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41.
Lorenzo Minchiotti Monica Galliano Gianluca Caridi Ulrich Kragh-Hansen Theodore Peters Jr. 《Biochimica et Biophysica Acta (BBA)/General Subjects》2013
Background
DNA and mRNA sequencing of the coding regions of the human albumin gene (ALB) and of its intron/exon junctions has revealed twenty-one different molecular defects causing congenital analbuminaemia (CAA).Scope of review
To describe the mutations in molecular terms and to present the current knowledge about the most important biochemical and clinical effects of CAA.Major conclusions
CAA is rare, but its frequency seems to be significantly higher in restricted and minimally admixed populations. The condition affects especially the lipid metabolism but apart from a possible increased risk for atherosclerotic complications, it is generally associated with mild clinical symptoms in adults. By contrast, several reports indicate that analbuminaemic individuals may be at risk during the perinatal and childhood periods, in which they seem to show increased morbidity and mortality. The twenty-one causative defects include seven nonsense mutations, seven changes affecting splicing, five frame-shift/deletions, one frame-shift/insertion and one mutation in the start codon. These results indicate that the trait is an allelic heterogeneous disorder caused by homozygous (nineteen cases) or compound heterozygous (single case) inheritance of defects. Most mutations are unique, but one, named Kayseri, is responsible for about half of the known cases.General significance
Study of the defects in the ALB resulting in CAA allows the identification of “hot spot” regions and contributes to understanding the molecular mechanism underlying the trait. Such studies could also give molecular information about different aspects of ALB regulation and shed light on the regulatory mechanisms involved in the synthesis of the protein. This article is part of a Special Issue entitled Serum Albumin. 相似文献42.
43.
Marcela Simontacchi Carlos García-Mata Carlos G. Bartoli Guillermo E. Santa-María Lorenzo Lamattina 《Plant cell reports》2013,32(6):853-866
Nitric oxide (NO) is a small gaseous molecule, with a free radical nature that allows it to participate in a wide spectrum of biologically important reactions. NO is an endogenous product in plants, where different biosynthetic pathways have been proposed. First known in animals as a signaling molecule in cardiovascular and nervous systems, it has turned up to be an essential component for a wide variety of hormone-regulated processes in plants. Adaptation of plants to a changing environment involves a panoply of processes, which include the control of CO2 fixation and water loss through stomatal closure, rearrangements of root architecture as well as growth restriction. The regulation of these processes requires the concerted action of several phytohormones, as well as the participation of the ubiquitous molecule NO. This review analyzes the role of NO in relation to the signaling pathways involved in stomatal movement, plant growth and senescence, in the frame of its interaction with abscisic acid, auxins, gibberellins, and ethylene. 相似文献
44.
Lorenzo Tonetti Francesco Pasquini Marco Fabbri Massimiliano Belluzzi 《Chronobiology international》2013,30(1):145-153
The present study aimed to compare two commercially available actigraphs, with a concurrent polysomnographic (PSG) recording. Twelve healthy volunteers (six women; age range 19–28 yrs) simultaneously wore the Basic Mini‐Motionlogger® and Actiwatch® for seven overnight polysomnographic recordings. Comparisons of the following sleep measures were focused on: sleep onset latency (SOL), total sleep time, wake after sleep onset, and sleep efficiency. Both devices underestimated SOL in comparison to PSG, but they had similar performance compared to PSG for the other sleep measures. A limit of the study is that the results can be only generalized to healthy young subjects. 相似文献
45.
