Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 69
Filtrar
Mais filtros

País/Região como assunto
Tipo de documento
Intervalo de ano de publicação
1.
Proc Natl Acad Sci U S A ; 121(42): e2321342121, 2024 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-39374395

RESUMO

Carbonate minerals are of particular interest in paleoenvironmental research as they are an integral part of the carbon and water cycles, both of which are relevant to habitability. Given that these cycles are less constrained on Mars than they are on Earth, the identification of carbonates has been a point of emphasis for rover missions. Here, we present carbon (δ13C) and oxygen (δ18O) isotope data from four carbonates encountered by the Curiosity rover within the Gale crater. The carbon isotope values range from 72 ± 2‰ to 110 ± 3‰ Vienna Pee Dee Belemnite while the oxygen isotope values span from 59 ± 4‰ to 91 ± 4‰ Vienna Standard Mean Ocean Water (1 SE uncertainties). Notably, these values are isotopically heavy (13C- and 18O-enriched) relative to nearly every other Martian material. The extreme isotopic difference between the carbonates and other carbon- and oxygen-rich reservoirs on Mars cannot be reconciled by standard equilibrium carbonate-CO2 fractionation, thus requiring an alternative process during or prior to carbonate formation. This paper explores two processes capable of contributing to the isotopic enrichments: 1) evaporative-driven Rayleigh distillation and 2) kinetic isotope effects related to cryogenic precipitation. In isolation, each process cannot reproduce the observed carbonate isotope values; however, a combination of these processes represents the most likely source for the extreme isotopic enrichments.

2.
Proc Natl Acad Sci U S A ; 119(4)2022 01 25.
Artigo em Inglês | MEDLINE | ID: mdl-35042808

RESUMO

Obtaining carbon isotopic information for organic carbon from Martian sediments has long been a goal of planetary science, as it has the potential to elucidate the origin of such carbon and aspects of Martian carbon cycling. Carbon isotopic values (δ13CVPDB) of the methane released during pyrolysis of 24 powder samples at Gale crater, Mars, show a high degree of variation (-137 ± 8‰ to +22 ± 10‰) when measured by the tunable laser spectrometer portion of the Sample Analysis at Mars instrument suite during evolved gas analysis. Included in these data are 10 measured δ13C values less than -70‰ found for six different sampling locations, all potentially associated with a possible paleosurface. There are multiple plausible explanations for the anomalously depleted 13C observed in evolved methane, but no single explanation can be accepted without further research. Three possible explanations are the photolysis of biological methane released from the subsurface, photoreduction of atmospheric CO2, and deposition of cosmic dust during passage through a galactic molecular cloud. All three of these scenarios are unconventional, unlike processes common on Earth.

3.
Food Microbiol ; 124: 104616, 2024 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-39244368

RESUMO

Based on the previous research results that the addition of sucrose in the medium improved the biofilm formation of Tetragenococcus halophilus, the influence of sucrose on biofilm formation was explored. Moreover, the influence of exogenous expression of related genes sacA and galE from T. halophilus on the biofilm formation of L. lactis NZ9000 was investigated. The results showed that the addition of sucrose in the medium improved the biofilm formation, the resistance of biofilm cells to freeze-drying stress, and the contents of exopolysaccharides (EPS) and eDNA in the T. halophilus biofilms. Meanwhile, the addition of sucrose in the medium changed the monosaccharide composition of EPS and increased the proportion of glucose and galactose in the monosaccharide composition. Under 2.5% (m/v) salt stress condition, the expression of gene sacA promoted the biofilm formation and the EPS production of L. lactis NZ9000 with the sucrose addition in the medium and changed the EPS monosaccharide composition. The expression of gene galE up-regulated the proportion of rhamnose, galactose, and arabinose in the monosaccharide composition of EPS, and down-regulated the proportion of glucose and mannose. This study will provide a theoretical basis for regulating the biofilm formation of T. halophilus, and provide a reference for the subsequent research on lactic acid bacteria biofilms.


Assuntos
Biofilmes , Sacarose , Biofilmes/crescimento & desenvolvimento , Sacarose/metabolismo , Polissacarídeos Bacterianos/metabolismo , Enterococcaceae/genética , Enterococcaceae/metabolismo , Enterococcaceae/fisiologia , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Monossacarídeos/metabolismo , Regulação Bacteriana da Expressão Gênica , Liofilização
4.
Platelets ; 34(1): 2176699, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36846897

RESUMO

GALE gene encodes the uridine diphosphate [UDP]-galactose-4-epimerase, which catalyzes the bidirectional interconversion of UDP-glucose to UDP-galactose, and UDP-N-acetyl-glucosamine to UDP-N-acetyl-galactosamine. In that way, GALE balances, through reversible epimerization, the pool of four sugars that are essential during the biosynthesis of glycoproteins and glycolipids. GALE-related disorder presents an autosomal recessive inheritance pattern, and it is commonly associated with galactosemia. Peripheral galactosemia generally associates with non-generalized forms or even asymptomatic presentations, while classical galactosemia may be related to complications such as learning difficulties, developmental delay, cardiac failure, or dysmorphic features. Recently, GALE variants have been related to severe thrombocytopenia, pancytopenia, and in one patient, to myelodysplastic syndrome.


