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1.
MMWR Suppl ; 73(2): 8-16, 2024 Feb 29.
Artigo em Inglês | MEDLINE | ID: mdl-38412115

RESUMO

This report is the second of three reports in the MMWR supplement updating CDC's guidance for investigating and responding to suicide clusters. The first report, Background and Rationale - CDC Guidance for Assessing, Investigating, and Responding to Suicide Clusters, United States, 2024, describes an overview of suicide clusters, methods used to develop the supplement guidance, and intended use of the supplement reports. The final report, CDC Guidance for Community Response to Suicide Clusters, United States, 2024, describes how local public health and community leaders can develop a response plan for suicide clusters. This report provides updated guidance for the approach to assessing and investigating suspected suicide clusters. Specifically, this approach will guide lead agencies in determining whether a confirmed suicide cluster exists, what concerns are in the community, and what the specific characteristics are of the suspected or confirmed suicide cluster. The guidance in this report is intended to support and assist lead agencies and their community prepare for, assess, and investigate suicide clusters. The steps provided in this report can be adapted to the local context, culture, capacity, circumstances, and needs for each suspected suicide cluster.


Assuntos
Suicídio , Humanos , Estados Unidos/epidemiologia , Vigilância da População , Centers for Disease Control and Prevention, U.S. , Saúde Pública , Análise por Conglomerados
2.
MMWR Suppl ; 73(2): 17-26, 2024 Feb 29.
Artigo em Inglês | MEDLINE | ID: mdl-38412137

RESUMO

This is the third of three reports in the MMWR supplement that updates and expands CDC's guidance for assessing, investigating, and responding to suicide clusters based on current science and public health practice. The first report, Background and Rationale - CDC Guidance for Communities Assessing, Investigating, and Responding to Suicide Clusters, United States, 2024, describes an overview of suicide clusters, methods used to develop the supplement guidance, and intended use of the supplement reports. The second report, CDC Guidance for Community Assessment and Investigation of Suspected Suicide Clusters, United States, 2024, describes the potential methods, data sources, and analysis that communities can use to identify and confirm suspected suicide clusters and better understand the relevant issues. This report describes how local public health and community leaders can develop a response plan for suicide clusters. Specifically, the steps for responding to a suicide cluster include preparation, direct response, and action for prevention. These steps are not intended to be explicitly adopted but rather adapted into the local context, culture, capacity, circumstances, and needs for each suicide cluster.


Assuntos
Suicídio , Humanos , Estados Unidos/epidemiologia , Prática de Saúde Pública , Centers for Disease Control and Prevention, U.S.
3.
MMWR Suppl ; 73(2): 1-7, 2024 Feb 29.
Artigo em Inglês | MEDLINE | ID: mdl-38412112

RESUMO

To assist community leaders in public health, mental health, education, and other fields with developing a community response plan for suicide clusters or for situations that might develop into suicide clusters, in 1988, CDC published Recommendations for a Community Plan for the Prevention and Containment of Suicide Clusters (MMWR Suppl 1988;37[No. Suppl 6]:1-12). Since that time, the reporting and investigation of suicide cluster events has increased, and more is known about cluster risk factors, assessment, and identification. This supplement updates and expands CDC guidance for assessing, investigating, and responding to suicide clusters based on current science and public health practice. This report is the first of three in the MMWR supplement that describes an overview of suicide clusters, information about the other reports in this supplement, methods used to develop the supplement guidance, and the intended use of the supplement reports. The second report, CDC Guidance for Community Assessment and Investigation of Suspected Suicide Clusters - United States 2024, describes the potential methods, data sources and analysis that communities can use to identify and confirm suspected suicide clusters, and better understand the relevant issues. The final report, CDC Guidance for Community Response to Suicide Clusters - United States, 2024, describes how local public health and community leaders can develop a response plan for suicide clusters. The guidance in this supplement is intended as a conceptual framework that can be used by public health practitioners and state and local health departments to develop response plans for assessing and investigating suspected clusters that are tailored to the needs, resources, and cultural characteristics of their communities.


