In Vivo Imaging Reveals Dendritic Targeting of Laminated Afferents by Zebrafish Retinal Ganglion Cells

SummaryTargeting of axons and dendrites to particular synaptic laminae is an important mechanism by which precise patterns of neuronal connectivity are established. Although axons target specific laminae during development, dendritic lamination has been thought to occur largely by pruning of inappropriately placed arbors. We discovered by in vivo time-lapse imaging that retinal ganglion cell (RGC) dendrites in zebrafish show growth patterns implicating dendritic targeting as a mechanism for contacting appropriate synaptic partners. Populations of RGCs labeled in transgenic animals establish distinct dendritic strata sequentially, predominantly from the inner to outer retina. Imaging individual cells over successive days confirmed that multistratified RGCs generate strata sequentially, each arbor elaborating within a specific lamina. Simultaneous imaging of RGCs and subpopulations of presynaptic amacrine interneurons revealed that RGC dendrites appear to target amacrine plexuses that had already laminated. Dendritic targeting of prepatterned afferents may thus be a novel mechanism for establishing proper synaptic connectivity

Intercalibration of the barrel electromagnetic calorimeter of the CMS experiment at start-up

Calibration of the relative response of the individual channels of the barrel electromagnetic calorimeter of the CMS detector was accomplished, before installation, with cosmic ray muons and test beams. One fourth of the calorimeter was exposed to a beam of high energy electrons and the relative calibration of the channels, the intercalibration, was found to be reproducible to a precision of about 0.3%. Additionally, data were collected with cosmic rays for the entire ECAL barrel during the commissioning phase. By comparing the intercalibration constants obtained with the electron beam data with those from the cosmic ray data, it is demonstrated that the latter provide an intercalibration precision of 1.5% over most of the barrel ECAL. The best intercalibration precision is expected to come from the analysis of events collected in situ during the LHC operation. Using data collected with both electrons and pion beams, several aspects of the intercalibration procedures based on electrons or neutral pions were investigated

Safety of intravenous ferric carboxymaltose versus oral iron in patients with nondialysis-dependent CKD: an analysis of the 1-year FIND-CKD trial.

Background: The evidence base regarding the safety of intravenous (IV) iron therapy in patients with chronic kidney disease (CKD) is incomplete and largely based on small studies of relatively short duration. Methods: FIND-CKD (ClinicalTrials.gov number NCT00994318) was a 1-year, open-label, multicenter, prospective study of patients with nondialysis-dependent CKD, anemia and iron deficiency randomized (1:1:2) to IV ferric carboxymaltose (FCM), targeting higher (400-600 µg/L) or lower (100-200 µg/L) ferritin, or oral iron. A post hoc analysis of adverse event rates per 100 patient-years was performed to assess the safety of FCM versus oral iron over an extended period. Results: The safety population included 616 patients. The incidence of one or more adverse events was 91.0, 100.0 and 105.0 per 100 patient-years in the high ferritin FCM, low ferritin FCM and oral iron groups, respectively. The incidence of adverse events with a suspected relation to study drug was 15.9, 17.8 and 36.7 per 100 patient-years in the three groups; for serious adverse events, the incidence was 28.2, 27.9 and 24.3 per 100 patient-years. The incidence of cardiac disorders and infections was similar between groups. At least one ferritin level ≥800 µg/L occurred in 26.6% of high ferritin FCM patients, with no associated increase in adverse events. No patient with ferritin ≥800 µg/L discontinued the study drug due to adverse events. Estimated glomerular filtration rate remained the stable in all groups. Conclusions: These results further support the conclusion that correction of iron deficiency anemia with IV FCM is safe in patients with nondialysis-dependent CKD

