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1.
J Adolesc ; 96(2): 305-321, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37997033

RESUMO

INTRODUCTION: Adolescents' social network sites (SNS) use is prominent during the developmental period. Various adolescents' motivations for using  SNS have been reported. However, there is a lack of psychological perspectives in understanding the reasons for adolescents to use SNS. This study explored adolescents' motivation to use SNS, and a comprehensive psychological framework was used to dismantle adolescents' reasons and purposes for using SNS. Adolescents' ways of using SNS were explored to contextualize teens' SNS use. METHODS: Semistructured interviews with 18 Malaysian adolescents (Mage = 15; 50% female; 10 Malay, 5 Chinese, 1 Indian, 1 Other Bumiputera) were conducted. The qualitative data were collected in 2021 in Malaysia through online video calls. Reflexive thematic analysis was the analytic approach. RESULTS: Six motivations for using SNS were identified: social interaction, content subscription and exploration, emotional support, participation, distraction, and self-expression. Each of the motivations was explicitly linked with different psychological needs. Adolescents were found to use SNS differently in three aspects: deliberate use (i.e., on purpose of use and time spent on SNS), content-selective, and audience-selective. CONCLUSION: This study demonstrates that psychological needs are the psychological reasons for adolescents' motivations for using SNS. Adolescence developmental tasks like strong peer identification and identity explorations are parts of the basic and compound psychological needs. Teens are pursuing a sense of self-coherence by using SNS. Adolescents demonstrated to use SNS differently at being deliberate and selective, which is speculated to be a result of the conflict between reflexive and reflective thought processes during SNS use.


Assuntos
Comportamento do Adolescente , Motivação , Humanos , Adolescente , Feminino , Masculino , Grupo Associado , Comportamento do Adolescente/psicologia , Interação Social , Rede Social
2.
Hum Mol Genet ; 30(1): 5-20, 2021 03 25.
Artigo em Inglês | MEDLINE | ID: mdl-33395696

RESUMO

FEZ1-mediated axonal transport plays important roles in central nervous system development but its involvement in the peripheral nervous system is not well-characterized. FEZ1 is deleted in Jacobsen syndrome (JS), an 11q terminal deletion developmental disorder. JS patients display impaired psychomotor skills, including gross and fine motor delay, suggesting that FEZ1 deletion may be responsible for these phenotypes, given its association with the development of motor-related circuits. Supporting this hypothesis, our data show that FEZ1 is selectively expressed in the rat brain and spinal cord. Its levels progressively increase over the developmental course of human motor neurons (MN) derived from embryonic stem cells. Deletion of FEZ1 strongly impaired axon and dendrite development, and significantly delayed the transport of synaptic proteins into developing neurites. Concurring with these observations, Drosophila unc-76 mutants showed severe locomotion impairments, accompanied by a strong reduction of synaptic boutons at neuromuscular junctions. These abnormalities were ameliorated by pharmacological activation of UNC-51/ATG1, a FEZ1-activating kinase, with rapamycin and metformin. Collectively, the results highlight a role for FEZ1 in MN development and implicate its deletion as an underlying cause of motor impairments in JS patients.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal/genética , Proteínas do Citoesqueleto/genética , Proteínas de Drosophila/genética , Transtornos Neurológicos da Marcha/genética , Síndrome da Deleção Distal 11q de Jacobsen/genética , Proteínas do Tecido Nervoso/genética , Animais , Proteína Homóloga à Proteína-1 Relacionada à Autofagia , Transporte Axonal/genética , Encéfalo/metabolismo , Encéfalo/patologia , Transtornos Neurológicos da Marcha/fisiopatologia , Humanos , Síndrome da Deleção Distal 11q de Jacobsen/fisiopatologia , Locomoção/genética , Locomoção/fisiologia , Neurônios Motores/metabolismo , Neurônios Motores/patologia , Neurogênese/genética , Ratos
3.
J Autoimmun ; 140: 103126, 2023 Oct 12.
Artigo em Inglês | MEDLINE | ID: mdl-37837807

RESUMO

BACKGROUND: This systematic review aimed to characterise the cognitive outcomes of patients who received chimeric antigen receptor T-cell therapy. METHODS: A systematic search of the literature was performed using PubMed, PsycINFO, SCOPUS, EMBASE, Medline, and CINAHL (February 2023). Risk of bias was assessed using the JBI Checklist for Case Reports and the Risk of Bias Assessment Tool for Non-randomised Studies. RESULTS: Twenty-two studies met inclusion criteria with a total of 1104 participants. There was considerable methodological heterogeneity with differing study designs (e.g., cohort studies, clinical trials, case studies, a qualitative interview, and a focus group), measures of cognition (e.g., self-report, neuropsychological measures, clinician assessed/neurological examinations), and longest follow-up time points (i.e., five days to five years). DISCUSSION: Results of the studies were heterogenous with studies demonstrating stable, improved, or reduced cognition across differing time points. Overall, cognitive symptoms are common particularly in the acute stage (<2 weeks) post-infusion. Most deficits that arise in the acute stage resolve within one to two weeks, however, there is a subset of patients who continue to experience and self-report persistent deficits in the subacute and chronic stages. Future studies are needed to comprehensively analyse cognition using a combination of self-report and psychometric measures following chimeric antigen receptor T-cell therapy in the acute, subacute, and chronic settings.