What is the context? GALE gene encodes for the UDP-Galactose 4-Epimerase, an enzyme involved in the Leloir pathway of galactose catabolism and protein glycosylation.Homozygous or compound heterozygous GALE variants associate with the disorder known as galactosemia type III.Three types of galactosemia can be distinguished: the peripheral, the intermediate, and the generalized form, which associate with different clinical symptoms and GALE genetic variants.Peripheral form is considered benign, while the intermediate and the generalized form is associated with severe and syndromic manifestations, including learning difficulties, delayed growth, sensorineural hearing loss, and early-onset cataracts, among others.What is new? In the last few years, GALE variants have been linked to hematological manifestations, such as anemia, febrile neutropenia, and severe thrombocytopenia.To date, the only GALE variants described in patients presenting hematological disorders are GALE p.Arg51Trp, p.Lys78ValfsX32, p.Val128Met, p.Thr150Met, p.Leu223Pro, and p.Gly237Asp.The thrombocytopenia observed in GALE patients is associated with reduced GPIbα and ß1 integrin glycosylation and externalization to the megakaryocyte and platelet surface, disrupting the actin cytoskeleton remodeling.What is the impact? GALE is an essential protein for the correct megakaryocyte and platelet glycosylation.


Assuntos
Galactosemias , Trombocitopenia , UDPglucose 4-Epimerase , Humanos , Galactose , Galactosemias/genética , Hemorragia , Trombocitopenia/genética , UDPglucose 4-Epimerase/genética
5.
Metab Eng ; 74: 61-71, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-36152932

RESUMO

Glycosylation of recombinant therapeutics like monoclonal antibodies (mAbs) is a critical quality attribute. N-glycans in mAbs are known to affect various effector functions, and thereby therapeutic use of such glycoproteins can depend on a particular glycoform profile to achieve desired efficacy. However, there are currently limited options for modulating the glycoform profile, which depend mainly on over-expression or knock-out of glycosyltransferase enzymes that can introduce or eliminate specific glycans but do not allow predictable glycoform modulation over a range of values. In this study, we demonstrate the ability to predictably modulate the glycoform profile of recombinant IgG. Using CRISPR/Cas9, we have engineered nucleotide sugar synthesis pathways in CHO cells expressing recombinant IgG for combinatorial modulation of galactosylation and fucosylation. Knocking out the enzymes UDP-galactose 4'-epimerase (Gale) and GDP-L-fucose synthase (Fx) resulted in ablation of de novo synthesis of UDP-Gal and GDP-Fuc. With Gale knock-out, the array of N-glycans on recombinantly expressed IgG is narrowed to agalactosylated glycans, mainly A2F glycan (89%). In the Gale and Fx double knock-out cell line, agalactosylated and afucosylated A2 glycan is predominant (88%). In the double knock-out cell line, galactosylation and fucosylation was entirely dependent on the salvage pathway, which allowed for modulation of UDP-Gal and GDP-Fuc synthesis and intracellular nucleotide sugar availability by controlling the availability of extracellular galactose and fucose. We demonstrate that the glycoform profile of recombinant IgG can be modulated from containing predominantly agalactosylated and afucosylated glycans to up to 42% and 96% galactosylation and fucosylation, respectively, by extracellular feeding of sugars in a dose-dependent manner. By simply varying the availability of extracellular galactose and/or fucose, galactosylation and fucosylation levels can be simultaneously and independently modulated. In addition to achieving the production of tailored glycoforms, this engineered CHO host platform can cater to the rapid synthesis of variably glycoengineered proteins for evaluation of biological activity.


