2,016 research outputs found

    An Updated Midline Rule: Visual Callosal Connections Anticipate Shape and Motion in Ongoing Activity across the Hemispheres

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    It is generally thought that callosal connections (CCs) in primary visual cortices serve to unify the visual scenery parted in two at the vertical midline (VM). Here, we present evidence that this applies also to visual features that do not cross yet but might cross the VM in the future. During reversible deactivation of the contralateral visual cortex in cats, we observed that ipsilaterally recorded neurons close to the border between areas 17 and 18 receive selective excitatory callosal input on both ongoing and evoked activity. In detail, neurons responding well to a vertical Gabor patch moving away from the deactivated hemifield decreased prestimulus and stimulus-driven activity much more than those preferring motion toward the cooled hemifield. Further, activity of neurons responding to horizontal lines decreased more than the response to vertical lines. Embedding a single Gabor into a collinear line context selectively stabilized responses, especially when the context was limited to the intact hemifield. These findings indicate that CCs interconnect not only neurons coding for similar orientations but also for similar directions of motion. We conclude that CCs anticipate stimulus features that are potentially relevant for both hemifields (i.e., coherent motion but also collinear shape) because already prestimulus activity and activity to stimuli not crossing the VM revealed feature specificity. Finally, we hypothesize that intrinsic and callosal networks processing different orientations and directions are anisotropic close to the VM facilitating perceptual grouping along likely future motion or (shape) trajectories before the visual stimulus arrives

    Specificity of Neuronal Responses in Primary Visual Cortex Is Modulated by Interhemispheric CorticoCortical Input

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    Within the visual cortex, it has been proposed that interhemispheric interactions serve to re-establish the continuity of the visual field across its vertical meridian (VM) by mechanisms similar to those used by intrinsic connections within a hemisphere. However, other specific functions of transcallosal projections have also been proposed, including contributing to disparity tuning and depth perception. Here, we consider whether interhemispheric connections modulate specific response properties, orientation and direction selectivity, of neurons in areas 17 and 18 of the ferret by combining reversible thermal deactivation in one hemisphere with optical imaging of intrinsic signals and single-cell electrophysiology in the other hemisphere. We found interhemispheric influences on both the strength and specificity of the responses to stimulus orientation and direction of motion, predominantly at the VM. However, neurons and domains preferring cardinal contours, in particular vertical contours, seem to receive stronger interhemispheric input than others. This finding is compatible with interhemispheric connections being involved in horizontal disparity tuning. In conclusion, our results support the view that interhemispheric interactions mainly perform integrative functions similar to those of connections intrinsic to one hemisphere

    Global DNA hypomethylation prevents consolidation of differentiation programs and allows reversion to the embryonic stem cell state.

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    DNA methylation patterns change dynamically during mammalian development and lineage specification, yet scarce information is available about how DNA methylation affects gene expression profiles upon differentiation. Here we determine genome-wide transcription profiles during undirected differentiation of severely hypomethylated (Dnmt1⁻/⁻) embryonic stem cells (ESCs) as well as ESCs completely devoid of DNA methylation (Dnmt1⁻/⁻;Dnmt3a⁻/⁻;Dnmt3b⁻/⁻ or TKO) and assay their potential to transit in and out of the ESC state. We find that the expression of only few genes mainly associated with germ line function and the X chromosome is affected in undifferentiated TKO ESCs. Upon initial differentiation as embryoid bodies (EBs) wild type, Dnmt1⁻/⁻ and TKO cells downregulate pluripotency associated genes and upregulate lineage specific genes, but their transcription profiles progressively diverge upon prolonged EB culture. While Oct4 protein levels are completely and homogeneously suppressed, transcription of Oct4 and Nanog is not completely silenced even at late stages in both Dnmt1⁻/⁻ and TKO EBs. Despite late wild type and Dnmt1⁻/⁻ EBs showing a much higher degree of concordant expression, after EB dissociation and replating under pluripotency promoting conditions both Dnmt1⁻/⁻ and TKO cells, but not wild type cells rapidly revert to expression profiles typical of undifferentiated ESCs. Thus, while DNA methylation seems not to be critical for initial activation of differentiation programs, it is crucial for permanent restriction of developmental fate during differentiation

