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1.
BMJ Open ; 12(12): e067901, 2022 12 29.
Artigo em Inglês | MEDLINE | ID: mdl-36581434

RESUMO

INTRODUCTION: Increasing economic opportunities have attracted people from sub-Saharan Africa to migrate to the Asia-Pacific region in the last two decades. The information on the health situation of these migrants is limited. We aim to assess scientific evidence on the health of sub-Saharan African migrants in the Asia-Pacific region using a scoping review. METHODS AND ANALYSIS: The review will be conducted according to the JBI guide on evidence synthesis, and the final results will be organised and reported in line with the Preferred Reporting Items for Systematic reviews and Meta-Analyses extension for scoping reviews. Search strategies have been developed centred on population-concept-context elements including sub-Saharan Africa, Asia-Pacific, migration and health. A total of eight databases will be searched, including PubMed, Embase, Cumulative Index to Nursing and Allied Health Literature, ProQuest, Scopus, Web of Science, Wanfang and CNKI. Title and abstract screening and full-text screening will be conducted by two researchers independently. Data will be charted according to predesigned form. ETHICS AND DISSEMINATION: This study involves neither human participants nor unpublished secondary data. Institutional review board approval is therefore not required. Findings of this scoping review will be disseminated through publication in a peer-reviewed journal, through academic network and project report.


Assuntos
Migrantes , Humanos , População Negra , África Subsaariana/epidemiologia , Ásia , Projetos de Pesquisa , Revisões Sistemáticas como Assunto , Literatura de Revisão como Assunto
2.
Environ Int ; 161: 107143, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-35176575

RESUMO

With the advent of the SARS-CoV-2 pandemic, Wastewater-Based Epidemiology (WBE) has been applied to track community infection in cities worldwide and has proven succesful as an early warning system for identification of hotspots and changingprevalence of infections (both symptomatic and asymptomatic) at a city or sub-city level. Wastewater is only one of environmental compartments that requires consideration. In this manuscript, we have critically evaluated the knowledge-base and preparedness for building early warning systems in a rapidly urbanising world, with particular attention to Africa, which experiences rapid population growth and urbanisation. We have proposed a Digital Urban Environment Fingerprinting Platform (DUEF) - a new approach in hazard forecasting and early-warning systems for global health risks and an extension to the existing concept of smart cities. The urban environment (especially wastewater) contains a complex mixture of substances including toxic chemicals, infectious biological agents and human excretion products. DUEF assumes that these specific endo- and exogenous residues, anonymously pooled by communities' wastewater, are indicative of community-wide exposure and the resulting effects. DUEF postulates that the measurement of the substances continuously and anonymously pooled by the receiving environment (sewage, surface water, soils and air), can provide near real-time dynamic information about the quantity and type of physical, biological or chemical stressors to which the surveyed systems are exposed, and can create a risk profile on the potential effects of these exposures. Successful development and utilisation of a DUEF globally requires a tiered approach including: Stage I: network building, capacity building, stakeholder engagement as well as a conceptual model, followed by Stage II: DUEF development, Stage III: implementation, and Stage IV: management and utilization. We have identified four key pillars required for the establishment of a DUEF framework: (1) Environmental fingerprints, (2) Socioeconomic fingerprints, (3) Statistics and modelling and (4) Information systems. This manuscript critically evaluates the current knowledge base within each pillar and provides recommendations for further developments with an aim of laying grounds for successful development of global DUEF platforms.


Assuntos
COVID-19 , Vigilância Epidemiológica Baseada em Águas Residuárias , COVID-19/epidemiologia , Saúde Global , Humanos , Pandemias , SARS-CoV-2 , Águas Residuárias
4.
Artigo em Inglês | MEDLINE | ID: mdl-34690392

RESUMO

We propose PET scanners using low atomic number media that undergo a persistent local change of state along the paths of the Compton recoil electrons. Measurement of the individual scattering locations and angles, deposited energies, and recoil electron directions allows using the kinematical constraints of the 2-body Compton scattering process to perform a statistical time-ordering of the scatterings, with a high probability of precisely identifying where the gamma first interacted in the detector. In these cases the Line-of-Response is measured with high resolution, determined by the underlying physics processes and not the detector segmentation. There are multiple such media that act through different mechanisms. As an example in which the change of state is quantum-mechanical through a change in molecular configuration, rather than thermodynamic, as in a bubble chamber, we present simulations of a two-state photoswitchable organic dye, a 'Switchillator', that is activated to a fluorescent-capable state by the ionization of the recoil electrons. The activated state is persistent, and can be optically excited multiple times to image individual activated molecules. Energy resolution is provided by counting the activated molecules. Location along the LOR is implemented by large-area time-of-flight MCP-PMT photodetectors with single photon time resolution in the tens of ps and sub-mm spatial resolution. Simulations indicate a large reduction of dose.