4.
J Immunol ; 206(4): 849-860, 2021 02 15.
Artigo em Inglês | MEDLINE | ID: mdl-33441440

RESUMO

HLA class I molecules that represent ligands for the inhibitory killer cell Ig-like receptor (KIR) 3DL1 found on NK cells are categorically defined as those HLA-A and HLA-B allotypes containing the Bw4 motif, yet KIR3DL1 demonstrates hierarchical recognition of these HLA-Bw4 ligands. To better understand the molecular basis underpinning differential KIR3DL1 recognition, the HLA-ABw4 family of allotypes were investigated. Transfected human 721.221 cells expressing HLA-A*32:01 strongly inhibited primary human KIR3DL1+ NK cells, whereas HLA-A*24:02 and HLA-A*23:01 displayed intermediate potency and HLA-A*25:01 failed to inhibit activation of KIR3DL1+ NK cells. Structural studies demonstrated that recognition of HLA-A*24:02 by KIR3DL1 used identical contacts as the potent HLA-B*57:01 ligand. Namely, the D1-D2 domains of KIR3DL1 were placed over the α1 helix and α2 helix of the HLA-A*24:02 binding cleft, respectively, whereas the D0 domain contacted the side of the HLA-A*24:02 molecule. Nevertheless, functional analyses showed KIR3DL1 recognition of HLA-A*24:02 was more sensitive to substitutions within the α2 helix of HLA-A*24:02, including residues Ile142 and Lys144 Furthermore, the presence of Thr149 in the α2 helix of HLA-A*25:01 abrogated KIR3DL1+ NK inhibition. Together, these data demonstrate a role for the HLA class I α2 helix in determining the hierarchy of KIR3DL1 ligands. Thus, recognition of HLA class I is dependent on a complex interplay between the peptide repertoire, polymorphisms within and proximal to the Bw4 motif, and the α2 helix. Collectively, the data furthers our understanding of KIR3DL1 ligands and will inform genetic association and immunogenetics studies examining the role of KIR3DL1 in disease settings.


Assuntos
Antígenos HLA-A , Células Matadoras Naturais , Receptores KIR3DL1 , Antígenos HLA-A/química , Antígenos HLA-A/imunologia , Humanos , Células Matadoras Naturais/química , Células Matadoras Naturais/imunologia , Conformação Proteica em alfa-Hélice , Domínios Proteicos , Receptores KIR3DL1/química , Receptores KIR3DL1/imunologia
5.
Support Care Cancer ; 31(8): 494, 2023 Jul 27.
Artigo em Inglês | MEDLINE | ID: mdl-37498423

RESUMO

PURPOSE: The study aimed to characterize the incidence of both oral and gastrointestinal (GI) mucositis, its' associated temporal changes in local and systemic pro-inflammatory cytokines, and to explore predictive clinical and immunological factors associated with their occurrences in hematopoietic stem cell transplant (HSCT). METHODS: Autologous HSCT patients aged 18 years old and above were recruited from Hospital Ampang, Malaysia, between April 2019 to December 2020. Mucositis assessments were conducted daily, whilst blood and saliva were collected prior to conditioning regimen, on Day 0, Day+7 and 6-month. Baseline and inflammatory predictors in a repeated time measurement of moderate-severe mucositis were assessed by multiple logistic regression and generalized estimating equations, respectively. RESULTS: Of the 142 patients analyzed, oral mucositis and diarrhea (representing GI mucositis) were reported as 68.3% and 95.8%, respectively. Predictive factors for moderate-severe oral mucositis were BEAM or busulphan-based regimens (odds ratio (OR)=9.2, 95% confidence interval (CI)=1.16-72.9, p-value (p) = 0.005) and vomiting (OR=4.6, 95% CI 1.68-12.3, p = 0.004). Predictive factors for moderate-severe GI mucositis were BEAM or busulphan-based regimens (OR=3.9, 95% CI 1.05-14.5, p = 0.023), female sex (OR = 3.3, 95% CI 1.43-7.44, p = 0.004) and body mass index (OR=1.08, 95% CI 1.02-1.15, p = 0.010). Cytokines analyses were performed in 96 patients. Saliva and plasma interleukin-6 (OR=1.003, 95% CI 1.001-1.004, p < 0.001 and OR=1.01, 95% CI 1.001-1.015, p = 0.029), and plasma tumor necrosis factor-alpha (OR=0.91, 95% CI 0.85-0.99, p = 0.019) were predictive of moderate-severe oral mucositis in a time-dependent model. CONCLUSION: This study provides real-world evidence and insights into patient- and treatment-related factors affecting oral and GI mucositis in HSCT.


