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1.
Nat Commun ; 14(1): 7656, 2023 Nov 23.
Article in English | MEDLINE | ID: mdl-37996419

ABSTRACT

Hundreds of E3 ligases play a critical role in recognizing specific substrates for modification by ubiquitin (Ub). Separating genuine targets of E3s from E3-interactors remains a challenge. We present BioE3, a powerful approach for matching substrates to Ub E3 ligases of interest. Using BirA-E3 ligase fusions and bioUb, site-specific biotinylation of Ub-modified substrates of particular E3s facilitates proteomic identification. We show that BioE3 identifies both known and new targets of two RING-type E3 ligases: RNF4 (DNA damage response, PML bodies), and MIB1 (endocytosis, autophagy, centrosome dynamics). Versatile BioE3 identifies targets of an organelle-specific E3 (MARCH5) and a relatively uncharacterized E3 (RNF214). Furthermore, BioE3 works with NEDD4, a HECT-type E3, identifying new targets linked to vesicular trafficking. BioE3 detects altered specificity in response to chemicals, opening avenues for targeted protein degradation, and may be applicable for other Ub-likes (UbLs, e.g., SUMO) and E3 types. BioE3 applications shed light on cellular regulation by the complex UbL network.


Subject(s)
Ubiquitin-Protein Ligases , Ubiquitin , Ubiquitin-Protein Ligases/metabolism , Ubiquitin/metabolism , Ubiquitination , Proteomics , Proteolysis
2.
Int J Mol Sci ; 23(23)2022 Dec 06.
Article in English | MEDLINE | ID: mdl-36499752

ABSTRACT

Delayed cerebral ischemia (DCI) and vasospasm are two complications of subarachnoid hemorrhages (SAHs) which entail high risks of morbidity and mortality. However, it is unknown why only some patients who suffer SAHs will experience DCI and vasospasm. The purpose of this review is to describe the main genetic single nucleotide polymorphisms (SNPs) that have demonstrated a relationship with these complications. The SNP of the nitric oxide endothelial synthase (eNOS) has been related to the size and rupture of an aneurysm, as well as to DCI, vasospasm, and poor neurological outcome. The SNPs responsible for the asymmetric dimetilarginine and the high-mobility group box 1 have also been associated with DCI. An association between vasospasm and the SNPs of the eNOS, the haptoglobin, and the endothelin-1 receptor has been found. The SNPs of the angiotensin-converting enzyme have been related to DCI and poor neurological outcome. Studies on the SNPs of the Ryanodine Receptor yielded varying results regarding their association with vasospasm.


Subject(s)
Brain Ischemia , Subarachnoid Hemorrhage , Vasospasm, Intracranial , Humans , Subarachnoid Hemorrhage/complications , Subarachnoid Hemorrhage/genetics , Vasospasm, Intracranial/genetics , Brain Ischemia/complications , Brain Ischemia/genetics , Cerebral Infarction/complications , Polymorphism, Single Nucleotide , Disease Susceptibility
4.
Nat Commun ; 12(1): 6671, 2021 11 18.
Article in English | MEDLINE | ID: mdl-34795231

ABSTRACT

The fast dynamics and reversibility of posttranslational modifications by the ubiquitin family pose significant challenges for research. Here we present SUMO-ID, a technology that merges proximity biotinylation by TurboID and protein-fragment complementation to find SUMO-dependent interactors of proteins of interest. We develop an optimized split-TurboID version and show SUMO interaction-dependent labelling of proteins proximal to PML and RANGAP1. SUMO-dependent interactors of PML are involved in transcription, DNA damage, stress response and SUMO modification and are highly enriched in SUMO Interacting Motifs, but may only represent a subset of the total PML proximal proteome. Likewise, SUMO-ID also allow us to identify interactors of SUMOylated SALL1, a less characterized SUMO substrate. Furthermore, using TP53 as a substrate, we identify SUMO1, SUMO2 and Ubiquitin preferential interactors. Thus, SUMO-ID is a powerful tool that allows to study the consequences of SUMO-dependent interactions, and may further unravel the complexity of the ubiquitin code.