Formation of the digestive system in zebrafish. I. liver morphogenesis

AbstractDespite the essential functions of the digestive system, much remains to be learned about the cellular and molecular mechanisms responsible for digestive organ morphogenesis and patterning. We introduce a novel zebrafish transgenic line, the gutGFP line, that expresses GFP throughout the digestive system, and use this tool to analyze the development of the liver. Our studies reveal two phases of liver morphogenesis: budding and growth. The budding period, which can be further subdivided into three stages, starts when hepatocytes first aggregate, shortly after 24 h postfertilization (hpf), and ends with the formation of a hepatic duct at 50 hpf. The growth phase immediately follows and is responsible for a dramatic alteration of liver size and shape. We also analyze gene expression in the developing liver and find a correlation between the expression of certain transcription factor genes and the morphologically defined stages of liver budding. To further expand our understanding of budding morphogenesis, we use loss-of-function analyses to investigate factors potentially involved in this process. It had been reported that no tail mutant embryos appear to lack a liver primordium, as assessed by gata6 expression. However, analysis of gutGFP embryos lacking Ntl show that the liver is in fact present. We also find that, in these embryos, the direction of liver budding does not correlate with the direction of intestinal looping, indicating that the left/right behavior of these tissues can be uncoupled. In addition, we use the cloche mutation to analyze the role of endothelial cells in liver morphogenesis, and find that in zebrafish, unlike what has been reported in mouse, endothelial cells do not appear to be necessary for the budding of this organ

Geochemical focusing and sequestration of manganese during eutrophication of Lake Stechlin (NE Germany)

Significant sedimentation of manganese (Mn) in form of manganese oxides (MnOx) and the subsequent formation of authigenic calcium-rich rhodochrosite (Mn(Ca)CO3) were observed in the seasonally stratified hard water Lake Stechlin in north-eastern Germany. This manganese enrichment was assumed to be associated with recent eutrophication of the formerly oligotrophic lake. The mechanisms and processes involved were examined by analysing: (i) short sediment cores obtained from seven locations along a depth transect ranging from 69.5 m (the deepest point) to 38 m; (ii) sediment traps located at 20 m and 60 m water depths; (iii) water column profiles; and (iv) porewater profiles at 69.5 m and 58 m depths. Sedimentary Mn enrichment was observed at water depths below 56 m and increased to more than 25 wt% at the deepest site. Between 2010 and 2017, Mn accumulation at the deepest site was 815 g Mn m−2. Transfer of Mn from the shallower towards the deepest parts of the lake was initiated by reductive dissolution of MnOx and diffusion of dissolved Mn from the sediment to the overlying water column. Manganese was then dissipated via turbulent mixing and subsequently oxidised to MnOx before being transported towards the deepest zone. Transformation of the redeposited MnOx to Mn(Ca)CO3 favoured the final burial of Mn. We show that eutrophication and the areal spreading of anoxic conditions may intensify diagenetic processes and cause the spatial redistribution of Mn as well as its effective burial. Contrary to many previous findings, we show that increases of Mn and Mn/Fe can also be used as indicators for increasing anoxic conditions in previously oligotrophic lakes.Leibniz-Gemeinschaft http://dx.doi.org/10.13039/501100001664Leibniz-Institut für Gewässerökologie und Binnenfischerei (IGB) im Forschungsverbund Berlin e.V. (3473

Geochemical focusing and sequestration of manganese during eutrophication of Lake Stechlin (NE Germany)

Significant sedimentation of manganese (Mn) in form of manganese oxides (MnOₓ) and the subsequent formation of authigenic calcium-rich rhodochrosite (Mn(Ca)CO₃) were observed in the seasonally stratified hard water Lake Stechlin in north-eastern Germany. This manganese enrichment was assumed to be associated with recent eutrophication of the formerly oligotrophic lake. The mechanisms and processes involved were examined by analysing: (i) short sediment cores obtained from seven locations along a depth transect ranging from 69.5 m (the deepest point) to 38 m; (ii) sediment traps located at 20 m and 60 m water depths; (iii) water column profiles; and (iv) porewater profiles at 69.5 m and 58 m depths. Sedimentary Mn enrichment was observed at water depths below 56 m and increased to more than 25 wt% at the deepest site. Between 2010 and 2017, Mn accumulation at the deepest site was 815 g Mn m⁻². Transfer of Mn from the shallower towards the deepest parts of the lake was initiated by reductive dissolution of MnOₓ and diffusion of dissolved Mn from the sediment to the overlying water column. Manganese was then dissipated via turbulent mixing and subsequently oxidised to MnOₓ before being transported towards the deepest zone. Transformation of the redeposited MnOₓ to Mn(Ca)CO₃ favoured the final burial of Mn. We show that eutrophication and the areal spreading of anoxic conditions may intensify diagenetic processes and cause the spatial redistribution of Mn as well as its effective burial. Contrary to many previous findings, we show that increases of Mn and Mn/Fe can also be used as indicators for increasing anoxic conditions in previously oligotrophic lakes

