O fra Bernardinu Splićaninu, priređivaču prvog izdanja hrvatskog lekcionara, ponovo!

The use of miniaturised isotachophoresis to allow the simultaneous determination of two inorganic selenium species has been investigated using a poly(methyl methacrylate) chip with a 44-mm-long, 200-μm-wide, 300-μm-deep separation channel. The miniaturised device included an integrated on-column, dual-electrode conductivity detector and was used in conjunction with a hydrodynamic fluid transport system. A simple electrolyte system has been developed which allowed the separation of selenium(IV) and selenium(VI) species to be made in under 210 s. The limits of detection were calculated to be 0.52 mg L−1 for selenium(IV) and 0.65 mg L−1 for selenium(VI). The method allowed the separation of the selenium species from a range of common anions including fluoride, nitrate, nitrite, phosphate, sulfate and sulfite

Cdk Activity Couples Epigenetic Centromere Inheritance to Cell Cycle Progression

Centromeres form the site of chromosome attachment to microtubules during mitosis. Identity of these loci is maintained epigenetically by nucleosomes containing the histone H3 variant CENP-A. Propagation of CENP-A chromatin is uncoupled from DNA replication initiating only during mitotic exit. We now demonstrate that inhibition of Cdk1 and Cdk2 activities is sufficient to trigger CENP-A assembly throughout the cell cycle in a manner dependent on the canonical CENP-A assembly machinery. We further show that the key CENP-A assembly factor Mis18BP1(HsKNL2) is phosphorylated in a cell cycle-dependent manner that controls its centromere localization during mitotic exit. These results strongly support a model in which the CENP-A assembly machinery is poised for activation throughout the cell cycle but kept in an inactive noncentromeric state by Cdk activity during S, G2, and M phases. Alleviation of this inhibition in G1 phase ensures tight coupling between DNA replication, cell division, and subsequent centromere maturation.FCT doctoral fellowship: (SFRH/BD/33219/2007); FCT grant: (BIA-BCM/100557/2008); Fundação Calouste Gulbenkian; European Commission FP7 programme; EMBO installation grant

The heart in sporadic inclusion body myositis: a study in 51 patients

The purpose of this study was to explore the prevalence and nature of cardiac abnormalities in sporadic inclusion body myositis (sIBM). Fifty-one sIBM patients were cross-sectionally studied using history-taking, physical examination, measurements of serum creatine kinase activity, the MB fraction (CK-MB), cardiac troponin T (cTnT) and I (cTnI), a 12-lead electrocardiogram (ECG) and 2-dimensional echocardiography. Present cardiac history was abnormal in 12 (24%) out of 51 patients, 12 (24%) patients had abnormalities on ECG, mostly aspecific, and in 12 (24%) patients the echocardiograph showed abnormalities. Elevated CK-MB was present in 42 (82%) patients and 40 (78%) had an elevated cTnT in the absence of acute cardiac pathology. In contrast, in one patient (2%) cTnI was elevated. There was no apparent association between elevated biomarkers, ECG or echocardiographic abnormalities. The prevalence of cardiac abnormalities in sIBM does not seem to be higher than would be expected in these elderly patients. Elevated CK-MB and cTnT levels are common, in contrast to cTnI, but do not reflect cardiac pathology