Subject(s)
Protein Interaction Mapping/methods , Protein Interaction Maps , Protein Processing, Post-Translational , Small Ubiquitin-Related Modifier Proteins/metabolism , Sumoylation , Cell Line, Tumor , GTPase-Activating Proteins/metabolism , HEK293 Cells , Humans , Promyelocytic Leukemia Protein/metabolism , Protein Binding , SUMO-1 Protein/metabolism , Transcription Factors/metabolism , Tumor Suppressor Protein p53/metabolism , Ubiquitin/metabolism
5.
Front Cell Dev Biol ; 9: 715868, 2021.
Article in English | MEDLINE | ID: mdl-34621739

ABSTRACT

Development is orchestrated through a complex interplay of multiple transcription factors. The comprehension of this interplay will help us to understand developmental processes. Here we analyze the relationship between two key transcription factors: CBX4, a member of the Polycomb Repressive Complex 1 (PRC1), and SALL1, a member of the Spalt-like family with important roles in embryogenesis and limb development. Both proteins localize to nuclear bodies and are modified by the small ubiquitin-like modifier (SUMO). Our results show that CBX4 and SALL1 interact in the nucleoplasm and that increased SALL1 expression reduces ubiquitination of CBX4, enhancing its stability. This is accompanied by an increase in the number and size of CBX4-containing Polycomb bodies, and by a greater repression of CBX4 target genes. Thus, our findings uncover a new way of SALL1-mediated regulation of Polycomb bodies through modulation of CBX4 stability, with consequences in the regulation of its target genes, which could have an impact in cell differentiation and development.

6.
Hum Mol Genet ; 27(11): 1955-1971, 2018 06 01.
Article in English | MEDLINE | ID: mdl-29788202

ABSTRACT

Angelman syndrome is a complex neurodevelopmental disorder caused by the lack of function in the brain of a single gene, UBE3A. The E3 ligase coded by this gene is known to build K48-linked ubiquitin chains, a modification historically considered to target substrates for degradation by the proteasome. However, a change in protein abundance is not proof that a candidate UBE3A substrate is indeed ubiquitinated by UBE3A. We have here used an unbiased ubiquitin proteomics approach, the bioUb strategy, to identify 79 proteins that appear more ubiquitinated in the Drosophila photoreceptor cells when Ube3a is over-expressed. We found a significantly high number of those proteins to be proteasomal subunits or proteasome-interacting proteins, suggesting a wide proteasomal perturbation in the brain of Angelman patients. We focused on validating the ubiquitination by Ube3a of Rngo, a proteasomal component conserved from yeast (Ddi1) to humans (DDI1 and DDI2), but yet scarcely characterized. Ube3a-mediated Rngo ubiquitination in fly neurons was confirmed by immunoblotting. Using human neuroblastoma SH-SY5Y cells in culture, we also observed that human DDI1 is ubiquitinated by UBE3A, without being targeted for degradation. The novel observation that DDI1 is expressed in the developing mice brain, with a significant peak at E16.5, strongly suggests that DDI1 has biological functions not yet described that could be of relevance for Angelman syndrome clinical research.


Subject(s)
Angelman Syndrome/genetics , Aspartic Acid Proteases/genetics , Drosophila Proteins/genetics , Ubiquitin-Protein Ligases/genetics , Angelman Syndrome/physiopathology , Animals , Drosophila , Gene Expression Regulation/genetics , Humans , Mice , Neurons/metabolism , Neurons/pathology , Photoreceptor Cells/metabolism , Photoreceptor Cells/pathology , Proteomics , Saccharomyces cerevisiae Proteins/genetics , Ubiquitination/genetics
7.
Sci Rep ; 7: 40756, 2017 01 18.
Article in English | MEDLINE | ID: mdl-28098257

ABSTRACT

Post-translational modification by ubiquitin and ubiquitin-like proteins (UbLs) is fundamental for maintaining protein homeostasis. Efficient isolation of UbL conjugates is hampered by multiple factors, including cost and specificity of reagents, removal of UbLs by proteases, distinguishing UbL conjugates from interactors, and low quantities of modified substrates. Here we describe bioUbLs, a comprehensive set of tools for studying modifications in Drosophila and mammals, based on multicistronic expression and in vivo biotinylation using the E. coli biotin protein ligase BirA. While the bioUbLs allow rapid validation of UbL conjugation for exogenous or endogenous proteins, the single vector approach can facilitate biotinylation of most proteins of interest. Purification under denaturing conditions inactivates deconjugating enzymes and stringent washes remove UbL interactors and non-specific background. We demonstrate the utility of the method in Drosophila cells and transgenic flies, identifying an extensive set of putative SUMOylated proteins in both cases. For mammalian cells, we show conjugation and localization for many different UbLs, with the identification of novel potential substrates for UFM1. Ease of use and the flexibility to modify existing vectors will make the bioUbL system a powerful complement to existing strategies for studying this important mode of protein regulation.