Mounting evidence indicates that genital HSV-2 infection may increase susceptibility to HIV infection and that co-infection may increase infectiousness. Accordingly, antiviral treatment of people with HSV-2 may mitigate the incidence of HIV in populations where both pathogens occur. To better understand the epidemiological synergy between HIV and HSV-2, we formulate a deterministic compartmental model that describes the transmission dynamics of these pathogens. Unlike earlier models, ours incorporates gender and heterogeneous mixing between activity groups. We derive explicit expressions for the reproduction numbers of HSV-2 and HIV, as well as the invasion reproduction numbers via next generation matrices. A qualitative analysis of the system includes the local and global behavior of the model. Simulations reinforce these analytical results and demonstrate epidemiological synergy between HSV-2 and HIV. In particular, numerical results show that HSV-2 favors the invasion of HIV, may dramatically increase the peak as well as reducing the time-to-peak of HIV prevalence, and almost certainly has exacerbated HIV epidemics. The potential population-level impact of HSV-2 on HIV is demonstrated by calculating the fraction of HIV infections attributable to HSV-2 and the difference between HIV prevalence in the presence and absence of HSV-2. The potential impact of treating people with HSV-2 on HIV control is demonstrated by comparing HIV prevalence with and without HSV-2 therapy. Most importantly, we illustrate that the aforementioned aspects of the population dynamics can be significantly influenced by the sexual structure of the population. 相似文献
46.
R. M. González-Rodríguez R. Serrato J. Molina C. E. Aragón V. Olalde L. E. Pulido B. Dibut J. C. Lorenzo 《Acta Physiologiae Plantarum》2013,35(12):3483-3487
This study highlights some of the effects of the application of Azotobacter chroococcum (INIFAT5 strain) on in vitro-pineapple plantlets during acclimatization. The bacteria were sprayed immediately after transplanting to the ex vitro environment; the plants were then sprayed every 4 week. Subsequently (4 months) the evaluated variables included plantlet fresh and dry weights, leaf and root lengths, and composition of minerals, amino-acids, carbohydrates and proteins. Photosynthesis indicators were also evaluated. Significant effects of the application of Azotobacter over pineapple plantlets during acclimatization were observed in the mineral, amino-acid, carbohydrate and protein levels, as well as, in the photosynthesis indicators. Contrastingly, plant growth parameters showed modest increases caused by the bacteria, although they were statistically significant. Looking into specific minerals, the following significant effects of Azotobacter should be highlighted: increased levels of nitrogen, phosphorous, potassium, magnesium, copper and zinc. Moreover, contents of all amino-acids recorded showed significant increases in their levels in sprayed plantlets. Carbohydrates were also increased in leaves of plantlets bio-fertilized with the bacteria, mainly sucrose and fructose. Chlorophyll b levels were also significantly increased by Azotobacter. The biofertilizer did not modify levels of calcium, iron or manganese. 相似文献
47.
Adrián Pablos Ignacio Martínez Carlos Lorenzo Ana Gracia Nohemi Sala Juan Luis Arsuaga 《Journal of human evolution》2013
Here we present and describe comparatively 25 talus bones from the Middle Pleistocene site of the Sima de los Huesos (SH) (Sierra de Atapuerca, Burgos, Spain). These tali belong to 14 individuals (11 adult and three immature). Although variation among Middle and Late Pleistocene tali tends to be subtle, this study has identified unique morphological characteristics of the SH tali. They are vertically shorter than those of Late Pleistocene Homo sapiens, and show a shorter head and a broader lateral malleolar facet than all of the samples. Moreover, a few shared characters with Neanderthals are consistent with the hypothesis that the SH population and Neanderthals are sister groups. These shared characters are a broad lateral malleolar facet, a trochlear height intermediate between modern humans and Late Pleistocene H. sapiens, and a short middle calcaneal facet. It has been possible to propose sex assignment for the SH tali based on their size. Stature estimates based on these fossils give a mean stature of 174.4 cm for males and 161.9 cm for females, similar to that obtained based on the long bones from this same site. 相似文献
48.
Claudio Battilocchio Giovanna Poce Salvatore Alfonso Giulio Cesare Porretta Sara Consalvi Lidia Sautebin Simona Pace Antonietta Rossi Carla Ghelardini Lorenzo Di Cesare Mannelli Silvia Schenone Antonio Giordani Luigia Di Francesco Paola Patrignani Mariangela Biava 《Bioorganic & medicinal chemistry》2013,21(13):3695-3701
We report the synthesis and bio-pharmacological evaluation of a class of pyrrole derivatives featuring a small appendage fragment (carbaldehyde, oxime, nitrile) on the central core. Compound 1c proved to be extremely effective in vivo, showing an interesting anti-nociceptic profile that is comparable to reference compounds already marketed, hence representing a great stimulus for a further improvement of this class of molecules. 相似文献
49.