Assuntos
Transplante de Células-Tronco Hematopoéticas , Mucosite , Estomatite , Adulto , Humanos , Feminino , Adolescente , Mucosite/epidemiologia , Mucosite/etiologia , Bussulfano , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Estudos Prospectivos , Estomatite/epidemiologia , Estomatite/etiologia , Citocinas , Transplante de Células-Tronco/efeitos adversos , Fatores de Risco , Fatores Imunológicos , Condicionamento Pré-Transplante/efeitos adversos
6.
Proc Natl Acad Sci U S A ; 117(21): 11636-11647, 2020 05 26.
Artigo em Inglês | MEDLINE | ID: mdl-32404419

RESUMO

Micropolymorphisms within human leukocyte antigen (HLA) class I molecules can change the architecture of the peptide-binding cleft, leading to differences in peptide presentation and T cell recognition. The impact of such HLA variation on natural killer (NK) cell recognition remains unclear. Given the differential association of HLA-B*57:01 and HLA-B*57:03 with the control of HIV, recognition of these HLA-B57 allomorphs by the killer cell immunoglobulin-like receptor (KIR) 3DL1 was compared. Despite differing by only two polymorphic residues, both buried within the peptide-binding cleft, HLA-B*57:01 more potently inhibited NK cell activation. Direct-binding studies showed KIR3DL1 to preferentially recognize HLA-B*57:01, particularly when presenting peptides with positively charged position (P)Ω-2 residues. In HLA-B*57:01, charged PΩ-2 residues were oriented toward the peptide-binding cleft and away from KIR3DL1. In HLA-B*57:03, the charged PΩ-2 residues protruded out from the cleft and directly impacted KIR3DL1 engagement. Accordingly, KIR3DL1 recognition of HLA class I ligands is modulated by both the peptide sequence and conformation, as determined by the HLA polymorphic framework, providing a rationale for understanding differences in clinical associations.


Assuntos
Antígenos de Histocompatibilidade Classe I/genética , Células Matadoras Naturais/fisiologia , Polimorfismo Genético/genética , Antígenos de Histocompatibilidade Classe I/química , Antígenos de Histocompatibilidade Classe I/fisiologia , Humanos , Ativação Linfocitária/genética , Modelos Moleculares , Polimorfismo Genético/fisiologia , Receptores KIR/genética
7.
Br J Nutr ; 127(5): 763-772, 2022 03 14.
Artigo em Inglês | MEDLINE | ID: mdl-33910654

RESUMO

There is limited data on the dietary patterns of 5-year-old children in Asia. The study examined childhood dietary patterns and their maternal and child correlates in a multi-ethnic Asian cohort. Based on caregiver-reported 1-month quantitative FFQ of 777 children from the Growing Up in Singapore Towards healthy Outcomes cohort, cluster analysis identified two mutually exclusive clusters. Children in the 'Unhealthy' cluster (43·9 %) consumed more fries, processed meat, biscuits and ice cream, and less fish, fruits and vegetables compared with those in the 'Healthy' cluster (56·1 %). Children with mothers of lower educational attainment had twice the odds of being assigned to the 'Unhealthy' cluster (adjusted OR (95 % CI) = 2·19 (95 % CI 1·49-3·24)). Children of Malay and Indian ethnicities had higher odds of being assigned to the 'Unhealthy' cluster (adjusted OR = 25·46 (95 % CI 15·40, 42·10) and 4·03 (95 % CI 2·68-6·06), respectively), relative to Chinese ethnicity. In conclusion, this study identified two dietary patterns in children, labelled as the 'Unhealthy' and 'Healthy' clusters. Mothers' educational attainment and ethnicity were two correlates that were associated with the children's assignments to the clusters. These findings can assist in informing health promotion programmes targeted at Asian children.


Assuntos
Etnicidade , Verduras , Povo Asiático , Criança , Pré-Escolar , Estudos de Coortes , Dieta , Comportamento Alimentar , Frutas , Humanos
8.
Transfusion ; 61(2): 379-384, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33410173

RESUMO

BACKGROUND: Yta is a high frequency red blood cell (RBC) antigen, present in 99.7% of studied populations. It is extremely immunogenic, and when anti-Yta is present, provision of Yt(a-) blood is often challenging. The objectives of our study were to assess the incidence and severity of acute hemolytic transfusion reactions to Yt(a+) donor RBCs in recipients with preformed anti-Yta and to identify any patient factors associated with severe hemolytic reactions. STUDY DESIGN AND METHODS: Patients with anti-Yta identified by the Red Cell Reference Laboratories of the Australian Red Cross Lifeblood over the past 20 years were included. Their transfusion records were collected via the referring laboratory to ascertain if any patients received RBC transfusion and if there was any evidence of transfusion reactions. RESULTS: Fifty-two patients with anti-Yta were identified; only 12 were confirmed to have received a RBC transfusion. Nine received Yt(a+) or untyped allogeneic RBCs, including four patients who received a total of 16 indirect antiglobulin test (IAT) crossmatch incompatible, likely Yt(a+) RBCs. None of the nine patients had documented acute hemolytic reactions. CONCLUSION: There are limited published data describing the clinical significance of anti-Yta . Based on our data, it appears that transfusing patients with anti-Yta using incompatible crossmatched RBCs does not pose a significant risk of an acute hemolytic transfusion reaction when the antibody reaction strength is weak ≤2+ (0-4) by IAT crossmatch. For strong examples of the antibody, in the absence of other assay data, such as the monocyte monolayer assay, Yt(a-) blood should continue to be sourced where possible.


