Evaluating LINE-1 methylation in cleft lip tissues and its association with early pregnancy exposures

Aim: To pilot investigation of methylation of long interspersed nucleotide element-1 in lip tissues from infants with nonsyndromic cleft lip, and its association with maternal periconceptional exposures. Methods: The lateral and medial sides of the cleft lips of 23 affected infants were analyzed for long interspersed nucleotide element-1 methylation by bisulfite conversion and pyrosequencing. Results: The medial side showed 1.8% higher methylation compared with the lateral side; p = 0.031, particularly in male infants (2.7% difference; p = 0.011) or when the mothers did not take folic acid during periconceptional period (2.4% difference; p = 0.011). These results were not statistically significant when Bonferroni adjustment was used. Conclusion: The observed differences in DNA methylation, although nonsignificant after correction for multiple comparisons, suggest that differential regulation of the two sides may impact lip fusion and warrant larger-scale replication

Mid-term outcomes for Endoscopic versus Open Vein Harvest: a case control study

<p>Abstract</p> <p>Background</p> <p>Saphenous vein remains the most common conduit for coronary artery bypass grafting with increasing uptake of minimally invasive harvesting techniques. While Endoscopic Vein Harvest (EVH) has been demonstrated to improve early morbidity compared to Open Vein Harvest (OVH), recent literature suggests that this may be at the expense of graft patency at one year and survival at three years.</p> <p>Methods</p> <p>We undertook a retrospective single-centre, single-surgeon, case-control study of EVH (n = 89) and OVH (n = 182). The primary endpoint was death with secondary endpoints including acute coronary syndrome, revascularisation or other major adverse cardiac events. Freedom from angina, wound complications and self-rated health status were also assessed. Where repeat angiography had been performed, this was reviewed.</p> <p>Results</p> <p>Both groups were well matched demographically and for peri-operative characteristics. All cause mortality was 2/89 (2%) and 11/182 (6%) in the EVH and OVH groups respectively. This was shown by Cox Log-Rank analysis to be non-significant (p = 0.65), even if adjusting for inpatient mortality (p = 0.74). There was no difference in the rates of freedom from angina (p = 1.00), re-admission (p = 0.78) or need for further anti-anginals (p = 1.00). There was a significant reduction in the incidence of leg wound infections and complications in the endoscopic group (EVH: 7%; OVH: 28%; p = 0.0008) and the skew of high patient self-rated health scores in the EVH group (61% compared to 52% in the open group) approached statistical significance (p = 0.06).</p> <p>Conclusions</p> <p>While aware of the limitations of this small retrospective study, we are heartened by the preliminary results and consider our data to be justification for continuing to provide patients the opportunity to have minimally invasive conduit harvest in our centre. More robust evidence is still required to elucidate the implications of endoscopic techniques on conduit patency and patient outcome, but until the results of a large, prospective and randomised trial are available, we believe we can confidently offer our patients the option and benefits of EVH.</p

A LigA Three-Domain Region Protects Hamsters from Lethal Infection by Leptospira interrogans

The leptospiral LigA protein consists of 13 bacterial immunoglobulin-like (Big) domains and is the only purified recombinant subunit vaccine that has been demonstrated to protect against lethal challenge by a clinical isolate of Leptospira interrogans in the hamster model of leptospirosis. We determined the minimum number and location of LigA domains required for immunoprotection. Immunization with domains 11 and 12 was found to be required but insufficient for protection. Inclusion of a third domain, either 10 or 13, was required for 100% survival after intraperitoneal challenge with Leptospira interrogans serovar Copenhageni strain Fiocruz L1-130. As in previous studies, survivors had renal colonization; here, we quantitated the leptospiral burden by qPCR to be 1.2×103 to 8×105 copies of leptospiral DNA per microgram of kidney DNA. Although renal histopathology in survivors revealed tubulointerstitial changes indicating an inflammatory response to the infection, blood chemistry analysis indicated that renal function was normal. These studies define the Big domains of LigA that account for its vaccine efficacy and highlight the need for additional strategies to achieve sterilizing immunity to protect the mammalian host from leptospiral infection and its consequences