Assuntos
Fucose , Galactose , Cricetinae , Animais , Células CHO , Cricetulus , Glicosilação , Fucose/genética , Fucose/metabolismo , Galactose/genética , Galactose/metabolismo , Polissacarídeos/genética , Anticorpos Monoclonais/genética , Imunoglobulina G , Nucleotídeos/metabolismo , Difosfato de Uridina/metabolismo
6.
J Biol Chem ; 295(5): 1225-1239, 2020 01 31.
Artigo em Inglês | MEDLINE | ID: mdl-31819007

RESUMO

Glycan biosynthesis relies on nucleotide sugars (NSs), abundant metabolites that serve as monosaccharide donors for glycosyltransferases. In vivo, signal-dependent fluctuations in NS levels are required to maintain normal cell physiology and are dysregulated in disease. However, how mammalian cells regulate NS levels and pathway flux remains largely uncharacterized. To address this knowledge gap, here we examined UDP-galactose 4'-epimerase (GALE), which interconverts two pairs of essential NSs. Using immunoblotting, flow cytometry, and LC-MS-based glycolipid and glycan profiling, we found that CRISPR/Cas9-mediated GALE deletion in human cells triggers major imbalances in NSs and dramatic changes in glycolipids and glycoproteins, including a subset of integrins and the cell-surface death receptor FS-7-associated surface antigen. In particular, we observed substantial decreases in total sialic acid, galactose, and GalNAc levels in glycans. These changes also directly impacted cell signaling, as GALE-/- cells exhibited FS-7-associated surface antigen ligand-induced apoptosis. Our results reveal a role of GALE-mediated NS regulation in death receptor signaling and may have implications for the molecular etiology of illnesses characterized by NS imbalances, including galactosemia and metabolic syndrome.


Assuntos
Glicolipídeos/metabolismo , Glicoproteínas/metabolismo , Açúcares/metabolismo , UDPglucose 4-Epimerase/química , UDPglucose 4-Epimerase/metabolismo , Receptor fas/metabolismo , Apoptose/genética , Cromatografia Líquida , Desoxiaçúcares/metabolismo , Técnicas de Inativação de Genes , Glicolipídeos/biossíntese , Glicolipídeos/química , Glicoproteínas/biossíntese , Glicoproteínas/química , Glicosilação , Células HEK293 , Células HeLa , Humanos , Espectrometria de Massas , Ácido N-Acetilneuramínico/metabolismo , Polissacarídeos/química , Polissacarídeos/metabolismo , Receptores de Superfície Celular/metabolismo , UDPglucose 4-Epimerase/genética , Receptor fas/química
7.
Traffic ; 19(6): 463-480, 2018 06.
Artigo em Inglês | MEDLINE | ID: mdl-29573151

RESUMO

The conserved oligomeric Golgi (COG) complex controls membrane trafficking and ensures Golgi homeostasis by orchestrating retrograde vesicle trafficking within the Golgi. Human COG defects lead to severe multisystemic diseases known as COG-congenital disorders of glycosylation (COG-CDG). To gain better understanding of COG-CDGs, we compared COG knockout cells with cells deficient to 2 key enzymes, Alpha-1,3-mannosyl-glycoprotein 2-beta-N-acetylglucosaminyltransferase and uridine diphosphate-glucose 4-epimerase (GALE), which contribute to proper N- and O-glycosylation. While all knockout cells share similar defects in glycosylation, these defects only account for a small fraction of observed COG knockout phenotypes. Glycosylation deficiencies were not associated with the fragmented Golgi, abnormal endolysosomes, defective sorting and secretion or delayed retrograde trafficking, indicating that these phenotypes are probably not due to hypoglycosylation, but to other specific interactions or roles of the COG complex. Importantly, these COG deficiency specific phenotypes were also apparent in COG7-CDG patient fibroblasts, proving the human disease relevance of our CRISPR knockout findings. The knowledge gained from this study has important implications, both for understanding the physiological role of COG complex in Golgi homeostasis in eukaryotic cells, and for better understanding human diseases associated with COG/Golgi impairment.


Assuntos
Complexo de Golgi/metabolismo , Açúcares/metabolismo , Proteínas Adaptadoras de Transporte Vesicular/fisiologia , Linhagem Celular , Glicosilação , Células HEK293 , Humanos , Fenótipo , Transporte Proteico/fisiologia
8.
Proc Natl Acad Sci U S A ; 114(9): 2166-2170, 2017 02 28.
Artigo em Inglês | MEDLINE | ID: mdl-28167765