Subject(s)
Ubiquitins/metabolism , Animals , Animals, Genetically Modified , Biotinylation , Cell Line , Drosophila/genetics , Drosophila/metabolism , Drosophila Proteins/genetics , Drosophila Proteins/metabolism , Humans , Protein Processing, Post-Translational , Repressor Proteins/genetics , Repressor Proteins/metabolism , Small Ubiquitin-Related Modifier Proteins , Sumoylation , Ubiquitins/genetics
8.
Front Neurosci ; 11: 732, 2017.
Article in English | MEDLINE | ID: mdl-29354028

ABSTRACT

Key scientific discoveries have resulted from genetic studies of Drosophila melanogaster, using a multitude of transgenic fly strains, the majority of which are constructed in a genetic background containing mutations in the white gene. Here we report that white mutant flies from w1118 strain undergo retinal degeneration. We observed also that w1118 mutants have progressive loss of climbing ability, shortened life span, as well as impaired resistance to various forms of stress. Retinal degeneration was abolished by transgenic expression of mini-white+ in the white null background w1118 . We conclude that beyond the classical eye-color phenotype, mutations in Drosophila white gene could impair several biological functions affecting parameters like mobility, life span and stress tolerance. Consequently, we suggest caution and attentiveness during the interpretation of old experiments employing white mutant flies and when planning new ones, especially within the research field of neurodegeneration and neuroprotection. We also encourage that the use of w1118 strain as a wild-type control should be avoided.

9.
MULTIMED ; 21(5)2017. tab
Article in Spanish | CUMED | ID: cum-72508

ABSTRACT

Introducción: la bronquiolitis es la infección respiratoria baja más común en los infantes. Objetivo: determinar los costos hospitalarios en pacientes con bronquiolitis ingresados en el Hospital Pediátrico Docente Gral. Luis A. Milanés Tamayo Método: se realizó un estudio descriptivo, retrospectivo, transversal, de costos hospitalarios, en 289 pacientes ingresados con diagnóstico de bronquiolitis, período julio - octubre del 2015 en el Hospital Pediátrico Docente Luis A. Milanés Tamayo de Bayamo. Los datos recogidos se llevaron a base de datos, se analizaron a través de estadísticos descriptivos, con empleo de frecuencias absolutas y relativas, programa SPSS 22 para Windows. Resultados: predominaron los menores de un año(98.2 %); el 4,8 % ingresó directamente en UCIP, el 95,2% ingresó en sala de respiratorio, de ellos el 82.4 % permaneció en el servicio de respiratorio y el 12, 8% de los pacientes se trasladó posteriormente a la unidad de cuidados intensivos pediátricos (UCIP). Todos los pacientes ingresados en servicio de respiratorio recibieron inicialmente tratamiento sintomático, este y la oxigenoterapia precoz fueron los más utilizados. El costo total por medicamentos, ascendió a $826.00, el sulfato de magnesio, salbutamol solución y la vancomicina fueron los que más incidieron. Los rayos X de tórax y los estudios microbiológicos fueron los complementarios que más costos aportaron. Conclusiones: el costo final por hospitalización fue bajo, la mayoría de los pacientes tuvieron una estadía hospitalaria menor de 72 horas, y todos los pacientes evolucionaron satisfactoriamente(AU)


Subject(s)
Humans , Respiratory Tract Infections , Bronchiolitis/diagnosis , Bronchiolitis/therapy , Health Care Costs , Epidemiology, Descriptive , Cross-Sectional Studies , Retrospective Studies , Child, Preschool
10.
Mol Biol Evol ; 33(2): 568-84, 2016 Feb.
Article in English | MEDLINE | ID: mdl-26538142

