While the first binary post-AGB stars were serendipitously discovered, the distinct characteristics of their Spectral Energy Distribution (SED) allowed us to launch a more systematic search for ...binaries. We selected post-AGB objects which show a broad dust excess often starting already at H or K, pointing to the presence of a gravitationally bound dusty disc in the system. We started a very extensive multi-wavelength study of those systems and here we report on our radial velocity and photometric monitoring results for six stars of early F type, which are pulsators of small amplitude. To determine the radial velocity of low signal-to-noise time-series, we constructed dedicated auto-correlation masks. The radial velocity variations were subjected to detailed analysis to differentiate between pulsational variability and variability due to orbital motion. Finally orbital minimalisation was performed to constrain the orbital elements. All of the six objects are binaries, with orbital periods ranging from 120 to 1800 days. Five systems have non-circular orbits. The mass functions range from 0.004 to 0.57 solar mass and the companions are likely unevolved objects of (very) low initial mass. We argue that these binaries must have been subject to severe binary interaction when the primary was a cool supergiant. Although the origin of the circumstellar disc is not well understood, the disc is generally believed to be formed during this strong interaction phase. The eccentric orbits of these highly evolved objects remain poorly understood. With the measured orbits and mass functions we conclude that the circumbinary discs seem to have a major impact on the evolution of a significant fraction of binary systems.
The increasing urbanization process is hypothesized to drastically alter (semi‐)natural environments with a concomitant major decline in species abundance and diversity. Yet, studies on this effect ...of urbanization, and the spatial scale at which it acts, are at present inconclusive due to the large heterogeneity in taxonomic groups and spatial scales at which this relationship has been investigated among studies. Comprehensive studies analysing this relationship across multiple animal groups and at multiple spatial scales are rare, hampering the assessment of how biodiversity generally responds to urbanization. We studied aquatic (cladocerans), limno‐terrestrial (bdelloid rotifers) and terrestrial (butterflies, ground beetles, ground‐ and web spiders, macro‐moths, orthopterans and snails) invertebrate groups using a hierarchical spatial design, wherein three local‐scale (200 m × 200 m) urbanization levels were repeatedly sampled across three landscape‐scale (3 km × 3 km) urbanization levels. We tested for local and landscape urbanization effects on abundance and species richness of each group, whereby total richness was partitioned into the average richness of local communities and the richness due to variation among local communities. Abundances of the terrestrial active dispersers declined in response to local urbanization, with reductions up to 85% for butterflies, while passive dispersers did not show any clear trend. Species richness also declined with increasing levels of urbanization, but responses were highly heterogeneous among the different groups with respect to the richness component and the spatial scale at which urbanization impacts richness. Depending on the group, species richness declined due to biotic homogenization and/or local species loss. This resulted in an overall decrease in total richness across groups in urban areas. These results provide strong support to the general negative impact of urbanization on abundance and species richness within habitat patches and highlight the importance of considering multiple spatial scales and taxa to assess the impacts of urbanization on biodiversity.
We studied the effect of local‐ and landscape‐scale urbanization on the abundance and species richness of aquatic (cladocerans), limno‐terrestrial (rotifers) and terrestrial (butterflies, ground beetles, ground‐ and web spiders, macro‐moths, orthopterans and snails) invertebrate groups. Abundances of the terrestrial active dispersers declined, often dramatically, in response to local urbanization, while passive dispersers did not show any clear trend. Species richness also declined with increasing urbanization due to biotic homogenization and/or local species loss, but responses were highly heterogeneous in magnitude and spatial scale. Overall, these results strongly support the general negative impact of urbanization on species communities.
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection disproportionally affects frail, elderly patients and those with multiple chronic comorbidities. Whether patients on RRT have an ...additional risk because of their specific exposure and complex immune dysregulation is controversial.
To describe the incidence, characteristics, and outcomes of SARS-CoV-2 infection, we conducted a prospective, multicenter, region-wide registry study in adult patients on RRT versus the general population from March 2 to May 25, 2020. This study comprised all patients undergoing RRT in the Flanders region of Belgium, a country that has been severely affected by coronavirus disease 2019 (COVID-19).
At the end of the epidemic wave, crude and age-standardized cumulative incidence rates of SARS-CoV-2 infection were 5.3% versus 2.5%, respectively, among 4297 patients on hemodialysis, and 1.4% versus 1.6%, respectively, among 3293 patients with kidney transplants (compared with 0.6% in the general population). Crude and age-standardized cumulative mortality rates were 29.6% versus 19.9%, respectively, among patients on hemodialysis, and 14.0% versus 23.0%, respectively, among patients with transplants (compared with 15.3% in the general population). We found no excess mortality in the hemodialysis population when compared with mean mortality rates during the same 12-week period in 2015-2019 because COVID-19 mortality was balanced by lower than expected mortality among uninfected patients. Only 0.18% of the kidney transplant population died of SARS-CoV-2 infection.