RESUMO

Carbon dioxide is an essential atmospheric component in martian climate models that attempt to reconcile a faint young sun with planetwide evidence of liquid water in the Noachian and Early Hesperian. In this study, we use mineral and contextual sedimentary environmental data measured by the Mars Science Laboratory (MSL) Rover Curiosity to estimate the atmospheric partial pressure of CO2 (PCO2) coinciding with a long-lived lake system in Gale Crater at ∼3.5 Ga. A reaction-transport model that simulates mineralogy observed within the Sheepbed member at Yellowknife Bay (YKB), by coupling mineral equilibria with carbonate precipitation kinetics and rates of sedimentation, indicates atmospheric PCO2 levels in the 10s mbar range. At such low PCO2 levels, existing climate models are unable to warm Hesperian Mars anywhere near the freezing point of water, and other gases are required to raise atmospheric pressure to prevent lake waters from being lost to the atmosphere. Thus, either lacustrine features of Gale formed in a cold environment by a mechanism yet to be determined, or the climate models still lack an essential component that would serve to elevate surface temperatures, at least locally, on Hesperian Mars. Our results also impose restrictions on the potential role of atmospheric CO2 in inferred warmer conditions and valley network formation of the late Noachian.

9.
Asian-Australas J Anim Sci ; 33(11): 1725-1731, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32106650

RESUMO

OBJECTIVE: An initial RNA-Sequencing study revealed that UDP-galactose-4-epimerase (GALE) was one of the most promising candidates for milk protein concentration in Chinese Holstein cattle. This enzyme catalyzes the interconversion of UDP-galactose and UDP-glucose, an important step in galactose catabolism. To further validate the genetic effect of GALE on milk protein traits, genetic variations were identified, and genotypes-phenotypes associations were performed. METHODS: The entire coding region and the 5'-regulatory region (5'-UTR) of GALE were re-sequenced using pooled DNA of 17 unrelated sires. Association studies for five milk production traits were performed using a mixed linear animal model with a population encompassing 1,027 Chinese Holstein cows. RESULTS: A total of three variants in GALE were identified, including two novel variants (g.2114 A>G and g.2037 G>A) in the 5'-UTR and one previously reported variant (g.3836 G>C) in an intron. All three single nucleotide polymorphisms (SNPs) were associated with milk yield (p<0.0001), fat yield (p = 0.0006 to <0.0001), protein yield (p = 0.0232 to <0.0001) and protein percentage (p<0.0001), while no significant associations were detected between the SNPs and fat percentage. A strong linkage disequilibrium (D' = 0.96 to 1.00) was observed among all three SNPs, and a 5 Kb haplotype block involving three main haplotypes with GAG, AGC, and AGG was formed. The results of haplotype association analyses were consistent with the results of single locus association analysis (p<0.0001). The phenotypic variance ratio above 3.00% was observed for milk protein yield that was explained by SNP-g.3836G >C. CONCLUSION: Overall, our findings provided new insights into the polymorphic variations in bovine GALE gene and their associations with milk protein concentration. The data indicate their potential uses for marker-assisted breeding or genetic selection schemes.

10.
Trop Med Int Health ; 24(3): 280-293, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30582783

RESUMO

We conducted a systematic review of the treatment, prevention and public health control of skin infections including impetigo, scabies, crusted scabies and tinea in resource-limited settings where skin infections are endemic. The aim is to inform strategies, guidelines and research to improve skin health in populations that are inequitably affected by infections of the skin and the downstream consequences of these. The systematic review is reported according to the PRISMA statement. From 1759 titles identified, 81 full text studies were reviewed and key findings outlined for impetigo, scabies, crusted scabies and tinea. Improvements in primary care and public health management of skin infections will have broad and lasting impacts on overall quality of life including reductions in morbidity and mortality from sepsis, skeletal infections, kidney and heart disease.


Nous avons effectué une analyse systématique du traitement, de la prévention et du contrôle de santé publique des infections cutanées comprenant l'impétigo, la gale, la gale en croûte et la teigne, dans des cadres à ressources limitées où les infections cutanées sont endémiques. Le but étant d'informer les stratégies, les directives et la recherche pour améliorer la santé de la peau dans les populations qui sont touchées de manière inéquitable par les infections cutanées et leurs conséquences plus tard. La revue systématique est rapportée selon la déclaration PRISMA. Sur 1759 titres recensés, 81 études en texte intégral ont été passées en revue et les principaux résultats rapportés concernant l'impétigo, la gale, la gale en croûte et la teigne. Les améliorations apportées dans la prise en charge des infections de la peau dans les soins de santé primaires et les soins de santé publique auront des répercussions vastes et durables sur la qualité de vie en général, notamment une réduction de la morbidité et de la mortalité dues au sepsis, aux infections du squelette, aux maladies du rein et du cœur.