ABSTRACT

SUMOylation, the covalent binding of Small Ubiquitin-like Modifier (SUMO) to target proteins, is a posttranslational modification that regulates critical cellular processes in eukaryotes. In insects, SUMOylation has been studied in holometabolous species, particularly in the dipteran Drosophila melanogaster, which contains a single SUMO gene (smt3). This has led to the assumption that insects contain a single SUMO gene. However, the analysis of insect genomes shows that basal insects contain two SUMO genes, orthologous to vertebrate SUMO1 and SUMO2/3. Our phylogenetical analysis reveals that the SUMO gene has been duplicated giving rise to SUMO1 and SUMO2/3 families early in Metazoan evolution, and that later in insect evolution the SUMO1 gene has been lost after the Hymenoptera divergence. To explore the consequences of this loss, we have examined the characteristics and different biological functions of the two SUMO genes (SUMO1 and SUMO3) in the hemimetabolous cockroach Blattella germanica and compared them with those of Drosophila Smt3. Here, we show that the metamorphic role of the SUMO genes is evolutionary conserved in insects, although there has been a regulatory switch from SUMO1 in basal insects to SUMO3 in more derived ones. We also show that, unlike vertebrates, insect SUMO3 proteins cannot form polySUMO chains due to the loss of critical lysine residues within the N-terminal part of the protein. Furthermore, the formation of polySUMO chains by expression of ectopic human SUMO3 has a deleterious effect in Drosophila. These findings contribute to the understanding of the functional consequences of the evolution of SUMO genes.


Subject(s)
Biological Evolution , Insecta/metabolism , SUMO-1 Protein/metabolism , Amino Acid Motifs , Amino Acid Sequence , Animals , Ecdysteroids/biosynthesis , Evolution, Molecular , Humans , Insecta/classification , Insecta/genetics , Metamorphosis, Biological/genetics , Models, Molecular , Molecular Sequence Data , Mutation , Phenotype , Phylogeny , Protein Conformation , Protein Interaction Domains and Motifs , SUMO-1 Protein/chemistry , SUMO-1 Protein/genetics , Sequence Alignment , Sumoylation
11.
Sci Rep ; 5: 12383, 2015 Jul 22.
Article in English | MEDLINE | ID: mdl-26198204

ABSTRACT

Animals have a determined species-specific body size that results from the combined action of hormones and signaling pathways regulating growth rate and duration. In Drosophila, the steroid hormone ecdysone controls developmental transitions, thereby regulating the duration of the growth period. Here we show that ecdysone promotes the growth of imaginal discs in mid-third instar larvae, since imaginal discs from larvae with reduced or no ecdysone synthesis are smaller than wild type due to smaller and fewer cells. We show that insulin-like peptides are produced and secreted normally in larvae with reduced ecdysone synthesis, and upstream components of insulin/insulin-like signaling are activated in their discs. Instead, ecdysone appears to regulate the growth of imaginal discs via Thor/4E-BP, a negative growth regulator downstream of the insulin/insulin-like growth factor/Tor pathways. Discs from larvae with reduced ecdysone synthesis have elevated levels of Thor, while mutations in Thor partially rescue their growth. The regulation of organ growth by ecdysone is evolutionarily conserved in hemimetabolous insects, as shown by our results obtained using Blattella germanica. In summary, our data provide new insights into the relationship between components of the insulin/insulin-like/Tor and ecdysone pathways in the control of organ growth.


Subject(s)
Drosophila melanogaster/growth & development , Ecdysone/metabolism , Imaginal Discs/growth & development , Somatomedins/metabolism , Animals , Body Size/physiology , Drosophila Proteins/metabolism , Drosophila melanogaster/metabolism , Female , Insulin/metabolism , Larva/growth & development , Larva/metabolism , Signal Transduction/physiology
12.
Neurocir. - Soc. Luso-Esp. Neurocir ; 26(1): 32-38, ene.-feb. 2015. tab
Article in Spanish | IBECS | ID: ibc-133396

ABSTRACT

Objetivo: Evaluar y predecir factores que influyan en el pronóstico y/o resultado clínico a los 6 meses de pacientes con hemorragia subaracnoidea espontánea, en grados iv y v de la World Federation of Neurosurgical Societies (WFNS). Material y métodos: Estudio retrospectivo de una serie consecutiva de 394 pacientes que ingresaron en nuestro hospital, con diagnóstico clínico y radiológico de hemorragia subaracnoidea espontánea, desde el 1 de enero de 1999 hasta el 30 de junio de 2009. Se seleccionaron 121 pacientes que reunían el criterio de estar en grado iv o v de la WFNS antes del tratamiento; se excluyeron 3 pacientes por pérdida de seguimiento. La variable resultado se evaluó a los 6 meses del evento mediante la Escala de Resultados de Glasgow. Se consideró un resultado estadísticamente significativo un valor de p < 0,05. Resultados: Ciento veintiún pacientes se incluyeron en el análisis estadístico. La edad media de la serie fue de 54 años (14-92). Los pacientes que presentaban una puntuación en la Escala de Coma de Glasgow media inferior a 7 puntos (p < 0,0001) y un grado de v (p < 0,0001) en la escala de la WFNS pretratamiento, así como los que presentaban trastorno pupilar (p = 0,002), mostraron un peor resultado clínico final; igualmente, los que asociaron hematoma intraparenquimatoso (p = 0,020) y aquellos a los que no se les efectuó ningún tipo de tratamiento (p = 0,020) también asociaron un mal resultado clínico final, siendo estos resultados estadísticamente significativos. Conclusiones: Los pacientes que ingresan con una gradación de v en la escala de la WFNS y/o presentan trastorno pupilar y/o hematoma intraparenquimatoso asocian un peor resultado clínico final