5.
Sci Adv ; 6(42)2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-33067243

RESUMO

The ongoing debate about the nature of coupling between climate and tectonics in mountain ranges derives, in part, from an imperfect understanding of how topography, climate, erosion, and rock uplift are interrelated. Here, we demonstrate that erosion rate is nonlinearly related to fluvial relief with a proportionality set by mean annual rainfall. These relationships can be quantified for tectonically active landscapes, and calculations based on them enable estimation of erosion where observations are lacking. Tests of the predictive power of this relationship in the Himalaya, where erosion is well constrained, affirm the value of our approach. Our model allows estimation of erosion rates in fluvial landscapes using readily available datasets, and the underlying relationship between erosion and rainfall offers the promise of a deeper understanding of how climate and tectonic evolution affect erosion and topography in space and time and of the potential influence of climate on tectonics.

6.
Rev Sci Instrum ; 91(5): 053105, 2020 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-32486706

RESUMO

We have designed and prototyped the process steps for the batch production of large-area micro-channel-plate photomultipliers (MCP-PMT) using the "air-transfer" assembly process developed with single LAPPDTM modules. Results are presented addressing the challenges of designing a robust package that can transmit large numbers of electrical signals for pad or strip readout from inside the vacuum tube and of hermetically sealing the large-perimeter window-body interface. We have also synthesized a photocathode in a large-area low-aspect-ratio volume and have shown that the micro-channel plates recover their functionality after cathode synthesis. These steps inform a design for a multi-module batch facility employing dual nested low-vacuum and ultra-high-vacuum systems in a small-footprint. The facility design provides full access to multiple MCP-PMT modules prior to hermetic pinch-off for leak-checking and real-time photocathode optimization.

7.
J Plast Reconstr Aesthet Surg ; 72(2): 290-293, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30527711

RESUMO

INTRODUCTION: Non-melanoma skin cancer incidence is increasing in New Zealand. Increased cost of care has led to service pressure and a review of models of care. A high-volume skin surgery service at Waikato Hospital has been developed to reduce service costs. This study examines the oncological safety of the new model. METHODS: Prospective data for all skin lesions excised were collected from December 2014 to December 2016. Primary outcomes were rate of complete excision, rate of incomplete excision and rate of narrow excision. RESULTS: A total of 2076 lesions were excised: 92% were complete, 4.2% were narrow and 3.2% were incomplete. CONCLUSION: The rate of narrow and incomplete excisions was low in a service delivered by supervised surgical registrars. The Skin Shop model is safe, inexpensive and suitable for adaptation to safely reduce the cost of skin cancer surgery.


Assuntos
Procedimentos Cirúrgicos Dermatológicos/métodos , Procedimentos Cirúrgicos Dermatológicos/estatística & dados numéricos , Neoplasias Cutâneas/cirurgia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Anestesia , Procedimentos Cirúrgicos Dermatológicos/economia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Modelos Organizacionais , Estudos Prospectivos , Centro Cirúrgico Hospitalar/organização & administração , Adulto Jovem
8.
Ecology ; 99(2): 312-321, 2018 02.
Artigo em Inglês | MEDLINE | ID: mdl-29315515

RESUMO

Long-term observations of ecological communities are necessary for generating and testing predictions of ecosystem responses to climate change. We investigated temporal trends and spatial patterns of soil fauna along similar environmental gradients in three sites of the McMurdo Dry Valleys, Antarctica, spanning two distinct climatic phases: a decadal cooling trend from the early 1990s through the austral summer of February 2001, followed by a shift to the current trend of warming summers and more frequent discrete warming events. After February 2001, we observed a decline in the dominant species (the nematode Scottnema lindsayae) and increased abundance and expanded distribution of less common taxa (rotifers, tardigrades, and other nematode species). Such diverging responses have resulted in slightly greater evenness and spatial homogeneity of taxa. However, total abundance of soil fauna appears to be declining, as positive trends of the less common species so far have not compensated for the declining numbers of the dominant species. Interannual variation in the proportion of juveniles in the dominant species was consistent across sites, whereas trends in abundance varied more. Structural equation modeling supports the hypothesis that the observed biological trends arose from dissimilar responses by dominant and less common species to pulses of water availability resulting from enhanced ice melt. No direct effects of mean summer temperature were found, but there is evidence of indirect effects via its weak but significant positive relationship with soil moisture. Our findings show that combining an understanding of species responses to environmental change with long-term observations in the field can provide a context for validating and refining predictions of ecological trends in the abundance and diversity of soil fauna.