Assuntos
Dermatomicoses/terapia , Impetigo/terapia , Escabiose/terapia , Dermatomicoses/prevenção & controle , Humanos , Impetigo/prevenção & controle , Saúde Pública , Escabiose/prevenção & controle
11.
Bull Math Biol ; 81(4): 1089-1121, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30564990

RESUMO

Bistability and multistationarity are properties of reaction networks linked to switch-like responses and connected to cell memory and cell decision making. Determining whether and when a network exhibits bistability is a hard and open mathematical problem. One successful strategy consists of analyzing small networks and deducing that some of the properties are preserved upon passage to the full network. Motivated by this, we study chemical reaction networks with few chemical complexes. Under mass action kinetics, the steady states of these networks are described by fewnomial systems, that is polynomial systems having few distinct monomials. Such systems of polynomials are often studied in real algebraic geometry by the use of Gale dual systems. Using this Gale duality, we give precise conditions in terms of the reaction rate constants for the number and stability of the steady states of families of reaction networks with one non-flow reaction.


Assuntos
Redes e Vias Metabólicas , Modelos Biológicos , Fenômenos Bioquímicos , Células/metabolismo , Simulação por Computador , Cinética , Conceitos Matemáticos
12.
Proc Natl Acad Sci U S A ; 113(26): 7071-6, 2016 06 28.
Artigo em Inglês | MEDLINE | ID: mdl-27298370

RESUMO

Tridymite, a low-pressure, high-temperature (>870 °C) SiO2 polymorph, was detected in a drill sample of laminated mudstone (Buckskin) at Marias Pass in Gale crater, Mars, by the Chemistry and Mineralogy X-ray diffraction instrument onboard the Mars Science Laboratory rover Curiosity The tridymitic mudstone has ∼40 wt.% crystalline and ∼60 wt.% X-ray amorphous material and a bulk composition with ∼74 wt.% SiO2 (Alpha Particle X-Ray Spectrometer analysis). Plagioclase (∼17 wt.% of bulk sample), tridymite (∼14 wt.%), sanidine (∼3 wt.%), cation-deficient magnetite (∼3 wt.%), cristobalite (∼2 wt.%), and anhydrite (∼1 wt.%) are the mudstone crystalline minerals. Amorphous material is silica-rich (∼39 wt.% opal-A and/or high-SiO2 glass and opal-CT), volatile-bearing (16 wt.% mixed cation sulfates, phosphates, and chlorides-perchlorates-chlorates), and has minor TiO2 and Fe2O3T oxides (∼5 wt.%). Rietveld refinement yielded a monoclinic structural model for a well-crystalline tridymite, consistent with high formation temperatures. Terrestrial tridymite is commonly associated with silicic volcanism, and detritus from such volcanism in a "Lake Gale" catchment environment can account for Buckskin's tridymite, cristobalite, feldspar, and any residual high-SiO2 glass. These cogenetic detrital phases are possibly sourced from the Gale crater wall/rim/central peak. Opaline silica could form during diagenesis from high-SiO2 glass, as amorphous precipitated silica, or as a residue of acidic leaching in the sediment source region or at Marias Pass. The amorphous mixed-cation salts and oxides and possibly the crystalline magnetite (otherwise detrital) are primary precipitates and/or their diagenesis products derived from multiple infiltrations of aqueous solutions having variable compositions, temperatures, and acidities. Anhydrite is post lithification fracture/vein fill.

13.
J Bacteriol ; 200(5)2018 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-29229702

RESUMO

Bacillus anthracis, the causative agent of anthrax disease, elaborates a secondary cell wall polysaccharide (SCWP) that is essential for bacterial growth and cell division. B. anthracis SCWP is comprised of trisaccharide repeats with the structure, [→4)-ß-ManNAc-(1→4)-ß-GlcNAc(O3-α-Gal)-(1→6)-α-GlcNAc(O3-α-Gal, O4-ß-Gal)-(1→]6-12 The genes whose products promote the galactosylation of B. anthracis SCWP are not yet known. We show here that the expression of galE1, encoding a UDP-glucose 4-epimerase necessary for the synthesis of UDP-galactose, is required for B. anthracis SCWP galactosylation. The galE1 mutant assembles surface (S) layer and S layer-associated proteins that associate with ketal-pyruvylated SCWP via their S layer homology domains similarly to wild-type B. anthracis, but the mutant displays a defect in γ-phage murein hydrolase binding to SCWP. Furthermore, deletion of galE1 diminishes the capsulation of B. anthracis with poly-d-γ-glutamic acid (PDGA) and causes a reduction in bacterial virulence. These data suggest that SCWP galactosylation is required for the physiologic assembly of the B. anthracis cell wall envelope and for the pathogenesis of anthrax disease.IMPORTANCE Unlike virulent Bacillus anthracis isolates, B. anthracis strain CDC684 synthesizes secondary cell wall polysaccharide (SCWP) trisaccharide repeats without galactosyl modification, exhibits diminished growth in vitro in broth cultures, and is severely attenuated in an animal model of anthrax. To examine whether SCWP galactosylation is a requirement for anthrax disease, we generated variants of B. anthracis strains Sterne 34F2 and Ames lacking UDP-glucose 4-epimerase by mutating the genes galE1 and galE2 We identified galE1 as necessary for SCWP galactosylation. Deletion of galE1 decreased the poly-d-γ-glutamic acid (PDGA) capsulation of the vegetative form of B. anthracis and increased the bacterial inoculum required to produce lethal disease in mice, indicating that SCWP galactosylation is indeed a determinant of anthrax disease.


