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Abstract Acquisition of specialized cellular features is controlled by the ordered expression of transcription factors (TFs) along differentiation trajectories. Here, we find a member of the Onecut TF family, ONECUT3, expressed in postmitotic neurons that leave their Ascl1 +/Onecut1/2 + proliferative domain in the vertebrate hypothalamus to instruct neuronal differentiation. We combined single-cell RNA-seq and gain-of-function experiments for gene network reconstruction to show that ONECUT3 affects the polarization and morphogenesis of both hypothalamic GABA-derived dopamine and thyrotropin-releasing hormone (TRH)+ glutamate neurons through neuron navigator-2 (NAV2). In vivo, siRNA-mediated knockdown of ONECUT3 in neonatal mice reduced NAV2 mRNA, as well as neurite complexity in Onecut3-containing neurons, while genetic deletion of Onecut3/ceh-48 in C. elegans impaired neurocircuit wiring, and sensory discrimination-based behaviors. Thus, ONECUT3, conserved across neuronal subtypes and many species, underpins the polarization and morphological plasticity of phenotypically distinct neurons that descend from a common pool of Ascl1 + progenitors in the hypothalamus.

The lectotype and paralectotype of Synodontis victoriae Boulenger, 1906, designated by Poll (1971), were examined. Inconsistencies between data presented for the designated lectotype and the illustrated individual raise the question of whether lectotypification by Poll is valid. This case is not formally regulated by the International Code of Zoological Nomenclature, but based on Article 74.5, the lectotypification for S. victoriae should be considered invalid because it cannot unambiguously indicate a single name-bearing specimen. Thus, we designate a new lectotype for S. victoriae (BMNH 1906.5.30.191, Entebbe, standard length 188.2 mm) out of two syntypes and provide illustrations and new morphometric and meristic data for both specimens.

Abstract Background Epiretinal membranes (ERM) represent one of the most common findings in retinal examination. Structural changes of the retinal layers in patients with ERM can be visualized and classified using OCT. The purpose of this study is to evaluate structural and functional changes related to surgical treatment of ERM. Methods Monocentric retrospective analysis of 92 patients who underwent 23-gauge-pars plana vitrectomy (ppV) combined with cataract surgery for idiopathic ERM from 2015 to 2020. Visual acuity was determined directly preoperatively, at four weeks and three months postoperatively. Disease stage and tomographic biomarkers related to ERM were assessed in OCT imaging. Results 92 eyes of 92 patients were included. At the time of surgery, the mean patient age was 71 years. Visual acuity improved significantly by 2 lines postoperatively, on average from LogMar 0.4 to 0.2 (p

Abstract In this study we use comparative genomics to uncover a gene with uncharacterized function (1700011H14Rik/C14orf105/CCDC198), which we hereby name FAME (Factor Associated with Metabolism and Energy). We observe that FAME shows an unusually high evolutionary divergence in birds and mammals. Through the comparison of single nucleotide polymorphisms, we identify gene flow of FAME from Neandertals into modern humans. We conduct knockout experiments on animals and observe altered body weight and decreased energy expenditure in Fame knockout animals, corresponding to genome-wide association studies linking FAME with higher body mass index in humans. Gene expression and subcellular localization analyses reveal that FAME is a membrane-bound protein enriched in the kidneys. Although the gene knockout results in structurally normal kidneys, we detect higher albumin in urine and lowered ferritin in the blood. Through experimental validation, we confirm interactions between FAME and ferritin and show co-localization in vesicular and plasma membranes.

