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Structural maintenance of chromosomes (SMC) proteins are required for DNA elimination in Paramecium.
Get PDFChromosome (SMC) proteins are a large family of ATPases that play important roles in the organization and dynamics of chromatin. They are central regulators of chromosome dynamics and the core component of condensin. DNA elimination during zygotic somatic genome development is a characteristic feature of ciliated protozoa such as Paramecium This process occurs after meiosis, mitosis, karyogamy, and another mitosis, which result in the formation of a new germline and somatic nuclei. The series of nuclear divisions implies an important role of SMC proteins in Paramecium sexual development. The relationship between DNA elimination and SMC has not yet been described. Here, we applied RNA interference, genome sequencing, mRNA sequencing, immunofluorescence, and mass spectrometry to investigate the roles of SMC components in DNA elimination. Our results show that SMC4-2 is required for genome rearrangement, whereas SMC4-1 is not. Functional diversification of SMC4 in Paramecium led to a formation of two paralogues where SMC4-2 acquired a novel, development-specific function and differs from SMC4-1. Moreover, our study suggests a competitive relationship between these two proteins
Will Getting Out the Thrombus Mechanically Keep the Deep Vein Thrombosis Patient Out of (Double) Trouble?
No full textPopulation genetic insights into establishment, adaptation, and dispersal of the invasive quagga mussel across perialpine lakes
Get PDFHuman activities have facilitated the invasion of freshwater ecosystems by various organisms. Especially, invasive bivalves such as the quagga mussels, Dreissena bugensis, have the potential to alter ecosystem function as they heavily affect the food web. Quagga mussels occur in high abundance, have a high filtration rate, quickly spread within and between waterbodies via pelagic larvae, and colonize various substrates. They have invaded various waterbodies across the Northern Hemisphere. In Central Europe, they have invaded multiple large and deep perialpine lakes with first recordings in Lake Geneva in 2015 and 2016 in Lake Constance. In the deep perialpine lakes, quagga mussels quickly colonized the littoral zone but are also abundant deeper (>80 m), where they are often thinner and brighter shelled. We analysed 675 quagga mussels using ddRAD sequencing to gain in-depth insights into the genetic population structure of quagga mussels across Central European lakes and across various sites and depth habitats in Lake Constance. We revealed substantial genetic differentiation amongst quagga mussel populations from three unconnected lakes, and all populations showed high genetic diversity and effective population size. In Lake Constance, we detected no genetic differentiation amongst quagga mussels sampled across different sites and depth habitats. We also did not identify any convincing candidate loci evidential for adaptation along a depth gradient and a transplant experiment showed no indications of local adaptation to living in the deep based on investigating growth and survival. Hence, the shallow-water and the deep-water morphotypes seem to be a result of phenotypic plasticity rather than local adaptation to depth. In conclusion, our ddRAD approach revealed insight into the establishment of genetically distinct quagga mussel populations in three perialpine lakes and suggests that phenotypic plasticity and life history traits (broadcast spawner with high fecundity and dispersing pelagic larvae) facilitate the fast spread and colonization of various depth habitats by the quagga mussel
Smartwatches for non-invasive hypoglycaemia detection during cognitive and psychomotor stress.
Get PDFFactorization of Holomorphic Matrices and Kazhdan's Property (T)
No full textIn this article we deduce some algebraic properties for the group Sp_{2n}(O(X)) of holomorphic symplectic matrices on a Stein space X: holomorphic factorization, exponential factorization, and Kazhdan's property (T). In holomorphic factorization we combine a recent result of the third author and K-theory tools to give explicit bounds for the case when X is one-dimensional or two-dimensional. Next we use them to find bounds for exponential factorization. As a further application, we show that the elementary symplectic group Ep_{2n}(O(X)) admits Kazhdan's property (T)
Patient-specific risk factors for reintervention following primary endovascular treatment of iliac artery disease.
No full textOBJECTIVES
Predictive models for reintervention may guide clinicians to optimize selection, education and follow-up of patients undergoing endovascular iliac revascularization. While the impact of lesion- and device-related characteristics on iliac restenosis and reintervention risk is well-defined, data on patient-specific risk factors are scarce and conflicting. This study aimed to explore the value of patient-related factors in predicting the need for clinically-driven target-vessel revascularization (CD-TVR) in patients undergoing primary endovascular treatment of iliac artery disease.
METHODS
Consecutively enrolled patients undergoing endovascular revascularization for symptomatic iliac artery disease at a tertiary vascular referral center between January 2008 and June 2020 were retrospectively analyzed. Primary and secondary outcomes were CD-TVR occurrence within 24 months and time to CD-TVR, respectively. Patients who died or did not require CD-TVR within 24 months were censored at the date of death or at 730 days, respectively. Multiple imputation was used to account for missing data in primary analyses.