Assuntos
Antraz/microbiologia , Bacillus anthracis/metabolismo , Bacillus anthracis/patogenicidade , Proteínas de Bactérias/genética , Galactose/metabolismo , Polissacarídeos Bacterianos/metabolismo , Animais , Bacillus anthracis/genética , Bacillus anthracis/crescimento & desenvolvimento , Proteínas de Bactérias/metabolismo , Divisão Celular , Parede Celular/química , Parede Celular/genética , Parede Celular/fisiologia , Feminino , Galactose/genética , Galactosidases/metabolismo , Glicoproteínas de Membrana/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Mutação , Trissacarídeos/química , Trissacarídeos/metabolismo , UDPglucose 4-Epimerase/genética , Uridina Difosfato Galactose/biossíntese , Uridina Difosfato Galactose/metabolismo
14.
Hum Mutat ; 39(1): 52-60, 2018 01.
Artigo em Inglês | MEDLINE | ID: mdl-28961353

RESUMO

Galactosemia Proteins Database 2.0 is a Web-accessible resource collecting information about the structural and functional effects of the known variations associated to the three different enzymes of the Leloir pathway encoded by the genes GALT, GALE, and GALK1 and involved in the different forms of the genetic disease globally called "galactosemia." It represents an evolution of two available online resources we previously developed, with new data deriving from new structures, new analysis tools, and new interfaces and filters in order to improve the quality and quantity of information available for different categories of users. We propose this new resource both as a landmark for the entire world community of galactosemia and as a model for the development of similar tools for other proteins object of variations and involved in human diseases.


Assuntos
Bases de Dados de Proteínas , Navegador , Galactosemias/genética , Galactosemias/metabolismo , Variação Genética , Humanos , Conformação Proteica , Relação Estrutura-Atividade , UDPglucose 4-Epimerase/química , UDPglucose 4-Epimerase/genética , UDPglucose 4-Epimerase/metabolismo , UDPglucose-Hexose-1-Fosfato Uridiltransferase/química , UDPglucose-Hexose-1-Fosfato Uridiltransferase/genética , UDPglucose-Hexose-1-Fosfato Uridiltransferase/metabolismo
15.
Proc Natl Acad Sci U S A ; 112(19): 5974-8, 2015 May 12.
Artigo em Inglês | MEDLINE | ID: mdl-25918366

RESUMO

Assortative mating--marriage of a man and a woman with similar social characteristics--is a commonly observed phenomenon. In the existing literature in both sociology and economics, this phenomenon has mainly been attributed to individuals' conscious preferences for assortative mating. In this paper, we show that patterns of assortative mating may arise from another structural source even if individuals do not have assortative preferences or possess complementary attributes: dynamic processes of marriages in a closed system. For a given cohort of youth in a finite population, as the percentage of married persons increases, unmarried persons who newly enter marriage are systematically different from those who married earlier, giving rise to the phenomenon of assortative mating. We use microsimulation methods to illustrate this dynamic process, using first the conventional deterministic Gale-Shapley model, then a probabilistic Gale-Shapley model, and then two versions of the encounter mating model.


Assuntos
Casamento , Cônjuges , Comportamento de Escolha , Simulação por Computador , Feminino , Humanos , Masculino , Modelos Estatísticos , Comportamento Social , Fatores de Tempo
16.
Sensors (Basel) ; 18(6)2018 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-29874803

RESUMO

In this paper, we work on a Cache and Multi-layer MEC enabled C-RAN (CMM-CRAN) to handle various user tasks with minimized latency and energy cost. We intend to solve two particular problems of CMM-CRAN. First, because CMM-CRAN has to maximally cache the most frequently requested data from Service Provide Server (SPS) to Remote Radio Head (RRH) and later offered to proximity mobile users, the cache content placement from SPSs to RRHs becomes a many-to-many matching problem with peer effects. Second, because of multi-layer MEC, a user task has to be dynamically controlled to be offloaded to the best fit cloud, i.e., either local MEC or remote MEC, to get served. This dynamic task offloading is a Multi-Dimension Multiple-Choice Knapsack (MMCK) problem. To solve these two problems, we provide a Joint Cache content placement and task Offloading Solution (JCOS) to CMM-CRAN that utilizes Proportional Fairness (PF) as the user scheduling policy. JCOS applies a Gale-Shaply (GS) method to work out the cache content placement, and a Population Evolution (PE) game theory coupled with a use of Analytic Hierarchy Process(AHP) to work out the dynamic user task offloading. According to the simulation results, CMM-CRAN with JCOS is proved to be able to provide highly desired low-latency communication and computation services with decreased energy cost to mobile users.