Assuntos
Suicídio , Humanos , Estados Unidos/epidemiologia , Prática de Saúde Pública , Centers for Disease Control and Prevention, U.S. , Escolaridade , Fonte de Informação
4.
MMWR Morb Mortal Wkly Rep ; 72(19): 502-512, 2023 May 12.
Artigo em Inglês | MEDLINE | ID: mdl-37167103

RESUMO

The U.S. adolescent mental and behavioral health crisis is ongoing,* with high pre-COVID-19 pandemic baseline rates† (1) and further increases in poor mental health (2), suicide-related behaviors (3), and drug overdose deaths (4) reported during 2020-2021. CDC examined changes in U.S. emergency department (ED) visits for mental health conditions (MHCs) overall and for nine specific MHCs,§ suicide-related behaviors (including suspected suicide attempts), and drug-involved overdoses (including opioids) among children and adolescents aged 12-17 years (adolescents) during January 2019-February 2023, overall and by sex. Compared with fall 2021, by fall 2022, decreases in weekly ED visits were reported among all adolescents, and females specifically, for MHCs overall, suicide-related behaviors, and drug overdoses; weekly ED visits among males were stable. During this same period, increases in weekly ED visits for opioid-involved overdoses were detected. Mean weekly ED visits in fall 2022 for suicide-related behaviors and MHCs overall were at or lower than the 2019 prepandemic baseline, respectively, and drug overdose visits were higher. Differences by sex were observed; levels among females were at or higher than prepandemic baselines for these conditions. These findings suggest some improvements as of fall 2022 in the trajectory of adolescent mental and behavioral health, as measured by ED visits; however, poor mental and behavioral health remains a substantial public health problem, particularly among adolescent females. Early identification and trauma-informed interventions, coupled with expanded evidence-based, comprehensive prevention efforts, are needed to support adolescents' mental and behavioral health.


Assuntos
COVID-19 , Overdose de Drogas , Serviço Hospitalar de Emergência , Transtornos Mentais , Comportamento Autodestrutivo , Adolescente , Criança , Feminino , Humanos , Masculino , COVID-19/epidemiologia , Overdose de Drogas/epidemiologia , Serviço Hospitalar de Emergência/estatística & dados numéricos , Saúde Mental , Overdose de Opiáceos/epidemiologia , Pandemias , Estados Unidos/epidemiologia , Transtornos Mentais/epidemiologia , Comportamento Autodestrutivo/epidemiologia , Suicídio
5.
MMWR Suppl ; 72(1): 45-54, 2023 Apr 28.
Artigo em Inglês | MEDLINE | ID: mdl-37104546

RESUMO

Suicide is the third leading cause of death among high school-aged youths aged 14-18 years. The 2021 suicide rate for this age group was 9.0 per 100,000 population. Updating a previous analysis of the Youth Risk Behavior Survey during 2009-2019, this report uses 2019 and 2021 data to examine high school students' reports of suicidal thoughts and behaviors. Prevalence estimates are reported by grade, race and ethnicity, sexual identity, and sex of sexual contacts. Unadjusted logistic regression models were used to calculate prevalence differences comparing 2019 to 2021 and prevalence ratios comparing suicidal behavior between subgroups across demographic characteristics to a referent group. From 2019 to 2021, female students had an increased prevalence of seriously considered attempting suicide (from 24.1% to 30%), an increase in making a suicide plan (from 19.9% to 23.6%), and an increase in suicide attempts (from 11.0% to 13.3%). In addition, from 2019 to 2021, Black or African American (Black), Hispanic or Latino (Hispanic), and White female students had an increased prevalence of seriously considered attempting suicide. In 2021, Black female students had an increased prevalence of suicide attempts and Hispanic female students had an increased prevalence of suicide attempts that required medical treatment compared with White female students. Prevalence of suicidal thoughts and behaviors remained stable overall for male students from 2019 to 2021. A comprehensive approach to suicide prevention with a focus on health equity is needed to address these disparities and reduce prevalence of suicidal thoughts and behaviors for all youths. School and community-based strategies include creating safe and supportive environments, promoting connectedness, teaching coping and problem solving, and gatekeeper training.