The luxS mutation causes loosely-bound biofilms in Shewanella oneidensis

<p>Abstract</p> <p>Background</p> <p>The <it>luxS </it>gene in <it>Shewanella oneidensis </it>was shown to encode an autoinducer-2 (AI-2)-like molecule, the postulated universal bacterial signal, but the impaired biofilm growth of a <it>luxS </it>deficient mutant could not be restored by AI-2, indicating it might not have a signalling role in this organism.</p> <p>Findings</p> <p>Here, we provide further evidence regarding the metabolic role of a <it>luxS </it>mutation in <it>S. oneidensis</it>. We constructed a <it>luxS </it>mutant and compared its phenotype to a wild type control with respect to its ability to remove AI-2 from the medium, expression of secreted proteins and biofilm formation. We show that <it>S. oneidensis </it>has a cell-dependent mechanism by which AI-2 is depleted from the medium by uptake or degradation at the end of the exponential growth phase. As AI-2 depletion is equally active in the <it>luxS </it>mutant and thus does not require AI-2 as an inducer, it appears to be an unspecific mechanism suggesting that AI-2 for <it>S. oneidensis </it>is a metabolite which is imported under nutrient limitation. Secreted proteins were studied by iTraq labelling and liquid chromatography mass spectrometry (LC-MS) detection. Differences between wild type and mutant were small. Proteins related to flagellar and twitching motility were slightly up-regulated in the <it>luxS </it>mutant, in accordance with its loose biofilm structure. An enzyme related to cysteine metabolism was also up-regulated, probably compensating for the lack of the LuxS enzyme. The <it>luxS </it>mutant developed an undifferentiated, loosely-connected biofilm which covered the glass surface more homogenously than the wild type control, which formed compact aggregates with large voids in between.</p> <p>Conclusions</p> <p>The data confirm the role of the LuxS enzyme for biofilm growth in <it>S. oneidensis </it>and make it unlikely that AI-2 has a signalling role in this organism.</p

Are mice good models for human neuromuscular disease? Comparing muscle excursions in walking between mice and humans

The mouse is one of the most widely used animal models to study neuromuscular diseases and test new therapeutic strategies. However, findings from successful pre-clinical studies using mouse models frequently fail to translate to humans due to various factors. Differences in muscle function between the two species could be crucial but often have been overlooked. The purpose of this study was to evaluate and compare muscle excursions in walking between mice and humans

An industry consensus study on an HPLC fluorescence method for the determination of (±)-catechin and (±)-epicatechin in cocoa and chocolate products

<p>Abstract</p> <p>Background</p> <p>This manuscript describes the results of an HPLC study for the determination of the flavan-3-ol monomers, (±)-catechin and (±)-epicatechin, in cocoa and plain dark and milk chocolate products. The study was performed under the auspices of the National Confectioners Association (NCA) and involved the analysis of a series of samples by laboratories of five member companies using a common method.</p> <p>Methodology</p> <p>The method reported in this paper uses reversed phase HPLC with fluorescence detection to analyze (±)-epicatechin and (±)-catechin extracted with an acidic solvent from defatted cocoa and chocolate. In addition to a variety of cocoa and chocolate products, the sample set included a blind duplicate used to assess method reproducibility. All data were subjected to statistical analysis with outliers eliminated from the data set.</p> <p>Results</p> <p>The percent coefficient of variation (%CV) of the sample set ranged from approximately 7 to 15%.</p> <p>Conclusions</p> <p>Further experimental details are described in the body of the manuscript and the results indicate the method is suitable for the determination of (±)-catechin and (±)-epicatechin in cocoa and chocolate products and represents the first collaborative study of this HPLC method for these compounds in these matrices.</p

Cognitive impairment induced by delta9-tetrahydrocannabinol occurs through heteromers between cannabinoid CB1 and serotonin 5-HT2A receptors

Delta-9-tetrahydrocannabinol (THC), the main psychoactive compound of marijuana, induces numerous undesirable effects, including memory impairments, anxiety, and dependence. Conversely, THC also has potentially therapeutic effects, including analgesia, muscle relaxation, and neuroprotection. However, the mechanisms that dissociate these responses are still not known. Using mice lacking the serotonin receptor 5-HT2A, we revealed that the analgesic and amnesic effects of THC are independent of each other: while amnesia induced by THC disappears in the mutant mice, THC can still promote analgesia in these animals. In subsequent molecular studies, we showed that in specific brain regions involved in memory formation, the receptors for THC and the 5-HT2A receptors work together by physically interacting with each other. Experimentally interfering with this interaction prevented the memory deficits induced by THC, but not its analgesic properties. Our results highlight a novel mechanism by which the beneficial analgesic properties of THC can be dissociated from its cognitive side effects

A piece of the human heart: variance of protein phosphorylation in left ventricular samples from end-stage primary cardiomyopathy patients