In a recent paper published in Cell, He and colleagues reported the identification and functional characterization of Beclin 2, a mammal-specific homolog of the evolutionarily conserved autophagy-regulatory and oncosuppressive factor Beclin 1. In spite of a non-negligible degree of sequence identity, Beclin 1 and Beclin 2 differ from each other in multiple aspects, including their functional profile as well as the genomic organization of the respective loci.Originally identified as a BCL-2-interacting partner capable of protecting mice from viral encephalitis1, Beclin 1 — the mammalian ortholog of yeast Atg6 — is nowadays well known as a core component of the class III phosphoinosite-3-kinase (PI3K) enzymatic complex that initiates the formation of autophagosomes in the course of macroautophagy (hereafter referred to as autophagy)2. Presumably owing to the critical function of autophagy in embryonic development, mice lacking both copies of the Beclin 1-coding gene (Becn1) die early during embryogenesis. Moreover, Becn1+/− mice suffer from a high incidence of spontaneous tumors, indicating that Beclin 1 acts as a haploinsufficient tumor suppressor3. At least in part, this reflects the central role that autophagy plays in the maintenance of intracellular homeostasis. Indeed, baseline levels of autophagy mediate the removal of various cytoplasmic entities that might favor oncogenesis, including damaged mitochondria and protein aggregates4. Conversely, established neoplasms often harness the cytoprotective functions of autophagy to their own benefit2. The pathophysiological relevance of autophagy is not limited to cancer, but extends to a large panel of human diseases, including neurodegenerative, cardiovascular and infectious conditions5. Thus, during the last decade autophagy-regulatory signaling pathways have been intensively investigated.Until now, Beclin 1 was considered as the only Beclin encoded by the mammalian genome, sharing some degree of structural homology with so-called “BH3-only” proteins, pro-apoptotic members of the BCL-2 family that are involved in the activation of cell death in response to stress6. In a recent paper published in Cell, the research group led by Beth Levine7 identified a human and a mouse protein sharing 57% and 44% sequence identity with human and mouse Beclin 1, respectively, de facto unveiling the existence of an additional, mammal-specific ortholog of Atg6, Beclin 2. The mouse Beclin 2 mRNA was detected in multiple organs including the brain, skeletal muscle, placenta, thymus and uterus, as was the human protein in both fetal and adult brain tissues. These data demonstrate that the current classification of mouse and human Beclin 2-encoding genes (i.e., and NG_022940) as pseudogenes is incorrect.The knockdown of Beclin 2 reduced several manifestations of basal or starvation-induced autophagy in cultured mammalian cells, including the degradation of the autophagic substrate p62, the aggregation of a fluorescent form of LC3 into cytoplasmic dots and the lipidation of endogenous LC3. All such effects, which were not due to an increased autophagosomal turnover (as verified in the presence of the lysosomal inhibitor bafilomycin A1), could be rescued upon the transgene-driven expression of a non-interferable Beclin 2 variant. Thus, similar to Beclin 1, Beclin 2 regulates autophagy NG_0284517. In fact, Beclin 2 turned out to physically interact with several (but not all) components of the class III PI3K complex organized around Beclin 1, including the catalytic subunit VPS34 as well as the regulatory factors ATG14, AMBRA1 and UVRAG, but not RUBICON (Figure 1A). Beclin 2 also appeared to share with Beclin 1 the ability to bind BCL-2, although only the latter gets dissociated from such an interaction in the course of stress-induced autophagy7,8. As the greatest divergence between mammalian Beclins involves their N terminus, He and colleagues employed the N-terminal domain of Beclin 2 as a bait in a yeast two-hybrid screen, and identified G protein-coupled receptor (GPCR)-associated sorting protein 1 (GASP1) as a Beclin 2-specific interactor. Thus, similar