Objective: To evaluate and predict factors influencing prognosis and/or clinical outcome at 6 months in patients with spontaneous subarachnoid haemorrhage, World Federation of Neurosurgical Societies (WFNS) grades iv and v. Material and methods: This was a retrospective study of a consecutive series of 394 patients admitted to our hospital with clinical and radiological diagnosis of spontaneous subarachnoid haemorrhage, from 1 January 1999 to 30 June 2009. We selected 121 patients who met the criteria of being in WFNS grades iv or v before treatment; 3 patients were excluded due to loss of tracking. The outcome variable was assessed 6 months after the event using the Glasgow Outcome Scale. A P value < .05 was considered statistically significant. Results: One hundred and twenty-one patients were included in the statistical analysis. The average age of the patients in the series was 54 years (14-92). Patients who had a mean Glasgow Coma Scale lower than 7 points (P < .0001), those who were grade v (P < .0001) in the pre-treatment WFNS scale and those with pupillary disorder (P = .002) had a worse clinical outcome. Likewise, those with associated intraparenchymal hematoma (P = .020) and those not receiving any treatment (P = .020) were also associated with a poor clinical outcome. These results were statistically significant. Conclusions: Patients admitted with a WFNS grade v and/or presenting pupil disorder and/or intraparenchymal hematoma were associated with worse clinical outcomes


Subject(s)
Humans , Intracranial Aneurysm/surgery , Subarachnoid Hemorrhage/surgery , Endovascular Procedures/methods , Prognosis , Treatment Outcome , Statistics on Sequelae and Disability
13.
Neurocirugia (Astur) ; 26(1): 32-8, 2015.
Article in Spanish | MEDLINE | ID: mdl-25455762

ABSTRACT

OBJECTIVE: To evaluate and predict factors influencing prognosis and/or clinical outcome at 6 months in patients with spontaneous subarachnoid haemorrhage, World Federation of Neurosurgical Societies (WFNS) grades iv and v. MATERIAL AND METHODS: This was a retrospective study of a consecutive series of 394 patients admitted to our hospital with clinical and radiological diagnosis of spontaneous subarachnoid haemorrhage, from 1 January 1999 to 30 June 2009. We selected 121 patients who met the criteria of being in WFNS grades iv or v before treatment; 3 patients were excluded due to loss of tracking. The outcome variable was assessed 6 months after the event using the Glasgow Outcome Scale. A P value<.05 was considered statistically significant. RESULTS: One hundred and twenty-one patients were included in the statistical analysis. The average age of the patients in the series was 54 years (14-92). Patients who had a mean Glasgow Coma Scale lower than 7 points (P<.0001), those who were grade v (P<.0001) in the pre-treatment WFNS scale and those with pupillary disorder (P=.002) had a worse clinical outcome. Likewise, those with associated intraparenchymal hematoma (P=.020) and those not receiving any treatment (P=.020) were also associated with a poor clinical outcome. These results were statistically significant. CONCLUSIONS: Patients admitted with a WFNS grade v and/or presenting pupil disorder and/or intraparenchymal hematoma were associated with worse clinical outcomes.


Subject(s)
Subarachnoid Hemorrhage , Adolescent , Adult , Aged , Aged, 80 and over , Female , Humans , Male , Middle Aged , Prognosis , Retrospective Studies , Severity of Illness Index , Subarachnoid Hemorrhage/classification , Subarachnoid Hemorrhage/diagnosis , Subarachnoid Hemorrhage/therapy , Young Adult
14.
PLoS Genet ; 9(4): e1003473, 2013 Apr.
Article in English | MEDLINE | ID: mdl-23637637