Assuntos
Comportamento do Adolescente , Ideação Suicida , Humanos , Masculino , Adolescente , Feminino , Estados Unidos/epidemiologia , Criança , Tentativa de Suicídio , Assunção de Riscos , Estudantes
6.
MMWR Morb Mortal Wkly Rep ; 71(41): 1301-1305, 2022 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-36227769

RESUMO

Social and educational disruptions during the COVID-19 pandemic have exacerbated concerns about adolescents' mental health and suicidal behavior. Data from the 2021 Adolescent Behaviors and Experiences Survey (ABES) indicate that 37.1% of U.S. high school students reported poor mental health during the COVID-19 pandemic, with 19.9% considering and 9.0% attempting suicide in the preceding year (1). Adverse childhood experiences (ACEs)* are associated with poor mental health and suicidal behaviors (2,3), and high prevalence of some ACEs have been documented during the pandemic (4). ACEs are preventable, potentially traumatic events that occur in childhood (ages 0-17 years) such as neglect, experiencing or witnessing violence, or having a family member attempt or die by suicide. Also included are aspects of a child's environment that can undermine their sense of safety, stability, and bonding. Associations between ACEs occurring during the pandemic and mental health or suicidal behaviors among U.S. high school students were examined using ABES data. Experience of one to two ACEs was associated with poorer mental health and increased suicidal behaviors, and these deleterious outcomes increased with additional ACE exposure. After adjusting for demographic characteristics, adolescents who reported four or more ACEs during the pandemic had a prevalence of poor current mental health four times as high as, and a prevalence of past-year suicide attempts 25 times as high as, those without ACEs during the pandemic. Experience of specific ACE types (e.g., emotional abuse) was associated with higher prevalences of poor mental health and suicidal behaviors. Prevention and intervention strategies (5), including early identification and trauma-informed mental health service and support provision, for ACEs and their acute and long-term impacts could help address the U.S. child and adolescent mental health and suicide crisis.†.


Assuntos
Comportamento do Adolescente , Experiências Adversas da Infância , COVID-19 , Adolescente , Comportamento do Adolescente/psicologia , COVID-19/epidemiologia , Criança , Pré-Escolar , Humanos , Lactente , Recém-Nascido , Saúde Mental , Pandemias , Estudantes , Ideação Suicida , Estados Unidos/epidemiologia
7.
MMWR Morb Mortal Wkly Rep ; 71(37): 1161-1168, 2022 Sep 16.
Artigo em Inglês | MEDLINE | ID: mdl-36107803

RESUMO

Compared with the general U.S. population, American Indian or Alaska Native (AI/AN) persons, particularly those who are not Hispanic or Latino (Hispanic) AI/AN, are disproportionately affected by suicide; rates among this group consistently surpass those among all other racial and ethnic groups (1). Suicide rates among non-Hispanic AI/AN persons increased nearly 20% from 2015 (20.0 per 100,000) to 2020 (23.9), compared with a <1% increase among the overall U.S. population (13.3 and 13.5, respectively) (1). Understanding characteristics of suicide among AI/AN persons is critical to developing and implementing effective prevention strategies. A 2018 report described suicides in 18 states among non-Hispanic AI/AN persons only (2). The current study used 2015-2020 National Violent Death Reporting System (NVDRS) data among 49 states, Puerto Rico, and the District of Columbia to examine differences in suicide characteristics and contributing circumstances among Hispanic and non-Hispanic AI/AN populations, including multiracial AI/AN. Results indicated higher odds across a range of circumstances, including 10 of 14 relationship problems (adjusted odds ratio [aOR] range = 1.2-3.8; 95% CI range = 1.0-5.3) and six of seven substance use problems (aOR range = 1.2-2.3; 95% CI range = 1.1-2.5), compared with non-AI/AN persons. Conversely, AI/AN decedents had reduced odds of having any current known mental health condition, any history of mental health or substance use treatment, and other common risk factors (aOR range = 0.6-0.8; 95% CI = 0.2-0.9). Suicide is preventable. Communities can implement a comprehensive public health approach to suicide prevention that addresses long-standing inequities affecting AI/AN populations (3).