Cardiomyocyte contraction is regulated by phosphorylation of sarcomeric proteins. Throughout the heart regional and transmural differences may exist in protein phosphorylation. In addition, phosphorylation of sarcomeric proteins is altered in cardiac disease. Heterogeneity in protein phosphorylation may be larger in hypertrophic cardiomyopathy (HCM) and dilated cardiomyopathy (DCM) as it may be caused by multiple mutations in genes encoding different sarcomeric proteins. Moreover, HCM is characterized by asymmetric remodelling of the heart. In the present study we assessed if local differences in sarcomeric protein phosphorylation are more evident in primary HCM or DCM than in non-failing donors. Thereto, phosphorylation of the two main target proteins of the beta-adrenergic receptor pathway, troponin I (cTnI) and myosin binding protein C (cMyBP-C) was analysed in different parts in the free left ventricular wall of end–stage failing HCM and DCM patients and donors obtained during transplant surgery. Intra-patient variability in protein phosphorylation within tissue samples of approximately 2 g wet weight was comparable between donor, HCM and DCM samples and could partly be attributed to the precision of the technique. Thus, our data indicate that within the precision of the measurements small, biopsy-sized cardiac tissue samples are representative for the region of the free left ventricular wall from which they were obtained

Tethered Spinal Cord due to Thoracic Spinal Cord Lipoma: Minimally Invasive Surgical Management Case Report and Literature Review

An unusual case of a thoracic spine lipoma presenting with profound progressive numbness along with difficult to interpret preoperative imaging is discussed. A uniquely minimally invasive surgical treatment approach with successful outcome and improved neurologic symptoms is presented. A literature review and discussion of the benefits and limitations of a minimally invasive surgical technique are provided. A male presented with several months of progressive bilateral lower extremity numbness that ascended to the mid-thoracic spine. Spine magnetic resonance imaging demonstrated a 9 mm intradural, thoracic spinal mass, which was thought preoperatively to represent an arachnoid cyst with an adhesion or a localized dural ectasia. Subsequent imaging demonstrated a band at the cranial margin of the mass appearing to tether the spinal cord to the dorsal-lateral spinal canal without an arachnoid cyst or osseous defect. Surgical exploration revealed an intradural exophytic, intramedullary fatty mass tethering the spinal cord to the dorsolateral dura. An abnormal patch of dura was observed overlying the fatty attachment but no dural defect was identified. Pathology demonstrated fragments of fibroconnective tissue, scattered mature adipocytes, and entrapped meningeal cells, yielding the diagnosis of a spinal cord lipoma. Follow up imaging demonstrated no residual tethering of the spinal cord

Individual, family and environmental factors associated with pediatric excess weight in Spain: a cross-sectional study

Background: There is a growing worldwide trend of obesity in children. Identifying the causes and modifiable factors associated with child obesity is important in order to design effective public health strategies. Our objective was to provide empirical evidence of the association that some individual and environmental factors may have with child excess weight.Method: A cross-sectional study was performed using multi-stage probability sampling of 978 Spanish children aged between 8 and 17 years, with objectively measured height and weight, along with other individual, family and neighborhood variables. Crude and adjusted odds ratios were calculated.Results: In 2012, 4 in 10 children were either overweight or obese with a higher prevalence amongst males and in the 8–12 year age group. Child obesity was associated negatively with the socio-economic status of the adult responsible for the child’s diet, OR 0.78 (CI95% 0.59–1.00), girls OR 0.75 (CI95% 0.57–0.99), older age of the child (0.41; CI95% 0.31–0.55), daily breakfast (OR 0.59; p = 0.028) and half an hour or more of physical activity every day. No association was found for neighborhood variables relating to perceived neighborhood quality and safety.Conclusion: This study identifies potential modifiable factors such as physical activity, daily breakfast and caregiver education as areas for public health policies. To be successful, an intervention should take into account both individual and family factors when designing prevention strategies to combat the worldwide epidemic of child excess weight.This study was funded by grant number PI10/02018, Ministerio de Economía y Competitividad del Reino de España (Ministry of Economy and Competitiveness, Spain), Instituto de Salud Carlos III-FEDER