4,129 research outputs found
Intermittent energy dissipation by turbulent reconnection
Magnetic reconnection—the process responsible for many explosive phenomena in both nature and laboratory—is efficient at dissipating magnetic energy into particle energy. To date, exactly how this dissipation happens remains unclear, owing to the scarcity of multipoint measurements of the “diffusion region” at the sub-ion scale. Here we report such a measurement by Cluster—four spacecraft with separation of 1/5 ion scale. We discover numerous current filaments and magnetic nulls inside the diffusion region of magnetic reconnection, with the strongest currents appearing at spiral nulls (O-lines) and the separatrices. Inside each current filament, kinetic-scale turbulence is significantly increased and the energy dissipation, E′ ⋅ j, is 100 times larger than the typical value. At the jet reversal point, where radial nulls (X-lines) are detected, the current, turbulence, and energy dissipations are surprisingly small. All these features clearly demonstrate that energy dissipation in magnetic reconnection occurs at O-lines but not X-lines
Diversity of methanogens in the hindgut of grower and finisher pigs
This study examined the diversity of the methanogens in the hindgut of two different weight groups of pigs and correlated it with the amount of digested organic carbon (OC) and various components of dietary fiber. Five grower (58.9 ± 1.15 kg) and five finisher (89.4 ± 0.85 kg) Duroc × Landrace × Large Yorkshire female pigs were allocated into two groups and individually housed in cages. During the experiment, feed intake and fecal output were recorded for determination of apparent digestibility of OC, crude fiber (CF), neutral detergent fiber (NDF) and acid detergent fiber (ADF). At the end of the digestibility trial, pigs were sacrificed, and the contents of five segments of hindgut were sterilely collected to determine diversity of methanogens. Total microbial DNA of the hindgut contents was used as template for amplification of the methanogen16S rRNA gene, and the PCR products were further subjected to denaturing gradient gel electrophoresis (DGGE) analysis. Results show that the number of DGGE bands and Shannon diversity index for the 90 kg pigs were higher (P<0.05) than those for the 60 kg pigs. Methanogen communities did not alter along the different segments of the hindgut for the two weight groups. In addition, the amount of OC, CF, NDF and ADF digested (g/d) for the 90 kg pigs (1018.77, 23.11, 268.86 and 99.16, respectively) was higher (P<0.05) than the respective values for the 60 kg pigs (669.27, 13.77, 222.31 and 69.07), indicating that the higher diversity of methanogens in the former group was related to the higher quantity of fiber materials fermented in the hindgut. The positive correlation (p<0.05) between number of DGGE bands and Shannon diversity index with quantity of digested OC and ADF further reaffirmed the above suggestion.Key words: Methanogen, pig, Shannon diversity index, polymerase chain reaction-denaturing gradient gel electrophoresis (PCR-DGGE)
Physical mapping of a powdery mildew resistance related gene Hv-S/TPK by FISH with a TAC clone in wheat
Dissertação de mestrado integrado em Medicina (Hematologia), apresentado á Faculdade de Medicina da Universidade de Coimbra.A Policitemia Vera (PV) Ă© uma doença clonal de etiologia desconhecida, na maior parte dos casos, que envolve a cĂ©lula estaminal progenitora hematopoiĂ©tica multipotencial. É uma neoplasia mieloproliferativa crĂłnica (NMP) que se caracteriza pela expansĂŁo das trĂŞs linhas celulares hematopoiĂ©ticas: eritrĂłide, granulocĂtica e megacariocĂtica, com predomĂnio da primeira, de modo independente dos mecanismos normais de regulação da eritropoiese. AlĂ©m disso, as cĂ©lulas tĂŞm aspecto morfolĂłgico normal, a fibrose medular Ă© pouco significativa e os nĂveis de eritropoietina (Epo) sĂŁo habitualmente normais a baixos. AlĂ©m da hipercelularidade medular com sobreprodução de uma ou de todas as linhas celulares, a doença cursa com hematopoiese extramedular, hiperviscosidade, propensĂŁo para complicações como trombose ou hemorragia e risco de desenvolvimento de mielofibrose ou transformação em leucemia aguda.
