Transcatheter indirect mitral annuloplasty induces annular and left atrial remodelling in secondary mitral regurgitation

Aims Mitral annuloplasty using the Carillon Mitral Contour System (CMCS) reduces secondary mitral regurgitation (SMR) and leads to reverse left ventricular remodelling. The aim of this study was to evaluate the effect of the CMCS on the mitral valve annulus (MA) and left atrial volume (LAV). Methods and results We retrospectively evaluated the data of all patients treated with the CMCS at our centre. Using transthoracic echocardiography, MA diameters were assessed by measuring the anterolateral to posteromedial extend (ALPM) and the anterior to posterior (AP) dimensions, respectively. Also, LAV and left ventricular end‐diastolic volume (LVEDV) were assessed. Patients were examined at three time points: baseline, at 20–60 days (30dFUP), and at 9–15 months (1yFUP), using paired analysis. From July 2014 until March 2019, 75 cases of severe SMR were treated using CMCS. Cases in which other devices were used in combination (COMBO therapy, n = 35) or in which the device could not be implanted (implant failure, n = 3) were excluded, leaving 37 patients in the present analysis. Analysis at 30dFUP showed a significant reduction of 16% in the mean ALPM diameter (7.27 ± 5.40 mm) and 15% in the AP diameter (6.57 ± 5.33 mm). Analysis of LAV also showed a significant reduction of 21% (36.61 ± 82.67 mL), with no significant change in LVEDV. At 1yFUP, the reduction of both the mean ALPM diameter of 14% (6.24 ± 5.70 mm) and the mean AP diameter of 12% (5.46 ± 4.99 mm) remained significant and stable. The reduction in LAV was also maintained at 23% (37.03 ± 56.91 mL). LAV index was significantly reduced by 17% at 30dFUP (15.44 ± 40.98 mL/m2) and by 13% at 1yFUP (11.56 ± 31.87 mL/m2), respectively. LVEDV index showed no significant change at 30dFUP and a non‐significant 10% reduction at 1yFUP (17.75 ± 58.79 mL/m2). Conclusions The CMCS successfully treats symptomatic SMR with a stable reduction of not only the AP diameter of the MA, but the current study also demonstrates an additional reduction of the ALPM dimension at both 30dFUP and 1yFUP. We have also shown for the first time that LAV and LAV index are significantly reduced at both 30dFUP and 1yFUP and a non‐significant positive remodelling of the LVEDV. This positive left atrial remodelling has not been looked for and demonstrated in earlier randomized studies of CMCS

Wolbachia and DNA barcoding insects: patterns, potential and problems

Wolbachia is a genus of bacterial endosymbionts that impacts the breeding systems of their hosts. Wolbachia can confuse the patterns of mitochondrial variation, including DNA barcodes, because it influences the pathways through which mitochondria are inherited. We examined the extent to which these endosymbionts are detected in routine DNA barcoding, assessed their impact upon the insect sequence divergence and identification accuracy, and considered the variation present in Wolbachia COI. Using both standard PCR assays (Wolbachia surface coding protein – wsp), and bacterial COI fragments we found evidence of Wolbachia in insect total genomic extracts created for DNA barcoding library construction. When >2 million insect COI trace files were examined on the Barcode of Life Datasystem (BOLD) Wolbachia COI was present in 0.16% of the cases. It is possible to generate Wolbachia COI using standard insect primers; however, that amplicon was never confused with the COI of the host. Wolbachia alleles recovered were predominantly Supergroup A and were broadly distributed geographically and phylogenetically. We conclude that the presence of the Wolbachia DNA in total genomic extracts made from insects is unlikely to compromise the accuracy of the DNA barcode library; in fact, the ability to query this DNA library (the database and the extracts) for endosymbionts is one of the ancillary benefits of such a large scale endeavor – for which we provide several examples. It is our conclusion that regular assays for Wolbachia presence and type can, and should, be adopted by large scale insect barcoding initiatives. While COI is one of the five multi-locus sequence typing (MLST) genes used for categorizing Wolbachia, there is limited overlap with the eukaryotic DNA barcode region

Genetic analysis of a major international collection of cultivated apple varieties reveals previously unknown historic heteroploid and inbred relationships