Intraocular pressure (IOP) lowering surgery has been shown to alter microvascular density in glaucoma patients. The aim of this study is to report changes in retinal flow density (FD) over the course of treatment with the Preserflo MicroShunt, using optical coherence tomography angiography (OCTA). 34 eyes from 34 patients who underwent Preserflo MicroShunt implantation were prospectively enrolled in this study. OCTA imaging was conducted at the superficial (SCP), deep (DCP) and radial peripapillary plexus (RPC) levels. The progression of FD and IOP was assessed at different time points from baseline to six months postoperatively for the entire patient population, as well as disease severity subgroups. The Preserflo MicroShunt achieved a significant reduction in IOP over the course of six months (median: 8 mmHg; p < 0.01). FD values of the SCP and DCP did not show significant fluctuations, even after adjusting for disease severity. FD of the RPC decreased significantly over the course of six months postoperatively from 42.31 at baseline to 39.59 at six months postoperatively (p < 0.01). The decrease in peripapillary FD was strongest in patients with advanced glaucoma (median: −3.58). These observations hint towards dysfunctional autoregulatory mechanisms in capillaries surrounding the optic nerve head in advanced glaucoma. In comparison, the microvascular structure of the macula appeared more resilient to changes in IOP.

Abstract Background Nile tilapia, Oreochromis niloticus (Linnaeus, 1758) is among the economically most important freshwater fish species in East Africa, and a major source of protein for local consumption. Human induced translocations of non-native stocks for aquaculture and fisheries have been found as a potential threat to the genetic diversity and integrity of local populations. In the present study, we investigate the genetic structure of O. niloticus from 16 waterbodies across Ethiopia using 37 microsatellite loci with SSR-GBAS techniques. Results The samples are structured into three main clusters shaped either by biogeographic factors or stocking activities. High F ST values (Global F ST = 0.438) between populations indicate a high level of genetic differentiation and may suggest long term isolation even within the same drainage systems. Natural populations of the Omo-Turkana system and the lakes in the Southern Main Ethiopian Rift showed the highest genetic variability while low variability was found in stocked populations of lakes Hora, Hashenge and Hayq. Conclusions The results presented herein, may provide an essential basis for the management and conservation of the unique genetic resources in northern East Africa, and advance our understanding of biodiversity, phylogeny, evolution and development towards phylogenetically more accurate taxonomic classifications.

On the African continent, the genus Garra consists of several species often insufficiently separated from each other by diagnostic characters. Herein, a detailed morphological redescription of Garra makiensis from the Awash River drainage is presented, together with additional data on the type specimens of G. makiensis and G. rothschildi. Mitochondrial CO1 sequence data are also provided, including the historic paralectotype of G. makiensis, with a comparison to Garra species from Africa and the Middle East. Based on these sequences, G. makiensis clusters outside the group of African congeners and is a sister lineage to species from the south-east of the Arabian Peninsula. Although morphologically variable, G. makiensis is characterised by having a single unbranched pectoral-fin ray, a short distance between vent and anal-fin origin (7.3–19.7 % of pelvic – anal distance), chest and belly covered with scales, and a prominent axillary scale at base of pelvic fin (18.8–35.5 % of pelvic-fin length).

In the present study, populations of small-sized smiliogastrin barbs with a thickened and serrated last simple dorsal-fin ray distributed in the Main Ethiopian Rift were analysed. An integrated approach combining genetic markers and a variety of morphological methods based on a wide set of characters, including osteology and sensory canals, proved to be very productive for taxonomy in this group of fishes. The results showed that Ethiopian Enteromius species with a serrated dorsal-fin ray are distant from the true E. paludinosus (with E. longicauda as a synonym) and the so-called E. paludinosus complex involves several supposedly valid species with two distinct species occurring in the Main Ethiopian Rift area. A new species, Enteromius yardiensis sp. nov., is described from the Afar Depression in the north-eastern part of the Northern Main Ethiopian Rift. Enteromius akakianus is resurrected as a valid species including populations from the Central Main Ethiopian Rift (basins of lakes Langano, Ziway, and Awasa). No genetic data were available for E. akakianus from its type locality. Enteromius yardiensis sp. nov. is clearly distant from E. akakianus from the Central Main Ethiopian Rift by CO1 and cytb barcodes: pairwise distances between the new species and the Ethiopian congeners were 5.4 % to 11.0 %. Morphologically, the new species most clearly differs from all examined Ethiopian congeners by three specialisations which are unique in the group: the absence of the anterior barbel, the absence of the medial branch of the supraorbital sensory canal, and few, 1–3, commonly two, scale rows between the lateral line and the anus.

