood cognitive ability or late-life cognitive ability. 相似文献
2.
Riccardo Montioli Carlotta Zamparelli Carla Borri Voltattorni Barbara Cellini 《The protein journal》2017,36(3):174-185
Human ornithine δ-aminotransferase (hOAT) (EC 2.6.1.13) is a mitochondrial pyridoxal 5′-phosphate (PLP)-dependent aminotransferase whose deficit is associated with gyrate atrophy, a rare autosomal recessive disorder causing progressive blindness and chorioretinal degeneration. Here, both the apo- and holo-form of recombinant hOAT were characterized by means of spectroscopic, kinetic, chromatographic and computational techniques. The results indicate that apo and holo-hOAT (a) show a similar tertiary structure, even if apo displays a more pronounced exposure of hydrophobic patches, (b) exhibit a tetrameric structure with a tetramer-dimer equilibrium dissociation constant about fivefold higher for the apoform with respect to the holoform, and (c) have apparent Tm values of 46 and 67?°C, respectively. Moreover, unlike holo-hOAT, apo-hOAT is prone to unfolding and aggregation under physiological conditions. We also identified Arg217 as an important hot-spot at the dimer–dimer interface of hOAT and demonstrated that the artificial dimeric variant R217A exhibits spectroscopic properties, Tm values and catalytic features similar to those of the tetrameric species. This finding indicates that the catalytic unit of hOAT is the dimer. However, under physiological conditions the apo-tetramer is slightly less prone to unfolding and aggregation than the apo-dimer. The possible implications of the data for the intracellular stability and regulation of hOAT are discussed. 相似文献
3.
Intrinsic processes are assumed to underlie life history expression and trade‐offs, but extrinsic inputs are theorised to shift trait expression and mask trade‐offs within species. Here, we explore application of this theory across species. We do this based on parentally induced embryo temperature as an extrinsic input, and mass‐specific embryo metabolism as an intrinsic process, underlying embryonic development rate. We found that embryonic metabolism followed intrinsic allometry rules among 49 songbird species from temperate and tropical sites. Extrinsic inputs via parentally induced temperatures explained the majority of variation in development rates and masked a relationship with metabolism; metabolism explained a minor proportion of the variation in development rates among species, and only after accounting for temperature effects. We discuss evidence that temperature further obscures the expected interspecific trade‐off between development rate and offspring quality. These results demonstrate the importance of considering extrinsic inputs to trait expression and trade‐offs across species. 相似文献
4.
Marina Pitto Anna Miglio Gunther Kirschner Alberta Leon Riccardo Ghidoni 《Neurochemical research》1991,16(11):1187-1192
Semisynthetic single-chain GM1 derivatives containing N-acetyl-sphingosine (LIGA4) or N-dichloroacetyl-sphingosine (LIGA20) were recently reported to exert strong protection against glutamate-induced neuronal death in primary cultures of cerebellar granule cells. Elucidation of the molecular mechanism underlying the evoked effect requires knowledge of the metabolic fate of such molecules in the same cultured cells. For this, LIGA4 and LIGA20 were made radioactive on the long chain base moiety and added to cerebellar granule cells in culture in parallel with GM1 ganglioside. The metabolic fate was then investigated. It was found that both these molecules were easily taken up by the cells and promptly metabolized in a fashion qualitatively similar to that of control GM1. The highest amount processed was attributed to the different aggregation properties of LIGAs in solution. Among metabolites, higher accumulation of the single-chain ceramide residues was found after LIGA administration. Interestingly, sphingomyelin was generated, regardless the added compound, suggesting a recycling of the free long chain base. 相似文献
5.
Fragments of ascidian eggs, but at random in any plane and ranging in size from 10 to 90% of the total egg volume, displayed the electrical characteristics of the intact egg, having a resting potential of -86 mV and giving rise to an action potential upon stimulation by electrical current injection. Following insemination, the fragments generated fertilization potentials, comparable to those of intact eggs, although the repolarization phase was shorter. Our data show that there are sufficient ion channels throughout the egg surface to generate action potentials and fertilization potentials in excised egg fragments, irrespective of their global origin. Furthermore, the fertilizing spermatozoon is capable of activating fertilization channels in areas of the egg plasma membrane not destined for sperm entry. 相似文献
6.