Diffusion-Weighted MRI for Verification of Electroporation-Based Treatments

Clinical electroporation (EP) is a rapidly advancing treatment modality that uses electric pulses to introduce drugs or genes into, e.g., cancer cells. The indication of successful EP is an instant plasma membrane permeabilization in the treated tissue. A noninvasive means of monitoring such a tissue reaction represents a great clinical benefit since, in case of target miss, retreatment can be performed immediately. We propose diffusion-weighted magnetic resonance imaging (DW-MRI) as a method to monitor EP tissue, using the concept of the apparent diffusion coefficient (ADC). We hypothesize that the plasma membrane permeabilization induced by EP changes the ADC, suggesting that DW-MRI constitutes a noninvasive and quick means of EP verification. In this study we performed in vivo EP in rat brains, followed by DW-MRI using a clinical MRI scanner. We found a pulse amplitude–dependent increase in the ADC following EP, indicating that (1) DW-MRI is sensitive to the EP-induced changes and (2) the observed changes in ADC are indeed due to the applied electric field

In silico transcriptional regulation and functional analysis of dengue shock syndrome associated SNPs in PLCE1 and MICB genes

YesSingle nucleotide polymorphisms (SNPs) in PLCE1 and MICB genes increase risk for the development of dengue shock syndrome (DSS). We used Bioinformatics tools to predict alterations at the transcriptional and posttranslational levels driven by PLCE1 and MICB SNPs associated with DSS. Functional and phenotypic analysis conducted to determine deleterious SNPs and impact of amino acid substitution on the structure and function of proteins identified rs2274223 (H1619R) as deleterious to protein coding as it induces structural change in the C2 domain of PLCε, with the mutant residue more positively charged than the wild-type residue (RMSD score, 1.75 Å).Moreover, rs2274223 condenses the chromatinrepressing PLCε expression in DSS. Briefly, this study presents the impact of a single nucleotide transition at SNPs associated with DSS on differential protein binding patterns with PLCE1 and MICB genes and on protein structure modification and their possible role in the pathogenesis of DSS

Leadership and Path Characteristics during Walks Are Linked to Dominance Order and Individual Traits in Dogs

Movement interactions and the underlying social structure in groups have relevance across many social-living species. Collective motion of groups could be based on an “egalitarian” decision system, but in practice it is often influenced by underlying social network structures and by individual characteristics. We investigated whether dominance rank and personality traits are linked to leader and follower roles during joint motion of family dogs. We obtained high-resolution spatio-temporal GPS trajectory data (823,148 data points) from six dogs belonging to the same household and their owner during 14 30–40 min unleashed walks. We identified several features of the dogs' paths (e.g., running speed or distance from the owner) which are characteristic of a given dog. A directional correlation analysis quantifies interactions between pairs of dogs that run loops jointly. We found that dogs play the role of the leader about 50–85% of the time, i.e. the leader and follower roles in a given pair are dynamically interchangable. However, on a longer timescale tendencies to lead differ consistently. The network constructed from these loose leader–follower relations is hierarchical, and the dogs' positions in the network correlates with the age, dominance rank, trainability, controllability, and aggression measures derived from personality questionnaires. We demonstrated the possibility of determining dominance rank and personality traits of an individual based only on its logged movement data. The collective motion of dogs is influenced by underlying social network structures and by characteristics such as personality differences. Our findings could pave the way for automated animal personality and human social interaction measurements

Evaluation of metals that are potentially toxic to agricultural surface soils, using statistical analysis, in northwestern Saudi Arabia

© 2015, Springer-Verlag Berlin Heidelberg. Heavy metals in agricultural soils enter the food chain when taken up by plants. The main purpose of this work is to determine metal contamination in agricultural farms in northwestern Saudi Arabia. Fifty surface soil samples were collected from agricultural areas. The study focuses on the geochemical behavior of As, Cd, Co, Cr, Cu, Hg, Pb and Zn, and determines the enrichment factor and geoaccumulation index. Multivariate statistical analysis, including principle component analysis and cluster analysis, is also applied to the acquired data. The study shows considerable variation in the concentrations of the analyzed metals in the studied soil samples. This variation in concentration is attributed to the intensity of agricultural activities and, possibly, to nearby fossil fuel combustion activities, as well as to traffic flows from highways and local roads. Multivariate analysis suggests that As, Cd, Hg and Pb are associated with anthropogenic activities, whereas Co, Cr, Cu and Zn are mainly controlled by geogenic activities. Hg and Pb show the maximum concentration in the analyzed samples as compared to the background concentration