Mortality associated with SARS-CoV-2 infection is high in patients on RRT. Nevertheless, the epidemic's overall effect on the RRT population remained remarkably limited in Flanders. Calculation of excess mortality and age standardization provide a more reliable picture of the mortality burden of COVID-19 among patients on RRT.
Thoracic aortic aneurysm and dissection (TAAD) is typically inherited in an autosomal dominant manner, but rare X-linked families have been described. So far, the only known X-linked gene is FLNA, ...which is associated with the periventricular nodular heterotopia type of Ehlers-Danlos syndrome. However, mutations in this gene explain only a small number of X-linked TAAD families.
We performed targeted resequencing of 368 candidate genes in a cohort of 11 molecularly unexplained Marfan probands. Subsequently, Sanger sequencing of BGN in 360 male and 155 female molecularly unexplained TAAD probands was performed.
We found five individuals with loss-of-function mutations in BGN encoding the small leucine-rich proteoglycan biglycan. The clinical phenotype is characterized by early-onset aortic aneurysm and dissection. Other recurrent findings include hypertelorism, pectus deformity, joint hypermobility, contractures, and mild skeletal dysplasia. Fluorescent staining revealed an increase in TGF-β signaling, evidenced by an increase in nuclear pSMAD2 in the aortic wall. Our results are in line with those of prior reports demonstrating that Bgn-deficient male BALB/cA mice die from aortic rupture.
In conclusion, BGN gene defects in humans cause an X-linked syndromic form of severe TAAD that is associated with preservation of elastic fibers and increased TGF-β signaling.
Genet Med19 4, 386–395.
An increasing amount of studies integrate mRNA sequencing data into MS-based proteomics to complement the translation product search space. However, several factors, including extensive regulation of ...mRNA translation and the need for three- or six-frame-translation, impede the use of mRNA-seq data for the construction of a protein sequence search database. With that in mind, we developed the PROTEOFORMER tool that automatically processes data of the recently developed ribosome profiling method (sequencing of ribosome-protected mRNA fragments), resulting in genome-wide visualization of ribosome occupancy. Our tool also includes a translation initiation site calling algorithm allowing the delineation of the open reading frames (ORFs) of all translation products. A complete protein synthesis-based sequence database can thus be compiled for mass spectrometry-based identification. This approach increases the overall protein identification rates with 3% and 11% (improved and new identifications) for human and mouse, respectively, and enables proteome-wide detection of 5'-extended proteoforms, upstream ORF translation and near-cognate translation start sites. The PROTEOFORMER tool is available as a stand-alone pipeline and has been implemented in the galaxy framework for ease of use.
There is a vivid debate on the relative importance of local and regional factors in shaping microbial communities, and on whether microbial organisms show a biogeographic signature in their ...distribution. Taking a metacommunity approach, spatial factors can become important either through dispersal limitation (compare large spatial scales) or mass effects (in case of strongly connected systems). We here analyze two datasets on bacterial communities characterized by community fingerprinting through denaturing gradient gel electrophoresis (DGGE) in meso- to eutrophic shallow lakes to investigate the importance of spatial factors at three contrasting scales. Variation partitioning on datasets of both the bacterial communities of 11 shallow lakes that are part of a strongly interconnected and densely packed pond system <1 km apart, three groups of shallow lakes almost equal to100 km apart, as well as these three groups of shallow lakes combined that span a large part of a North-South gradient in Europe (>2,500 km) shows a strong impact of local environmental factors on bacterial community composition, with a marginal impact of spatial distance. Our results indicate that dispersal is not strongly limiting even at large spatial scales, and that mass effects do not have a strong impact on bacterial communities even in physically connected systems. We suggest that the fast population growth rates of bacteria facilitate efficient species sorting along environmental gradients in bacterial communities over a very broad range of dispersal rates.
Display omitted
•Algae production in a biorefinery in The Netherlands for animal feed applications.•Exergy analysis of the integrated algal biorefiner.•Resource footprint of a basket of products ...(electricity, digestate, heat, oil, meal).•Comparison between soybean based linear economy and integrated algal biorefinery.•Sensitivity analysis of the algal meal production.