Assuntos
Transtornos Relacionados ao Uso de Substâncias , Suicídio , Etnicidade , Hispânico ou Latino , Humanos , Estados Unidos/epidemiologia
8.
Front Genet ; 12: 665888, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34149808

RESUMO

RNA sequencing (RNAseq) has been widely used to generate bulk gene expression measurements collected from pools of cells. Only relatively recently have single-cell RNAseq (scRNAseq) methods provided opportunities for gene expression analyses at the single-cell level, allowing researchers to study heterogeneous mixtures of cells at unprecedented resolution. Tumors tend to be composed of heterogeneous cellular mixtures and are frequently the subjects of such analyses. Extensive method developments have led to several protocols for scRNAseq but, owing to the small amounts of RNA in single cells, technical constraints have required compromises. For example, the majority of scRNAseq methods are limited to sequencing only the 3' or 5' termini of transcripts. Other protocols that facilitate full-length transcript profiling tend to capture only polyadenylated mRNAs and are generally limited to processing only 96 cells at a time. Here, we address these limitations and present a novel protocol that allows for the high-throughput sequencing of full-length, total RNA at single-cell resolution. We demonstrate that our method produced strand-specific sequencing data for both polyadenylated and non-polyadenylated transcripts, enabled the profiling of transcript regions beyond only transcript termini, and yielded data rich enough to allow identification of cell types from heterogeneous biological samples.

9.
Environ Health ; 20(1): 50, 2021 04 28.
Artigo em Inglês | MEDLINE | ID: mdl-33910568

RESUMO

BACKGROUND: Rice is an important dietary source for methylmercury; however, rice does not contain the same beneficial nutrients as fish. Our main objective was to assess associations of prenatal methylmercury exposure through rice ingestion with child neurodevelopment in rural China. METHODS: Eligible peripartum women were enrolled (n = 391), provided peripartum hair samples, and children's neurodevelopment was assessed at 12 months (n = 264, 68%) and 36 months (n = 190, 48%) using the Bayley Scales of Infant Development, 2nd Edition, including the Mental Developmental Index (MDI) and the Psychomotor Developmental Index (PDI). Associations between prenatal methylmercury exposure during the third trimester [log2 maternal hair total mercury (THg)] and child's neurodevelopment were assessed using linear mixed models for repeated measures. RESULTS: In adjusted models, a doubling in maternal hair THg corresponded to a 1.3-point decrement in the MDI score [95% confidence interval (CI): - 2.6, - 0.14], and a 1.2-point decrement in the PDI score (95% CI: - 2.6, 0.14). Overall, adverse associations between maternal hair THg and MDI scores attenuated over time. However, associations were robust and stable over time among children whose primary caregiver was their parent(s). During the study follow-up, an increasing proportion of children were raised by grandparents (12 months: 9% versus 36 months: 27%), a trend associated with rural-to-urban parental migration for work. CONCLUSIONS: For young children living in rural China, a biomarker of prenatal methylmercury exposure was associated with decrements in cognitive function assessed between 12 and 36 months of age. Changes in the family structure over the study follow-up time interval potentially impacted children's sensitivity to prenatal methylmercury exposure.