Moving to capture children’s attention: developing a methodology for measuring visuomotor attention

Attention underpins many activities integral to a child’s development. However, methodological limitations currently make large-scale assessment of children’s attentional skill impractical, costly and lacking in ecological validity. Consequently we developed a measure of ‘Visual Motor Attention’ (VMA) - a construct defined as the ability to sustain and adapt visuomotor behaviour in response to task-relevant visual information. In a series of experiments, we evaluated the capability of our method to measure attentional processes and their contributions in guiding visuomotor behaviour. Experiment 1 established the method’s core features (ability to track stimuli moving on a tablet-computer screen with a hand-held stylus) and demonstrated its sensitivity to principled manipulations in adults’ attentional load. Experiment 2 standardised a format suitable for use with children and showed construct validity by capturing developmental changes in executive attention processes. Experiment 3 tested the hypothesis that children with and without coordination difficulties would show qualitatively different response patterns, finding an interaction between the cognitive and motor factors underpinning responses. Experiment 4 identified associations between VMA performance and existing standardised attention assessments and thereby confirmed convergent validity. These results establish a novel approach to measuring childhood attention that can produce meaningful functional assessments that capture how attention operates in an ecologically valid context (i.e. attention's specific contribution to visuomanual action)

Full-length human placental sFlt-1-e15a isoform induces distinct maternal phenotypes of preeclampsia in mice

<div><p>Objective</p><p>Most anti-angiogenic preeclampsia models in rodents utilized the overexpression of a truncated soluble fms-like tyrosine kinase-1 (sFlt-1) not expressed in any species. Other limitations of mouse preeclampsia models included stressful blood pressure measurements and the lack of postpartum monitoring. We aimed to 1) develop a mouse model of preeclampsia by administering the most abundant human placental sFlt-1 isoform (hsFlt-1-e15a) in preeclampsia; 2) determine blood pressures in non-stressed conditions; and 3) develop a survival surgery that enables the collection of fetuses and placentas and postpartum (PP) monitoring.</p><p>Methods</p><p>Pregnancy status of CD-1 mice was evaluated with high-frequency ultrasound on gestational days (GD) 6 and 7. Telemetry catheters were implanted in the carotid artery on GD7, and their positions were verified by ultrasound on GD13. Mice were injected through tail-vein with adenoviruses expressing hsFlt-1-e15a (n = 11) or green fluorescent protein (GFP; n = 9) on GD8/GD11. Placentas and pups were delivered by cesarean section on GD18 allowing PP monitoring. Urine samples were collected with cystocentesis on GD6/GD7, GD13, GD18, and PPD8, and albumin/creatinine ratios were determined. GFP and hsFlt-1-e15a expression profiles were determined by qRT-PCR. Aortic ring assays were performed to assess the effect of hsFlt-1-e15a on endothelia.</p><p>Results</p><p>Ultrasound predicted pregnancy on GD7 in 97% of cases. Cesarean section survival rate was 100%. Mean arterial blood pressure was higher in hsFlt-1-e15a-treated than in GFP-treated mice (∆MAP = 13.2 mmHg, p = 0.00107; GD18). Focal glomerular changes were found in hsFlt-1-e15a -treated mice, which had higher urine albumin/creatinine ratios than controls (109.3±51.7μg/mg vs. 19.3±5.6μg/mg, p = 4.4x10^-2; GD18). Aortic ring assays showed a 46% lesser microvessel outgrowth in hsFlt-1-e15a-treated than in GFP-treated mice (p = 1.2x10^-2). Placental and fetal weights did not differ between the groups. One mouse with liver disease developed early-onset preeclampsia-like symptoms with intrauterine growth restriction (IUGR).</p><p>Conclusions</p><p>A mouse model of late-onset preeclampsia was developed with the overexpression of hsFlt-1-e15a, verifying the <i>in vivo</i> pathologic effects of this primate-specific, predominant placental sFlt-1 isoform. HsFlt-1-e15a induced early-onset preeclampsia-like symptoms associated with IUGR in a mouse with a liver disease. Our findings support that hsFlt-1-e15a is central to the terminal pathway of preeclampsia, and it can induce the full spectrum of symptoms in this obstetrical syndrome.</p></div