19 research outputs found
The effect of three years of TNF alpha blocking therapy on markers of bone turnover and their predictive value for treatment discontinuation in patients with ankylosing spondylitis: a prospective longitudinal observational cohort study
No full textINTRODUCTION: The aim of this study was to investigate the effect of three years of tumor necrosis factor-alpha (TNF-alpha) blocking therapy on bone turnover as well as to analyze the predictive value of early changes in bone turnover markers (BTM) for treatment discontinuation in patients with ankylosing spondylitis (AS). METHODS: This is a prospective cohort study of 111 consecutive AS outpatients who started TNF-alpha blocking therapy. Clinical assessments and BTM were assessed at baseline, three and six months, as well as at one, two, and three years. Z-scores of BTM were calculated to correct for age and gender. Bone mineral density (BMD) was assessed yearly. RESULTS: After three years, 72 patients (65%) were still using their first TNF-alpha blocking agent. In these patients, TNF-alpha blocking therapy resulted in significantly increased bone-specific alkaline phosphatase, a marker of bone formation; decreased serum collagen-telopeptide (sCTX), a marker of bone resorption; and increased lumbar spine and hip BMD compared to baseline. Baseline to three months decrease in sCTX Z-score (HR: 0.394, 95% CI: 0.263 to 0.591), AS disease activity score (ASDAS; HR: 0.488, 95% CI: 0.317 to 0.752), and physician's global disease activity (HR: 0.739, 95% CI: 0.600 to 0.909) were independent inversely related predictors of time to treatment discontinuation because of inefficacy or intolerance. Early decrease in sCTX Z-score correlated significantly with good long-term response regarding disease activity, physical function and quality of life. CONCLUSIONS: Three years of TNF-alpha blocking therapy results in a bone turnover balance that favors bone formation, especially mineralization, in combination with continuous improvement of lumbar spine BMD. Early change in sCTX can serve as an objective measure in the evaluation of TNF-alpha blocking therapy in AS, in addition to the currently used more subjective measures
In Situ Single Photon Confocal Imaging of Cardiomyocyte T-tubule System from Langendorff-Perfused Hearts
No full textTransverse tubules (T-tubules) are orderly invaginations of the sarcolemma in mammalian cardiomyocytes. The integrity of T-tubule architecture is critical for cardiac excitation-contraction coupling function. T-tubule remodeling is recognized as a key player in cardiac dysfunction. Early studies on T-tubule structure were based on electron microscopy, which uncovered important information about the T-tubule architecture. The advent of fluorescent membrane probes allowed the application of confocal microscopy to investigations of T-tubule structure. Studies have now been extended beyond single cardiomyocytes to examine the T-tubule network in intact hearts through in situ confocal imaging of Langendorff-perfused hearts. This technique has allowed visualization of T-tubule organization in their natural habitat, avoiding the damage induced by isolation of cardiomyocytes. Additionally, it is possible to obtain T-tubule images in different subepicardial regions in a single intact heart. We review how this state-of-the-art imaging technique has provided important mechanistic insights into maturation of T-tubules in developing hearts and defined the role of T-tubule remodeling in development and progression of heart failure
Parcellation of the Primary Cerebral Cortices based on Local Connectivity Profiles
No full textPrimary cerebral cortices are of great importance for our understanding of the human brain. Although their functions are relatively monomodal, primary cerebral cortices have been suggested to compromise structurally and functionally distinct subregions from many evidences, for example, cytoarchitectionics, myeloarchitectonics and functional brain imaging. In recent years, structural connectivity-based parcellation using diffusion MRI has been extensively used to do parcellation of subcortical areas and association cortex. However, it has rarely been employed to primary cerebral cortices. In connectivity-based parcellation, connectivity profiles are very vital. Different researchers used different information of connectivity profiles, such as global connectivity profiles (the connectivity information from seed to the whole brain) and long connectivity profiles (the connectivity information from seed to other brain regions after excluding the seed). Given that primary cerebral cortices are rich of local hierarchical connections and possess high local functional connectivity profiles, we proposed that local connectivity profiles (the connectivity information in the seed region of interest (ROI)) might be used for parcellating primary cerebral cortices. Global, long and local connectivity profiles were compared on M1, A1, S1 and V1. We found that results using the three were all in good consistency with cytoarchitectonic results. More importantly, results using local connectivity profiles showed less inter-subject variability than results using the other two. This suggests that for parcellation of primary cerebral cortices local connectivity profiles are superior to global and long connectivity profiles. This also infers us that different connectivity profiles should be adopted according to the characteristics of the cerebral cortices
A Performance Practice Guide for :only.just.almost.never for Solo Vibraphone by Jay Alan Yim
No full textAbstract
Currently, there exists little scholarship on Dr. Jay Alan Yim’s percussion music, and none exists for :only.just.almost.never for solo vibraphone. Establishing a performance practice guide will allow future percussionists a glimpse into the compositional process of Yim and allow them to expand their repertoire to include this challenging music. The purpose of this project is to create a comprehensive performance practice guide for :only.just.almost.never for solo vibraphone by Jay Alan Yim. Resources Required
This project relies mainly on the score of :only.just.almost.never for solo vibraphone. I have also conducted multiple interviews with Yim regarding his compositional process, sketches, and companion pieces within this writing paradigm. It should be noted that this work can be played with Yim’s other modular works in his cycle for piano,[1] string quartet,[2] woodwind trio,[3] and chamber ensemble;[4] all of these scores are available from the composer. Project Format
This project is a written performance practice guide for :only.just.almost.never for solo vibraphone.[5] Thus, it consists of pedagogical advice in learning and performing this work accompanied by specific score examples, visual diagrams, photos, and audio links. In addition, this paper discusses practical analyses of this composition’s complex rhythms. The author has recorded :only.just.almost.never, which has informed the pedagogical writings within this project.