A descrição relativamente recente da associação de uma mutação no gene JAK2, localizado no cromosoma 9p24, com as doenças mieloproliferativas clássicas negativas para BCR-ABL, como a PV, veio permitir avanços significativos na compreensão da patofisiologia deste grupo de doenças hematológicas. A mutação provoca uma alteração do aminoácido V (valina) para F (fenilalanina) na posição 617 (JAK2V617F). De acordo com os dados publicados, a frequência da detecção da mutação JAK2V617F em doentes com PV é de cerca de 95%.
A proteĂna JAK2 Ă© uma tirosina cinase citoplasmática, que se encontra associada ao domĂnio intracelular dos receptores de citocinas (como a Epo e trombopoietina - Tpo), e de factores de crescimento, essenciais para a função destes receptores. A mutação da JAK2 conduz Ă activação constitutiva dos receptores, independente da ligação Ă respectiva citocina e/ou hipersensibilidade a factores de crescimento, com consequente activação de mĂşltiplas vias de sinalização intracelulares como a JAK/STAT (Janus Kinase/Signal Transductor and activator of transcription), a PI3K (fosfatidilinositol 3 cinase) e a MAPK (proteĂna cinase activadora de mitose), envolvidas na transformação e proliferação dos progenitores hematopoiĂ©ticos. Por outro lado, as cĂ©lulas evidenciam alteração na diferenciação terminal e resistĂŞncia Ă apoptose in vitro que poderá estar relacionada com o aumento da expressĂŁo da proteĂna anti-apoptĂłtica Bcl-XL.
Além dos avanços no diagnóstico, a detecção da mutação JAK2V617F tem contribuido para melhorar a classificação e a terapêutica dos doentes com PV. Deste modo, o conhecimento dos mecanismos moleculares envolvidos na PV tem levado os investigadores à descoberta de novos fármacos dirigidos ao defeito molecular, permitindo novas abordagem terapêuticas mais eficazes e provavelmente de menor toxicidade.
Este trabalho procura fazer uma revisĂŁo sobre o actual conhecimento da caracterização molecular e clĂnica da PV e quais as suas implicações no diagnĂłstico e abordagem terapĂŞutica desta NMP.Polycythemia Vera (PV) is a clonal disease of unknown etiology, which often involves the pluripotential hematopoietic stem cell. This disease integrates the family of chronic myeloproliferative neoplasm (MPN) and is characterized by the growth of the three hematopoietic celular lineages: granulocytic, megakaryocytic and erythroid, with predominance of the last one and regardless the normal mechanisms of erythropoiesis regulation. Moreover, cells have normal morphological aspect, bone marrow shows slight fibrosis and the levels of erythropoietin (Epo) usually vary from normal to low. Besides marrow hypercellularity with overproduction of one or all the celular lineages, the disease courses with extramedullary hematopoiesis, hyperviscosity, leading to complications such as thrombosis or bleeding and risk of transformation to myelofibrosis or acute leukemia.
Recently it has been described the association between the mutation in the JAK2 gene, located on chromosome 9p24, with the classic myeloproliferative disorders BCR-ABL negative, such as PV, which has brought significant advances in the understanding of the pathophysiology of this group of hematologic malignancies. The mutation causes a change of amino acid V (valine) to F (phenylalanine) at position 617 (JAK2V617F). According to published data, the frequency of JAK2V617F mutation detected in patients with PV is about 95%.
JAK2 protein is a cytoplasmic tyrosine kinase, which is associated to the intracelular domain of cytokine receptors, such as Epo and thrombopoietin (Tpo), and growth factors which are essential to the function of these receptors. JAK2 mutation leads to the constitutive receptors activation, independent of connection to their cytokine and / or hypersensitivity to growth factors, with consequent activation of multiple intracellular signaling pathways such as JAK / STAT (Janus Kinase / Signal transducer and transcription activator), the PI3K (phosphatidylinositol 3 kinase) and MAPK (Mitogen-activated protein), involved in the transformation and proliferation of hematopoietic progenitors. Moreover, the cells show changes in terminal differentiation and resistance to in vitro apoptosis which is possibly related to the increasing expression of anti-apoptotic protein Bcl-XL.
In addition to the advances in diagnosis, detection of JAK2V617F mutation has contributed to the improvement of classification and treatment in patients with PV. Thus, knowledge of the molecular mechanisms involved in PV has led investigators to the discovery of new drugs targeting molecular defects, allowing new therapeutic approach more efficient and probably less toxic.