to GASP1 (but not to Beclin 1), Beclin 2 was required for the agonist-induced lysosomal degradation of a subset of GPCRs including opioid receptor δ1 (DOR) and cannabinoid receptor 1 (CB1R). Importantly, such an activity, but not the capacity of Beclin 2 to regulate autophagic responses, appears to rely on the physical interaction between Beclin 2 and GASP1.Open in a separate windowFigure 1Common and divergent functions of mammalian Beclins. Specificity of the main interactors (A) and functions (B) ascribed to mammalian Beclin 1 and Beclin 2 to date. GPCR, G protein-coupled receptor; RTK, receptor tyrosine kinase.To obtain insights into the physiological functions of Beclin 2, He and colleagues attempted to generate Becn2−/− mice, finding that these animals survived embryonic and early post-natal development at sub-Mendelian rates (approximately 4%). Not only Becn2+/− and Becn2−/− mouse embryonic fibroblasts, but also the brain of Becn2+/− animals exhibited significant autophagic defects, corroborating the role of Beclin 2 in the regulation of autophagy in vivo. Moreover, these genotypes were associated with increased basal levels of multiple GPCRs, including CB1R and dopamine receptor D2 (DRD2)7. In line with the notion that increased CB1R signaling accrues food intake and hence favors obesity and insulin resistance, while pharmacological or genetic CB1R inhibition has opposite effects9, Becn2+/− mice accumulated more weight than their wild-type littermates in response to a standard (as well as to a high-fat) diet. At odds with their Becn1+/− counterparts, Becn2+/− mice also exhibited impaired glucose tolerance and decreased insulin sensitivity, two effects that could be reverted by a chemical CB1R antagonist7. Taken together, these data demonstrate that besides regulating autophagy, Beclin 2 plays a unique role in glucose metabolism.Beclin 1 is known to regulate various processes other than autophagy, including vacuolar protein sorting and the degradation of specific growth factor receptors10. Thus, in spite of 44% - 57% sequence identity, the two mammalian Beclins described to date are relatively different from each other, exhibiting functional profiles that overlap to a limited degree (Figure 1B). Interestingly, He and colleagues have previously shown that defects in stimulus-induced autophagy (including those introduced by the Becn1+/− genotype) are coupled to decreased endurance and altered glucose metabolism during acute exercise, as well as with an impaired capacity of training to protect mice against diet-induced glucose intolerance8. Part of these phenomena were shown to reflect defects in the AMP-activated protein kinase (AMPK)-dependent exposure of glucose transporters on the plasma membrane of skeletal muscle cells. It is therefore tempting to speculate that the metabolic phenotype of Becn2+/− may in part originate from peripheral defects in glucose handling linked to autophagy. Thus, although the force driving the divergence of mammalian Beclins remains to be elucidated, it may reflect the need for an integrated regulation of central and peripheral mechanisms of metabolic homeostasis. Further studies are required to address this hypothesis. 相似文献
50.
Claudio Tabolacci Stefania Rossi Alessandro Lentini Bruno Provenzano Lorenzo Turcano Francesco Facchiano Simone Beninati 《Amino acids》2013,44(1):293-300
Aloin, a natural anthracycline from aloe plant, is a hydroxyanthraquinone derivative shown to have antitumor properties. This study demonstrated that aloin exerted inhibition of cell proliferation, adhesion and invasion abilities of B16-F10 melanoma cells under non-cytotoxic concentrations. Furthermore, aloin induced melanoma cell differentiation through the enhancement of melanogenesis and transglutaminase activity. To improve the growth-inhibiting effect of anticancer agents, we found that the combined treatment of cells with aloin and low doses of cisplatin increases the antiproliferative activity of aloin. The results suggest that aloin possesses antineoplastic and antimetastatic properties, exerted likely through the induction of melanoma cell differentiation. 相似文献