[1] Jay Alan Yim, :[ten]dril (Shinkyoku Edition, 1999).
[2] Jay Alan Yim, :memo/ryCircle (Shinkyoku Edition, 1998).
[3] Jay Alan Yim, :circl/eSong (Shinkyoku Edition, 1997).
[4] Jay Alan Yim, :dreamin/gField (Shinkyoku Edition, 1997).
[5] Jay Alan Yim, :only.just.almost.never (Shinkyoku Edition, 2018)
Involvement of calmodulin in regulation of primary root elongation by N-3-oxo-hexanoyl homoserine lactone in Arabidopsis thaliana
No full textMany bacteria use signal molecules of low molecular weight to monitor their local population density and to coordinate their collective behavior in a process called quorum sensing (QS). N-acyl-homoserine lactones (AHLs) are the primary QS signals among Gram-negative bacteria. AHL-mediated QS plays an essential role in diverse bacterial physiological processes. Recent evidence shows that plants are able to sense bacterial AHLs and respond to them appropriately. However, little is known about the mechanism by which plants perceive and transduce the bacterial AHLs within cells. In this study, we found that the stimulatory effect of N-3-oxo-hexanoyl homoserine lactone (3OC6-HSL) on primary root elongation of Arabidopsis was abolished by the calmodulin (CaM) antagonists N-(6-aminohexyl)-5-chloro-1-naphthalene sulfonamide (W-7) and trifluoperazine (TFP). Western-blot and ELISA analysis revealed that the concentration of CaM protein in Arabidopsis roots increased after treatment with 1 μM 3OC6-HSL. Results from quantitative RT-PCR demonstrated that the transcription of all nine CaM genes in Arabidopsis genome was up-regulated in the plants treated with 3OC6-HSL. The loss-of-function mutants of each AtCaM gene (AtCaM1-9) were insensitive to 3OC6-HSL-stimulation of primary root elongation. On the other hand, the genetic evidence showed that CaM may not participates the inhibition of primary root length caused by application of long-chained AHLs such as C10-HSL and C12-HSL. Nevertheless, our results suggest that CaM is involved in the bacterial 3OC6-HSL signaling in plant cells. These data offer new insight into the mechanism of plant response to bacterial QS signals
Citrus PH5-like H+-ATPase genes: identification and transcript analysis to investigate their possible relationship with citrate accumulation in fruits
No full textPH5 is a petunia gene that encodes a plasma membrane H+-ATPase and determines the vacuolar pH. The citrate content of fruit cell vacuoles influences citrus organoleptic qualities. Although citrus could have PH5-like homologs that are involved in citrate accumulation, the details are still unknown. In this study, extensive data-mining with the PH5 sequence and PCR amplification confirmed that there are at least eight PH5-like genes (CsPH1-8) in the citrus genome. CsPHs have a molecular mass of approximately 100 kDa, and they have high similarity to PhPH5, AtAHA10 or AtAHA2 (from 64.6% to 80.9%). They contain 13-21 exons and 12-20 introns and were evenly distributed into four subgroups of the P3A-subfamily (CsPH1, CsPH2, and CsPH3 in Group I, CsPH4 and CsPH5 in Group II, CsPH6 in Group IV, and CsPH7 and CsPH8 in Group III together with PhPH5). A transcript analysis showed that CsPH1, 3, and 4 were predominantly expressed in mature leaves, whereas CsPH2 and 7 were predominantly expressed in roots, CsPH5 and 6 were predominantly expressed in flowers, and CsPH8 was predominantly expressed in fruit juice sacs. Moreover, the CsPH transcript profiles differed between orange and pummelo, as well as between high-acid and low-acid cultivars. The low-acid orange ‘Honganliu’ exhibits low transcript levels of CsPH3, CsPH4, CsPH5, and CsPH8, whereas the acid-free pummelo has only a low transcript level of CsPH8. In addition, ABA injection increased the citrate content significantly, which was accompanied by the obvious induction of CsPH2, 6, 7, and 8 transcript levels. Taken together, we suggest that CsPH8 seems likely to regulate citrate accumulation in the citrus fruit vacuole
Beyond NK cells: the expanding universe of Innate Lymphoid Cells.
