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1.
Work ; 2019 Aug 16.
Artigo em Inglês | MEDLINE | ID: mdl-31450531

RESUMO

BACKGROUNDChildren regularly use tablets in a variety of postures. Previous studies have shown that prolonged use of such an IT device increases the risk of musculoskeletal pain.OBJECTIVETo investigate pain and muscle activity during tablet use by children in three different workstation positions-on the table with a case set, on a table, and on the lap.METHODSTwenty five healthy and right-handed participants aged 10-12 years were recruited and assigned to play computer games for 15 minutes in each workstation. Pain(VAS) was measured at the neck, shoulder, upper back, and forearm regions immediately after tablet use. Electromyography (EMG) was measured at the cervical erector spinae (CES), upper trapezius (UT), middle trapezius (MT), and wrist extensors (WE) muscles during the final two minutes.RESULTSResults showed that using a tablet on the table with a case set caused the least pain in the neck region (p <  0.05), compared with the use on the table and on the lap(which had pain scales of 0.37±0.86, 1.74±1.77, 1.72±1.90, respectively; mean±SD). EMG of cervical erector spinae during tablet use on the table with a case set was significantly lower (p <  0.05) than those on the table and on the lap(muscle activity of 22.38±9.54,35.37±16.82, 35.29±13.30 respectively).CONCLUSIONSTablet use on the table with a case set demonstrated a significantly lower severity of pain at the neck region than tablet use on the table and on the lap. To prevent musculoskeletal disorders, tablet use on the table with a case set is recommended as the optimal workstation for children.

2.
Work ; 63(3): 361-367, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31256105

RESUMO

BACKGROUND: Laptop computers are used in various places and situations. The number of laptop users experiencing musculoskeletal disorders (MSDs) has increased drastically due to, in part, inappropriate workstations. OBJECTIVE: To investigate the neck and shoulder postures, and muscle activity relative to perceived pain when using the laptop at a low-height table, sofa, and bed. METHODS: Twenty male participants aged 18-25 years were randomly assigned to perform laptop computer operation at 3 workstations for 10 minutes during which neck and shoulder angles, muscle activity, and pain were recorded by using an Electrogoniometer, Electromyography (EMG), and visual analog scale (VAS), respectively. RESULTS: Neck flexions when working at the sofa (18.6°±12.2°) and bed (17.2°±10.5°) were significantly (p < 0.05) greater than that at the low-height table (7.8°±6.5°). However, shoulder flexion when working at the low-height table (28.2°±13.0°) was significantly (p < 0.05) greater than that at the sofa (13.8°±8.6°) and bed (10.91°±7.8°). Working at the low-height table caused the shoulder flexor muscle activity to be significantly (p < 0.05) higher than working at the sofa and bed. Neck pain was reported during laptop computer use at the sofa and bed, and upper back pain when working at the low-height table. CONCLUSIONS: High neck flexion and pain were found while working at sofa and bed, whereas high muscle activity at shoulder and upper back pain were found while working at the low-height table.