Assuntos
Desenvolvimento Infantil , Cognição , Exposição Dietética , Cabelo/química , Exposição Materna , Mercúrio/análise , Compostos de Metilmercúrio/análise , Efeitos Tardios da Exposição Pré-Natal , Pré-Escolar , China/epidemiologia , Feminino , Contaminação de Alimentos , Humanos , Lactente , Masculino , Oryza , Gravidez , Estudos Prospectivos , População Rural
10.
Sci Rep ; 11(1): 7384, 2021 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-33795717

RESUMO

We investigated cross-sectional associations between children's neurodevelopment and their gut microbiota composition. Study children (36 months of age) lived in rural China (n = 46). Neurodevelopment was assessed using the Bayley Scales of Infant Development, 2nd Edition, yielding the Mental Developmental Index (MDI) and Psychomotor Developmental Index (PDI). Children's gut microbiota was assessed using 16S rRNA gene profiling. Microbial diversity was characterized using alpha diversity patterns. Additionally, 3 coabundance factors were determined for the 25 most abundant taxa. Multivariable linear regression models were constructed to examine the relationships between Bayley scores (MDI and PDI) and children's gut microbiota. In adjusted models, MDI and PDI scores were not associated with alpha diversity indices. However, in adjusted models, MDI and PDI scores were positively associated with the first coabundance factor, which captured positive loadings for the genera Faecalibacterium, Sutterella, and Clostridium cluster XIVa. For an interquartile range increase in the first coabundance factor, MDI scores increased by 3.9 points [95% confidence interval (CI): 0, 7.7], while PDI scores increased by 8.6 points (95% CI 3.1, 14). Our results highlight the potential for gut microbial compositional characteristics to be important correlates of children's Bayley Scales performance at 36 months of age.


Assuntos
Microbioma Gastrointestinal , Adulto , Desenvolvimento Infantil , Pré-Escolar , China , Estudos Transversais , Fezes/microbiologia , Feminino , Seguimentos , Humanos , Masculino , Idade Materna , Modelos Neurológicos , Mães , Análise Multivariada , Estudos Prospectivos , RNA Ribossômico 16S/metabolismo , População Rural , Adulto Jovem
11.
Genome Biol Evol ; 12(7): 1174-1179, 2020 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-32449750

RESUMO

Plant mitochondrial genomes vary widely in size. Although many plant mitochondrial genomes have been sequenced and assembled, the vast majority are of angiosperms, and few are of gymnosperms. Most plant mitochondrial genomes are smaller than a megabase, with a few notable exceptions. We have sequenced and assembled the complete 5.5-Mb mitochondrial genome of Sitka spruce (Picea sitchensis), to date, one of the largest mitochondrial genomes of a gymnosperm. We sequenced the whole genome using Oxford Nanopore MinION, and then identified contigs of mitochondrial origin assembled from these long reads based on sequence homology to the white spruce mitochondrial genome. The assembly graph shows a multipartite genome structure, composed of one smaller 168-kb circular segment of DNA, and a larger 5.4-Mb single component with a branching structure. The assembly graph gives insight into a putative complex physical genome structure, and its branching points may represent active sites of recombination.


Assuntos
Genoma Mitocondrial , Genoma de Planta , Picea/genética , Estrutura Molecular
12.
Biotechniques ; 66(2): 85-92, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30744412

RESUMO

The analysis of cell-free circulating tumor DNA (ctDNA) is potentially a less invasive, more dynamic assessment of cancer progression and treatment response than characterizing solid tumor biopsies. Standard isolation methods require separation of plasma by centrifugation, a time-consuming step that complicates automation. To address these limitations, we present an automatable magnetic bead-based ctDNA isolation method that eliminates centrifugation to purify ctDNA directly from peripheral blood (PB). To develop and test our method, ctDNA from cancer patients was purified from PB and plasma. We found that allelic fractions of somatic single-nucleotide variants from target gene capture libraries were comparable, indicating that the PB ctDNA purification method may be a suitable replacement for the plasma-based protocols currently in use.