No full textFor a long time NK cells were thought to be the only immune innate lymphoid population capable of responding to invading pathogens under the influence of changing environmental cues. In the last few years, an increasing amount of evidence has shown that a number of different Innate Lymphoid Cells found at mucosal sites rapidly respond to locally produced cytokines in order to establish or maintain homeostasis. ILC populations closely mirror the phenotype of adaptive Thelper subsets in their ability to secrete soluble factors. Early in the immune response, ILCs are responsible for setting the stage to mount an adaptive T cell response appropriate to the incoming insult. Here we review the diversity of ILC subsets and discuss similarities and differences between ILCs and NK cells in function and key transcriptional factors required for their development
Genome-wide identification of VQ motif-containing proteins and their expression profiles under abiotic stresses in maize
No full textVQ motif-containing proteins play crucial roles in abiotic stress responses in plants. Recent studies have shown that some VQ proteins physically interact with WRKY transcription factors to activate downstream genes. In the present study, we identified and characterized genes encoding VQ motif-containing proteins using the most recent version of the maize genome sequence. In total, 61VQ genes were identified. In a cluster analysis, these genes clustered into nine groups together with their homologous genes in rice and Arabidopsis. Most of the VQ genes (57 out of 61 numbers) identified in maize were found to be single-copy genes. Analyses of RNA-seq data obtained using seedlings under long-term drought treatment showed that the expression levels of most ZmVQ genes (41 out of 61 members) changed during the drought stress response. Quantitative real-time PCR analyses showed that most of the ZmVQ genes were responsive to NaCl treatment. Also, approximately half of the ZmVQ genes were co-expressed with ZmWRKY genes. The identification of these VQ genes in the maize genome and knowledge of their expression profiles under drought and osmotic stresses will provide a solid foundation for exploring their specific functions in the abiotic stress responses of maize
Internal transcribed spacer 2 barcode: A good tool for identifying Acanthopanacis cortex
No full textAcanthopanacis cortex has been used in clinical applications for a long time. Considering some historical and geographical factors, Acanthopanacis cortex is easily confused with other herbs in medicine markets, thereby causing potential safety issues. In this study, we used the internal transcribed spacer 2 (ITS2) barcode to identify 69 samples belonging to six species, including Acanthopanacis cortex and its adulterants. The nearest distance, single-nucleotide polymorphisms (SNPs), and neighbor-joining (NJ) tree methods were used to evaluate the identification ability of the ITS2 barcode. According to the kimura-2-parameter model, the intraspecific distance of Eleutherococcus nodiflorus ITS2 sequences ranged from 0 to 0.0132. The minimum interspecific distance between E. nodiflorus and E. giraldii was 0.0221, which was larger than the maximum intraspecific distance of E. nodiflorus. Three stable SNPs in ITS2 can be used to distinguish Acanthopanacis cortex and its closely related species. The NJ tree indicated that the Acanthopanacis cortex samples clustered into one clade, which can be distinguished clearly from the adulterants of this herb. A secondary structure of ITS2 provided another dimensionality to identify species. In conclusion, the ITS2 barcode effectively identifies Acanthopanacis cortex, and DNA barcoding is a convenient tool for medicine market supervision
Diagnostic value of microRNA for Alzheimer's disease: a systematic review and meta-analysis
No full textSound evidence indicates that micro-RNA s (miRNAs) are aberrantly expressed in Alzheimer's disease (AD) patients. We performed a systematic review and meta-analysis investigating the role of miRNA in AD pathogenesis and their clinical diagnostic value, a systematic review of literature and meta-analysis of clinical trials were performed. In the systematic review, 236 papers were included and we reviewed the dysregulated miRNA expression in different parts of AD patients in order to identify the relationship between aberrantly expressed miRNAs and AD pathology. In the subsequent meta-analysis, seven studies were statistically analyzed with the following results: pooled sensitivity 0.86 (95%CI 0.79-0.90), pooled specificity 0.87 (95%CI 0.72-0.95), diagnostic odds ratio 28.29 and the area under the curve 0.87. In conclusion, our review indicated that aberrant expression of various miRNAs play an important role in the pathological process of AD, and statistical analysis of quantitative studies reveal the potential value of specific miRNAs in the diagnosis of AD