Assuntos
Antígenos de Grupos Sanguíneos/imunologia , Incompatibilidade de Grupos Sanguíneos/imunologia , Transfusão de Eritrócitos , Isoanticorpos/imunologia , Reação Transfusional/imunologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Tipagem e Reações Cruzadas Sanguíneas , Teste de Coombs , Transfusão de Eritrócitos/efeitos adversos , Feminino , Hemólise/imunologia , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Reação Transfusional/etiologia , Adulto Jovem
9.
Int J Syst Evol Microbiol ; 71(10)2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34596504

RESUMO

A novel bacterium, strain SJAQ100T, was isolated from a freshwater aquarium and was characterized taxonomically and phylogenetically. Strain SJAQ100T was a Gram-stain-negative, aerobic, rod-shaped and non-motile bacterium. The strain grew optimally with 0 % NaCl and at 25-37 °C on Reasoner's 2A agar. Phylogenetic analysis based on the 16S rRNA gene sequences revealed that the strain SJAQ100T clustered with members of Burkholderiales incertae sedis in the order Burkholderiales, but sequence similarities to known species were less than 96.5 %. The genomic DNA G+C content of strain SJAQ100T was 71.2 mol%. Genomic comparisons of strain SJAQ100T with species in the order Burkholderiales were made using the Genome-to-Genome Distance Calculator, average nucleotide identity and average amino acid identity analyses (values indicated ≤22.1, ≤78.1, and ≤68.1 % respectively). Strain SJAQ100T contained C16 : 0 and C16 : 1 ω7c/C16 : 1 ω6c as major fatty acids and Q-8 as the major quinone. The major polyamines were putrescine and cadaverine. Strain SJAQ100T contained phosphatidylethanolamine and diphosphatidylglycerol as major polar lipids. Based on the genotypic, chemotaxonomic and phenotypic results, strain SJAQ100T represents a novel genus and species, Aquariibacter albus gen. nov., sp. nov., which belongs to order Burkholderiales and the class Betaproteobacteria. The type strain is SJAQ100T (=KCTC 72203T=CGMCC 1.18869T=MCC 4385T).


Assuntos
Burkholderiales , Água Doce/microbiologia , Filogenia , Técnicas de Tipagem Bacteriana , Composição de Bases , Burkholderiales/classificação , Burkholderiales/isolamento & purificação , DNA Bacteriano/genética , Ácidos Graxos/química , Fosfolipídeos/química , Poliaminas/química , RNA Ribossômico 16S/genética , Análise de Sequência de DNA , Ubiquinona/química
10.
Int J Syst Evol Microbiol ; 70(2): 915-922, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31697228

RESUMO

A novel bacterium, strain Seoho-28T, was isolated from a shallow eutrophic lake during the end of cyanobacterial harmful algal blooms and was characterized taxonomically and phylogenetically. Strain Seoho-28T was a Gram-stain-negative, aerobic, rod-shaped and non-motile bacterium. The strain grew optimally with 0 % NaCl and at 25-30 °C on Reasoner's 2A medium. The phylogenetic analysis based on 16S rRNA gene sequences positioned the novel strain among the order Solirubrobacterales, but sequence similarities to known species were less than 94.7 %. The genomic DNA G+C content of the strain Seoho-28T was 74.2 mol%. Genomic comparisons of strain Seoho-28T with families in the order Solirubrobacterales were made using the Genome-to-Genome Distance Calculator, average nucleotide identity and average amino acid identity analyses (values indicated ≤14.9, ≤73.5 and ≤57.8 %, respectively). Strain Seoho-28T contained C16 : 0-iso, C18 : 1 ω9c and C16 : 0 as major fatty acids and MK-7 (H4) as the major quinone. Strain Seoho-28T contained diphosphatidylglycerol, phosphatidylinositol and an unidentified phospholipid as major polar lipids. Meso- and ll-diaminopimelic acids were the diagnostic diamino acids in the cell-wall peptidoglycan. Based on the genotypic, chemotaxonomic and phenotypic results, strain Seoho-28T represents a novel genus and species, Paraconexibacter algicola gen. nov., sp. nov., which belongs to a new family Paraconexibacteraceae in the order Solirubrobacterales and the class Thermoleophilia. The type strain is Seoho-28T (=KCTC 39791T=JCM 31881T).


Assuntos
Actinobacteria/classificação , Proliferação Nociva de Algas , Lagos/microbiologia , Filogenia , Actinobacteria/isolamento & purificação , Técnicas de Tipagem Bacteriana , Composição de Bases , Cianobactérias , DNA Bacteriano/genética , Ácido Diaminopimélico/química , Ácidos Graxos/química , Peptidoglicano/química , Fosfolipídeos/química , RNA Ribossômico 16S/genética , República da Coreia , Análise de Sequência de DNA , Vitamina K 2/análogos & derivados , Vitamina K 2/química
11.
Antonie Van Leeuwenhoek ; 112(5): 723-729, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30506271