ABSTRACT

SUMOylation participates in ecdysteroid biosynthesis at the onset of metamorphosis in Drosophila melanogaster. Silencing the Drosophila SUMO homologue smt3 in the prothoracic gland leads to reduced lipid content, low ecdysone titers, and a block in the larval-pupal transition. Here we show that the SR-BI family of Scavenger Receptors mediates SUMO functions. Reduced levels of Snmp1 compromise lipid uptake in the prothoracic gland. In addition, overexpression of Snmp1 is able to recover lipid droplet levels in the smt3 knockdown prothoracic gland cells. Snmp1 expression depends on Ftz-f1 (an NR5A-type orphan nuclear receptor), the expression of which, in turn, depends on SUMO. Furthermore, we show by in vitro and in vivo experiments that Ftz-f1 is SUMOylated. RNAi-mediated knockdown of ftz-f1 phenocopies that of smt3 at the larval to pupal transition, thus Ftz-f1 is an interesting candidate to mediate some of the functions of SUMO at the onset of metamorphosis. Additionally, we demonstrate that the role of SUMOylation, Ftz-f1, and the Scavenger Receptors in lipid capture and mobilization is conserved in other steroidogenic tissues such as the follicle cells of the ovary. smt3 knockdown, as well as ftz-f1 or Scavenger knockdown, depleted the lipid content of the follicle cells, which could be rescued by Snmp1 overexpression. Therefore, our data provide new insights into the regulation of metamorphosis via lipid homeostasis, showing that Drosophila Smt3, Ftz-f1, and SR-BIs are part of a general mechanism for uptake of lipids such as cholesterol, required during development in steroidogenic tissues.


Subject(s)
Drosophila melanogaster , Drosophila , Animals , DNA-Binding Proteins/metabolism , Drosophila/metabolism , Drosophila Proteins/metabolism , Drosophila melanogaster/metabolism , Molecular Sequence Data , Receptors, Scavenger , Transcription Factors/metabolism
15.
BMC Genomics ; 13: 483, 2012 Sep 15.
Article in English | MEDLINE | ID: mdl-22978642

ABSTRACT

BACKGROUND: Neurodegenerative diseases are progressive and irreversible and they can be initiated by mutations in specific genes. Spalt-like genes (Sall) encode transcription factors expressed in the central nervous system. In humans, SALL mutations are associated with hereditary syndromes characterized by mental retardation, sensorineural deafness and motoneuron problems, among others. Drosophila sall mutants exhibit severe neurodegeneration of the central nervous system at embryonic stage 16, which surprisingly reverts later in development at embryonic stage 17, suggesting a potential to recover from neurodegeneration. We hypothesize that this recovery is mediated by a reorganization of the transcriptome counteracting SALL lost. To identify genes associated to neurodegeneration and neuroprotection, we used mRNA-Seq to compare the transcriptome of Drosophila sall mutant and wild type embryos from neurodegeneration and reversal stages. RESULTS: Neurodegeneration stage is associated with transcriptional changes in 220 genes, of which only 5% were already described as relevant for neurodegeneration. Genes related to the groups of Redox, Lifespan/Aging and Mitochondrial diseases are significantly represented at this stage. By contrast, neurodegeneration reversal stage is associated with significant changes in 480 genes, including 424 not previously associated with neuroprotection. Immune response and Salt stress are the most represented groups at this stage. CONCLUSIONS: We identify new genes associated to neurodegeneration and neuroprotection by using an mRNA-Seq approach. The strong homology between Drosophila and human genes raises the possibility to unveil novel genes involved in neurodegeneration and neuroprotection also in humans.


Subject(s)
Drosophila Proteins/genetics , Drosophila/genetics , Neurodegenerative Diseases/genetics , Transcriptome , Animals , Computational Biology , Drosophila/embryology , Gene Expression Regulation, Developmental , Genes, Insect , Sequence Analysis, RNA
16.
Int J Dev Biol ; 55(6): 603-11, 2011.
Article in English | MEDLINE | ID: mdl-21948708

ABSTRACT

In mammals, cholesterol is transformed into steroid hormones in the adrenal gland, the ovaries or the testes. The Scavenger Receptors Class B Type I (SR-BI) are membrane proteins that belong to the CD36 family and participate in the selective uptake of high density lipoprotein cholesteryl ester in the mammalian steroidogenic tissues. Fourteen members of the CD36 family have been identified in Diptera, although their expression patterns remain uncharacterized. Using in situ hybridization we have characterized the expression patterns of the fourteen SR-BIs in Drosophila melanogaster. We analyzed three different developmental larval stages prior to and during the peak of the insect steroid hormone ecdysone, which triggers the larval to pupal transition. We focused on the steroidogenic tissues, such as the prothoracic gland, the ovaries and the testes, and extended our analysis to non-steroidogenic tissues, such as the fat body, salivary glands, the gut, the gastric caeca or the central nervous system. Our results show highly regulated expression patterns, with three genes crq, pes and Snmp being upregulated in steroidogenic tissues at the onset of pupariation when steroidogenesis is crucial. This study underlines the importance of the transport of cholesterol and steroids in the process of ecdysone synthesis.