    Social Support and Modelling in Relation to Physical Activity Participation and Outdoor Play in Preschool Children

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    Physical activity during early childhood is a prerequisite for healthy development in many cases. The aim of this study was to assess the relationships of social modelling and support from parents, peers, and siblings and domain-specific physical activity participation in a nationwide sample of preschool boys and girls from Germany. 519 preschool children aged 4–6 and one of their parents participated in the ‘MoMo’ Wave 1 Study between 2009 and 2012. Participants and their parents provided self-reported data on social support modelling, and domain-specific physical activity participation (physical activity in sports clubs, physical activity outside of sports clubs, and outdoor play). Parental, peer, and sibling support and modelling were related to domain-specific physical activity: Parental support was particularly relevant for physical activity in sports clubs, and peer support for outdoor play. Parental modelling was only related to physical activity outside of sports clubs: Maternal modelling was a positive correlate in girls and paternal modelling in boys, respectively. Sibling and peer modelling were especially relevant for physical activity in sports clubs. The results were heterogeneous regarding types and providers of support and modelling. Thus, different providers and types of support should be targeted in physical activity promotion programs for preschool children

    Communication and signal exchange in the Rhizobium bradyrhizobium legume system

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    A new comprehensive communication concept in the Rhizobium/Bradyrhizobium legume symbiosis was developed. It includes a root zone specific flavonoid exudation, the differential activity of phenylpropane/acetate pathway derivatives on chemotaxis, nod-gene inducing activity and phytoalexin resistance induction on the microsymbiont side (Bradyrhizobium). Nod factor production from the microsymbiont affects the host plant in root hair curling and meristem induction. Phytoalexin production in the host plant is also an early response, however repressed to a low level after a few hours. Another strategy of the microsymbiont to overcome phytoalexin effects is degradation of phytoalexins in Rhizobium leguminosarum bv. vicieae. Competitiveness within the same infection group of the microsymbiont was studied with gus-gene fusion, using the blue coloured nodules to easily discriminate marked strains from unmarked competitors. New exopolysaccharide (EPS) mutants of Bradyrhizobium japonicum were reconstructed homologous with a DNA region to exoB gene of Rhizobium meliloti. Their clearly reduced competitiveness of nodulation, demonstrates that exopolysaccharides of Bradyrhizohium japonicum also have an important function during the early stages of this symbiotic interaction

    Iohexol-based measurement of intestinal permeability in birds

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    Background: Iohexol has been successfully used as a marker to assess intestinal permeability in humans and various other mammals. The objective of this study was to evaluate the use of oral iohexol as an intestinal permeability marker in four anatomically and nutritionally diverse bird species. Methods: Three dosages (1 ml/kg, 2 ml/kg, 4 ml/kg) of iohexol (755 mg/ml) were administered orally to each six clinically healthy pigeons and chickens at two-week intervals. Iohexol plasma concentration was determined 45, 90 and 180 minutes after administration. A comparative study was performed by administering iohexol twice to each six clinically healthy cockatiels and falcons, and determining iohexol plasma concentration at 45 or 90 minutes after administration. Results: The recommended iohexol dosage for permeability testing in birds was determined to be 1 ml/kg. Median plasma iohexol concentrations were 27.77 mu g/ml in pigeons, 12.97 mu g/ml in chickens, 14.24 mu g/ml in cockatiels, and 47.81 mu g/ml in falcons, 45 minutes after this dosage was administered. At 90 minutes after administration, median plasma iohexol concentrations were 40.68 mu g/ml in pigeons, 21.59 mu g/ml in chickens, 32.03 mu g/ml in cockatiels, and 55.96 mu g/ml in falcons. Conclusions and clinical relevance: Oral iohexol was a safe and feasible marker for intestinal permeability assessment in birds. Further investigations are warranted to establish species-specific reference intervals in larger numbers of healthy birds, and to examine the use of iohexol as a permeability marker in birds with disorders associated with altered intestinal permeability.Peer reviewe