In Vivo Imaging Reveals Dendritic Targeting of Laminated Afferents by Zebrafish Retinal Ganglion Cells

SummaryTargeting of axons and dendrites to particular synaptic laminae is an important mechanism by which precise patterns of neuronal connectivity are established. Although axons target specific laminae during development, dendritic lamination has been thought to occur largely by pruning of inappropriately placed arbors. We discovered by in vivo time-lapse imaging that retinal ganglion cell (RGC) dendrites in zebrafish show growth patterns implicating dendritic targeting as a mechanism for contacting appropriate synaptic partners. Populations of RGCs labeled in transgenic animals establish distinct dendritic strata sequentially, predominantly from the inner to outer retina. Imaging individual cells over successive days confirmed that multistratified RGCs generate strata sequentially, each arbor elaborating within a specific lamina. Simultaneous imaging of RGCs and subpopulations of presynaptic amacrine interneurons revealed that RGC dendrites appear to target amacrine plexuses that had already laminated. Dendritic targeting of prepatterned afferents may thus be a novel mechanism for establishing proper synaptic connectivity

<i>KCNJ6</i> variants modulate reward-related brain processes and impact executive functions in attention-deficit/hyperactivity disorder

KCNJ6, encoding a potassium channel subunit, regulates the excitability of dopaminergic neurons and is expressed in attention-deficit/hyperactivity disorder (ADHD)-relevant brain regions. As a potential ADHD risk gene, KCNJ6, therefore, may contribute to the endophenotypic variation of the disorder. The impact of two SNPs, rs7275707 and rs6517442, both located in the transcriptional control region of KCNJ6, on reporter gene expression was explored in cultured cells. The KCNJ6 variants were then tested for association with ADHD and personality traits in a family-based sample (165 affected children) and an adult case-control sample (450 patients, 426 controls). Furthermore, the genotypic influence on performance in an n-back task and a cued continuous performance test (cCPT) was investigated by electroencephalography recordings. Finally, rs6517442 function was assessed by a reward anticipation paradigm using functional magnetic resonance imaging. Different haplotypes of rs7275707 and rs6517442 significantly influenced KCNJ6 gene expression proving their functional relevance on the molecular level. In the family-based children sample rs7275707 was associated with ADHD (p = .038). Moreover, rs7275707 showed association with the personality trait of Reward Dependence (p = .031). In the ADHD group, both rs7275707 and rs6517442 influenced the Go-centroid location in the cCPT and the N200 amplitude in the n-back task. Furthermore, ventral striatal activation was impacted by rs6517442 during reward anticipation. Our data indicate that functional variants of KCNJ6 influence brain activity during reward-related and executive processes supporting the view of a differential, age-dependent modulatory impact of dopamine-related brain processes in ADHD risk

Timing and geometry of early Gondwana breakup

The Mesozoic opening history of the southern ocean between South America, Africa and Antarctica is one of the largest gaps in knowledge on the evolution of this region. Competing geodynamic models were published during the last two decades to explain the geophysical and geological observations. Here we report on aeromagnetic data collected along the East Antarctic coast during five seasons. These data provide new constraints on the timing and geometry of the early Gondwana break-up. In the Riiser-Larsen Sea/Mozambique Basin, the first oceanic crust between Africa and Antarctica formed around 155 Ma. In the west the Weddell Rift propagated from west to east with a velocity of 63 km/Myr between chrons M19N and M17N. At chron M14N South America and Africa finally were split off the Antarctic continent. Stretching in the area of the South Atlantic started at the latest from 155 Myr onwards. The different spreading velocities and directions of South America and Africa created at chron M9N the first oceanic crust in the South Atlantic. A new model indicates that the Karoo and Dronning Maud Land magmatism occurred well before any new ocean floor was created and, therefore, the first formation of new oceanic crust cannot directly be related to a plume interaction