Subject(s)
CD36 Antigens/genetics , Cholesterol Esters/metabolism , Drosophila melanogaster/growth & development , Drosophila melanogaster/genetics , Ecdysone/biosynthesis , Gene Expression Regulation, Developmental , Lipoproteins, HDL/metabolism , Animals , Biological Transport, Active , CD36 Antigens/biosynthesis , Drosophila Proteins/biosynthesis , Drosophila Proteins/genetics , Drosophila melanogaster/metabolism , Ecdysone/metabolism , In Situ Hybridization , Larva/growth & development , Larva/metabolism , Pupa/growth & development , Pupa/metabolism , Receptors, Pheromone/biosynthesis , Receptors, Pheromone/genetics , Receptors, Scavenger/biosynthesis , Receptors, Scavenger/genetics
17.
MULTIMED ; 15(3)2011. tab
Article in Spanish | CUMED | ID: cum-55216

ABSTRACT

Se realizó un estudio, de pacientes y controles, con el objetivo de identificar, algunos factores de riesgo, para adquirir infección respiratoria aguda alta en la comunidad, en niños menores de 15 años, perteneciente a los consultorios 145 B y del 18 Plantas del Policlínico Jimmy Hitrzel, Bayamo, Granma. La muestra estuvo constituida por 111 pacientes y 222 controles de un universo de 341 niños. Se seleccionaron como controles, niños menores de 15 años, sin síntomas respiratorios, perteneciente al mismo consultorio. Se investigó la asociación entre la enfermedad respiratoria aguda con factores de riesgos, como son, ambientales, nutricionales y otros relacionados con la madre. Entre los resultados se obtuvo que la baja escolaridad de la madre fue un factor de riesgo estadísticamente significativo (OR:6.67, IC: 5.67-7.84), con relación al riesgos de que los niños adquirieran infección aguda respiratoria , se evidencio que los niños cuyos padres son fumadores tuvieron mas riesgos de adquirir la enfermedad (OR: 4.50, IC: 3.34-6.0) Se concluye con que todos los factores investigados contribuyeron al riesgo para adquirir infección respiratoria aguda alta en la comunidad, siendo los de mayor significación, la escolaridad de la madre, desnutrición y exposición pasiva al humo de cigarro.(AU)


It was performed a research and some controls to patients with the objective to identify some risk factors of the Acute Respiratory Infection in children under 15 years old belonging to the consults 145B and 18 Floor- Building of Jimmy Hirtzel polyclinic in Bayamo, Granma. The sample was made by 111 patients and 222 controls from a universe of 341 children. For the controls there were selected children under 15 years without respiratory symptoms, they belonged to the same consult. It was studied the association between the acute respiratory disease with the risk factors like: environmental, nutritional and some others related to the mother. The results showed that the low scholarity of the mother was a risk factor statistically outstanding. (OR: 6.67 IC: 5.67-7.84) in relation to the risk of children who acquire acute respiratory infections. It was evidenced that the children whose parents are smokers presented more risks to acquire this disease (OR 4.50, IC 3.34-6.0). Conclusions: all of the studied risk factors contributed to the risk to acquire High Acute Respiratory Infections in the community. The most significant factors were the mother scholarity level, undernutrition and passive exposure to the smoke.(EU)


Subject(s)
Humans , Child , Respiratory Tract Infections/diagnosis , Respiratory Tract Infections/epidemiology , Respiratory Tract Infections/therapy , Risk Factors , Case-Control Studies
18.
J Biol Chem ; 285(33): 25841-9, 2010 Aug 13.
Article in English | MEDLINE | ID: mdl-20562097

ABSTRACT

The Spalt-like family of zinc finger transcription factors is conserved throughout evolution and is involved in fundamental processes during development and during embryonic stem cell maintenance. Although human SALL1 is modified by SUMO-1 in vitro, it is not known whether this post-translational modification plays a role in regulating the activity of this family of transcription factors. Here, we show that the Drosophila Spalt transcription factors are modified by sumoylation. This modification influences their nuclear localization and capacity to induce vein formation through the regulation of target genes during wing development. Furthermore, spalt genes interact genetically with the sumoylation machinery to repress vein formation in intervein regions and to attain the wing final size. Our results suggest a new level of regulation of Sall activity in vivo during animal development through post-translational modification by sumoylation. The evolutionary conservation of this family of transcription factors suggests a functional role for sumoylation in vertebrate Sall members.


