A role for p38 MAPK in the regulation of ciliary motion in a eukaryote

Background  

Motile cilia are essential to the survival and reproduction of many eukaryotes; they are responsible for powering swimming of protists and small multicellular organisms and drive fluids across respiratory and reproductive surfaces in mammals. Although tremendous progress has been made to comprehend the biochemical basis of these complex evolutionarily-conserved organelles, few protein kinases have been reported to co-ordinate ciliary beat. Here we present evidence for p38 mitogen-activated protein kinase (p38 MAPK) playing a role in the ciliary beat of a multicellular eukaryote, the free-living miracidium stage of the platyhelminth parasite Schistosoma mansoni.     

Multi-component based cross correlation beat detection in electrocardiogram analysis

Background  

The first stage in computerised processing of the electrocardiogram is beat detection. This involves identifying all cardiac cycles and locating the position of the beginning and end of each of the identifiable waveform components. The accuracy at which beat detection is performed has significant impact on the overall classification performance, hence efforts are still being made to improve this process.     

Identification of three wheat globulin genes by screening a Triticum aestivum BAC genomic library with cDNA from a diabetes-associated globulin

Background  

Exposure to dietary wheat proteins in genetically susceptible individuals has been associated with increased risk for the development of Type 1 diabetes (T1D). Recently, a wheat protein encoded by cDNA WP5212 has been shown to be antigenic in mice, rats and humans with autoimmune T1D. To investigate the genomic origin of the identified wheat protein cDNA, a hexaploid wheat genomic library from Glenlea cultivar was screened.     

Study protocol to investigate the effects of testosterone therapy as an adjunct to exercise rehabilitation in hypogonadal males with chronic heart failure

Background

Most studies on risk factors for development of coronary heart disease (CHD) have been based on the clinical outcome of CHD. Our aim was to identify factors that could predict the development of ECG markers of CHD, such as abnormal Q/QS patterns, ST segment depression and T wave abnormalities, in 70-year-old men, irrespective of clinical outcome.

Methods

Predictors for development of different ECG abnormalities were identified in a population-based study using stepwise logistic regression. Anthropometrical and metabolic factors, ECG abnormalities and vital signs from a health survey of men at age 50 were related to ECG abnormalities identified in the same cohort 20 years later.

Results

At the age of 70, 9% had developed a major abnormal Q/QS pattern, but 63% of these subjects had not been previously hospitalized due to MI, while 57% with symptomatic MI between age 50 and 70 had no major Q/QS pattern at age 70. T wave abnormalities (Odds ratio 3.11, 95% CI 1.18–8.17), high lipoprotein (a) levels, high body mass index (BMI) and smoking were identified as significant independent predictors for the development of abnormal major Q/QS patterns. T wave abnormalities and high fasting glucose levels were significant independent predictors for the development of ST segment depression without abnormal Q/QS pattern.

Conclusion

T wave abnormalities on resting ECG should be given special attention and correlated with clinical information. Risk factors for major Q/QS patterns need not be the same as traditional risk factors for clinically recognized CHD. High lipoprotein (a) levels may be a stronger risk factor for silent myocardial infarction (MI) compared to clinically recognized MI.     

Hydrophobic profiles of the tail anchors in SLMAP dictate subcellular targeting

Background  

Tail anchored (TA) membrane proteins target subcellular structures via a C-terminal transmembrane domain and serve prominent roles in membrane fusion and vesicle transport. Sarcolemmal Membrane Associated Protein (SLMAP) possesses two alternatively spliced tail anchors (TA1 or TA2) but their specificity of subcellular targeting remains unknown.     

A wavelet-based ECG delineation algorithm for 32-bit integer online processing

Background  

Since the first well-known electrocardiogram (ECG) delineator based on Wavelet Transform (WT) presented by Li et al. in 1995, a significant research effort has been devoted to the exploitation of this promising method. Its ability to reliably delineate the major waveform components (mono- or bi-phasic P wave, QRS, and mono- or bi-phasic T wave) would make it a suitable candidate for efficient online processing of ambulatory ECG signals. Unfortunately, previous implementations of this method adopt non-linear operators such as root mean square (RMS) or floating point algebra, which are computationally demanding.     

Real time electrocardiogram QRS detection using combined adaptive threshold

Background  

QRS and ventricular beat detection is a basic procedure for electrocardiogram (ECG) processing and analysis. Large variety of methods have been proposed and used, featuring high percentages of correct detection. Nevertheless, the problem remains open especially with respect to higher detection accuracy in noisy ECGs     

Cancer risks of dermatomyositis and polymyositis: a nationwide cohort study in Taiwan

Introduction  

The association of idiopathic inflammatory myositis (IIM) and malignancies has been reported, but rarely in Asian countries. Our aim was to investigate the risk of cancer among IIM patients without a prior history of malignancies, in Taiwan.     