Assuntos
Mudança Climática , Solo/química , Animais , Regiões Antárticas , Ecossistema , Microbiologia do Solo
9.
Arch Pediatr ; 24(7): 630-633, 2017 Jul.
Artigo em Francês | MEDLINE | ID: mdl-28583780

RESUMO

AIM: Nephrogenic syndrome of inappropriate antidiuresis (NSIAD) is a rare disease characterized by a kidney disability to dilute urine and, as a result, severe recurrent hyponatremia. Due to wide variability in clinical expression, the diagnosis still remains a challenge for clinicians. We report our experience of a case in which NSIAD was diagnosed early. We also stress the importance of early diagnosis and treatment, which protects an infant with NSAID from severe hyponatremia. BACKGROUND: A 1-month-old boy was referred to our hospital for persistent hyponatremia and intense vomiting. He was born full term after a normal pregnancy with a normal birth weight. The parents were healthy, nonconsanguineous, of Moroccan origin. They already had healthy twin girls. The physical examination was normal upon admission with no signs of dehydration and normal weight gain since birth. Plasma sodium was very low (125mmol/L) associated with low plasma urea (5mg/dL), osmolality (258 mOsm/kg) and low natriuresis (59mmol/L). These laboratory results suggested inappropriate antidiuretic hormone secretion (SIAD) and the infant was consequently treated with oral urea (he was already receiving sodium supplements that were later stopped). Due to exclusive breastfeeding, water restriction was impossible. Further biological investigation revealed undetectable plasma arginine vasopressin (AVP), suggesting the diagnosis of NSIAD. This was confirmed by genetic sequencing of the AVP receptor (AVPR2), demonstrating the presence of an R137C mutation. CONCLUSIONS: We herein report a case of a genetic fluid balance disorder due to an activating mutation of AVPR2. NSIAD is an X-linked disease, first described in 2005 by Feldman et al., which involved severe recurrent hyponatremia. The very early diagnosis (at 7 weeks of life) and appropriate treatment with urea prevented seizures and cerebral damage due to severe recurrent hyponatremia. Clinicians should consider the diagnosis of NSIAD in infants with recurrent hyponatremia with hemodilution and low AVP serum level. Genetic analysis of the AVPR2 sequence on the X chromosome will confirm the diagnosis and, given the wide variability of clinical expression, sequencing of the family members should be done.


Assuntos
Doenças Genéticas Ligadas ao Cromossomo X/diagnóstico , Hiponatremia/prevenção & controle , Síndrome de Secreção Inadequada de HAD/diagnóstico , Diagnóstico Precoce , Doenças Genéticas Ligadas ao Cromossomo X/genética , Humanos , Síndrome de Secreção Inadequada de HAD/genética , Recém-Nascido , Masculino , Mutação , Receptores de Vasopressinas/genética , Ureia/uso terapêutico
10.
J Hand Surg Eur Vol ; 42(4): 415-421, 2017 May.
Artigo em Inglês | MEDLINE | ID: mdl-28399786

RESUMO

A variety of surgical techniques are used to treat the arthritic distal radioulnar joint, which is influenced by aetiology and previous procedures. Four types of ulnar head arthroplasty exist: total ulnar head, partial ulnar head, unlinked total distal radioulnar joint, and linked distal radioulnar joint. Although long-term outcome studies are sparse, short-term clinical and biomechanical studies have shown encouraging results, leading to expanded indications. Based on our experience and a literature review, patients are advised that pain is improved but minor pain is common after strenuous activity. Ulnar neck resorption is common, however, implant loosening is rare. Sigmoid notch erosion is concerning, but appears to stabilize and not affect outcome. A partial ulnar head replacement that retains bony architecture and soft tissue restraints may have benefit over a total ulnar head in appropriate patients. If appropriate selection criteria are met, ulnar head replacement typically produces reliable results, with low revision.


Assuntos
Artroplastia de Substituição , Prótese Articular , Ulna/cirurgia , Articulação do Punho , Humanos , Desenho de Prótese
11.
Oncogene ; 36(4): 512-524, 2017 01 26.
Artigo em Inglês | MEDLINE | ID: mdl-27321180

RESUMO

Elucidating the mechanisms involved in sensitizing radioresistant tumors to ionizing radiation (IR) treatments while minimizing injury to surrounding normal tissue is an important clinical goal. Due to their sequence-derived specificity and properties as gene regulators in IR-affected pathways, microRNAs (miRNAs) could serve as adjuvant therapeutic agents that alter cellular sensitivity to radiation treatment. To identify radiosensitizing miRNAs, we initially utilized the Caenorhabditis elegans vulval cell model, an in vivo system developed to study IR-dependent radiosensitivity as a measure of clonogenic cell death. We tested several candidate miRNA-deletion mutants post γ-irradiation and identified cel-mir-237 as a miRNA which when deleted caused animals to be more resistant to IR, whereas cel-mir-237 overexpressing strains were IR sensitive. In addition, wild-type animals downregulated cel-mir-237 levels post IR in a time-dependent manner. We identified jun-1 (JUN transcription factor homolog) as a novel target of cel-mir-237. Specifically, jun-1 transcript levels increased in wild-type animals post γ-irradiation, and loss of cel-mir-237 also resulted in higher jun-1 expression. As expected, loss of jun-1 resulted in IR sensitivity, similar to the phenotype of cel-mir-237 overexpressors. As miR-237 is the homolog of human miR-125, we validated our findings in MCF-7 and MDA-MB-231 breast cancer cell lines, which harbor lower hsa-miR-125b levels than normal human mammary epithelial cells (HMECs). Forced expression of hsa-miR-125b in these cells resulted in radiosensitivity, as seen by reduced clonogenic survival, enhanced apoptotic activity and enhanced senescence post IR. Finally, re-expression of c-JUN in MDA-MB-231 cells promoted radioresistance and abrogated miR-125-mediated radiosensitization. Our findings suggest that overexpression of cel-mir-237 and its homolog, hsa-miR-125b, functions as sensitizers to γ-irradiation in both a nematode in vivo model and breast cancer cells, and could potentially be utilized as an adjuvant therapeutic to enhance radiation sensitivity.


Assuntos
Caenorhabditis elegans/efeitos da radiação , MicroRNAs/genética , MicroRNAs/metabolismo , Animais , Proteínas de Caenorhabditis elegans/genética , Proteínas de Caenorhabditis elegans/metabolismo , Proteínas de Caenorhabditis elegans/efeitos da radiação , Linhagem Celular Tumoral , Humanos , Células MCF-7 , Masculino , Radiação Ionizante , Transdução de Sinais , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Fatores de Transcrição/efeitos da radiação
12.
Osteoarthritis Cartilage ; 24(11): 1928-1939, 2016 11.
Artigo em Inglês | MEDLINE | ID: mdl-27450884

RESUMO

OBJECTIVE: The aim of this study was to investigate whether inflammogen-induced temporal and spatial gait changes in a rodent forced-ambulation paradigm were sensitive to pharmacological intervention with both clinically validated and novel analgesics. METHODS: Using the GaitScan (CleverSys Inc., Reston, VA) treadmill system, we identified four functional endpoints inspired by clinical literature and sensitive to unilateral joint injury induced by intra-articular Complete Freund's Adjuvant (CFA). These endpoints included: range of motion, normalized stance distance, stance/swing ratio, and paw print size as a measure of guarding; collectively, these measures are proposed to serve as a high fidelity index of joint pain. We then examined the ability of known analgesic mechanisms to attenuate gait impairment as measured by this index. RESULTS: Clinically efficacious opioids, Nonsteroidal anti-inflammatory drugs (NSAIDs), and the yet unapproved anti-NGF antibody dose-dependently attenuated the CFA)-induced gait deficits, while a TNF-alpha fusion protein blocker had no effect on gait, but did produce a reduction in swelling. As well, the time course for gait impairment in the model appears to be distinct from the traditional endpoint of tactile hypersensitivity, offering the potential to assess a novel functional pain phenotype. CONCLUSIONS: In response to the call for more functional pain measures, we submit this composite gait score as a novel endpoint to interrogate joint pain pre-clinically. As the etiology of human osteoarthritis (OA) remains unclear, this model/endpoint cannot attempt to improve construct validity, but may provide an additional dimension to interrogate pain-induced gait deficits.


Assuntos
Marcha , Analgésicos , Animais , Dor , Roedores
13.
Sci Rep ; 6: 26189, 2016 05 18.
Artigo em Inglês | MEDLINE | ID: mdl-27189430

RESUMO

Although most models suggest continental Antarctica was covered by ice during the Last Glacial Maximum (LGM) it has been speculated that endemic species of soil invertebrates could have survived the Pleistocene at high elevation habitats protruding above the ice sheets. We analyzed a series of soil samples from different elevations at three locations along the Beardmore Glacier in the Transantarctic Mountains (in order of increasing elevation): Ebony Ridge (ER), Cloudmaker (CM), and Meyer Desert (MD). Geochemical analyses show the MD soils, which were exposed during the LGM, were the least weathered compared to lower elevations, and also had the highest total dissolved solids (TDS). MD soils are dominated by nitrate salts (NO3/Cl ratios >10) that can be observed in SEM images. High δ(17)O and δ(18)O values of the nitrate indicate that its source is solely of atmospheric origin. It is suggested that nitrate concentrations in the soil may be utilized to determine a relative "wetting age" to better assess invertebrate habitat suitability. The highest elevation sites at MD have been exposed and accumulating salts for the longest times, and because of the salt accumulations, they were not suitable as invertebrate refugia during the LGM.


Assuntos
Ecossistema , Solo/química , Regiões Antárticas , Fenômenos Geológicos , Camada de Gelo , Nitratos/análise
14.
J Econ Entomol ; 109(3): 1161-1166, 2016 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-27063843

RESUMO

Field experiments were conducted in Starkville and Stoneville, MS; Marianna, AR; Winnsboro, LA; and Jackson, TN, during 2012 and 2014 to evaluate the relationship of corn earworm, Helicoverpa zea (Boddie), larval density and yield and the relationship between the percentage of damaged pods and yield in Mid-South soybean systems. Corn earworm moths were infested into field cages at R2 for 5-11 d to achieve a range of larval densities within each plot. Larval density was estimated at 14 d after infestation. Total pods and damaged pods were determined at 19 days after infestation to obtain the percentage of damaged pods. Plots were harvested at the end of each growing season and yield recorded. Data were subjected to regression analysis, and the relationship between larval density and yield and the relationship between the percentage of damaged pods and yield both can be described by a linear relationship. Each increase of one larvae per row-m resulted in a yield loss of 45.4 kg/ha. Similarly, each increase of 1% damaged pods resulted in a yield loss of 29.4 kg/ha. From these data, economic injury levels were developed for a range of crop values and control costs. These data suggest that current corn earworm threshold use in the Mid-South should be reduced.

15.
Opt Lett ; 41(9): 1977-80, 2016 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-27128053

RESUMO

A hard x-ray pump-probe spectrometer using a multi-crystal Bragg reflector is demonstrated at a third generation synchrotron source. This device derives both broadband pump and monochromatic probe pulses directly from a single intense, broadband x-ray pulse centered at 8.767 keV. We present a proof-of-concept experiment which directly measures x-ray induced crystalline lattice strain.

16.
Glob Public Health ; 11(9): 1135-47, 2016 10.
Artigo em Inglês | MEDLINE | ID: mdl-26400191

RESUMO

Guangzhou is China's third most populous city, and the region's burgeoning manufacturing economy has attracted many young African businessmen and entrepreneurs to the city. The aims of this study were to examine strategies that African migrants in Guangzhou have adopted in response to health-care barriers, and explore their perceptions of how to address their needs. Twenty-five semi-structured interviews and two focus groups were conducted among African migrants residing in Guangzhou, China. Facing multiple barriers to care, African migrants have adopted a number of suboptimal and unsustainable approaches to access health care. These included: using their Chinese friends or partners as interpreters, self-medicating, using personal connections to medical doctors, and travelling to home countries or countries that offer English-speaking doctors for health care. Health-care providers and health organisations in Guangzhou have not yet acquired sufficient cultural competence to address the needs of African migrants residing in the city. Introducing linguistically and culturally competent health-care services in communities concentrated with African migrants may better serve the population. With the growing international migration to China, it is essential to develop sustainable approaches to improving health-care access for international migrants, particularly those who are marginalised.