RESUMO

A novel Gram-stain negative, rod-shaped and motile bacterial strain, designated strain Seoho-38T, was isolated from a eutrophic lake in South Korea. Polyphasic taxonomic studies were performed to investigate the taxonomic position of the new isolate. The phylogenetic analysis based on the 16S rRNA gene sequences revealed that strain Seoho-38T formed a distinct cluster with Nevskia ramosa Soe1T, Nevskia persephonica G6M-30T, Nevskia soli GR15-1T, Nevskia terrae KIS13-15T and Nevskia aquatilis F2-63T with bootstrap resampling value of 100%. Of those Nevskia strains, the new isolate shows high sequence similarity with N. ramosa Soe1T (98.7%) and N. persephonica G6M-30T (97.2%), and values lower than 96.5% with the other type strains. The new isolate was observed to grow aerobically in 0-1.5% (w/v) NaCl (optimum 0%), at pH 7.0-9.0 (optimum pH 7.0) and temperature 15-36 °C (optimum 20-30 °C) on R2A medium. DNA-DNA relatedness values between strain Seoho-38T and the type strains of reference species in the genus Nevskia were < 24%. The genomic DNA G + C content was determined to be 67.4 mol%. Ubiquinone-8 (Q-8) (95%) and ubiquinone-7 (Q-7) (5%) were identified as the respiratory quinones. The cellular polar lipids were identified as diphosphatidylglycerol, phosphatidylglycerol, phosphatidylethanolamine, a phosphoaminolipid, two glycolipids, an aminolipid and four unidentified lipids. The major fatty acid components were found to include summed feature 3 (C16:1ω7c and/or C16:1ω6c), summed feature 8 (C18:0ω7c and/or C18:0ω6c), C16:0 and C14:0. Based on the above polyphasic evidence, strain Seoho-38T (= KCTC 52221T = JCM 31888T) represents a new species of the genus Nevskia, for which the name Nevskia lacus sp. nov. is proposed.


Assuntos
Lagos/microbiologia , Xanthomonadaceae/isolamento & purificação , Técnicas de Tipagem Bacteriana , Composição de Bases , DNA Bacteriano/genética , Eutrofização , Ácidos Graxos/química , Ácidos Graxos/metabolismo , Lagos/química , Filogenia , RNA Ribossômico 16S/genética , República da Coreia , Xanthomonadaceae/classificação , Xanthomonadaceae/genética , Xanthomonadaceae/metabolismo
12.
Int J Syst Evol Microbiol ; 68(9): 2872-2877, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-30016227

RESUMO

A novel Gram-negative bacterium, designated 4G11T, was isolated from the sea surface microlayer of a marine inlet. On the basis of 16S rRNA gene sequence analysis, the strain showed the closest similarity to Amylibacter ulvae KCTC 32465T (99.0 %). However, DNA-DNA hybridization values showed low DNA relatedness between strain 4G11T and its close phylogenetic neighbours, Amylibacter marinus NBRC 110140T (8.0±0.4 %) and Amylibacter ulvae KCTC 32465T (52.9±0.9 %). Strain 4G11T had C18 : 1, C16 : 0 and C18 : 2 as the major fatty acids. The only isoprenoid quinone detected for strain 4G11T was ubiquinone-10. The major polar lipids were phosphatidylglycerol, phosphatidylcholine, one unidentified polar lipid, one unidentified phospholipid and one unidentified aminolipid. The DNA G+C content of strain 4G11T was 50.0 mol%. Based on phenotypic and chemotaxonomic characteristics and analysis of the 16S rRNA gene sequence, the novel strain should be assigned to a novel species, for which the name Amylibacter kogurei sp. nov. is proposed. The type strain of Amylibacter kogurei is 4G11T (KY463497=KCTC 52506T=NBRC 112428T).


Assuntos
Filogenia , Rhodobacteraceae/classificação , Água do Mar/microbiologia , Técnicas de Tipagem Bacteriana , Composição de Bases , Baías , DNA Bacteriano/genética , Ácidos Graxos/química , Japão , Hibridização de Ácido Nucleico , Fosfolipídeos/química , RNA Ribossômico 16S/genética , Rhodobacteraceae/genética , Rhodobacteraceae/isolamento & purificação , Análise de Sequência de DNA , Ubiquinona/química
13.
J Cell Sci ; 128(3): 527-40, 2015 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-25501809

RESUMO

WD40-repeat protein 62 (WDR62) is a spindle pole protein required for normal cell division and neuroprogenitor differentiation during brain development. Microcephaly-associated mutations in WDR62 lead to mitotic mislocalization, highlighting a crucial requirement for precise WDR62 spatiotemporal distribution, although the regulatory mechanisms are unknown. Here, we demonstrate that the WD40-repeat region of WDR62 is required for microtubule association, whereas the disordered C-terminal region regulates cell-cycle-dependent compartmentalization. In agreement with a functional requirement for the WDR62­JNK1 complex during neurogenesis, WDR62 specifically recruits JNK1 (also known as MAPK8), but not JNK2 (also known as MAPK9), to the spindle pole. However, JNK-mediated phosphorylation of WDR62 T1053 negatively regulated microtubule association, and loss of JNK signaling resulted in constitutive WDR62 localization to microtubules irrespective of cell cycle stage. In contrast, we identified that Aurora A kinase (AURKA) and WDR62 were in complex and that AURKA-mediated phosphorylation was required for the spindle localization of WDR62 during mitosis. Our studies highlight complex regulation of WDR62 localization, with opposing roles for JNK and AURKA in determining its spindle association.