Abstract Background In this study we sought to retrospectively evaluate whether a very brief cardiac magnetic resonance imaging (CMR) protocol sufficiently distinguishes patients with relevant myocardial changes with need for further examination from healthy subjects. Methods Patients with clinical indication for CMR (n = 160) were included in the study. Patients were categorized into two groups depending on presence of left ventricular (LV) dysfunction. ROC-analysis was done for results of T1-, T2- mapping and extracellular volume evaluation in patients without LV dysfunction. Binary endpoint was correctly depicted pathology of the conventional qualitative CMR techniques and report. Results In the patient cohort without LV dysfunction (49%), AUC for T1 mapping was 82% (p

Anti-Vascular Endothelial Growth Factor (VEGF) agents are the first-line treatment for retinal neovascular diseases, which represent the most prevalent causes of acquired vision loss world-wide. VEGF-Trap (Aflibercept, AFL), a recombinant decoy receptor recognizing ligands of both VEGFR-1 and -2, was recently reported to be highly efficient in improving visual acuity and preserving retinal anatomy in individuals affected by diabetic macular edema. However, the precise molecular and cell biological mechanisms underlying the beneficial effects of this novel tool have yet to be elucidated. Using the mouse oxygen-induced retinopathy (OIR) model as a surrogate of retinopathies with sterile post-ischemic inflammation, such as late proliferative diabetic retinopathy (PDR), retinopathy of prematurity (ROP), and diabetic macular edema (DME), we provide evidence that AFL modulates inflammation in response to hypoxia by regulating the morphology of microglial cells, a parameter commonly used as a proxy for changes in their activation state. We show that AFL administration during the hypoxic period of OIR leads to an increased number of ramified Iba1+ microglial cells/macrophages while subsequently limiting the accumulation of these cells in particular retinal layers. Our results suggest that, beyond its well-documented beneficial effects on microvascular regeneration, AFL might exert important modulatory effects on post-ischemic retinal inflammation.

P53 is known as the most critical tumor suppressor and is often referred to as the guardian of our genome. More than 40 years after its discovery, we are still struggling to understand all molecular details on how this transcription factor prevents oncogenesis or how to leverage current knowledge about its function to improve cancer treatment. Multiple cues, including DNA-damage or mitotic errors, can lead to the stabilization and nuclear translocation of p53, initiating the expression of multiple target genes. These transcriptional programs may be cell-type- and stimulus-specific, as is their outcome that ultimately imposes a barrier to cellular transformation. Cell cycle arrest and cell death are two well-studied consequences of p53 activation, but, while being considered critical, they do not fully explain the consequences of p53 loss-of-function phenotypes in cancer. Here, we discuss how mitotic errors alert the p53 network and give an overview of multiple ways that p53 can trigger cell death. We argue that a comparative analysis of different types of p53 responses, elicited by different triggers in a time-resolved manner in well-defined model systems, is critical to understand the cell-type-specific cell fate induced by p53 upon its activation in order to resolve the remaining mystery of its tumor-suppressive function.

A novel cytoplasmic dye-decolorizing peroxidase from Dictyostelium discoideum was investigated that oxidizes anthraquinone dyes, lignin model compounds, and general peroxidase substrates such as ABTS efficiently. Unlike related enzymes, an aspartate residue replaces the first glycine of the conserved GXXDG motif in Dictyostelium DyPA. In solution, Dictyostelium DyPA exists as a stable dimer with the side chain of Asp146 contributing to the stabilization of the dimer interface by extending the hydrogen bond network connecting two monomers. To gain mechanistic insights, we solved the Dictyostelium DyPA structures in the absence of substrate as well as in the presence of potassium cyanide and veratryl alcohol to 1.7, 1.85, and 1.6 Å resolution, respectively. The active site of Dictyostelium DyPA has a hexa-coordinated heme iron with a histidine residue at the proximal axial position and either an activated oxygen or CN− molecule at the distal axial position. Asp149 is in an optimal conformation to accept a proton from H2O2 during the formation of compound I. Two potential distal solvent channels and a conserved shallow pocket leading to the heme molecule were found in Dictyostelium DyPA. Further, we identified two substrate-binding pockets per monomer in Dictyostelium DyPA at the dimer interface. Long-range electron transfer pathways associated with a hydrogen-bonding network that connects the substrate-binding sites with the heme moiety are described.