Domesticated apple (Malus x domestica Borkh.) is a major global crop and the genetic diversity held within the pool of cultivated varieties is important for the development of future cultivars. The aim of this study was to investigate the diversity held within the domesticated form, through the analysis of a major international germplasm collection of cultivated varieties, the UK National Fruit Collection, consisting of over 2,000 selections of named cultivars and seedling varieties. We utilised Diversity Array Technology (DArT) markers to assess the genetic diversity within the collection. Clustering attempts, using the software STRUCTURE revealed that the accessions formed a complex and historically admixed group for which clear clustering was challenging. Comparison of accessions using the Jaccard similarity coefficient allowed us to identify clonal and duplicate material as well as revealing pairs and groups that appeared more closely related than a standard parent-offspring or full-sibling relations. From further investigation, we were able to propose a number of new pedigrees, which revealed that some historically important cultivars were more closely related than previously documented and that some of them were partially inbred. We were also able to elucidate a number of parent-offspring relationships that had resulted in a number of important polyploid cultivars. This included reuniting polyploid cultivars that in some cases dated as far back as the 18th century, with diploid parents that potentially date back as far as the 13th century

Assessing cardiovascular risk in chronic kidney disease patients prior to kidney transplantation: clinical usefulness of a standardised cardiovascular assessment protocol.

BACKGROUND: Despite pre-kidney-transplant cardiovascular (CV) assessment being routine care to minimise perioperative risk, the utility of such assessment is not well established. The study reviewed the evaluation and outcome of a standardised CV assessment protocol. METHODS: Data were analysed for 231 patients (age 53.4 ± 12.9 years, diabetes 34.6%) referred for kidney transplantation between 1/2/2012-31/12/2014. One hundred forty-three patients were high-risk (age > 60 years, diabetes, CV disease, heart failure, peripheral vascular disease) and offered dobutamine stress echocardiography (DSE); 88 patients were low-risk and offered ECG and echocardiography with/without exercise treadmill test. RESULTS: At the end of follow-up (579 ± 289 days), 35 patients underwent kidney transplantation and 50 were active on the waitlist. There were 24 events (CV or death), none were perioperative. One hundred fifteen patients had DSE with proportionally more events in DSE-positive compared to DSE-negative patients (6/34 vs. 7/81, p = 0.164). In 42 patients who underwent coronary angiography due to a positive DSE or ischaemic heart disease symptoms, 13 (31%) had events, 6 were suspended, 11 removed from waitlist, 3 wait-listed, 1 transplanted and 17 still undergoing assessment. Patients with significant coronary artery disease requiring intervention had poorer event-free survival compared to those without intervention (56% vs. 83% at 2 years, p = 0.044). However, the association became non-significant after correction for CV risk factors (HR = 3.17, 95% CI 0.51-19.59, p = 0.215). CONCLUSIONS: The stratified CV risk assessment protocol using DSE in all high-risk patients was effective in identifying patients with coronary artery disease. The coronary angiograms identified the event-prone patients effectively but coronary interventions were not associated with improved survival

Train design features affecting boarding and alighting of passengers

Accurately predicting train dwell time is critical to running an effective and efficient service. With high-density passenger services, large numbers of passengers must be able to board and alight the train quickly – and within scheduled dwell times. Using a specially constructed train mock-up in a pedestrian movement laboratory, the experiments outlined in this paper examine the impact of train carriage design factors such as door width, seat type, platform edge doors and horizontal gap on the time taken by passengers to board and alight. The findings illustrate that the effectiveness of design features depends on whether there are a majority of passengers boarding or alighting. An optimum door width should be between 1.7 and 1.8 m. The use of a central pole and platform edge doors produced no major effects, but a 200 mm horizontal gap could increase the movement of passengers. There is no clear effect of the type of seats and neither the standbacks between 50, 300 and 500 mm. Further research will look for the relationship between the dwell time and the characteristics of passengers such as personal space

Ecological effects of extreme drought on Californian herbaceous plant communities

Understanding the consequences of extreme climatic events is a growing challenge in ecology. Climatic extremes may differentially affect varying elements of biodiversity, and may not always produce ecological effects exceeding those of "normal" climatic variation in space and time. We asked how the extreme drought years of 2013- 2014 affected the cover, species richness, functional trait means, functional diversity, and phylogenetic diversity of herbaceous plant communities across the California Floristic Province. We compared the directions and magnitudes of these drought effects with expectations from four "pre-drought" studies of variation in water availability: (1) a watering experiment, (2) a long- Term (15-yr) monitoring of interannual variability, (3) a resampling of historic (57-yr- old) plots within a warming and drying region, and (4) natural variation in communities over a broad geographic gradient in precipitation. We found that the drought was associated with consistent reductions in species richness and cover, especially for annual forbs and exotic annual grasses, but not with changes in functional or phylogenetic diversity. Except for total cover and cover of exotic annual grasses, most drought effects did not exceed quantitative expectations based on the four pre-drought studies. Qualitatively, plant community responses to the drought were most concordant with responses to pre-drought interannual rainfall variability in the 15-yr monitoring study, and least concordant with responses to the geographic gradient in precipitation. Our results suggest that, at least in the short term, extreme drought may cause only a subset of community metrics to respond in ways that exceed normal background variability

Architecture of Pol II(G) and molecular mechanism of transcription regulation by Gdown1.