The aim of this article is to review the current knowledge of clinical and molecular characterization of PV, and its implications on the diagnosis and therapeutic approach of this myeloproliferative disorder
Physical mapping of a powdery mildew resistance related gene Hv-S/TPK by FISH with a TAC clone in wheat
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Autoionization dynamics of (2P1/2)ns/d states in krypton probed by noncollinear wave mixing with attosecond extreme ultraviolet and few-cycle near infrared pulses.
The autoionization dynamics of the (2P1/2)ns/d Rydberg states in krypton are investigated using spatially isolated wave-mixing signals generated with a short train of subfemtosecond extreme ultraviolet (XUV) pulses and noncollinear, few-cycle near infrared pulses. Despite ubiquitous quantum beat oscillations from XUV-induced coherences within the excited-state manifold, these wave-mixing spectra allow for the simultaneous evaluation of autoionization lifetimes from a series of Rydberg states above the first ionization potential. Experimentally measured lifetimes of 22 ± 8 fs, 33 ± 6 fs, and 49 ± 6 fs for the wave-mixing signals emitting from the (2P1/2)6d/8s, (2P1/2)7d/9s, and (2P1/2)8d/10s resonances compare favorably with lifetimes for the (2P1/2)6d, 7d, and 8d Rydberg states determined from spectral linewidths. Analysis of the quantum beats reveals that the enhancement of wave-mixing pathways that couple the (2P1/2)nd states to themselves leads to individual reporter state-dependent decays in the wave-mixing signals. The results demonstrate the promise of wave-mixing spectroscopies with subfemtosecond XUV pulses to provide valuable insights into processes governed by electronic dynamics
Near-Infrared Super Resolution Imaging with Metallic Nanoshell Particle Chain Array
We propose a near-infrared super resolution imaging system without a lens or
a mirror but with an array of metallic nanoshell particle chain. The imaging
array can plasmonically transfer the near-field components of dipole sources in
the incoherent and coherent manners and the super resolution images can be
reconstructed in the output plane. By tunning the parameters of the metallic
nanoshell particle, the plasmon resonance band of the isolate nanoshell
particle red-shifts to the near-infrared region. The near-infrared super
resolution images are obtained subsequently. We calculate the field intensity
distribution at the different planes of imaging process using the finite
element method and find that the array has super resolution imaging capability
at near-infrared wavelengths. We also show that the image formation highly
depends on the coherence of the dipole sources and the image-array distance.Comment: 15 pages, 6 figure
A role for cell sex in stem cell-mediated skeletal muscle regeneration: Female cells have higher muscle regeneration efficiency
We have shown that muscle-derived stem cells (MDSCs) transplanted into dystrophic (mdx) mice efficiently regenerate skeletal muscle. However, MDSC populations exhibit heterogeneity in marker profiles and variability in regeneration abilities. We show here that cell sex is a variable that considerably influences MDSCs' regeneration abilities. We found that the female MDSCs (F-MDSCs) regenerated skeletal muscle more efficiently. Despite using additional isolation techniques and cell cloning, we could not obtain a male subfraction with a regeneration capacity similar to that of their female counterparts. Rather than being directly hormonal or caused by host immune response, this difference in MDSCs' regeneration potential may arise from innate sex-related differences in the cells' stress responses. In comparison with F-MDSCs, male MDSCs have increased differentiation after exposure to oxidative stress induced by hydrogen peroxide, which may lead to in vivo donor cell depletion, and a proliferative advantage for F-MDSCs that eventually increases muscle regeneration. These findings should persuade researchers to report cell sex, which is a largely unexplored variable, and consider the implications of relying on cells of one sex. © The Rockefeller University Press
Structure-Function Analysis of Diacylglycerol Acyltransferase Sequences from 70 Organisms
<p>Abstract</p> <p>Background</p> <p>Diacylglycerol acyltransferase families (DGATs) catalyze the final and rate-limiting step of triacylglycerol (TAG) biosynthesis in eukaryotic organisms. Understanding the roles of DGATs will help to create transgenic plants with value-added properties and provide clues for therapeutic intervention for obesity and related diseases. The objective of this analysis was to identify conserved sequence motifs and amino acid residues for better understanding of the structure-function relationship of these important enzymes.