17.
West Afr J Med ; 40(12 Suppl 1): S16-S17, 2023 Dec 04.
Artigo em Francês | MEDLINE | ID: mdl-38063492

RESUMO

Introduction: La gale, "maladie tropicale négligée" depuis 2017, est un problème de santé publique dans de nombreuses régions tropicales. L'objectif était d'étudier les aspects épidémiologique et clinique de la gale humaine en population générale à Parakou en 2022. Méthodes: Il s'est agi d'une étude transversale descriptive et à visée analytique menée à Parakou du 16 mai au 26 juin 2022. Un échantillonnage par sondage en grappes a été réalisé et l'analyse des données a été effectuée avec le logiciel Epi info version 7.2.4. Résultats: Au total, 727 sujets ont été enquêtés et 653 répondaient aux critères d'inclusion parmi lesquels 49 présentaient la gale humaine (7,5%). Parmi ces derniers, une prédominance masculine 51,1% a été observée (sex-ratio 1,23). L'âge moyen était de 21,4±14,4 ans avec des extrêmes de 1 et 70 ans. Le prurit généralisé est observé chez tous avec une notion de contage familial dans 40,8% des cas. La vésicule perlée était le principal signe (77,1%) et les mains constituaient le siège de prédilection des lésions cutanées (79,2%). Le bas niveau d'instruction universitaire (p=0,027), l'utilisation de lait corporel dépigmentant (p=0,023), les faibles fréquences de changement de vêtements (p=0,034) et de la literie (p=0,001) ainsi que le nombre élevé de personnes par lit (p=0,001) étaient les principaux facteurs associés. Conclusion: La prévalence de la gale humaine demeure non négligeable à Parakou. Il urge d'œuvrer à divers niveaux pour limiter sa propagation au sein de la population béninoise. Mots clés: Gale, épidémiologie, clinique, Parakou.

18.
Ann Dermatol Venereol ; 145(2): 89-94, 2018 Feb.
Artigo em Francês | MEDLINE | ID: mdl-29128241

RESUMO

BACKGROUND: Although there is evidence suggesting an epidemiologic increase of scabies in France, few studies have assessed medical practice in terms of diagnosis and treatment. OBJECTIVES: To describe the management of scabies by general practitioners (GPs). PATIENTS AND METHODS: A questionnaire was addressed to the 524 GPs of the Doubs department in France regarding the management of cases of scabies diagnosed between January and June 2015. RESULTS: The response rate was 57 % (n=299). At least one case of scabies was observed by 89 % of GPs in the previous six months and more than three cases were diagnosed by 59 % of GPs. The main clinical criterion for diagnosis was the specific localization of pruritus (82 %). No diagnostic test was used by 94 % of GPs other than except direct parasitological examination, which was used by 6 %. A systematic examination by a dermatologist was prescribed by 3 % of GPs, by 78 % of them in the case of diagnostic doubt, and not at all by 19 %, even though 66 % of GPs' offices were located under 10 kilometers from a dermatologist's office. Ivermectin (IVM) alone was prescribed by 38 % of GPs, either as a single dose (22 %) or as two repeated doses (16 %). Topical treatment alone was prescribed by 2 % of GPs and the association of IVM and topical treatment was used by 26 %, either as a single dose (19 %) or as two repeated doses (7 %). All household members and any sexual contacts were systematically treated by 77 % of GPs, but 9 % did not prescribe any treatment. Decontamination advice was given by 100 % of GPs. Recurrence of scabies was observed by 25 % of GPs despite systematic treatment (93 %) of patients' close contacts. DISCUSSION: Our study confirms the frequency of scabies in general medicine and the interest of GPs in this evaluation of practice. Our data also demonstrate the heterogeneity of management by GPs and the limitations of/poor compliance with national recommendations on scabies proposed by the Haut conseil de santé publique (Public Health Council) in 2012. CONCLUSION: Our study emphasizes the critical role of GPs in the management of scabies and the need for specific recommendations concerning their practices.