Assuntos
Ácidos Nucleicos Livres/sangue , DNA Tumoral Circulante/sangue , Ensaios de Triagem em Larga Escala/métodos , Neoplasias/sangue , Biomarcadores Tumorais/sangue , Biomarcadores Tumorais/isolamento & purificação , Ácidos Nucleicos Livres/isolamento & purificação , DNA Tumoral Circulante/isolamento & purificação , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Mutação , Neoplasias/genética
13.
Nucleic Acids Res ; 47(2): e12, 2019 01 25.
Artigo em Inglês | MEDLINE | ID: mdl-30418619

RESUMO

Tissues used in pathology laboratories are typically stored in the form of formalin-fixed, paraffin-embedded (FFPE) samples. One important consideration in repurposing FFPE material for next generation sequencing (NGS) analysis is the sequencing artifacts that can arise from the significant damage to nucleic acids due to treatment with formalin, storage at room temperature and extraction. One such class of artifacts consists of chimeric reads that appear to be derived from non-contiguous portions of the genome. Here, we show that a major proportion of such chimeric reads align to both the 'Watson' and 'Crick' strands of the reference genome. We refer to these as strand-split artifact reads (SSARs). This study provides a conceptual framework for the mechanistic basis of the genesis of SSARs and other chimeric artifacts along with supporting experimental evidence, which have led to approaches to reduce the levels of such artifacts. We demonstrate that one of these approaches, involving S1 nuclease-mediated removal of single-stranded fragments and overhangs, also reduces sequence bias, base error rates, and false positive detection of copy number and single nucleotide variants. Finally, we describe an analytical approach for quantifying SSARs from NGS data.


Assuntos
Artefatos , Fixadores , Formaldeído , Sequenciamento de Nucleotídeos em Larga Escala , Análise de Sequência de DNA , Animais , Biblioteca Genômica , Genômica , Temperatura Alta , Camundongos Endogâmicos C57BL , Inclusão em Parafina
14.
J Public Health Manag Pract ; 25 Suppl 1, Lead Poisoning Prevention: S105-S110, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30507778

RESUMO

On May 17, 2017, the Food and Drug Administration (FDA) issued a safety recall for the Magellan Diagnostics' LeadCare Testing Systems due to the potential for inaccurately low blood lead test results when used with venous blood samples. The Centers for Disease Control and Prevention (CDC) announced a health alert with retesting recommendations because those with a blood lead level of concern may have been missed and not connected to the appropriate follow-up services. A qualitative evaluation of 9 state childhood lead poisoning prevention programs' experiences is presented in this report. Interviewees reported using a variety of media and notification methods to inform key stakeholders about the recall and recommendations. Challenges experienced by programs in responding to retesting recommendations include incomplete and out-of-date lists of LeadCare users; missing or inaccurate information in their surveillance database; not having large laboratories and hospitals consider contacting persons for retesting to be within their purview; and having limited staff members to conduct emergency response activities. Two of the 9 states report subsequent challenges with their retesting rates. The retesting recommendations were generally viewed positively. The interviewees' comments provide insight into steps CDC might take to better serve state and local lead programs. Programs' experiences have led to a better understanding of the roles of their program when emergency events occur, their relationship with stakeholders as related to the blood lead testing and reporting process, and areas of improvement in surveillance databases. Public health agencies at all levels have important roles to play in preventing lead exposures and providing needed services when exposures occur. Programs may achieve long-term benefits by improving surveillance systems and having a better understanding of laboratory practices. CDC will continue to provide timely information and recommendations to state and local public health agencies to inform both routine and emergency response activities.


Assuntos
Centers for Disease Control and Prevention, U.S./normas , Chumbo/análise , Recall de Dispositivo Médico/normas , Centers for Disease Control and Prevention, U.S./organização & administração , Centers for Disease Control and Prevention, U.S./estatística & dados numéricos , Humanos , Chumbo/sangue , Intoxicação por Chumbo/prevenção & controle , Vigilância da População/métodos , Avaliação de Programas e Projetos de Saúde/métodos , Estados Unidos , United States Food and Drug Administration/organização & administração , United States Food and Drug Administration/estatística & dados numéricos
15.
IEEE Trans Neural Syst Rehabil Eng ; 20(6): 771-7, 2012 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-22875260