RESULTS
1538 iliac interventions were performed in 1113 patients (26% females, 68 years). CD-TVR occurred in 108 limbs (74 patients, 7.0%) with a median time to CD-TVR of 246 days. On multivariable analysis, increasing age was associated with lower likelihood of CD-TVR [odds ratio (OR) 0.64, 95%CI 0.50-0.83, p=0.001] and decreased risk of CD-TVR at any given time [hazard ratio (HR) 0.66, 95%CI 0.52-0.84, p=0.001]. Similarly, a lower likelihood of CD-TVR (OR 0.75, 95%CI 0.59-0.95, p=0.017) and decreased risk of CD-TVR at any given time (HR 0.73, 95%CI 0.58-0.93, p=0.009) were observed with higher glomerular filtration rates. Lastly, revascularization of common vs external iliac artery disease was associated with lower likelihood of CD-TVR (OR 0.48, 95%CI 0.24-0.93, p=0.030) and decreased risk of CD-TVR at any given time (HR 0.48, 95%CI 0.25-0.92, p=0.027). No associations were observed between traditional cardiovascular risk factors (sex, hypertension, higher low-density lipoprotein cholesterol, higher haemoglobin A1c, smoking) and CD-TVR.
CONCLUSION
In this retrospective cohort study, younger age, impaired kidney function and external iliac artery disease were associated with CD-TVR. Traditional markers of cardiovascular risk were not seen to predict reintervention
Muscarinic drug shows efficacy in schizophrenia but much is left to be discovered [comment].
No full textVE-cadherin junction dynamics in initial lymphatic vessels promotes lymph node metastasis.
Get PDFThe endothelial junction component vascular endothelial (VE)-cadherin governs junctional dynamics in the blood and lymphatic vasculature. Here, we explored how lymphatic junction stability is modulated by elevated VEGFA signaling to facilitate metastasis to sentinel lymph nodes. Zippering of VE-cadherin junctions was established in dermal initial lymphatic vessels after VEGFA injection and in tumor-proximal lymphatics in mice. Shape analysis of pan-cellular VE-cadherin fragments revealed that junctional zippering was accompanied by accumulation of small round-shaped VE-cadherin fragments in the lymphatic endothelium. In mice expressing a mutant VEGFR2 lacking the Y949 phosphosite (Vegfr2 Y949F/Y949F ) required for activation of Src family kinases, zippering of lymphatic junctions persisted, whereas accumulation of small VE-cadherin fragments was suppressed. Moreover, tumor cell entry into initial lymphatic vessels and subsequent metastatic spread to lymph nodes was reduced in mutant mice compared with WT, after challenge with B16F10 melanoma or EO771 breast cancer. We conclude that VEGFA mediates zippering of VE-cadherin junctions in initial lymphatics. Zippering is accompanied by increased VE-cadherin fragmentation through VEGFA-induced Src kinase activation, correlating with tumor dissemination to sentinel lymph nodes
Aortic Valve Planimetry in Aortic Stenosis Quantification: Reliability of Three-Dimensional-Multiplane Reconstruction and Comparison With Established Methods.
No full textWe aim to evaluate the reliability and consistency of measuring the aortic valve area (AVA) using 3-dimensional (3D) transesophageal echocardiography and compare it with invasive and noninvasive methods using a continuity equation (CE). Measurements were taken from 119 patients with different severity of aortic stenosis and with normal aortic valve who underwent elective transesophageal echocardiography encompassing the whole spectrum of aortic opening. Three methods were compared to determine AVA. First, the effective AVA was calculated with the standard CE, where the left ventricular outflow tract area was calculated from its 2-dimensional diameter (AVA-CEstd). Second, a modified CE method (AVA-CEmod) was used, in which the left ventricular outflow tract area was measured using 3D-multiplane reconstruction. Third, the geometric AVA was directly measured using 3D-multiplane reconstruction planimetry (AVA-3D). Interobserver and intraobserver variability were analyzed using intraclass correlation coefficients (ICCs). The values were measured by two blinded readers for interobserver variability and by one observer on the same dataset. AVA-3D was significantly larger than AVA-CEmod and AVA-CEstd (1.87 ± 1.00 cm2 vs 1.81 ± 0.92 cm2 p = 0.03 and 1.87 ± 1.00 cm2 vs 1.71 ± 0.85 cm2 p <0.001). However, in the subset of patients with AVA-3D <1.5 cm2, there was no significant difference between AVA-3D and AVA-CEmod (1.06 ± 0.24 vs 1.08 ± 0.26 cm2, paired t test: t = 0.77, degree of freedom = 58, p = 0.44). The ICC between the measurements of AVA-3D and AVA-CEmod (ICC 0.979), and AVA-3D and AVA- CEstd (ICC 0.940), were excellent. AVA-3D delivers very similar results as compared with more established echocardiographic parameters. The difference between effective and geometric AVA did not appear to be clinically relevant in patients with a higher degree of stenosis
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