Tight binding of Gdown1 represses RNA polymerase II (Pol II) function in a manner that is reversed by Mediator, but the structural basis of these processes is unclear. Although Gdown1 is intrinsically disordered, its Pol II interacting domains were localized and shown to occlude transcription factor IIF (TFIIF) and transcription factor IIB (TFIIB) binding by perfect positioning on their Pol II interaction sites. Robust binding of Gdown1 to Pol II is established by cooperative interactions of a strong Pol II binding region and two weaker binding modulatory regions, thus providing a mechanism both for tight Pol II binding and transcription inhibition and for its reversal. In support of a physiological function for Gdown1 in transcription repression, Gdown1 co-localizes with Pol II in transcriptionally silent nuclei of early Drosophila embryos but re-localizes to the cytoplasm during zygotic genome activation. Our study reveals a self-inactivation through Gdown1 binding as a unique mode of repression in Pol II function

Feeding spectra and activity of the freshwater crab Trichodactylus kensleyi (Decapoda: Brachyura: Trichodactylidae) at La Plata basin

Background: In inland water systems, it is important to characterize the trophic links in order to identify the ‘trophic species’ and, from the studies of functional diversity, understand the dynamics of matter and energy in these environments. The aim of this study is to analyze the natural diet of Trichodactylus kensleyi of subtropical rainforest streams and corroborate the temporal variation in the trophic activity during day hours. Results: A total of 15 major taxonomic groups were recognized in gut contents. The index of relative importance identified the following main prey items in decreasing order of importance: vegetal remains, oligochaetes, chironomid larvae, and algae. A significant difference was found in the amount of full stomachs during day hours showing a less trophic activity at midday and afternoon. The index of relative importance values evidenced the consumption of different prey according to day moments. Results of the gut content indicate that T. kensleyi is an omnivorous crab like other trichodactylid species. Opportunistic behavior is revealed by the ingestion of organisms abundant in streams such as oligochaetes and chironomid larvae. The consumption of allochthonous plant debris shows the importance of this crab as shredder in subtropical streams. However, the effective assimilation of plant matter is yet unknown in trichodactylid crabs. Conclusions: This research provides knowledge that complements previous studies about trophic relationships of trichodactylid crabs and supported the importance of T. kensleyi in the transference of energy and matter from benthic community and riparian sources to superior trophic levels using both macro- and microfauna.Fil: Williner, Verónica. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Instituto Nacional de Limnología. Universidad Nacional del Litoral. Instituto Nacional de Limnología; Argentina. Universidad Nacional del Litoral. Facultad de Humanidades y Ciencias; ArgentinaFil: de Azevedo Carvalho, Debora. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Instituto Nacional de Limnología. Universidad Nacional del Litoral. Instituto Nacional de Limnología; ArgentinaFil: Collins, Pablo Agustin. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Instituto Nacional de Limnología. Universidad Nacional del Litoral. Instituto Nacional de Limnología; Argentina. Universidad Nacional del Litoral. Facultad de Bioquímica y Ciencias Biológicas; Argentin

KIAA0101 Is Overexpressed, and Promotes Growth and Invasion in Adrenal Cancer

Background: KIAA0101 is a proliferating cell nuclear antigen-associated factor that is overexpressed in some human malignancies. Adrenocortical neoplasm is one of the most common human neoplasms for which the molecular causes are poorly understood. Moreover, it is difficult to distinguish between localized benign and malignant adrenocortical tumors. For these reasons, we studied the expression, function and possible mechanism of dysregulation of KIAA0101 in human adrenocortical neoplasm. Methodology/Principal Findings: KIAA0101 mRNA and protein expression levels were determined in 112 adrenocortical tissue samples (21 normal adrenal cortex, 80 benign adrenocortical tumors, and 11 adrenocortical carcinoma (ACC). SiRNA knockdown was used to determine the functional role of KIAA0101 on cell proliferation, cell cycle, apoptosis, soft agar anchorage independent growth and invasion in the ACC cell line, NCI-H295R. In addition, we explored the mechanism of KIAA0101 dysregulation by examining the mutational status. KIAA0101 mRNA (9.7 fold) and protein expression were significantly higher in ACC (p,0.0001). KIAA0101 had sparse protein expression in only a few normal adrenal cortex samples, which was confined to adrenocortical progenitor cells. KIAA0101 expression levels were 84 % accurate for distinguishing between ACC and normal and benign adrenocortical tumor samples. Knockdown of KIAA0101 gene expression significantly decreased anchorage independent growth by 80 % and invasion by 60 % (p = 0.001; p = 0.006). W