Framingham Stroke Risk Profile and poor cognitive function: a population-based study

Background  

The relationship between stroke risk and cognitive function has not previously been examined in a large community living sample other than the Framingham cohort. The objective of this study was to examine the relationship between 10-year risk for incident stroke and cognitive function in a large population-based sample.     

Novel route of tannic acid biotransformation and their effect on major biopolymer synthesis in Azotobacter sp. SSB81

Aims

To examine tannic acid (TA) utilization capacity by nitrogen‐fixing bacteria, Azotobacter sp. SSB81, and identify the intermediate products during biotransformation. Another aim of this work is to investigate the effects of TA on major biopolymers like extracellular polysaccharide (EPS) and polyhydroxybutyrate (PHB) synthesis.

Methods and Results

Tannic acid utilization and tolerance capacity of the strain was determined according to CLSI method. Intermediate products were identified using high‐performance liquid chromatography, LC‐MS/MS and ¹H NMR analysis. Intermediates were quantified by multiple reactions monitoring using LC‐MS/MS. The strain was able to tolerate a high level of TA and utilized through enzymatic system. Growth of Azotobacter in TA‐supplemented medium was characterized by an extended lag phase and decreased growth rate. Presence of TA catalytic enzymes as tannase, polyphenol oxidase (PPO) and phenol decarboxylase was confirmed in cell lysate using their specific substrates. PPO activity was more prominent in TA‐supplemented mineral medium after 48 h of growth when gallic to ellagic acid (EA) reversible reaction was remarkable. Phase contrast and scanning electron microscopic analysis revealed elongated and irregular size of Azotobacter cells in response to TA. ¹H NMR analysis indicated that TA was transformed into gallic acid (GA), EA and pyrogallol. Biopolymer (EPS and PHB) production was decreased several folds in the presence of TA compared with cells grown in only glucose medium.

Conclusions

This is the first evidence on the biotransformation of TA by Azotobacter and also elevated level of EA production from gallotannins. Azotobacter has developed the mechanism to utilize TA for their carbon and energy source.

Significance and Impact of the Study

The widespread occurrence and exploitation of Azotobacter sp. strain SSB81 in agricultural and forest soil have an additional advantage to utilize the soil‐accumulated TA and detoxifies the allelopathic effect of constant accumulated TA in soil.     

Delayed Contrast-Enhanced MRI of the Coronary Artery Wall in Takayasu Arteritis

Background

Takayasu arteritis (TA) is a rare form of chronic inflammatory granulomatous arteritis of the aorta and its major branches. Late gadolinium enhancement (LGE) with magnetic resonance imaging (MRI) has demonstrated its value for the detection of vessel wall alterations in TA. The aim of this study was to assess LGE of the coronary artery wall in patients with TA compared to patients with stable CAD.

Methods

We enrolled 9 patients (8 female, average age 46±13 years) with proven TA. In the CAD group 9 patients participated (8 male, average age 65±10 years). Studies were performed on a commercial 3T whole-body MR imaging system (Achieva; Philips, Best, The Netherlands) using a 3D inversion prepared navigator gated spoiled gradient-echo sequence, which was repeated 34–45 minutes after low-dose gadolinium administration.

Results

No coronary vessel wall enhancement was observed prior to contrast in either group. Post contrast, coronary LGE on IR scans was detected in 28 of 50 segments (56%) seen on T2-Prep scans in TA and in 25 of 57 segments (44%) in CAD patients. LGE quantitative assessment of coronary artery vessel wall CNR post contrast revealed no significant differences between the two groups (CNR in TA: 6.0±2.4 and 7.3±2.5 in CAD; p = 0.474).

Conclusion

Our findings suggest that LGE of the coronary artery wall seems to be common in patients with TA and similarly pronounced as in CAD patients. The observed coronary LGE seems to be rather unspecific, and differentiation between coronary vessel wall fibrosis and inflammation still remains unclear.     

Habituation to thaxtomin A in hybrid poplar cell suspensions provides enhanced and durable resistance to inhibitors of cellulose synthesis

Background  

Thaxtomin A (TA), a phytotoxin produced by the phytopathogen Streptomyces scabies, is essential for the development of potato common scab disease. TA inhibits cellulose synthesis but its actual mode of action is unknown. Addition of TA to hybrid poplar (Populus trichocarpa x Populus deltoides) cell suspensions can activate a cellular program leading to cell death. In contrast, it is possible to habituate hybrid poplar cell cultures to grow in the presence of TA levels that would normally induce cell death. The purpose of this study is to characterize TA-habituated cells and the mechanisms that may be involved in enhancing resistance to TA.     