Assuntos
Barreiras de Comunicação , Confidencialidade/psicologia , Assistência à Saúde Culturalmente Competente/normas , Acessibilidade aos Serviços de Saúde , Turismo Médico/psicologia , Programas Nacionais de Saúde/normas , Migrantes/psicologia , Adulto , África/etnologia , China/epidemiologia , Assistência à Saúde Culturalmente Competente/economia , Assistência à Saúde Culturalmente Competente/tendências , Feminino , Grupos Focais , Acessibilidade aos Serviços de Saúde/economia , Humanos , Entrevistas como Assunto , Idioma , Masculino , Turismo Médico/economia , Turismo Médico/tendências , Programas Nacionais de Saúde/economia , Pesquisa Qualitativa , Migrantes/estatística & dados numéricos
17.
J Econ Entomol ; 108(3): 1072-8, 2015 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-26470231

RESUMO

Field experiments were conducted in Starkville and Stoneville, MS, during 2012 and 2013 to evaluate fruit removal level and timing on soybean growth, crop maturity, and yield. Fruit removal treatments consisted of 0, 50, and 100% of all fruit removed at specified growth stages (R2, R3, R4, and R5.5). Plant heights were determined at least biweekly from the time damage was imposed until R7. The impact of fruit removal level and timing on crop maturity was determined by estimating the percentage of naturally abscised leaves at 137 days after planting (DAP) when control plots were ∼10-15 d from harvest and the percentage of nonsenesced main stems at 139 DAP. There was no significant impact of fruit removal timing or fruit removal level on plant height or canopy width. Significant delays in crop maturity were observed when fruit removal was imposed at the R5.5 growth stage. Significant reductions in yield and crop value were observed as early as R3 and R4 when 100% of fruit was removed. Both fruit removal levels at R5.5 resulted in a significant reduction in yield and crop value compared with the nontreated control. Indeterminate soybeans appear to have the ability to compensate for some fruit loss during the early to middle reproductive growth stages without delaying maturity. However, severe fruit loss causes increasingly more yield loss as the plant approached maturity. Thresholds and economic injury levels therefore need to be adjusted accordingly to account for the dynamic nature of yield losses and crop maturity delays.


Assuntos
Mariposas/fisiologia , Zea mays/crescimento & desenvolvimento , Animais , Comportamento Alimentar , Cadeia Alimentar , Larva/crescimento & desenvolvimento , Larva/fisiologia , Mississippi , Mariposas/crescimento & desenvolvimento
19.
Biochem J ; 469(2): 223-33, 2015 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-25967372

RESUMO

Cyclophilins are ubiquitously expressed proteins that bind to prolines and can catalyse cis/trans isomerization of proline residues. There are 17 annotated members of the cyclophilin family in humans, ubiquitously expressed and localized variously to the cytoplasm, nucleus or mitochondria. Surprisingly, all eight of the nuclear localized cyclophilins are found associated with spliceosomal complexes. However, their particular functions within this context are unknown. We have therefore adapted three established assays for in vitro pre-mRNA splicing to probe the functional roles of nuclear cyclophilins in the context of the human spliceosome. We find that four of the eight spliceosom-associated cyclophilins exert strong effects on splicing in vitro. These effects are dose-dependent and, remarkably, uniquely characteristic of each cyclophilin. Using both qualitative and quantitative means, we show that at least half of the nuclear cyclophilins can act as regulatory factors of spliceosome function in vitro. The present work provides the first quantifiable evidence that nuclear cyclophilins are splicing factors and provides a novel approach for future work into small molecule-based modulation of pre-mRNA splicing.


Assuntos
Ciclofilinas/metabolismo , Proteínas Nucleares/metabolismo , Precursores de RNA/metabolismo , Splicing de RNA/fisiologia , Spliceossomos/metabolismo , Sistema Livre de Células/química , Sistema Livre de Células/metabolismo , Ciclofilinas/química , Ciclofilinas/genética , Células HeLa , Humanos , Proteínas Nucleares/química , Proteínas Nucleares/genética , Precursores de RNA/química , Precursores de RNA/genética , Spliceossomos/química , Spliceossomos/genética
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