Christina Brahe Isabella Velonà Gerrit van der Steege Stefania Zappata Anneke Y. van de Veen Jan Osinga Carli M. J. Tops Riccardo Fodde P. Meera Khan Charles H. C. M. Buys Giovanni Neri 《Human genetics》1994,93(5):494-501
The locus responsible for the childhood-onset proximal spinal muscular atrophies (SMA) has recently been mapped to an area of 2–3 Mb in the region q12–13.3 of chromosome 5. We have used a series of radiation hybrids (RHs) containing distinct parts of the SMA region as defined by reference markers. A cosmid library was constructed from one RH. Thirteen clones were isolated and five of these were mapped within the SMA region. Both RH mapping and fluorescence in situ hybridization analysis showed that two clones map in the region between loci D5S125 and D5S351. One of the cosmids contains expressed sequences. Polymorphic dinucleotide repeats were identified in both clones and used for segregation analysis of key recombinant SMA families. One recombination between the SMA locus and the new marker 9Ic (D5S685) indicates that 9Ic is probably the closest distal marker. The absence of recombination between the SMA locus and marker Fc (D5S684) suggests that Fc is located close to the disease gene. These new loci should refine linkage analysis in SMA family studies and may facilitate the isolation of the disease gene. 相似文献
7.
Riccardo Pierantoni Mauro D'Antonio Silvia Fasano 《Environmental Biology of Fishes》1993,38(1-3):187-196
Synopsis The tetrapod hypothalamus-pars distalis axis contains a blood portal system. Contrarily, elasmobranchs appear to lack a direct vascular supply from the hypothalamus to the ventral lobe of the pituitary where gonadotropic activity resides. The hypothalamus contains GnRH immunoreactivity and GnRH causes an increase in plasma gonadal steroids, perhaps via ventral lobe stimulation. Therefore, the question arises as to how GnRH reaches the pituitary. We suggest that the general circulation route might be practicable. Indeed, in the plasma of the electric ray,Torpedo marmorata, a major early eluting form has been detected using high performance liquid chromatography coupled with region specific radioimmunoassay. The presence of GnRH in the blood may allow the molecule to reach the gonads and to act there by direct mechanisms. Intragonadal levels of steroids may have a paracrine and/or autocrine role in the regulation of steroidogenesis in the testis and in the development f specific germinal cell stages. Particularly, the zonated morphology of the testis supports the concept of a diverse environment for different spermatogenic stages. Finally, gonadal steroids may feed back to affect pituitary activity. 相似文献
8.
Riccardo Fedeli Andrea Vannini Martina Grattacaso Stefano Loppi 《The Annals of applied biology》2023,183(2):135-140
Potato is the fourth most widely consumed staple food in the world. This study investigated the effectiveness of 0.2% wood distillate (WD), a biostimulant derived from the pyrolysis of waste plant biomass, in boosting the nutritional quality of potato tubers. The results showed that application of WD significantly increased the content of soluble sugars (sucrose +56.3%; glucose +44.9%; fructose +62.2%), starch (+35.1%) and total carbohydrates (+16.8%). Antioxidants (total antioxidant power, polyphenols, flavonoids) and most mineral elements (K, Mg, Ca, Na, Fe, Zn) were not affected. A lower content of Cu (−17.8%) and P (−24.5%) was found in WD-treated potato. 相似文献
9.
Stefania Motta Marcello Monti Silvia Sesana Ruggero Caputo Stephana Carelli Riccardo Ghidoni 《生物化学与生物物理学报:疾病的分子基础》1993,1182(2):147-151
This paper investigates the ceramide composition of the psoriatic scale compared with that of normal human SC. A method was optimalized, based on TLC separation followed by densitometry, allowing the provision of good resolution and quantification of ceramide fractions from both normal and pathological specimens. Seven ceramide fractions were isolated and submitted to compositional analysis. The obtained results suggested a revisitation of previous ceramide designation. Therefore a simple classification is suggested, based on grouping ceramides carrying structural similarities under common codes. According to these rules, ceramides were grouped into five classes designated as: (1) Cer[EOS], which contains ester-linked fatty acids, ω-OH fatty acids and sphingosines; (2) Cer[NS], which contains non-OH fatty acids and sphingosines; (3) Cer[NP], which contains non-OH fatty acids and phytosphingosines; (4) Cer[AS], which contains α-OH fatty acids and sphingosines; (5) Cer[AP], which contains α-OH fatty acids and phytosphingosines. Analysis of ceramides from the psoriatic scale, compared to those from normal human SC, resulted in an impairment of the Cer[EOS] content as well as of the ceramides containing phytosphingosine, with concurrent increase in ceramides containing sphingosine, being the total amount maintained identical. Since one of the suggested pathways for phytosphingosine biosynthesis involves the water addition to the corresponding sphingosine double bond, we can speculate that the observed alterarion is due to a deranged water bioavailability, associated with psoriaris. 相似文献
10.