Cyclic nucleotides and mitogen-activated protein kinases: regulation of simvastatin in platelet activation

Background  

3-Hydroxy-3-methyl-glutaryl coenzyme A (HMG-CoA) reductase inhibitors (statins) have been widely used to reduce cardiovascular risk. These statins (i.e., simvastatin) may exert other effects besides from their cholesterol-lowering actions, including inhibition of platelet activation. Platelet activation is relevant to a variety of coronary heart diseases. Although the inhibitory effect of simvastatin in platelet activation has been studied; the detailed signal transductions by which simvastatin inhibit platelet activation has not yet been completely resolved.     

Trans-activation-based risk assessment of <Emphasis Type="Italic">BRCA1</Emphasis> BRCT variants with unknown clinical significance

Background

Deleterious variants in the tumour suppressor BRCA1 are known to cause hereditary breast and ovarian cancer syndrome (HBOC). Missense variants in BRCA1 pose a challenge in clinical care, as their effect on protein functionality often remains unknown. Many of the pathogenic missense variants found in BRCA1 are located in the BRCA1 C-terminal (BRCT) domains, domains that are known to be vital for key functions such as homologous recombination repair, protein-protein interactions and trans-activation (TA). We investigated the TA activity of 12 BRCA1 variants of unknown clinical significance (VUSs) located in the BRCT domains to aid in the classification of these variants.

Results

Twelve BRCA1 VUSs were investigated using a modified version of the dual luciferase TA activity assay (TA assay) that yielded increased sensitivity and sample throughput. Variants were classified according to American College of Medical Genetics and Genomics (ACMG) criteria using TA assay results and available data. In combining our TA-assay results and available data, in accordance with the ACMG guidelines for variant classification, we proposed the following variant classifications: c.5100A>G, c.5326C>T, c.5348T>C and c.5477A>T as likely benign (class 2) variants. c.5075A>C, c.5116G>A and c.5513T>G were likely pathogenic (class 4), whereas c.5096G>A likely represents a likely pathogenic variant with moderate penetrance. Variants c.5123C>T, c.5125G>A, c.5131A>C and c.5504G>A remained classified as VUSs (class 3).

Conclusions

The modified TA assay provides efficient risk assessment of rare missense variants found in the BRCA1 BRCT-domains. We also report that increased post-transfection incubation time yielded a significant increase in TA assay sensitivity.

     

Methylenetetrahydrofolate Reductase Gene Variant (MTHFR C677T) and Migraine: A Case Control Study and Meta-analysis

Background  

Migraine is a common disorder that often coexists with depression. While a functional polymorphism in methyleneterahydrofolate reductase gene (MTHFR C677T) has been implicated in depression; the evidence to support an association of MTHFR with migraine has been inconclusive. We aim to investigate the effect of this variant on propensity for migraine and to perform a systematic review and meta-analysis of studies of MTHFR and migraine to date.     

Increased frequency of circulating Th22 in addition to Th17 and Th2 lymphocytes in systemic sclerosis: association with interstitial lung disease

Introduction  

T cell abnormalities have been associated with the pathogenesis of systemic sclerosis (SSc). Recently, besides T helper (Th)17 cells, the Th22 subset has been identified in humans. Our purpose was to investigate the pattern of cytokines produced and chemokine-receptors expressed by peripheral blood (PB) Th cells in SSc and healthy donors (HD) focusing on cells producing interleukin (IL)-17 and IL-22 and to identify specific clinical associations.     

Low cortisol levels in blood from dairy cows with ketosis: a field study

Background  

An elevated plasma glucose concentration has been considered to be a potential risk factor in the pathogenesis of left-displaced abomasums (DA). Therefore the present study was performed to investigate if spontaneous disease (parturient paresis, metritis, ketosis etc) in dairy cows results in elevated concentrations of glucose and cortisol in blood as cortisol is the major regulator of glucose in ruminants.     

Dietary fatty acid intake affects the risk of developing bone marrow lesions in healthy middle-aged adults without clinical knee osteoarthritis: a prospective cohort study

Introduction  

Fatty acids have been implicated in osteoarthritis (OA), yet the mechanism by which fatty acids affect knee structure and consequently the risk of knee OA has not been fully elucidated. Higher intakes of fatty acids have been shown to be associated with the risk of bone marrow lesions (BMLs) in a healthy population. The aim of this study was to examine the association between fatty acid consumption and the incidence of BMLs in healthy middle-aged adults without clinical knee OA.