    Highly conserved serine residue 40 in HIV-1 p6 regulates capsid processing and virus core assembly

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    Background: The HIV-1 p6 Gag protein regulates the final abscission step of nascent virions from the cell membrane by the action of two late assembly (L-) domains. Although p6 is located within one of the most polymorphic regions of the HIV-1 gag gene, the 52 amino acid peptide binds at least to two cellular budding factors (Tsg101 and ALIX), is a substrate for phosphorylation, ubiquitination, and sumoylation, and mediates the incorporation of the HIV-1 accessory protein Vpr into viral particles. As expected, known functional domains mostly overlap with several conserved residues in p6. In this study, we investigated the importance of the highly conserved serine residue at position 40, which until now has not been assigned to any known function of p6. Results: Consistently with previous data, we found that mutation of Ser-40 has no effect on ALIX mediated rescue of HIV-1 L-domain mutants. However, the only feasible S40F mutation that preserves the overlapping pol open reading frame (ORF) reduces virus replication in T-cell lines and in human lymphocyte tissue cultivated ex vivo. Most intriguingly, L-domain mediated virus release is not dependent on the integrity of Ser-40. However, the S40F mutation significantly reduces the specific infectivity of released virions. Further, it was observed that mutation of Ser-40 selectively interferes with the cleavage between capsid (CA) and the spacer peptide SP1 in Gag, without affecting cleavage of other Gag products. This deficiency in processing of CA, in consequence, led to an irregular morphology of the virus core and the formation of an electron dense extra core structure. Moreover, the defects induced by the S40F mutation in p6 can be rescued by the A1V mutation in SP1 that generally enhances processing of the CA-SP1 cleavage site. Conclusions: Overall, these data support a so far unrecognized function of p6 mediated by Ser-40 that occurs independently of the L-domain function, but selectively affects CA maturation and virus core formation, and consequently the infectivity of released virions

    Isolation of human intrahepatic leukocytes for phenotypic and functional characterization by flow cytometry

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    With the growing appreciation of tissue-resident immunity, studying tissue-specific immune cells contributing to both homeostasis and disease is imperative. Here, we provide a protocol for the isolation of human intrahepatic leukocytes (IHL) maximizing viability, purity, and yield. Our protocol is scalable by tissue weight, allowing for reproducible and efficient IHL liberation suitable for functional characterization, cell isolation, and profiling by flow (or mass) cytometry. Furthermore, we provide a "guide" to determine an expected IHL yield per gram of tissue processed. For complete details on the use and execution of this protocol, please refer to Stegmann et al. (2016), Pallett et al. (2017), Easom et al. (2018), Swadling et al. (2020), Pallett et al. (2020), and Zakeri et al. (2022)

    Aging Studies for the Large Honeycomb Drift Tube System of the Outer Tracker of HERA-B

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    The HERA-B Outer Tracker consists of drift tubes folded from polycarbonate foil and is operated with Ar/CF4/CO2 as drift gas. The detector has to stand radiation levels which are similar to LHC conditions. The first prototypes exposed to radiation in HERA-B suffered severe radiation damage due to the development of self-sustaining currents (Malter effect). In a subsequent extended R&D program major changes to the original concept for the drift tubes (surface conductivity, drift gas, production materials) have been developed and validated for use in harsh radiation environments. In the test program various aging effects (like Malter currents, gain loss due to anode aging and etching of the anode gold surface) have been observed and cures by tuning of operation parameters have been developed.Comment: 14 pages, 6 figures, to be published in the Proceedings of the International Workshop On Aging Phenomena In Gaseous Detectors, 2-5 Oct 2001, Hamburg, German
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