Laser transmission welding is a well-known joining technology for thermoplastics, providing reliable and hermetical sealing without adhesives or particle formation. The main advantages of laser-based energy input - high precision, no additional adhesive and no particle emission - are essential for medical and optical applications. To obtain sufficient absorption in visually transparent polymers, thulium fibre lasers emitting in the polymers' intrinsic absorption spectrum are used. Optics with high numerical aperture provide large intensity gradients inside the specimen, enabling selective fusing in the joining zone. Although the basic feasibility has already been demonstrated, the welding process lacks stability and productivity. Aim of this work is the determination of optimized settings for a fast and reliable welding process. Thus, the interplay of process parameters as well as their impact on the seam are analysed by thermal simulations. Calculated settings are verified by welding tests with COC, PA6 and PETG, using a fixed-focus optics and a 3D laser scanner with up to 200 mm/s feed rate. [ABSTRACT FROM AUTHOR]

Objectives This study sought to develop a large, international registry to evaluate the diffusion of these approaches and investigate patient characteristics and initial clinical results. Background Several transcatheter tricuspid valve therapies are emerging as therapeutic options for patients with severe symptomatic tricuspid regurgitation (TR), generally a high-risk surgical population. Methods The TriValve (Transcatheter Tricuspid Valve Therapies) registry included 106 high-risk patients (76 ± 9 years of age; 60.4% women; European System for Cardiac Operative Risk Evaluation II 7.6 ± 5.7%) from 11 cardiac centers, with severe TR. Results A total of 35% of the patients had prior left heart valve intervention (surgical in 29 of 106 and transcatheter in 8 of 106 patients). Right ventricular (RV) dysfunction (tricuspid annular plane systolic excursion <17 mm) was present in 56.3% of the patients; 95% of the patients were in New York Heart Association functional class III to IV. The etiology of TR was functional in 95.2%, and the mean tricuspid annulus was 45.4 ± 11 mm. In 76.9% of the patients, the main location of the regurgitant jet was central; pre-procedural systolic pulmonary artery pressure was 39.7 ± 13.8 mm Hg; and the inferior vena cava was severely dilated in most of the patients (27.4 ± 6.8 mm). Implanted devices included MitraClip (n = 58), Trialign (n = 17), TriCinch (n = 15), FORMA (n = 7), Cardioband (n = 5), and caval valve implantation (n = 3). One case had combined Trialign + MitraClip. Patients treated with the different techniques were similar in terms of European System for Cardiac Operative Risk Evaluation II and degree of RV dysfunction. In 68% of the cases the tricuspid intervention was performed as an isolated procedure. Procedural success was achieved in 62% of cases. At 30-day follow-up, all-cause mortality was 3.7%, with an overall incidence of major adverse cardiac and cerebrovascular events of 26%; 58% of the patients were New York Heart Association functional class I or II at 30 days. Conclusions Patients currently undergoing transcatheter tricuspid valve therapy are mostly high risk, with a functional etiology and very severe central regurgitation, and do not have severely impaired RV function. Initial results suggest that transcatheter tricuspid valve therapy is feasible with different techniques, but clinical efficacy requires further investigation. [ABSTRACT FROM AUTHOR]

While terrestrial moss and other plants are frequently used for environmental mapping and monitoring projects, data on the regional geochemistry of humus are scarce. Humus, however, has a much larger life span than any plant material. It can be seen as the “environmental memory” of an area for at least the last 60–100 years. Here concentrations of 39 elements determined by ICP-MS and ICP AES, pH and ash content are presented for 259 samples of forest floor humus collected at an average sample density of 1 site/300km2 in the Czech Republic. The scale of anomalies linked to known contamination sources (e.g., lignite mining and burning, metallurgical industry, coal fired power plants, metal smelters) is documented and discussed versus natural processes influencing humus quality. Most maps indicate a local impact from individual contamination sources: often more detailed sampling than used here would be needed to differentiate between likely sources. [Copyright &y& Elsevier]