3.
Pain Pract ; 2019 Jul 18.
Artigo em Inglês | MEDLINE | ID: mdl-31319013

RESUMO

BACKGROUND: Musculoskeletal conditions are well documented in inflammatory bowel disease (IBD). However, whether IBD activity influences musculoskeletal pain experiences is uncertain. Central sensitization has been proposed in patients with IBD who are suffering from persistent pain. Identification of central sensitization symptomology using the Central Sensitization Inventory (CSI) has been reported in many pain-related disorders. Aims of this study were to explore predictive relationships between IBD activity and musculoskeletal pain experiences (severity/interference), and the mediating effects of the CSI. METHODS: A cross-sectional online survey was performed exploring self-reported musculoskeletal pain in adults with IBD. Survey questionnaires included IBD activity indices, numeric rating scales, PROMIS Pain Interference, and the CSI. Linear regression was used to examine the relationship between active IBD and pain experiences. Simple and serial mediation analyses were used to explore mediation models: independent variable (IBD activity), dependent variables (severity/interference), and mediators (CSI/severity). RESULTS: 208 adults with IBD, 18 to 88 years of age, reported musculoskeletal pain. Regression analysis identified IBD activity as a significant predictor of worse pain severity (R2  = 0.039, P < 0.005) and interference (R2  = 0.067, P < 0.001). Simple mediation showed a significant indirect effect from CSI scores between IBD activity and pain severity. Serial mediation analysis showed a significant indirect effect from CSI scores and pain severity, between IBD activity and pain interference. CONCLUSION: Active IBD demonstrated a positive association with worse musculoskeletal pain experiences. The CSI demonstrated significant mediation between active IBD and pain severity. Additionally, the CSI and pain severity demonstrated significant mediation between active IBD and pain interference. This suggests that symptoms of central sensitization significantly influence musculoskeletal pain experiences in IBD.

4.
MBio ; 10(3)2019 05 14.
Artigo em Inglês | MEDLINE | ID: mdl-31088926

RESUMO

In this study, we examined the relationships between anti-influenza virus serum antibody titers, clinical disease, and peripheral blood leukocyte (PBL) global gene expression during presymptomatic, acute, and convalescent illness in 83 participants infected with 2009 pandemic H1N1 virus in a human influenza challenge model. Using traditional statistical and logistic regression modeling approaches, profiles of differentially expressed genes that correlated with active viral shedding, predicted length of viral shedding, and predicted illness severity were identified. These analyses further demonstrated that challenge participants fell into three peripheral blood leukocyte gene expression phenotypes that significantly correlated with different clinical outcomes and prechallenge serum titers of antibodies specific for the viral neuraminidase, hemagglutinin head, and hemagglutinin stalk. Higher prechallenge serum antibody titers were inversely correlated with leukocyte responsiveness in participants with active disease and could mask expression of peripheral blood markers of clinical disease in some participants, including viral shedding and symptom severity. Consequently, preexisting anti-influenza antibodies may modulate PBL gene expression, and this must be taken into consideration in the development and interpretation of peripheral blood diagnostic and prognostic assays of influenza infection.IMPORTANCE Influenza A viruses are significant human pathogens that caused 83,000 deaths in the United States during 2017 to 2018, and there is need to understand the molecular correlates of illness and to identify prognostic markers of viral infection, symptom severity, and disease course. Preexisting antibodies against viral neuraminidase (NA) and hemagglutinin (HA) proteins play a critical role in lessening disease severity. We performed global gene expression profiling of peripheral blood leukocytes collected during acute and convalescent phases from a large cohort of people infected with A/H1N1pdm virus. Using statistical and machine-learning approaches, populations of genes were identified early in infection that correlated with active viral shedding, predicted length of shedding, or disease severity. Finally, these gene expression responses were differentially affected by increased levels of preexisting influenza antibodies, which could mask detection of these markers of contagiousness and disease severity in people with active clinical disease.


Assuntos
Anticorpos Antivirais/sangue , Glicoproteínas de Hemaglutininação de Vírus da Influenza/imunologia , Influenza Humana/imunologia , Leucócitos/imunologia , Neuraminidase/imunologia , Doença Aguda , Adolescente , Adulto , Convalescença , Proteção Cruzada , Feminino , Perfilação da Expressão Gênica , Voluntários Saudáveis , Testes de Inibição da Hemaglutinação , Experimentação Humana , Humanos , Vírus da Influenza A Subtipo H1N1 , Influenza Humana/sangue , Masculino , Pessoa de Meia-Idade , Eliminação de Partículas Virais , Adulto Jovem
5.
Reprod Fertil Dev ; 2019 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-30947806