RESUMO

After stroke, capacity to complete tasks in the treatment setting with the more-affected arm is an unreliable index of actual use of that extremity in daily life. Available objective methods for monitoring real-world arm use rely on placing movement sensors on patients. These methods provide information on amount but not type of arm activity, e.g., functional versus nonfunctional movement. This paper presents an approach that places sensors on patients and household objects, overcoming this limitation. An accelerometer and the transmitter component of a radio-frequency proximity sensor are attached to objects; the receiver component is attached to the arm of interest. The receiver triggers an on-board radio-frequency identification tag to signal proximity when that arm is within 23 cm of an instrumented object. In benchmark testing, this system detected perfectly which arm was used to move the target object on 200 trials. In a laboratory study with 35 undergraduates, increasing the amount of time target objects were moved with the arm of interest resulted in a corresponding increase in system output . Moreover, measurement error was low ( ≤ 2.5%). The results support this system's reliability and validity in individuals with unimpaired movement; testing is now warranted in stroke patients.


Assuntos
Braço/fisiologia , Monitorização Ambulatorial/métodos , Movimento/fisiologia , Rádio/instrumentação , Aceleração , Atividades Cotidianas , Adolescente , Adulto , Benchmarking , Interpretação Estatística de Dados , Feminino , Mãos/fisiologia , Humanos , Masculino , Pessoa de Meia-Idade , Desempenho Psicomotor/fisiologia , Ondas de Rádio , Reprodutibilidade dos Testes , Adulto Jovem
16.
Biochem Biophys Res Commun ; 364(3): 601-7, 2007 Dec 21.
Artigo em Inglês | MEDLINE | ID: mdl-18028878

RESUMO

The macrophage protein tyrosine phosphatase-1 SHP-1 has been implicated in the pathogenesis of infection with leishmania. To identify the factors that may interact with SHP-1, Leishmania donovani promastigote lysates were added to a GST-SHP-1 affinity matrix. A 44kDa specifically bound protein was identified as leishmania fructose-1,6-bisphosphate aldolase (aldolase). Purified leishmania aldolase bound to SHP-1 indicating that the interaction was direct. In contrast, purified mammalian aldolase did not bind to SHP-1. Consistent with this, leishmania aldolase activated SHP-1 in vitro, whereas mammalian aldolase did not. The presence of leishmania aldolase in the cytosolic fractions prepared from infected macrophages indicated that leishmania aldolase is exported from phagolysosomes in infected cells where it can target host cytosolic proteins. In fact, co-immunoprecipitation showed association of leishmania aldolase with SHP-1. Moreover, leishmania aldolase-expressing macrophages showed the deactivated phenotype of leishmania infected cells as judged by much reduced inability to induce expression of nitric-oxide synthase in response to interferon-gamma treatment. Collectively, these data show that leishmania aldolase is a novel SHP-1 binding and activating protein that contributes to macrophage dysfunction.


Assuntos
Frutose-Bifosfato Aldolase/metabolismo , Leishmania donovani/enzimologia , Macrófagos/enzimologia , Macrófagos/parasitologia , Proteína Tirosina Fosfatase não Receptora Tipo 6/química , Proteína Tirosina Fosfatase não Receptora Tipo 6/metabolismo , Animais , Cromatografia de Afinidade , Citosol/efeitos dos fármacos , Citosol/enzimologia , Ativação Enzimática/efeitos dos fármacos , Indução Enzimática/efeitos dos fármacos , Frutose-Bifosfato Aldolase/isolamento & purificação , Interferon gama/farmacologia , Leishmania donovani/efeitos dos fármacos , Macrófagos/citologia , Macrófagos/efeitos dos fármacos , Camundongos , Camundongos Endogâmicos BALB C , Óxido Nítrico Sintase Tipo II/biossíntese , Ligação Proteica/efeitos dos fármacos , Proteínas Recombinantes de Fusão/metabolismo , Domínios de Homologia de src
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