We present for the first time a two-dimensional velocity field of the central region of the grand-design spiral galaxy NGC 5248, at 0.9-arcsec spatial resolution. The Hα velocity field is dominated by circular rotation. While no systematic streaming motions are seen in the area of the nuclear grand-design spiral or the circumnuclear ring, the amplitude of residual velocities, after subtracting a model circular velocity field, reaches 20 km s[sup -1] in projection. The rotation curve levels out at around 140 km s[sup -1], after a well-resolved and rather shallow rise. We have generated an analytical model for the nuclear spiral and fitted it to our observations to obtain estimates of the pattern speed of the spiral and the speed of sound in the central region of NGC 5248. Our results are consistent with a low pattern speed, suggesting that the nuclear spiral rotates with the same rate as the main spiral structure in NGC 5248, and thus that the spiral structure is coupled from scales of a few hundred parsecs to several kiloparsecs. We have also compared the observed structure and kinematics between the nuclear regions of NGC 5248 and M100. Several similarities and differences are discussed, including the location of the peak emission regions on major and minor axes, and the spiral arm streaming motions. We find no kinematic evidence for the presence of a nuclear bar in NGC 5248. [ABSTRACT FROM AUTHOR]

Soil O and C horizon samples (N = 752) were collected at a sample density of 1 site/36 km 2 in Nord-Trøndelag and parts of Sør-Trøndelag (c. 25,000 km 2 ), and analysed for Pb and three of the four naturally occurring Pb isotopes ( 206 Pb, 207 Pb and 208 Pb) in a HNO 3 /HCl extraction. Soil O and C horizons are decoupled in terms of both Pb concentrations and Pb isotope ratios. In the soil C horizon the Grong-Olden Culmination, a continuous exposure of the Precambrian crystalline basement across the general grain of the Caledonian orogen, is marked by a distinct 206 Pb/ 207 Pb isotope ratio anomaly. No clear regional or even local patterns are detected when mapping the Pb isotope ratios in the soil O horizon samples. Variation in the isotope ratios declines significantly from the soil C to the O horizon. On average, Pb concentrations in the O horizon are four times higher and the 206 Pb/ 207 Pb isotope ratio is shifted towards a median of 1.15 in comparison to 1.27 in the C horizon. It is demonstrated that natural processes like weathering in combination with plant uptake need to be taken into account in order to distinguish anthropogenic input from natural influences on Pb concentration and the 206 Pb/ 207 Pb isotope ratio in the soil O horizon. [ABSTRACT FROM AUTHOR]

Analysis of soil C and O horizon samples in a recent regional geochemical survey of Nord-Trøndelag, central Norway (752 sample sites covering 25,000 km 2 ), identified a strong enrichment of several potentially toxic elements (PTEs) in the O horizon. Of 53 elements analysed in both materials, Cd concentrations are, on average, 17 times higher in the O horizon than in the C horizon and other PTEs such as Ag (11-fold), Hg (10-fold), Sb (8-fold), Pb (4-fold) and Sn (2-fold) are all strongly enriched relative to the C horizon. Geochemical maps of the survey area do not reflect an impact from local or distant anthropogenic contamination sources in the data for O horizon soil samples. The higher concentrations of PTEs in the O horizon are the result of the interaction of the underlying geology, the vegetation zone and type, and climatic effects. Based on the general accordance with existing data from earlier surveys in other parts of northern Europe, the presence of a location-independent, superordinate natural trend towards enrichment of these elements in the O horizon relative to the C horizon soil is indicated. The results imply that the O and C horizons of soils are different geochemical entities and that their respective compositions are controlled by different processes. Local mineral soil analyses (or published data for the chemical composition of the average continental crust) cannot be used to provide a geochemical background for surface soil. At the regional scale used here surface soil chemistry is still dominated by natural sources and processes. [ABSTRACT FROM AUTHOR]