Assuntos
Aurora Quinase A/metabolismo , Microtúbulos/metabolismo , Proteína Quinase 8 Ativada por Mitógeno/metabolismo , Proteínas do Tecido Nervoso/metabolismo , Fuso Acromático/metabolismo , Proteínas de Ciclo Celular , Linhagem Celular , Células HeLa , Humanos , Sistema de Sinalização das MAP Quinases/genética , Proteína Quinase 8 Ativada por Mitógeno/genética , Mitose/genética , Neurogênese/genética , Fosforilação , Estrutura Terciária de Proteína
14.
Int J Syst Evol Microbiol ; 67(7): 2199-2204, 2017 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-28699854

RESUMO

A rod-shaped, pale yellow-pigmented, aerobic, Gram-staining-negative strain with gliding motility, designated as strain SK-16T, was isolated from the coastal surface water of a semi-enclosed coastal inlet in Misaki, Japan. Analysis of 16S rRNA gene sequences revealed that SK-16T represented a member of the family Flavobacteriaceae and was closely related to the genus Algibacter, with sequence similarities ranging from 95.9 to 94.3 % to the type strains of species of the genus Algibacter. The major cellular fatty acids were iso-C15 : 0, iso-C17 : 0 3-OH, iso-C15 : 0 G and iso-C15 : 0 3-OH. Major polar lipids were phosphatidylethanolamine, an aminophospholipid and an unidentified phospholipid. The DNA G+C content of SK-16T was 32.3 mol% and MK-6 was the only predominant isoprenoid quinone. On the basis of the results of phenotypic, genotypic, chemotaxonomic and phylogenetic studies, it was suggested that SK-16T represents a novel species within the genus Algibacter, with the newly proposed name Algibacteraquaticus. The type strain is SK-16T (=NBRC 110220T=KCTC 32974T).


Assuntos
Flavobacteriaceae/classificação , Filogenia , Água do Mar/microbiologia , Técnicas de Tipagem Bacteriana , Composição de Bases , DNA Bacteriano/genética , Ácidos Graxos/química , Flavobacteriaceae/genética , Flavobacteriaceae/isolamento & purificação , Japão , Fosfolipídeos/química , Pigmentação , RNA Ribossômico 16S/genética , Análise de Sequência de DNA , Vitamina K 2/análogos & derivados , Vitamina K 2/química
15.
J Natl Compr Canc Netw ; 14(3): 311-9, 2016 03.
Artigo em Inglês | MEDLINE | ID: mdl-26957617

RESUMO

BACKGROUND: This study sought to understand the preferences of patients with cancer and the trade-offs between appointment attributes using discrete choice experiment (DCE). METHODS AND STUDY DESIGN: Patients with cancer at 3 hospitals completed a self-administered DCE. Each scenario described 6 attributes: expertise of health care professionals (HCPs), familiarity of doctors with patients' medical history, waiting time, accompaniment by family/friends, travel time, and out-of-pocket costs. Patient preferences were estimated using logistic regression. Willingness to pay (WTP) estimates were derived from regression coefficients. RESULTS: Of 512 patients contacted, 185 returned the questionnaire. The mean age was 61 years, and 60% of respondents were female. The mean time since cancer diagnosis was 34 months, 90% had received treatment; and 61% had early-stage disease. The most important attributes were expertise and familiarity of doctors with patients' medical history; distance traveled was least likely to influence patient preferences. The WTP analysis estimated that patients were willing to pay $680 (95% CI, 470-891) for an appointment with a specialist, $571 (95% CI, 388-754) for doctors familiar with their history, $422 (95% CI, 262-582) for shorter waiting times, $399 (95% CI, 249-549) to be accompanied by family/friends, and $301 (95% CI, 162-441) for shorter traveling times. Male patients had a stronger preference for accompaniment by family/friends. The expertise of HCP was the most important attribute for patients regardless of geographic remoteness. CONCLUSIONS: Our study can assist the development of patient-centered health care models that improve patient access to experienced HCPs, support the role of primary care providers during the cancer journey, and educate patients about the roles of non-oncology HCPs to cope with increasing demand for cancer care.


Assuntos
Agendamento de Consultas , Comportamento de Escolha , Gastos em Saúde , Neoplasias/psicologia , Preferência do Paciente/psicologia , Feminino , Gastos em Saúde/estatística & dados numéricos , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Neoplasias/economia , Neoplasias/terapia , Assistência Centrada no Paciente , Médicos de Atenção Primária , Inquéritos e Questionários
16.
Aust J Rural Health ; 24(2): 79-84, 2016 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-26122852

RESUMO

OBJECTIVE: This paper aims to describe cancer survival and examine association between survival and socio-demographic characteristics across Barwon South-Western region (BSWR) in Victoria, Australia. DESIGN: This study is based on the retrospective cohort database of patients accessing oncology services across BSWR. SETTING: Six rural and three urban hospital settings across the BSWR. PARTICIPANTS: The participants were patients who were diagnosed with cancer in 2009. MAIN OUTCOME MEASURES: Overall survival (OS) of participants was the main outcome measure. RESULTS: Total of 1778 eligible patients had four-year OS for all cancers combined of 59.7% (95% CI, 57.4-62.0). Improved OS was observed for patients in the upper socio-economic tertile (64.2%; 95% CI, 60.9-67.5) compared to the middle (59.3%; 95% CI, 55.5-63.1) and lowest tertiles (49.6%; 95% CI, 44.2-54.9) (P < 0.01). On multivariate analyses, higher socio-economic status remained a significant predictor of OS adjusting for gender, remoteness and age (HR [hazard ratio] 0.81; 95% CI 0.74-0.89; P < 0.01). Remoteness was significantly associated with improved OS after adjusting for age, gender and socio-economic status (HR 0.86; 95% CI, 0.77-0.97; P = 0.01). Older age ≥70 years compared to <70 years conferred inferior OS (HR 3.08; 95% CI, 2.64-3.59; P < 0.01). CONCLUSIONS: Our study confirmed improved survival outcomes for patients of higher socio-economic status and younger age. Future research to explain the unexpected survival benefit in patients who lived in more remote areas should examine factors including the correlation between geographical residence and eventual treatment facility as well as compare the BSWR care model to other regions' approaches.


Assuntos
Neoplasias , Sobrevida , Idoso , Idoso de 80 Anos ou mais , Bases de Dados Factuais , Feminino , Hospitais Urbanos , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias/mortalidade , Estudos Retrospectivos , Classe Social , Vitória/epidemiologia
17.
Appl Environ Microbiol ; 81(12): 4184-94, 2015 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-25862229

RESUMO

Dimethylsulfoniopropionate (DMSP) is mainly produced by marine phytoplankton but is released into the microbial food web and degraded by marine bacteria to dimethyl sulfide (DMS) and other products. To reveal the abundance and distribution of bacterial DMSP degradation genes and the corresponding bacterial communities in relation to DMS and DMSP concentrations in seawater, we collected surface seawater samples from DMS hot spot sites during a cruise across the Pacific Ocean. We analyzed the genes encoding DMSP lyase (dddP) and DMSP demethylase (dmdA), which are responsible for the transformation of DMSP to DMS and DMSP assimilation, respectively. The averaged abundance (±standard deviation) of these DMSP degradation genes relative to that of the 16S rRNA genes was 33% ± 12%. The abundances of these genes showed large spatial variations. dddP genes showed more variation in abundances than dmdA genes. Multidimensional analysis based on the abundances of DMSP degradation genes and environmental factors revealed that the distribution pattern of these genes was influenced by chlorophyll a concentrations and temperatures. dddP genes, dmdA subclade C/2 genes, and dmdA subclade D genes exhibited significant correlations with the marine Roseobacter clade, SAR11 subgroup Ib, and SAR11 subgroup Ia, respectively. SAR11 subgroups Ia and Ib, which possessed dmdA genes, were suggested to be the main potential DMSP consumers. The Roseobacter clade members possessing dddP genes in oligotrophic subtropical regions were possible DMS producers. These results suggest that DMSP degradation genes are abundant and widely distributed in the surface seawater and that the marine bacteria possessing these genes influence the degradation of DMSP and regulate the emissions of DMS in subtropical gyres of the Pacific Ocean.


Assuntos
Bactérias/classificação , Bactérias/metabolismo , Genes Bacterianos , Consórcios Microbianos , Água do Mar/microbiologia , Compostos de Sulfônio/metabolismo , Bactérias/isolamento & purificação , Liases de Carbono-Enxofre/genética , Clorofila , Clorofila A , DNA Bacteriano/genética , Consórcios Microbianos/genética , Consórcios Microbianos/fisiologia , Oxirredutases/genética , Oxirredutases/metabolismo , Oceano Pacífico , Filogenia , RNA Ribossômico 16S/genética , Roseobacter/genética , Roseobacter/isolamento & purificação , Roseobacter/metabolismo , Análise de Sequência de DNA , Sulfetos/metabolismo , Temperatura
18.
Int J Syst Evol Microbiol ; 65(10): 3276-3280, 2015 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-26296998

RESUMO

A slightly curved-rod-shaped, pink-pigmented, Gram-stain-negative, aerobic bacterial strain with gliding motility, designated SK-8T, was isolated from coastal surface water of Misaki, Japan. Phylogenetic trees generated using 16S rRNA gene sequences revealed that strain SK-8T belonged to the genus Fabibacter and showed 96.0 % sequence similarity to the type strain of the most closely related species, Fabibacter pacificus DY53T. The novel isolate was phenotypically and physiologically different from previously described strains. The major cellular fatty acids were iso-C15 : 1 G, iso-C15 : 0 and iso-C17 : 0 3-OH. Major polar lipids were phosphatidylethanolamine, two aminophospholipids and an unidentified phospholipid. The DNA G+C content was 39.1 mol% and MK-7 was the only predominant isoprenoid quinone. On the basis of this taxonomic study employing a polyphasic approach, it was suggested that strain SK-8T represents a novel species of the genus Fabibacter, with the newly proposed name Fabibacter misakiensis sp. nov. The type strain is SK-8T ( = NBRC 110216T = KCTC 32969T).


Assuntos
Flavobacteriaceae/classificação , Filogenia , Água do Mar/microbiologia , Técnicas de Tipagem Bacteriana , Composição de Bases , DNA Bacteriano/genética , Ácidos Graxos/química , Flavobacteriaceae/genética , Flavobacteriaceae/isolamento & purificação , Japão , Dados de Sequência Molecular , Fosfolipídeos/química , Pigmentação , RNA Ribossômico 16S/genética , Análise de Sequência de DNA , Vitamina K 2/análogos & derivados , Vitamina K 2/química , Microbiologia da Água
19.
Transfus Apher Sci ; 53(2): 196-204, 2015 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-25910537

RESUMO

There are few randomized trials comparing filgrastim and pegfilgrastim in peripheral blood stem cell mobilization (PBSCM). None of the trials studied the effects of the timing of pegfilgrastim administration on the outcomes of mobilization. We conducted a randomized triple blind control trial comparing the outcomes of filgrastim 5 µg/kg daily from day 3 onwards, 'early' pegfilgrastim 6 mg on day 3 and 'delayed' pegfilgrastim 6 mg on day 7 in cyclophosphamide PBSCM in patients with no previous history of mobilization. Peripheral blood (PB) CD34+ cell count was checked on day 8 and day 11 onward. Apheresis was started when PB CD34+ ≥ 10/µl from day 11 onward. The primary outcome was the successful mobilization rate, defined as cumulative collection of ≥ 2 × 10(6)/kg CD34+ cells in three or less apheresis. The secondary outcomes were the day of neutrophil and platelet engraftment post transplantation. There were 156 patients randomized and 134 patients' data analyzed. Pegfilgrastim 6 mg day 7 produced highest percentage of successful mobilization, 34 out of 48 (70.8%) analyzed patients, followed by daily filgrastim, 28 out of 44 (63.6%) and day 3 pegfilgrastim, 20 out of 42 (47.6%) (p = 0.075). Pegfilgrastim day 7 and daily filgrastim reported 1.48 (p = 0.014) and 1.49 (p = 0.013) times higher successful mobilization rate respectively as compared to pegfilgrastim day 3 after adjusting for disease, gender and exposure to myelotoxic agent. Multiple myeloma patients were three times more likely to achieve successful mobilization as compared to acute leukemia or lymphoma patients. Pegfilgrastim avoided the overshoot of white cells compared to filgrastim. There was no difference in the duration of both white cells and platelet recovery post transplantation between the three interventional arms.


Assuntos
Ciclofosfamida/administração & dosagem , Filgrastim/administração & dosagem , Fator Estimulador de Colônias de Granulócitos/administração & dosagem , Mobilização de Células-Tronco Hematopoéticas/métodos , Leucemia/sangue , Linfoma/sangue , Mieloma Múltiplo/sangue , Doença Aguda , Adolescente , Adulto , Autoenxertos , Criança , Método Duplo-Cego , Humanos , Leucemia/terapia , Linfoma/terapia , Pessoa de Meia-Idade , Mieloma Múltiplo/terapia , Transplante de Células-Tronco de Sangue Periférico , Polietilenoglicóis , Proteínas Recombinantes/administração & dosagem
20.
Exp Dermatol ; 23(12): 916-21, 2014 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-25346513

RESUMO

Dopachrome tautomerase (DCT) is involved in the formation of the photoprotective skin pigment eumelanin and has also been shown to have a role in response to apoptotic stimuli and oxidative stress. The effect of DCT on UVR DNA damage responses and survival pathways in human melanocytic cells was examined by knockdown experiments using melanoma cells, neonatal foreskin melanoblasts (MB) in monoculture and in co-culture with human keratinocytes. MB cell strains genotyped as either MC1R WT or MC1R RHC homozygotes, which are known to be deficient in DCT, were transduced with lentivirus vectors for either DCT knockdown or overexpression. We found melanoma cell survival was reduced by DCT depletion and by UVR over time. UVR-induced p53 and pp53-Ser15 levels were reduced with DCT depletion. Knockdown of DCT in MC1R WT and MC1R RHC MB cells reduced their survival after UVR exposure, whereas increased DCT protein levels enhanced survival. DCT depletion reduced p53 and pp53-Ser15 levels in WM266-4 melanoma and MC1R WT MB cells, while MC1R RHC MB cells displayed variable levels. Both MC1R WT and RHC genotypes of MB cells were responsive to UVR at 3 h with increases in both p53 and pp53-Ser15 proteins. MC1R WT MB cell strains in coculture with keratinocytes have an increased cell survival after UVR exposure when compared to those in monoculture, a protective effect which appears to be conferred by the keratinocytes.


Assuntos
Sobrevivência Celular/efeitos da radiação , Oxirredutases Intramoleculares/metabolismo , Melanócitos/metabolismo , Melanócitos/efeitos da radiação , Raios Ultravioleta/efeitos adversos , Técnicas de Cocultura , Dano ao DNA , Técnicas de Silenciamento de Genes , Humanos , Oxirredutases Intramoleculares/antagonistas & inibidores , Oxirredutases Intramoleculares/genética , Queratinócitos/metabolismo , Melanócitos/citologia , Melanoma/genética , Melanoma/metabolismo , Melanoma/patologia , RNA Interferente Pequeno/genética , Espécies Reativas de Oxigênio/metabolismo , Receptor Tipo 1 de Melanocortina/genética , Receptor Tipo 1 de Melanocortina/metabolismo , Regulação para Cima
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