</p> <p>Results</p> <p>117 DGAT sequences from 70 organisms including plants, animals, fungi and human are obtained from database search using tung tree DGATs. Phylogenetic analysis separates these proteins into DGAT1 and DGAT2 subfamilies. These DGATs are integral membrane proteins with more than 40% of the total amino acid residues being hydrophobic. They have similar properties and amino acid composition except that DGAT1s are approximately 20 kDa larger than DGAT2s. DGAT1s and DGAT2s have 41 and 16 completely conserved amino acid residues, respectively, although only two of them are shared by all DGATs. These residues are distributed in 7 and 6 sequence blocks for DGAT1s and DGAT2s, respectively, and located at the carboxyl termini, suggesting the location of the catalytic domains. These conserved sequence blocks do not contain the putative neutral lipid-binding domain, mitochondrial targeting signal, or ER retrieval motif. The importance of conserved residues has been demonstrated by site-directed and natural mutants.</p> <p>Conclusions</p> <p>This study has identified conserved sequence motifs and amino acid residues in all 117 DGATs and the two subfamilies. None of the completely conserved residues in DGAT1s and DGAT2s is present in recently reported isoforms in the multiple sequences alignment, raising an important question how proteins with completely different amino acid sequences could perform the same biochemical reaction. The sequence analysis should facilitate studying the structure-function relationship of DGATs with the ultimate goal to identify critical amino acid residues for engineering superb enzymes in metabolic engineering and selecting enzyme inhibitors in therapeutic application for obesity and related diseases.</p
Health-related quality of life as measured with EQ-5D among populations with and without specific chronic conditions: A population-based survey in Shaanxi province, China
© 2013 Tan et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.Introduction: The aim of this study was to examine health-related quality of life (HRQoL) as measured by EQ-5D and to investigate the influence of chronic conditions and other risk factors on HRQoL based on a distributed sample located in Shaanxi Province, China. Methods: A multi-stage stratified cluster sampling method was performed to select subjects. EQ-5D was employed to measure the HRQoL. The likelihood that individuals with selected chronic diseases would report any problem in the EQ-5D dimensions was calculated and tested relative to that of each of the two reference groups. Multivariable linear regression models were used to investigate factors associated with EQ VAS. Results: The most frequently reported problems involved pain/discomfort (8.8%) and anxiety/depression (7.6%). Nearly half of the respondents who reported problems in any of the five dimensions were chronic patients. Higher EQ VAS scores were associated with the male gender, higher level of education, employment, younger age, an urban area of residence, access to free medical service and higher levels of physical activity. Except for anemia, all the selected chronic diseases were indicative of a negative EQ VAS score. The three leading risk factors were cerebrovascular disease, cancer and mental disease. Increases in age, number of chronic conditions and frequency of physical activity were found to have a gradient effect. Conclusion: The results of the present work add to the volume of knowledge regarding population health status in this area, apart from the known health status using mortality and morbidity data. Medical, policy, social and individual attention should be given to the management of chronic diseases and improvement of HRQoL. Longitudinal studies must be performed to monitor changes in HRQoL and to permit evaluation of the outcomes of chronic disease intervention programs. © 2013 Tan et al.National Nature Science Foundation (No. 8107239
Digital PCR methods improve detection sensitivity and measurement precision of low abundance mtDNA deletions
Mitochondrial DNA (mtDNA) mutations are a common cause of primary mitochondrial disorders, and have also been implicated in a broad collection of conditions, including aging, neurodegeneration, and cancer. Prevalent among these pathogenic variants are mtDNA deletions, which show a strong bias for the loss of sequence in the major arc between, but not including, the heavy and light strand origins of replication. Because individual mtDNA deletions can accumulate focally, occur with multiple mixed breakpoints, and in the presence of normal mtDNA sequences, methods that detect broad-spectrum mutations with enhanced sensitivity and limited costs have both research and clinical applications. In this study, we evaluated semi-quantitative and digital PCR-based methods of mtDNA deletion detection using double-stranded reference templates or biological samples. Our aim was to describe key experimental assay parameters that will enable the analysis of low levels or small differences in mtDNA deletion load during disease progression, with limited false-positive detection. We determined that the digital PCR method significantly improved mtDNA deletion detection sensitivity through absolute quantitation, improved precision and reduced assay standard error
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