Sustainability in terms of the natural resource demands of protein-rich algal meal for livestock feed applications was examined. In The Netherlands, an integrated microalgal biorefinery delivered the following products: digestate, electricity, heat available for a nearby bio-ethanol facility and algae oil and meal. Pilot scale (500m2) data were used to conduct an exergy analysis (EA), which revealed the process inefficiencies of energy-intensive processes such as drying (44.01%) and inoculum production (54.98%). An attributional life cycle assessment (LCA) using system expansion exposed the high contribution of biomass digestion to the total resource footprint of the biorefinery (72.74%) due to the high daily demand for biomass and electricity consumption of the dosage system. In this study, algal meal was compared with soybean meal, which is the most commonly used protein-rich animal feed ingredient; it is produced in Brazil and transported to The Netherlands. Because algae production is a young, small-scale technology, the resource footprint of the large-scale soy meal production was a factor of 102 lower, mainly as a result of the energy-intensive algae cultivation stages. A sensitivity analysis showed that the resource footprint of algal meal production could be comparable with soy meal when, overall, the areal biomass productivity increases, electricity production is based on more renewable sources (wind) and the energy consumption from mixing and blowing flue gases into the ponds decreases.
Adams-Oliver syndrome (AOS) is a rare developmental disorder characterized by the presence of aplasia cutis congenita (ACC) of the scalp vertex and terminal limb-reduction defects. Cardiovascular ...anomalies are also frequently observed. Mutations in five genes have been identified as a cause for AOS prior to this report. Mutations in EOGT and DOCK6 cause autosomal-recessive AOS, whereas mutations in ARHGAP31, RBPJ, and NOTCH1 lead to autosomal-dominant AOS. Because RBPJ, NOTCH1, and EOGT are involved in NOTCH signaling, we hypothesized that mutations in other genes involved in this pathway might also be implicated in AOS pathogenesis. Using a candidate-gene-based approach, we prioritized DLL4, a critical NOTCH ligand, due to its essential role in vascular development in the context of cardiovascular features in AOS-affected individuals. Targeted resequencing of the DLL4 gene with a custom enrichment panel in 89 independent families resulted in the identification of seven mutations. A defect in DLL4 was also detected in two families via whole-exome or genome sequencing. In total, nine heterozygous mutations in DLL4 were identified, including two nonsense and seven missense variants, the latter encompassing four mutations that replace or create cysteine residues, which are most likely critical for maintaining structural integrity of the protein. Affected individuals with DLL4 mutations present with variable clinical expression with no emerging genotype-phenotype correlations. Our findings demonstrate that DLL4 mutations are an additional cause of autosomal-dominant AOS or isolated ACC and provide further evidence for a key role of NOTCH signaling in the etiology of this disorder.
Atherosclerosis is a chronic inflammatory disorder of the arterial wall leading to coronary artery disease, stroke, and peripheral arterial disease. Along with the discovery of dipeptidyl peptidase 4 ...(DPP4) as a therapeutic target in type 2 diabetes, a role for DPP4 in atherosclerosis is emerging. However, until now the expression and role of other DPPs such as DPP8 and DPP9 in atherosclerosis is completely unknown. In the present study, we first investigated DPP expression in human atherosclerotic plaques. DPP4 could only be observed in endothelial cells of plaque neovessels in half of the specimens. In contrast, DPP8 and DPP9 were abundantly present in macrophage-rich regions of plaques. We then focused on DPP expression and function in macrophage differentiation, activation and apoptosis. DPP8/9 was responsible for most of the DPP activity in macrophages. During monocyte to macrophage differentiation, DPP9 was upregulated both in pro-inflammatory M1 (3.7 ± 0.3-fold increase) and anti-inflammatory M2 macrophages (3.7 ± 0.4-fold increase) whereas DPP8 expression remained unchanged. Inhibition of DPP8/9 activity with compound 1G244 reduced activation of M1 macrophages (IL-6 88 ± 16 vs. 146 ± 19 pg/ml; TNFα 3.8 ± 1.0 vs. 6.6 ± 1.9 ng/ml in treated vs. untreated cells), but not of M2 macrophages. Likewise, DPP9 silencing reduced TNFα and IL-6 secretion, pointing to a DPP9-mediated effect of the inhibitor. DPP8/9 inhibition also enhanced macrophage apoptosis (15 ± 4 vs. 7 ± 3 % in untreated cells). Because pro-inflammatory macrophages play a key role in atherogenesis, plaque rupture and subsequent infarction, DPP9 inhibition might provide interesting therapeutic prospects in reducing atherosclerosis and/or in the prevention of plaque rupture.
PDF