RESUMO

Intrauterine infection and inflammation remain a major cause of preterm labour in women and mares, with little known about small RNA (sRNA) expression in tissue or circulation. To better characterise placental inflammation (placentitis), we examined sRNA expression in the endometrium, chorioallantois and serum of mares with and without placentitis. Disease was induced in 10 mares via intracervical inoculation of Streptococcus equi ssp. zooepidemicus, either with moderate or high levels of inoculum; three uninoculated gestationally matched mares were used as controls. Matched chorioallantois and endometrium were sampled in two locations: Region 1, gross inflammation near cervical star with placental separation and Region 2, gross inflammation without placental separation. In Region 1, 26 sRNAs were altered in chorioallantois, while 20 were altered in endometrium. Within Region 2, changes were more subdued in both chorioallantois (10 sRNAs) and endometrium (two sRNAs). Within serum, we identified nine significantly altered sRNAs. In summary, we have characterised the expression of sRNA in the chorioallantois, the endometrium and the serum of mares with experimentally induced placentitis using next-generation sequencing, identifying significant changes within each tissue examined. These data should provide valuable information about the physiology of placental inflammation to clinicians and researchers alike.

6.
J Cell Mol Med ; 23(4): 2753-2768, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30734465

RESUMO

Type 2 Diabetes Mellitus (T2DM) is the most prevalent form of diabetes in the USA, thus, the identification of biomarkers that could be used to predict the progression from prediabetes to T2DM would be greatly beneficial. Recently, circulating RNA including microRNAs (miRNAs) present in various body fluids have emerged as potential biomarkers for various health conditions, including T2DM. Whereas studies that examine the changes of miRNA spectra between healthy controls and T2DM individuals have been reported, the goal of this study is to conduct a baseline comparison of prediabetic individuals who either progress to T2DM, or remain prediabetic. Using an advanced small RNA sequencing library construction method that improves the detection of miRNA species, we identified 57 miRNAs that showed significant concentration differences between progressors (progress from prediabetes to T2DM) and non-progressors. Among them, 26 have been previously reported to be associated with T2DM in either body fluids or tissue samples. Some of the miRNAs identified were also affected by obesity. Furthermore, we identified miRNA panels that are able to discriminate progressors from non-progressors. These results suggest that upon further validation these miRNAs may be useful to predict the risk of conversion to T2DM from prediabetes.

7.
Harm Reduct J ; 16(1): 12, 2019 Feb 08.
Artigo em Inglês | MEDLINE | ID: mdl-30736817

RESUMO

BACKGROUND: Harmful gambling is a complex issue with diverse antecedents and resulting harms that have been studied from multiple disciplinary perspectives. Although previous bibliometric reviews of gambling studies have found a dominance of judgement and decision-making research, no bibliometric review has examined the concept of "harm" in the gambling literature, and little work has quantitatively assessed how gambling research priorities differ between countries. METHODS: Guided by the Conceptual Framework of Harmful Gambling (CFHG), an internationally relevant framework of antecedents to harmful gambling, we conducted a bibliometric analysis focusing on research outputs from three countries with different gambling regulatory environments: Canada, Australia, and New Zealand. Using a Web of Science database search, 1424 articles published from 2008 to 2017 were retrieved that could be mapped to the eight CFHG factors. A subsample of articles (n = 171) containing the word "harm" in the title, abstract, or keywords was then drawn. Descriptive statistics were used to examine differences between countries and trends over time with regard to CFHG factor and harm focus. RESULTS: Psychological and biological factors dominate gambling research in Canada whereas resources and treatment have received more attention in New Zealand. A greater percentage of Australia and New Zealand publications address the gambling environment and exposure to gambling than in Canada. The subset of articles focused on harm showed a stronger harms focus among New Zealand and Australian researchers compared to Canadian-authored publications. CONCLUSIONS: The findings provide preliminary bibliometric evidence that gambling research foci may be shaped by jurisdictional regulation of gambling. Countries with privately operated gambling focused on harm factors that are the operators' responsibility, whereas jurisdictions with a public health model focused on treatment and harm reduction resources. In the absence of a legislated requirement for public health or harm minimisation focus, researchers in jurisdictions with government-operated gambling tend to focus research on factors that are the individual's responsibility and less on the harms they experience. Given increased international attention to gambling-related harm, regulatory and research environments could promote and support more diverse research in this area.

10.
Nat Biotechnol ; 36(8): 746-757, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-30010675

RESUMO

RNA-seq is increasingly used for quantitative profiling of small RNAs (for example, microRNAs, piRNAs and snoRNAs) in diverse sample types, including isolated cells, tissues and cell-free biofluids. The accuracy and reproducibility of the currently used small RNA-seq library preparation methods have not been systematically tested. Here we report results obtained by a consortium of nine labs that independently sequenced reference, 'ground truth' samples of synthetic small RNAs and human plasma-derived RNA. We assessed three commercially available library preparation methods that use adapters of defined sequence and six methods using adapters with degenerate bases. Both protocol- and sequence-specific biases were identified, including biases that reduced the ability of small RNA-seq to accurately measure adenosine-to-inosine editing in microRNAs. We found that these biases were mitigated by library preparation methods that incorporate adapters with degenerate bases. MicroRNA relative quantification between samples using small RNA-seq was accurate and reproducible across laboratories and methods.

11.
FEMS Microbiol Lett ; 365(13)2018 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-29846577

RESUMO

Borrelia burgdorferi, a bacterium in the spirochete phylum, is the causative agent of Lyme disease. Borrelia burgdorferi has a linear chromosome with a number of circular and linear plasmids. Bacteria, including B. burgdorferi, release spherical outer membrane vesicles (OMVs) that are known to carry secretory products including metabolites, nucleic acids and proteins. Herein, we provide the first comparative transcriptomic analysis of the vesicles released from B. burgdorferi. We identified a total of ∼1200 unique transcripts with at least one mapped read from the bacterial cell and its OMVs. We compared the spectrum of transcripts between bacterial cell and its OMVs, and found a biased distribution based on the source of transcripts, i.e. plasmid-encoded transcripts are more likely to be enriched in the OMVs. We validated the distribution for some of the transcripts by qPCR. This analysis provides the first evidence that some of the B. burgdorferi transcripts are preferentially packaged in OMV, which further suggest that the bacteria might use its OMVs for bacteria-bacteria or bacteria-host communications. This report also suggests a possible involvement of Borrelia-derived OMVs in the development of Lyme disease in both early and post disease syndromes.

12.
Appl Plant Sci ; 6(2): e1022, 2018 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-29732253

RESUMO

Premise of the Study: Herbarium specimens provide a robust record of historical plant phenology (the timing of seasonal events such as flowering or fruiting). However, the difficulty of aggregating phenological data from specimens arises from a lack of standardized scoring methods and definitions for phenological states across the collections community. Methods and Results: To address this problem, we report on a consensus reached by an iDigBio working group of curators, researchers, and data standards experts regarding an efficient scoring protocol and a data-sharing protocol for reproductive traits available from herbarium specimens of seed plants. The phenological data sets generated can be shared via Darwin Core Archives using the Extended MeasurementOrFact extension. Conclusions: Our hope is that curators and others interested in collecting phenological trait data from specimens will use the recommendations presented here in current and future scoring efforts. New tools for scoring specimens are reviewed.

13.
J Cell Mol Med ; 22(5): 2760-2773, 2018 May.
Artigo em Inglês | MEDLINE | ID: mdl-29516617

RESUMO

Preterm birth (PTB) can lead to lifelong complications and challenges. Identifying and monitoring molecular signals in easily accessible biological samples that can diagnose or predict the risk of preterm labour (PTL) in pregnant women will reduce or prevent PTBs. A number of studies identified putative biomarkers for PTL including protein, miRNA and hormones from various body fluids. However, biomarkers identified from these studies usually lack consistency and reproducibility. Extracellular vesicles (EVs) in circulation have gained significant interest in recent years as these vesicles may be involved in cell-cell communication. We have used an improved small RNA library construction protocol and a newly developed size exclusion chromatography (SEC)-based EV purification method to gain a comprehensive view of circulating RNA in plasma and its distribution by analysing RNAs in whole plasma and EV-associated and EV-depleted plasma. We identified a number of miRNAs in EVs that can be used as biomarkers for PTL, and these miRNAs may reflect the pathological changes of the placenta during the development of PTL. To our knowledge, this is the first study to report a comprehensive picture of circulating RNA, including RNA in whole plasma, EV and EV-depleted plasma, in PTL and reveal the usefulness of EV-associated RNAs in disease diagnosis.

14.
Methods Mol Biol ; 1740: 163-175, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29388143

RESUMO

Next generation sequencing (NGS) is a powerful method for transcriptome analysis. Unlike other gene expression profiling methods, such as microarrays, NGS provides additional information such as splicing variants, sequence polymorphisms, and novel transcripts. For this reason, NGS is well suited for comprehensive profiling of the wide range of extracellular RNAs (exRNAs) in biofluids. ExRNAs are of great interest because of their possible biological role in cell-to-cell communication and for their potential use as biomarkers or for therapeutic purposes. Here, we describe a modified protocol for preparation of small RNA libraries for NGS analysis. This protocol has been optimized for use with low-input exRNA-containing samples, such as plasma or serum, and has modifications designed to reduce the sequence-specific bias typically encountered with commercial small RNA library construction kits.

15.
Pain Pract ; 18(7): 895-924, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-29350873

RESUMO

BACKGROUND: Test procedures that were developed to assess somatosensory abnormalities should possess optimal psychometric properties (PMPs) to be used in clinical practice. The aim of this systematic review was to evaluate the literature to assess the level of evidence for PMPs of test procedures investigated in individuals with peripheral joint pain (PJP). METHODS: A comprehensive electronic literature search was conducted in 7 databases from inception to March 2016. The Quality Appraisal for Reliability Studies (QAREL) checklist and the Consensus-based Standards for the Selection of Health Status Measurement Instruments (COSMIN) tool were used to assess risk for bias of the included studies. Level of evidence was evaluated based on the methodological quality and the quality of the measurement properties. RESULTS: Forty-one studies related to PJP were included. The majority of included studies were considered to be of insufficient methodological quality, and the level of evidence for PMPs varied across different test procedures. The level of evidence for PMPs varied across different test procedures in different types of PJP. Hand-held pressure algometry is the only test procedure that showed moderate positive evidence of intrarater reliability, agreement, and responsiveness, simultaneously, when it was investigated in patients with chronic knee osteoarthritis. CONCLUSIONS: This systematic review identified that the level of evidence for PMPs varied across different testing procedures to assess somatosensory abnormalities for different PJP populations. Further research with standardized protocols is recommended to further investigate the predictive ability and responsiveness of reported test procedures in order to warrant their extended utility in clinical practice.

16.
Nucleic Acids Res ; 45(21): 12140-12151, 2017 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-29069500

RESUMO

Although many tools have been developed to analyze small RNA sequencing (sRNA-Seq) data, it remains challenging to accurately analyze the small RNA population, mainly due to multiple sequence ID assignment caused by short read length. Additional issues in small RNA analysis include low consistency of microRNA (miRNA) measurement results across different platforms, miRNA mapping associated with miRNA sequence variation (isomiR) and RNA editing, and the origin of those unmapped reads after screening against all endogenous reference sequence databases. To address these issues, we built a comprehensive and customizable sRNA-Seq data analysis pipeline-sRNAnalyzer, which enables: (i) comprehensive miRNA profiling strategies to better handle isomiRs and summarization based on each nucleotide position to detect potential SNPs in miRNAs, (ii) different sequence mapping result assignment approaches to simulate results from microarray/qRT-PCR platforms and a local probabilistic model to assign mapping results to the most-likely IDs, (iii) comprehensive ribosomal RNA filtering for accurate mapping of exogenous RNAs and summarization based on taxonomy annotation. We evaluated our pipeline on both artificial samples (including synthetic miRNA and Escherichia coli cultures) and biological samples (human tissue and plasma). sRNAnalyzer is implemented in Perl and available at: http://srnanalyzer.systemsbiology.net/.


Assuntos
Sequenciamento de Nucleotídeos em Larga Escala/métodos , MicroRNAs/química , Análise de Sequência de RNA/métodos , Escherichia coli/genética , Perfilação da Expressão Gênica , Humanos , MicroRNAs/sangue , MicroRNAs/metabolismo , Análise de Sequência com Séries de Oligonucleotídeos , RNA Bacteriano/química , RNA Bacteriano/metabolismo , Pequeno RNA não Traduzido/química , Pequeno RNA não Traduzido/metabolismo , Reação em Cadeia da Polimerase em Tempo Real , Software
17.
Ann Neurol ; 82(1): 30-43, 2017 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-28574152

RESUMO

OBJECTIVE: Traumatic brain injury (TBI) is a common disabling condition with limited treatment options. Diffusion tensor imaging measures recovery of axonal injury in white matter (WM) tracts after TBI. Growth hormone deficiency (GHD) after TBI may impair axonal and neuropsychological recovery, and serum insulin-like growth factor-I (IGF-I) may mediate this effect. We conducted a longitudinal study to determine the effects of baseline serum IGF-I concentrations on WM tract and neuropsychological recovery after TBI. METHODS: Thirty-nine adults after TBI (84.6% male, median age = 30.5 years, 87.2% moderate-severe, median time since TBI = 16.3 months, n = 4 with GHD) were scanned twice, 13.3 months (range = 12.1-14.9) apart, and 35 healthy controls were scanned once. Symptom and quality of life questionnaires and cognitive assessments were completed at both visits (n = 33). Our main outcome measure was fractional anisotropy (FA), a measure of WM tract integrity, in a priori regions of interest: splenium of corpus callosum (SPCC) and posterior limb of internal capsule (PLIC). RESULTS: At baseline, FA was reduced in many WM tracts including SPCC and PLIC following TBI compared to controls, indicating axonal injury, with longitudinal increases indicating axonal recovery. There was a significantly greater increase in SPCC FA over time in patients with serum IGF-I above versus below the median for age. Only the higher IGF-I group had significant improvements in immediate verbal memory recall over time. INTERPRETATION: WM recovery and memory improvements after TBI were greater in patients with higher serum IGF-I at baseline. These findings suggest that the growth hormone/IGF-I system may be a potential therapeutic target following TBI. Ann Neurol 2017;82:30-43.


Assuntos
Lesões Encefálicas Traumáticas/patologia , Fator de Crescimento Insulin-Like I/metabolismo , Substância Branca/patologia , Adulto , Anisotropia , Estudos de Casos e Controles , Imagem de Tensor de Difusão , Feminino , Hormônio do Crescimento/deficiência , Humanos , Cápsula Interna/patologia , Estudos Longitudinais , Masculino , Neuroimagem , Testes Neuropsicológicos , Músculos Paraespinais/patologia , Qualidade de Vida , Adulto Jovem
18.
Sci Transl Med ; 9(385)2017 04 12.
Artigo em Inglês | MEDLINE | ID: mdl-28404864