Assuntos
Clínicos Gerais , Padrões de Prática Médica/estatística & dados numéricos , Escabiose/diagnóstico , Escabiose/tratamento farmacológico , Antiparasitários/uso terapêutico , França , Humanos , Ivermectina/uso terapêutico , Encaminhamento e Consulta/estatística & dados numéricos , Inquéritos e Questionários
19.
Int J Equity Health ; 16(1): 111, 2017 06 26.
Artigo em Inglês | MEDLINE | ID: mdl-28651621

RESUMO

BACKGROUND: Malnutrition remains one of the most common causes of morbidity and mortality among children throughout the world. This study aimed to assess prevalence of malnutrition and associated factors among children aged 6-59 months in Damot Gale, South Ethiopia. METHODS: A community based cross sectional study was conducted on 398 children aged 6-59 months in the Damot Gale district. A two-stage cluster sample design was used to select kebele and households. Anthropometric measurements and structured questionnaires were used to collect data. Bivariate and multivariate logistic regression was done by using SPSS version 20. RESULTS: The results of this study indicated that 27.6% of children were under-weight and 9% were wasted. Being male (AOR: 1.90; 95% CI: (1.10-3.32), children with shorter birth interval (AOR:2.89;95% CI: (1.23-6.80), children who had sickness some times for past 2 weeks (AOR:0.42; 95% CI:(0.10-0.93) and children whose mothers attended ANC (AOR:0.29; 95% CI: (0.16-0.52) were associated with underweight. Children whose mother's main occupation was non-farm (AOR: 7.06;95% CI: (1.31-38.21), presence of diarrhea (AOR:39.5, 95% CI: (13.68-114.30), and children whose mothers attended ANC (AOR:0.18,95% CI: (0 .18 (0.07-0.45) were associated with wasting. CONCLUSION: The prevalence of malnutrition in the study area was high. Health extension workers and stakeholders should give due concern on promotion of proper nutrition in the community.


Assuntos
Transtornos da Nutrição Infantil/epidemiologia , População Rural/estatística & dados numéricos , Pré-Escolar , Estudos Transversais , Etiópia/epidemiologia , Feminino , Humanos , Lactente , Masculino , Prevalência , Fatores de Risco
20.
Ann Dermatol Venereol ; 144(5): 349-355, 2017 May.
Artigo em Inglês | MEDLINE | ID: mdl-28325516

RESUMO

BACKGROUND: The infectious causes of cutaneous vasculitis are well known and include streptococcal infections among others. Cases resulting from parasitic infection are less frequent. Scabies, which is currently on the increase, has only been reported in a few isolated cases. Herein, we report two noteworthy cases of profuse scabies complicated by cutaneous vasculitis. PATIENTS AND METHODS: Case 1: a 90-year-old woman, residing in a nursing home, was admitted to our dermatology department complaining of pruritus, present for one month, predominantly on the inside of the thighs and on the buttocks, associated with purpuric lesions on the lower limbs. A skin biopsy revealed leukocytoclastic vasculitis. A diagnosis of scabies was based on severe pruritus and hypereosinophilia and was confirmed by microscopic examination of the parasitology sample and the skin biopsy sample. Despite thorough investigation, no other cause of vasculitis could be found. Complete regression of the skin lesions was achieved with scabies treatment only, without any specific treatment for the vasculitis. Case 2: a 74-year-old man, living in a nursing home, was hospitalized for purpuric papules on the lower limbs, present for one month. Physical examination revealed linear patterns in the interdigital spaces associated with scabies evident on dermoscopic examination. The skin biopsy revealed signs of vasculitis. As in our first case, no aetiology of vasculitis was found and a favorable outcome was achieved by means of scabies treatment alone with no specific treatment for vasculitis. DISCUSSION: Both of our patients presented scabies and vasculitis. In view of the absence of other causes of vasculitis and of the complete regression of lesions due to vasculitis without recurrence achieved with the scabies treatment alone, a diagnosis was made of scabietic vasculitis, probably as a result of cutaneous hypersensitivity reaction to humeral mediators.


Assuntos
Antiparasitários/uso terapêutico , Ivermectina/uso terapêutico , Piretrinas/administração & dosagem , Escabiose/diagnóstico , Vasculite/diagnóstico , Administração Oral , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Prurido/tratamento farmacológico , Prurido/parasitologia , Fatores de Risco , Escabiose/tratamento farmacológico , Escabiose/parasitologia , Creme para a Pele/administração & dosagem , Resultado do Tratamento , Vasculite/tratamento farmacológico , Vasculite/parasitologia
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA