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1.
bioRxiv ; 2023 Dec 19.
Artigo em Inglês | MEDLINE | ID: mdl-38187550

RESUMO

To ensure that the embryo can package exponentially increasing amounts of DNA, replication-dependent histones are some of the earliest transcribed genes from the zygotic genome. However, how the histone genes are identified is not known. The pioneer factors Zelda and CLAMP collaborate at a subset of genes to regulate zygotic genome activation in Drosophila melanogaster and target early activated genes to induce transcription. CLAMP also regulates the embryonic histone genes and helps establish the histone locus body, a suite of factors that controls histone mRNA biosynthesis. The relationship between Zelda and CLAMP led us to hypothesize that Zelda helps identify histone genes for early embryonic expression. We found that Zelda targets the histone locus early during embryogenesis, prior to histone gene expression. However, depletion of zelda in the early embryo does not affect histone mRNA levels or histone locus body formation. While surprising, these results concur with other investigations into Zelda's role in the early embryo, suggesting the earliest factors responsible for specifying the zygotic histone genes remain undiscovered.

2.
Asian J Psychiatr ; 62: 102745, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34216977

RESUMO

OBJECTIVES: Safe and efficient methods for introducing clozapine to patients with treatment-resistant schizophrenia (TRS) are needed. We investigated risk factors for clozapine discontinuation in the early phase of its introduction. METHODS: We conducted a nested case-control study at 14 psychiatric hospitals in Chiba, Japan. Data from pre-registered TRS patients were collected at 7 time points within 12 weeks before and after the start of clozapine introduction. We examined the demographic data, prior and concomitant psychotropic drugs, strategies for switching from prior antipsychotics, and blood test and Global Assessment of Function results. The Clinical Global Impression-Severity Scale was retrospectively scored at 12 weeks before and after clozapine introduction. RESULTS: Of 228 patients, clozapine treatment was continued in 213 (93.4 %) and discontinued in 15 (6.6 %) patients within 12 weeks. Clinical symptoms were improved to mild symptoms with a response rate of 14.9 %. Prior antipsychotics and concomitant psychotropic drugs except for mood stabilizers were significantly decreased. Histories of smoking (OR = 3.32, 95 %CI: 1.11-9.93) and antipsychotic treatment at chlorpromazine-equivalent doses <1200 mg within the past 5 years (OR = 3.93, 95 %CI: 1.24-12.50), but not antipsychotic switching strategy, were associated with clozapine discontinuation. Eosinophilia was the most frequent reason for discontinuation (n = 3, 20 %) and was associated with concomitant valproate at 4 weeks after the introduction. CONCLUSION: Clozapine is an effective option for TRS patients (especially those treated with higher doses of prior antipsychotics) in Japan. Clinicians should be cautious about concomitant valproate in the early phase of clozapine introduction due to a high risk of eosinophilia.


Assuntos
Antipsicóticos , Clozapina , Antipsicóticos/efeitos adversos , Estudos de Casos e Controles , Clozapina/efeitos adversos , Humanos , Japão , Estudos Retrospectivos , Fatores de Risco
3.
Neuropsychopharmacol Rep ; 40(3): 302-306, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32672008

RESUMO

AIMS: Since April 2020, the new Japanese mental health system has used the Intensive Case Management Screening Sheet (ICMSS) to identify patients' needs for case management services. This study aimed to examine the association between ICMSS score and service intensity and compare the magnitude of association between ICMSS score and service intensity with other scales. METHODS: We recruited patients who received case management services from a staff member in a psychiatric outpatient service, psychiatric day-care program, or outreach team based at one psychiatric hospital. Case management service needs and functioning were assessed using ICMSS, Global Assessment Functioning (GAF), and Personal and Social Performance (PSP). The case manager also documented all services received by the participant for 2 months. The association between each scale and service duration was examined. Furthermore, the magnitude of the association between each scale and service intensity was compared. RESULTS: Overall, 138 participants were included in the analysis. The most common diagnosis was schizophrenia. Mean total service duration was weakly but significantly correlated with ICMSS (Spearman's ρ = 0.320), GAF (ρ = -0.198), and PSP (ρ = -0.275) scores. Poisson's regression models and postestimation testing showed that the coefficient for ICMSS score (B = 0.144; 95% CI = 0.141, 0.148) was significantly larger than the coefficients for GAF (B = -0.017, 95% CI = -0.017, -0.016, χ2  = 15.70, P < 0.001) and PSP (B=-0.016, 95% CI = -0.017, -0.016, χ2  = 14.64, P < 0.001) scores. CONCLUSION: ICMSS may provide preliminary information on case management service needs, but the level of service should be based on the individual needs of each patient and shared decision-making between the patient and case manager.


Assuntos
Assistência Ambulatorial/métodos , Assistência Ambulatorial/tendências , Administração de Caso/tendências , Escalas de Graduação Psiquiátrica , Esquizofrenia/diagnóstico , Esquizofrenia/terapia , Adulto , Assistência Ambulatorial/normas , Administração de Caso/normas , Feminino , Humanos , Japão/epidemiologia , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Escalas de Graduação Psiquiátrica/normas , Esquizofrenia/epidemiologia
4.
Nat Commun ; 10(1): 5700, 2019 12 13.
Artigo em Inglês | MEDLINE | ID: mdl-31836703

RESUMO

The Drosophila genome encodes three BEN-solo proteins including Insensitive (Insv), Elba1 and Elba2 that possess activities in transcriptional repression and chromatin insulation. A fourth protein-Elba3-bridges Elba1 and Elba2 to form an ELBA complex. Here, we report comprehensive investigation of these proteins in Drosophila embryos. We assess common and distinct binding sites for Insv and ELBA and their genetic interdependencies. While Elba1 and Elba2 binding generally requires the ELBA complex, Elba3 can associate with chromatin independently of Elba1 and Elba2. We further demonstrate that ELBA collaborates with other insulators to regulate developmental patterning. Finally, we find that adjacent gene pairs separated by an ELBA bound sequence become less differentially expressed in ELBA mutants. Transgenic reporters confirm the insulating activity of ELBA- and Insv-bound sites. These findings define ELBA and Insv as general insulator proteins in Drosophila and demonstrate the functional importance of insulators to partition transcription units.


Assuntos
Cromatina/metabolismo , Proteínas Correpressoras/metabolismo , Proteínas de Ligação a DNA/metabolismo , Proteínas de Drosophila/metabolismo , Drosophila melanogaster/genética , Fatores de Transcrição/metabolismo , Ativação Transcricional , Animais , Animais Geneticamente Modificados , Linhagem Celular , Proteínas de Drosophila/genética , Embrião não Mamífero , Mutação , Fatores de Transcrição/genética
5.
Genetics ; 213(3): 865-876, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31551239

RESUMO

Boundaries in the Drosophila bithorax complex (BX-C) enable the regulatory domains that drive parasegment-specific expression of the three Hox genes to function autonomously. The four regulatory domains (iab-5, iab-6, iab-7, and iab-8) that control the expression of the Abdominal-B (Abd-B) gene are located downstream of the transcription unit, and are delimited by the Mcp, Fab-6, Fab-7, and Fab-8 boundaries. These boundaries function to block cross talk between neighboring regulatory domains. In addition, three of the boundaries (Fab-6, Fab-7, and Fab-8) must also have bypass activity so that regulatory domains distal to the boundaries can contact the Abd-B promoter. In the studies reported here, we have undertaken a functional dissection of the Fab-8 boundary using a boundary-replacement strategy. Our studies indicate that the Fab-8 boundary has two separable subelements. The distal subelement blocks cross talk, but cannot support bypass. The proximal subelement has only minimal blocking activity but is able to mediate bypass. A large multiprotein complex, the LBC (large boundary complex), binds to sequences in the proximal subelement and contributes to its bypass activity. The same LBC complex has been implicated in the bypass activity of the Fab-7 boundary.


Assuntos
Elementos Isolantes , Animais , Cromatina/genética , Cromatina/metabolismo , Proteínas de Drosophila/genética , Proteínas de Drosophila/metabolismo , Drosophila melanogaster , Proteínas de Homeodomínio/genética , Proteínas de Homeodomínio/metabolismo , Mutagênese
6.
Int J Soc Psychiatry ; 65(7-8): 621-630, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31394969

RESUMO

BACKGROUND: In intensive case management (ICM), users receive a wide variety of services of varying content, which makes it difficult to understand the global features of ICM programs. AIMS: The aim of this study was to examine the features of ICM programs using network analysis. METHODS: A total of 233 ICM users in two Japanese medical institutions were recruited to participate. All received services were recorded for 2 months. In the network analysis, nodes represented types of ICM services and edges between two nodes depicted when over 5% of participants received both types of services. RESULTS: We found high centrality values for 'H5. Hospital-based counseling', 'O13. Outreach support for mental health medications', 'H13. Hospital-based support for mental health medication', 'T5. Counseling via telecommunication', 'H3. Hospital-based coordination of services in the medical institution' and 'T2. Coordination of services with other institutions via telecommunication'. These results indicated that these services were associated with various other types of services. Social functioning was related to 'O13. Outreach support for mental health medication', whereas need for ICM was related to 'H13. Hospital-based support for mental health medications', 'T5. Counseling via telecommunication' and 'T2. Coordination of services with other institutions via telecommunication'. CONCLUSION: Based on these findings, we speculated that there are at least five types of core services in ICM: regular face-to-face contact, outreach services, hospital-based services, easy contacts and coordination. These findings clarified the features of ICM programs, which may help improve the understanding of case managers' practice.


Assuntos
Administração de Caso , Serviços Comunitários de Saúde Mental/métodos , Transtornos Mentais/terapia , Avaliação de Processos e Resultados em Cuidados de Saúde/métodos , Adulto , Feminino , Hospitalização/estatística & dados numéricos , Humanos , Japão , Masculino , Pessoa de Meia-Idade
7.
Nat Commun ; 10(1): 2367, 2019 05 30.
Artigo em Inglês | MEDLINE | ID: mdl-31147539

RESUMO

Nocturnin (NOCT) is a rhythmically expressed protein that regulates metabolism under the control of circadian clock. It has been proposed that NOCT deadenylates and regulates metabolic enzyme mRNAs. However, in contrast to other deadenylases, purified NOCT lacks the deadenylase activity. To identify the substrate of NOCT, we conducted a mass spectrometry screen and report that NOCT specifically and directly converts the dinucleotide NADP+ into NAD+ and NADPH into NADH. Further, we demonstrate that the Drosophila NOCT ortholog, Curled, has the same enzymatic activity. We obtained the 2.7 Šcrystal structure of the human NOCT•NADPH complex, which revealed that NOCT recognizes the chemically unique ribose-phosphate backbone of the metabolite, placing the 2'-terminal phosphate productively for removal. We provide evidence for NOCT targeting to mitochondria and propose that NADP(H) regulation, which takes place at least in part in mitochondria, establishes the molecular link between circadian clock and metabolism.

8.
J Gen Fam Med ; 20(3): 114-117, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-31065477

RESUMO

Schizophrenia patients have significantly lower life expectancy than the general population. Clozapine is the most effective antipsychotic to reduce the mortality rate in these patients. Here, we report a schizophrenic patient with clozapine-induced myocarditis and successful retrial. In the first trial, clozapine was discontinued due to myocarditis. In the second trial, the titration rate was slower, and sodium valproate was not coadministered with clozapine. The patient has not developed myocarditis over 3.5 years of observation. It may be possible to take clozapine for a long time even after clozapine-induced myocarditis, and thus improve the life expectancy of schizophrenia patients.

9.
Int J Ment Health Syst ; 13: 22, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30992714

RESUMO

BACKGROUND: In Japan, the mental health system has been shifting from hospitalization-based to community-based care; some organizations have gradually begun providing intensive case management (ICM) services. We developed an Intensive Case Management Screening Sheet (ICMSS) to screen for the need for ICM in people with mental illness. METHODS: The aim of this study was to examine the psychometric properties and discriminative ability of ICMSS. Subjects consisted of 911 people with mental illness. The ICMSS score was rated by a professional such as a nurse, social worker, or occupational therapist. RESULTS: Exploratory factor analysis showed a one-factor structure with 14 items. The factor structure was supported by confirmatory factor analysis (comparative fit index, 0.98; Tucker-Lewis index, 0.97; root mean square error test of close fit, 0.05). In the receiver operating characteristic analysis for discriminating between users and non-users of ICM services, the area under the curve (AUC) for ICMSS was significantly larger than for Global Assessment of Functioning and Personal and Social Performance Scale, indicating better discriminative ability. However, the AUC for ICMSS was moderate. Thus, we suggest that the need for ICM services is determined by quantitative assessment (i.e., ICMSS) and clinical judgment. CONCLUSION: ICMSS is a brief tool for mental health professionals that will be useful in routine clinical practice. We expect that ICMSS will be used as a measure that reflects the views of professionals from various disciplines in Japanese institutions.

10.
Epigenetics Chromatin ; 12(1): 2, 2019 01 03.
Artigo em Inglês | MEDLINE | ID: mdl-30602385

RESUMO

BACKGROUND: Boundaries in the Drosophila bithorax complex delimit autonomous regulatory domains that activate the parasegment (PS)-specific expression of homeotic genes. The Fab-7 boundary separates the iab-6 and iab-7 regulatory domains that control Abd-B expression in PS11 and PS12. This boundary is composed of multiple functionally redundant elements and has two key activities: it blocks crosstalk between iab-6 and iab-7 and facilitates boundary bypass. RESULTS: Here, we have used a structure-function approach to elucidate the biochemical properties and the in vivo activities of a conserved BEN domain protein, Insensitive, that is associated with Fab-7. Our biochemical studies indicate that in addition to the C-terminal BEN DNA-binding domain, Insv has two domains that mediate multimerization: one is a coiled-coil domain in the N-terminus, and the other is next to the BEN domain. These multimerization domains enable Insv to bind simultaneously to two canonical 8-bp recognition motifs, as well as to a ~ 100-bp non-canonical recognition sequence. They also mediate the assembly of higher-order multimers in the presence of DNA. Transgenic proteins lacking the N-terminal coiled-coil domain are compromised for boundary function in vivo. We also show that Insv interacts directly with CP190, a protein previously implicated in the boundary functions of several DNA-binding proteins, including Su(Hw) and dCTCF. While CP190 interaction is required for Insv binding to a subset of sites on polytene chromosomes, it has only a minor role in the boundary activity of Insv in the context of Fab-7. CONCLUSIONS: The subdivision of eukaryotic chromosomes into discrete topological domains depends upon the pairing of boundary elements. In flies, pairing interactions are specific and typically orientation dependent. They occur in cis between neighboring heterologous boundaries, and in trans between homologous boundaries. One potential mechanism for ensuring pairing-interaction specificity is the use of sequence-specific DNA-binding proteins that can bind simultaneously with two or more recognition sequences. Our studies indicate that Insv can assemble into a multivalent DNA-binding complex and that the N-terminal Insv multimerization domain is critical for boundary function.


Assuntos
Proteínas Correpressoras/química , Proteínas de Drosophila/química , Multimerização Proteica , Animais , Sítios de Ligação , Proteínas Correpressoras/genética , Proteínas Correpressoras/metabolismo , Drosophila , Proteínas de Drosophila/genética , Proteínas de Drosophila/metabolismo , Elementos Isolantes , Proteínas Associadas aos Microtúbulos/metabolismo , Proteínas Nucleares/metabolismo , Ligação Proteica
11.
PLoS Genet ; 14(8): e1007442, 2018 08.
Artigo em Inglês | MEDLINE | ID: mdl-30110328

RESUMO

Expression of the three bithorax complex homeotic genes is orchestrated by nine parasegment-specific regulatory domains. Autonomy of each domain is conferred by boundary elements (insulators). Here, we have used an in situ replacement strategy to reanalyze the sequences required for the functioning of one of the best-characterized fly boundaries, Fab-7. It was initially identified by a deletion, Fab-71, that transformed parasegment (PS) 11 into a duplicate copy of PS12. Fab-71 deleted four nuclease hypersensitive sites, HS*, HS1, HS2, and HS3, located between the iab-6 and iab-7 regulatory domains. Transgenic and P-element excision experiments mapped the boundary to HS*+HS1+HS2, while HS3 was shown to be the iab-7 Polycomb response element (PRE). Recent replacement experiments showed that HS1 is both necessary and sufficient for boundary activity when HS3 is also present in the replacement construct. Surprisingly, while HS1+HS3 combination has full boundary activity, we discovered that HS1 alone has only minimal function. Moreover, when combined with HS3, only the distal half of HS1, dHS1, is needed. A ~1,000 kD multiprotein complex containing the GAF protein, called the LBC, binds to the dHS1 sequence and we show that mutations in dHS1, that disrupt LBC binding in nuclear extracts, eliminate boundary activity and GAF binding in vivo. HS3 has binding sites for GAF and Pho proteins that are required for PRE silencing. In contrast, HS3 boundary activity only requires the GAF binding sites. LBC binding with HS3 in nuclear extracts, and GAF association in vivo, depend upon the HS3 GAF sites, but not the Pho sites. Consistent with a role for the LBC in HS3 boundary activity, the boundary function of the dHS1+HS3mPho combination is lost when the flies are heterozygous for a mutation in the GAF gene. Taken together, these results reveal a novel function for the iab-7 PREs in chromosome architecture.


Assuntos
Proteínas de Drosophila/genética , Drosophila/genética , Genes de Insetos , Proteínas do Grupo Polycomb/genética , Elementos de Resposta , Animais , Cromatina , Imunoprecipitação da Cromatina , Fragmentação do DNA , Drosophila/metabolismo , Proteínas de Drosophila/metabolismo , Epigênese Genética , Regulação da Expressão Gênica , Genes Homeobox , Elementos Isolantes , Masculino , Mutação , Proteínas do Grupo Polycomb/metabolismo
12.
Genetics ; 210(2): 573-585, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-30082280

RESUMO

Boundaries (insulators) in the Drosophila bithorax complex (BX-C) delimit autonomous regulatory domains that orchestrate the parasegment (PS)-specific expression of the BX-C homeotic genes. The Fab-7 boundary separates the iab-6 and iab-7 regulatory domains, which control Abd-B expression in PS11 and PS12, respectively. This boundary is composed of multiple functionally redundant elements and has two key functions: it blocks cross talk between iab-6 and iab-7 and facilitates boundary bypass. Here, we show that two BEN domain protein complexes, Insensitive and Elba, bind to multiple sequences located in the Fab-7 nuclease hypersensitive regions. Two of these sequences are recognized by both Insv and Elba and correspond to a CCAATTGG palindrome. Elba also binds to a related CCAATAAG sequence, while Insv does not. However, the third Insv recognition sequences is ∼100 bp in length and contains the CCAATAAG sequence at one end. Both Insv and Elba are assembled into large complexes (∼420 and ∼265-290 kDa, respectively) in nuclear extracts. Using a sensitized genetic background, we show that the Insv protein is required for Fab-7 boundary function and that PS11 identity is not properly established in insv mutants. This is the first demonstration that a BEN domain protein is important for the functioning of an endogenous fly boundary.


Assuntos
Proteínas Correpressoras/metabolismo , Proteínas de Drosophila/metabolismo , Regulação da Expressão Gênica no Desenvolvimento , Elementos Isolantes , Animais , Proteínas Correpressoras/genética , Drosophila , Proteínas de Drosophila/genética , Desenvolvimento Embrionário/genética , Ligação Proteica , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo
13.
Mol Cell Biol ; 37(21)2017 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-28784719

RESUMO

Chromatin entry sites (CES) are 100- to 1,500-bp elements that recruit male-specific lethal (MSL) complexes to the X chromosome to upregulate expression of X-linked genes in male flies. CES contain one or more ∼20-bp GA-rich sequences called MSL recognition elements (MREs) that are critical for dosage compensation. Recent studies indicate that CES also correspond to boundaries of X-chromosomal topologically associated domains (TADs). Here, we show that an ∼1,000-kDa complex called the late boundary complex (LBC), which is required for the functioning of the Bithorax complex boundary Fab-7, interacts specifically with a special class of CES that contain multiple MREs. Mutations in the MRE sequences of three of these CES that disrupt function in vivo abrogate interactions with the LBC. Moreover, reducing the levels of two LBC components compromises MSL recruitment. Finally, we show that several of the CES that are physically linked to each other in vivo are LBC interactors.


Assuntos
Proteínas de Drosophila/genética , Drosophila melanogaster/genética , Cromossomo X/genética , Animais , Mecanismo Genético de Compensação de Dose , Genes Ligados ao Cromossomo X , Loci Gênicos , Elementos Isolantes , Masculino , Mutação
14.
Hum Fertil (Camb) ; 20(4): 285-292, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-28325095

RESUMO

The objective of this study was to investigate the effects of low-dose hCG supplementation on ICSI outcomes and controlled ovarian stimulation (COS) cost. Three hundred and thirty patients undergoing ICSI were split into groups according to the COS protocol: (i) control group (n = 178), including patients undergoing conventional COS treatment; and (ii) low-dose hCG group (n = 152), including patients undergoing COS with low-dose hCG supplementation. Lower mean total doses of FSH administered and higher mean oestradiol level and mature oocyte rates were observed in the low-dose hCG group. A significantly higher fertilization rate, high-quality embryo rate and blastocyst formation rate were observed in the low-dose hCG group as compared to the control group. The miscarriage rate was significantly higher in the control group compared to the low-dose hCG group. A significantly lower incidence of OHSS was observed in the low-dose hCG group. There was also a significantly lower gonadotropin cost in the low-dose hCG group as compared to the control group ($1235.0 ± 239.0×$1763.0 ± 405.3, p < 0.001). The concomitant use of low-dose hCG and FSH results in a lower abortion rate and increased number of mature oocytes retrieved, as well as improved oocyte quality, embryo quality and blastocyst formation and reduced FSH requirements.


Assuntos
Gonadotropina Coriônica/administração & dosagem , Hormônio Foliculoestimulante/administração & dosagem , Oócitos/efeitos dos fármacos , Indução da Ovulação/métodos , Injeções de Esperma Intracitoplásmicas/métodos , Adulto , Transferência Embrionária , Feminino , Fase Folicular , Humanos , Gravidez , Taxa de Gravidez , Estudos Retrospectivos , Resultado do Tratamento , Adulto Jovem
15.
PLoS One ; 12(3): e0173602, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28296955

RESUMO

The Drosophila GAGA factor (GAF) has an extraordinarily diverse set of functions that include the activation and silencing of gene expression, nucleosome organization and remodeling, higher order chromosome architecture and mitosis. One hypothesis that could account for these diverse activities is that GAF is able to interact with partners that have specific and dedicated functions. To test this possibility we used affinity purification coupled with high throughput mass spectrometry to identify GAF associated partners. Consistent with this hypothesis the GAF interacting network includes a large collection of factors and complexes that have been implicated in many different aspects of gene activity, chromosome structure and function. Moreover, we show that GAF interactions with a small subset of partners is direct; however for many others the interactions could be indirect, and depend upon intermediates that serve to diversify the functional capabilities of the GAF protein.


Assuntos
Trifosfato de Adenosina/metabolismo , Proteínas de Ligação a DNA/fisiologia , Proteínas de Drosophila/fisiologia , Fatores de Transcrição/fisiologia , Animais , Cromatina/metabolismo , Drosophila , Ensaio de Desvio de Mobilidade Eletroforética , Espectrometria de Massas , Coelhos , Técnicas do Sistema de Duplo-Híbrido
16.
Genetics ; 205(2): 589-603, 2017 02.
Artigo em Inglês | MEDLINE | ID: mdl-28007886

RESUMO

Chromatin boundary elements subdivide chromosomes in multicellular organisms into physically independent domains. In addition to this architectural function, these elements also play a critical role in gene regulation. Here we investigated the evolution of a Drosophila Bithorax complex boundary element called Fab-7, which is required for the proper parasegment specific expression of the homeotic Abd-B gene. Using a "gene" replacement strategy, we show that Fab-7 boundaries from two closely related species, D. erecta and D. yakuba, and a more distant species, D. pseudoobscura, are able to substitute for the melanogaster boundary. Consistent with this functional conservation, the two known Fab-7 boundary factors, Elba and LBC, have recognition sequences in the boundaries from all species. However, the strategies used for maintaining binding and function in the face of sequence divergence is different. The first is conventional, and depends upon conservation of the 8 bp Elba recognition sequence. The second is unconventional, and takes advantage of the unusually large and flexible sequence recognition properties of the LBC boundary factor, and the deployment of multiple LBC recognition elements in each boundary. In the former case, binding is lost when the recognition sequence is altered. In the latter case, sequence divergence is accompanied by changes in the number, relative affinity, and location of the LBC recognition elements.


Assuntos
Cromatina/genética , Drosophila/genética , Evolução Molecular , Elementos Isolantes , Animais , Sequência Conservada , Proteínas de Drosophila/genética , Proteínas de Drosophila/metabolismo , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo
17.
ABCS health sci ; 46(2): 84-89, 15 ago. 2016. tab, ilus
Artigo em Português | LILACS | ID: biblio-827376

RESUMO

A Esclerose Lateral Amiotrófica (ELA) é uma doença neurodegenerativa do sistema nervoso central (SNC) que acomete tanto o neurônio motor superior (NMS) quanto o neurônio motor inferior (NMI), causando fraqueza e diminuição progressiva das habilidades funcionais. Entre os profissionais de saúde existe um déficit de informações sobre os objetivos e benefícios da fisioterapia nesta população. O objetivo deste estudo foi identificar os resultados da fisioterapia neurofuncional em pacientes com ELA. Realizou-se uma busca nas bases de dados Medline, Lilacs, SciELO, IBECS e PEDro, utilizando os seguintes descritores: esclerose lateral amiotrófica, espasticidade, força muscular, fadiga, fisioterapia, reabilitação, exercício e qualidade de vida. A busca resultou em dois artigos que tiveram seus resultados analisados, os dois avaliaram os resultados de um programa de exercícios domiciliares de intensidade moderada, associados ou não a outra conduta terapêutica. Os estudos encontrados apontaram menor deterioração na ALS Functional Rating Scale, e diminuição da espasticidade. Em conclusão, a fisioterapia neurofuncional mostrouse eficaz na manutenção da funcionalidade de pacientes com ELA por tempo mais prolongado.


Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder of the central nervous system that affects both the upper and lower motor neurons, causing weakness and a progressive decrease in functional skills. Among health professionals, there is a lack of information on the objectives and benefits of physical therapy in this population. The objective of this study was to identify the results of neurofunctional physical therapy in patients with ALS. A search of the Medline, Lilacs, SciELO, IBECS, and PEDro databases was performed by using the following keywords: "amyotrophic lateral sclerosis", "spasticity", "muscle strength", "fatigue", "physical therapy", "rehabilitation", "exercise", and "quality of life". The search led to analyze the results of two articles reviewing the data obtained from a moderate intensity home exercises program that was or was not associated with another therapeutic approach. The studies found showed less deterioration, according to the ALS Functional Rating Scale and decreased spasticity. In conclusion, neurofunctional physical therapy was shown to be effective in maintaining the functionality of patients with ALS for longer periods.


Assuntos
Humanos , Especialidade de Fisioterapia , Esclerose Lateral Amiotrófica/reabilitação , Qualidade de Vida , Atividades Cotidianas , Exercício Físico
18.
Sci Rep ; 6: 23276, 2016 Mar 18.
Artigo em Inglês | MEDLINE | ID: mdl-26987682

RESUMO

The development of a non-precious metal (NPM) fuel cell catalyst is extremely important to achieve globalization of polymer electrolyte fuel cells due to the cost and scarcity of platinum. Here, we report on a NPM cathode catalyst prepared by the pyrolysis of spherical polyimide nanoparticles that contain small amounts of Fe additive. 60 nm diameter Fe-containing polyimide nanoparticles were successfully synthesized by the precipitation polymerization of pyromellitic acid dianhydride and 1,3,5-tris(4-aminophenyl)benzene with Fe(acac)3 (acac = acetylacetonate) as an additive. The particles were subsequently carbonized by multistep pyrolysis to obtain the NPM catalyst while retaining the small particle size. The catalyst has good performance and promising durability for fuel cell applications. The fuel cell performance under a 0.2 MPa air atmosphere at 80 °C of 1.0 A cm(-2) at 0.46 V is especially remarkable and better than that previously reported.

19.
Rev. bras. ginecol. obstet ; 38(3): 140-146, Mar. 2016. tab, graf
Artigo em Inglês | LILACS | ID: lil-781450

RESUMO

Objective The aim of this study was to study the effects of Tribulus terrestris on sexual function in menopausal women. Methods This was a prospective, randomized, double-blind, placebo-controlled clinical trial that included 60 postmenopausal women with sexual dysfunction. The women were divided into two groups, placebo group and Tribulus group, and evaluated by using the Sexual Quotient-female version (SQ-F) and Female Intervention Efficacy Index (FIEI) questionnaires. Results There was no significant difference between the groups in age, age at menopause, civil status, race, and religion. In the evaluation with the SQ-F questionnaire, there were significant differences between the placebo (7.6±3.2) and Tribulus (10.2±3.2) groups in the domains of desire and sexual interest (p d" 0.001), foreplay (3.3±1.5 versus 4.2±1.0) (p d" 0.01), arousal and harmonious interaction with the partner (5.7±2.1 versus 7.2±2.6) (p d" 0.01), and comfort in sexual intercourse (6.5±2.4 versus 8.0±1.9) (p d" 0.01). There was no significant difference between the placebo and Tribulus groups in the domains of orgasm and sexual satisfaction (p = 0.28). In the FIEI questionnaire, there was a significant improvement (p < 0.001) in the domains of vaginal lubrication during coitus and/or foreplay (20 versus 83.3%), sensation in the genitalia during sexual intercourse or other stimuli (16.7 versus 76.7%), sensation in the genital region (20 versus 70%), sexual intercourse and/or other sexual stimulations (13.3 versus 43.3%), and the ability to reach orgasm (20% versus 73.3%). There was no significant difference in adverse effects between the two groups. Conclusions After 90 days of treatment, at the doses used, we found Tribulus terrestris to be effective in treating sexual problems among menopausal women.


Objetivo Estudar os efeitos doTribulus terrestris na função sexual demulheres após a menopausa. Métodos Ensaio clínico, prospectivo, randomizado, duplo-cego, placebo controlado, com 60 mulheres após a menopausa com disfunção sexual, divididas em dois grupos: Grupo Placebo e Grupo Tribulus, avaliadas através dos questionários Quociente Sexualversão Feminina (QS-F) e Female Intervention Efficacy Index (FIEI). Resultados Não houve diferença significante entre os grupos quanto à idade, idade de menopausa, estado civil, raça e religião. Na avaliação do questionário QS-F houve diferença significante entre os grupos Placebo (7,6±3,2) e Tribulus (10,2±3,2) nos aspectos desejo e interesse sexual (p d" 0,001), preliminares (3,3±1,5 versus 4,2±1,0) (p d" 0,01), excitação da mulher e sintonia com o parceiro (5,7±2,1 versus 7,2±2,6) (p d" 0,01) e no aspecto conforto na relação sexual (6,5±2,4 versus 8,0±1,9) (p d" 0,01). O aspecto orgasmo e satisfação sexual não houve diferença significante entre o Grupo Placebo e Tribulus (p = 0,28). No questionário FIEI houve melhora significante (p < 0,001) na lubrificação vaginal durante o coito e/ou preliminares (20 versus 83,3%), na sensação nas genitálias durante a relação sexual ou outros estímulos (16,7 versus 76,7%), na sensação na área genital (20 versus 70%), nas relações sexuais e/ou outras estimulações sexuais (13,3 versus 43,3%) e na capacidade de ter orgasmo (20% versus 73,3%). Quanto aos efeitos colaterais não houve diferença significante entre os dois Grupos. Conclusões Após noventa dias, podemos concluir que o Tribulus terrestris nas doses utilizadas demonstrou ser efetivo no tratamento das queixas sexuais dasmulheres após a menopausa.


Assuntos
Humanos , Feminino , Pessoa de Meia-Idade , Idoso , Menopausa , Fitoterapia , Extratos Vegetais/uso terapêutico , Disfunções Sexuais Fisiológicas/tratamento farmacológico , Tribulus , Método Duplo-Cego , Estudos Prospectivos , Comportamento Sexual
20.
Rev Bras Ginecol Obstet ; 38(3): 140-6, 2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-26902700

RESUMO

OBJECTIVE: The aim of this study was to study the effects of Tribulus terrestris on sexual function in menopausal women. METHODS: This was a prospective, randomized, double-blind, placebo-controlled clinical trial that included 60 postmenopausal women with sexual dysfunction. The women were divided into two groups, placebo group and Tribulus group, and evaluated by using the Sexual Quotient-female version (SQ-F) and Female Intervention Efficacy Index (FIEI) questionnaires. RESULTS: There was no significant difference between the groups in age, age at menopause, civil status, race, and religion. In the evaluation with the SQ-F questionnaire, there were significant differences between the placebo (7.6 ± 3.2) and Tribulus (10.2 ± 3.2) groups in the domains of desire and sexual interest (p ≤ 0.001), foreplay (3.3 ± 1.5 versus 4.2 ± 1.0) (p ≤ 0.01), arousal and harmonious interaction with the partner (5.7 ± 2.1 versus 7.2 ± 2.6) (p ≤ 0.01), and comfort in sexual intercourse (6.5 ± 2.4 versus 8.0 ± 1.9) (p ≤ 0.01). There was no significant difference between the placebo and Tribulus groups in the domains of orgasm and sexual satisfaction (p = 0.28). In the FIEI questionnaire, there was a significant improvement (p < 0.001) in the domains of vaginal lubrication during coitus and/or foreplay (20 versus 83.3%), sensation in the genitalia during sexual intercourse or other stimuli (16.7 versus 76.7%), sensation in the genital region (20 versus 70%), sexual intercourse and/or other sexual stimulations (13.3 versus 43.3%), and the ability to reach orgasm (20% versus 73.3%). There was no significant difference in adverse effects between the two groups. CONCLUSIONS: After 90 days of treatment, at the doses used, we found Tribulus terrestris to be effective in treating sexual problems among menopausal women.


Assuntos
Menopausa , Fitoterapia , Extratos Vegetais/uso terapêutico , Disfunções Sexuais Fisiológicas/tratamento farmacológico , Tribulus , Idoso , Método Duplo-Cego , Feminino , Humanos , Pessoa de Meia-Idade , Estudos Prospectivos , Comportamento Sexual
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