RESUMO

The 2013-2015 outbreak of Ebola virus disease in Guinea, Liberia, and Sierra Leone was unprecedented in the number of documented cases, but there have been few published reports on immune responses in clinical cases and their relationships with the course of illness and severity of Ebola virus disease. Symptoms of Ebola virus disease can include severe headache, myalgia, asthenia, fever, fatigue, diarrhea, vomiting, abdominal pain, and hemorrhage. Although experimental treatments are in development, there are no current U.S. Food and Drug Administration-approved vaccines or therapies. We report a detailed study of host gene expression as measured by microarray in daily peripheral blood samples collected from a patient with severe Ebola virus disease. This individual was provided with supportive care without experimental therapies at the National Institutes of Health Clinical Center from before onset of critical illness to recovery. Pearson analysis of daily gene expression signatures revealed marked gene expression changes in peripheral blood leukocytes that correlated with changes in serum and peripheral blood leukocytes, viral load, antibody responses, coagulopathy, multiple organ dysfunction, and then recovery. This study revealed marked shifts in immune and antiviral responses that preceded changes in medical condition, indicating that clearance of replicating Ebola virus from peripheral blood leukocytes is likely important for systemic viral clearance.


Assuntos
Ebolavirus/patogenicidade , Doença pelo Vírus Ebola/virologia , Leucócitos/metabolismo , Surtos de Doenças , Doença pelo Vírus Ebola/sangue , Humanos , Estudos Longitudinais , RNA Viral/sangue , RNA Viral/genética , Replicação Viral/fisiologia
19.
Sci Rep ; 7(1): 865, 2017 04 13.
Artigo em Inglês | MEDLINE | ID: mdl-28408752

RESUMO

The neutron Larmor diffraction technique has been implemented using superconducting magnetic Wollaston prisms in both single-arm and double-arm configurations. Successful measurements of the coefficient of thermal expansion of a single-crystal copper sample demonstrates that the method works as expected. The experiment involves a new method of tuning by varying the magnetic field configurations in the device and the tuning results agree well with previous measurements. The difference between single-arm and double-arm configurations has been investigated experimentally. We conclude that this measurement benchmarks the applications of magnetic Wollaston prisms in Larmor diffraction and shows in principle that the setup can be used for inelastic phonon line-width measurements. The achievable resolution for Larmor diffraction is comparable to that using Neutron Resonance Spin Echo (NRSE) coils. The use of superconducting materials in the prisms allows high neutron polarization and transmission efficiency to be achieved.

20.
Hum Mol Genet ; 26(5): 913-922, 2017 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-28334820

RESUMO

Huntington's disease is a dominantly inherited neurodegenerative disease caused by the expansion of a CAG repeat in the HTT gene. In addition to the length of the CAG expansion, factors such as genetic background have been shown to contribute to the age at onset of neurological symptoms. A central challenge in understanding the disease progression that leads from the HD mutation to massive cell death in the striatum is the ability to characterize the subtle and early functional consequences of the CAG expansion longitudinally. We used dense time course sampling between 4 and 20 postnatal weeks to characterize early transcriptomic, molecular and cellular phenotypes in the striatum of six distinct knock-in mouse models of the HD mutation. We studied the effects of the HttQ111 allele on the C57BL/6J, CD-1, FVB/NCr1, and 129S2/SvPasCrl genetic backgrounds, and of two additional alleles, HttQ92 and HttQ50, on the C57BL/6J background. We describe the emergence of a transcriptomic signature in HttQ111/+ mice involving hundreds of differentially expressed genes and changes in diverse molecular pathways. We also show that this time course spanned the onset of mutant huntingtin nuclear localization phenotypes and somatic CAG-length instability in the striatum. Genetic background strongly influenced the magnitude and age at onset of these effects. This work provides a foundation for understanding the earliest transcriptional and molecular changes contributing to HD pathogenesis.


Assuntos
Corpo Estriado/metabolismo , Proteína Huntingtina/genética , Doença de Huntington/genética , Expansão das Repetições de Trinucleotídeos/genética , Animais , Corpo Estriado/patologia , Modelos Animais de Doenças , Regulação da Expressão Gênica no Desenvolvimento , Técnicas de Introdução de Genes , Patrimônio Genético , Instabilidade Genômica/genética , Humanos , Proteína Huntingtina/biossíntese , Doença de Huntington/patologia , Camundongos , Mutação/genética , Neurônios/metabolismo , Neurônios/patologia , Fenótipo , Transcriptoma/genética
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