Subject(s)
Drosophila Proteins/metabolism , Homeodomain Proteins/metabolism , Small Ubiquitin-Related Modifier Proteins/metabolism , Transcription Factors/metabolism , Wings, Animal/metabolism , Animals , Cell Line , Drosophila , Drosophila Proteins/genetics , Gene Expression Regulation, Developmental/genetics , Gene Expression Regulation, Developmental/physiology , Homeodomain Proteins/genetics , Humans , Immunohistochemistry , Repressor Proteins/genetics , Repressor Proteins/metabolism , Small Ubiquitin-Related Modifier Proteins/genetics , Transcription Factors/genetics , Wings, Animal/growth & development
19.
Rev. cuba. salud pública ; 34(4)oct.-dic. 2008.
Article in Spanish | CUMED | ID: cum-37442

ABSTRACT

Con el desarrollo de la humanidad, y en particular con los avances en el terreno de la medicina, es necesario hacer un llamado para humanizar la asistencia en salud y ofrecer servicios de mayor calidad. La calidad en la atención médica debe estar basada en actividades encaminadas a garantizar los servicios de salud accesibles y equitativos con profesionales óptimos y teniendo en cuenta los recursos disponibles, logrando la satisfacción del usuario con la atención recibida. El presente trabajo tiene como objetivos reflexionar sobre la necesidad de integración de elementos de carácter técnico y también de procesos, objetivos y subjetivos, involucrados en el fenómeno de la calidad y enfatizar en su elemento subjetivo: la satisfacción, que representa la vivencia subjetiva derivada del cumplimiento o incumplimiento de las expectativas que tiene un sujeto con respecto a algo. Evaluar la satisfacción no sólo permite obtener un indicador de excelencia, es más aún, un instrumento de la excelencia(AU)


With the development of mankind and in particular, the advances in the medical field, it is required to make an appeal to humanize health care and to render higher quality services. Medical care quality must be based on activities that assure accessible and equitable health services offered by skilled professionals, taking the available resources into account, and make the user be satisfied with the medical care provided. The present paper was aimed at reflecting on the need of integration of technical elements and objective and subjective processes involved in quality and at putting emphasis on its subjective element, that is, the satisfaction that represents the subjective experience derived from the met or unmet expectations of an individual. The evaluation of satisfaction does not only allow obtaining an excellence indicator but also an excellence tool(AU)


Subject(s)
Patient Satisfaction , Quality Assurance, Health Care
20.
Rev. cuba. salud pública ; 34(4)oct.-dic. 2008.
Article in Spanish | LILACS | ID: lil-506532

ABSTRACT

Con el desarrollo de la humanidad, y en particular con los avances en el terreno de la medicina, es necesario hacer un llamado para humanizar la asistencia en salud y ofrecer servicios de mayor calidad. La calidad en la atención médica debe estar basada en actividades encaminadas a garantizar los servicios de salud accesibles y equitativos con profesionales óptimos y teniendo en cuenta los recursos disponibles, logrando la satisfacción del usuario con la atención recibida. El presente trabajo tiene como objetivos reflexionar sobre la necesidad de integración de elementos de carácter técnico y también de procesos, objetivos y subjetivos, involucrados en el fenómeno de la calidad y enfatizar en su elemento subjetivo: la satisfacción, que representa la vivencia subjetiva derivada del cumplimiento o incumplimiento de las expectativas que tiene un sujeto con respecto a algo. Evaluar la satisfacción no sólo permite obtener un indicador de excelencia, es más aún, un instrumento de la excelencia.


With the development of mankind and in particular, the advances in the medical field, it is required to make an appeal to humanize health care and to render higher quality services. Medical care quality must be based on activities that assure accessible and equitable health services offered by skilled professionals, taking the available resources into account, and make the user be satisfied with the medical care provided. The present paper was aimed at reflecting on the need of integration of technical elements and objective and subjective processes involved in quality and at putting emphasis on its subjective element, that is, the satisfaction that represents the subjective experience derived from the met or unmet expectations of an individual. The evaluation of satisfaction does not only allow obtaining an excellence indicator but also an excellence tool.


Subject(s)
Patient Satisfaction , Quality Assurance, Health Care
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