Altered functional brain network connectivity and glutamate system function in transgenic mice expressing truncated Disrupted-in-Schizophrenia 1

Considerable evidence implicates DISC1 as a susceptibility gene for multiple psychiatric diseases. DISC1 has been intensively studied at the molecular, cellular and behavioral level, but its role in regulating brain connectivity and brain network function remains unknown. Here, we utilize a set of complementary approaches to assess the functional brain network abnormalities present in mice expressing a truncated Disc1 gene (Disc1tr Hemi mice). Disc1tr Hemi mice exhibited hypometabolism in the prefrontal cortex (PFC) and reticular thalamus along with a reorganization of functional brain network connectivity that included compromised hippocampal–PFC connectivity. Altered hippocampal–PFC connectivity in Disc1tr Hemi mice was confirmed by electrophysiological analysis, with Disc1tr Hemi mice showing a reduced probability of presynaptic neurotransmitter release in the monosynaptic glutamatergic hippocampal CA1–PFC projection. Glutamate system dysfunction in Disc1tr Hemi mice was further supported by the attenuated cerebral metabolic response to the NMDA receptor (NMDAR) antagonist ketamine and decreased hippocampal expression of NMDAR subunits 2A and 2B in these animals. These data show that the Disc1 truncation in Disc1tr Hemi mice induces a range of translationally relevant endophenotypes underpinned by glutamate system dysfunction and altered brain connectivity

Analysis of complex trophic networks reveals the signature of land-use intensification on soil communities in agroecosystems

Increasing evidence suggests that agricultural intensification is a threat to many groups of soil biota, but how the impacts of land-use intensity on soil organisms translate into changes in comprehensive soil interaction networks remains unclear. Here for the first time, we use environmental DNA to examine total soil multi-trophic diversity and food web structure for temperate agroecosystems along a gradient of land-use intensity. We tested for response patterns in key properties of the soil food webs in sixteen fields ranging from arable crops to grazed permanent grasslands as part of a long-term management experiment. We found that agricultural intensification drives reductions in trophic group diversity, although taxa richness remained unchanged. Intensification generally reduced the complexity and connectance of soil interaction networks and induced consistent changes in energy pathways, but the magnitude of management-induced changes depended on the variable considered. Average path length (an indicator of food web redundancy and resilience) did not respond to our management intensity gradient. Moreover, turnover of network structure showed little response to increasing management intensity. Our data demonstrates the importance of considering different facets of trophic networks for a clearer understanding of agriculture-biodiversity relationships, with implications for nature-based solutions and sustainable agriculture

The impact of changes in taste, smell, and eating behavior in children with cancer undergoing chemotherapy:A qualitative study

Background and aims: Taste changes are the third most common bothersome symptom during treatment in children with cancer. However, it is still unclear what the essence of these taste changes are, to what degree concomitant changes in sense of smell qualify this bothersome treatment symptom and how much of an impact these changes have on the life of children with cancer. The aim of this study was to explore characteristics of both taste and smell changes and to gain insight into the impact of these changes in children with cancer receiving chemotherapy. Methods: Semi-structured interviews were performed until data saturation was achieved in each age group (6–12, 13–17 years). This resulted in an in-depth description of taste and smell changes, including its impact on the life of 27 children with various cancer types receiving chemotherapy. Thematic analysis of interview data was performed. Results: Interview data could be grouped into three main themes, namely changes in (1) taste, (2) smell, and (3) eating behavior. As expected, most children reported experiencing taste and smell changes just after start of treatment, but changes varied greatly between children; that is, some reported changes in intensity (increased or decreased), whereas others reported different perceptions or preferences (from sweet to savory). Taste and smell changes (regardless of direction) negatively impacted quality of life, with these changes commonly described as “disappointing” or “frustrating.” Interestingly, particular chemotherapeutic agents were frequently mentioned regarding taste and smell changes, prompting sensory-specific coping strategies. Children's eating behavior changed in terms of alterations in food liking and appetite, sometimes due to chemosensory changes, but children also mentioned specific medication or hospital food being responsible for their altered eating behavior. Conclusions: Both taste and smell changes are common in children with cancer. The essence of these changes varies widely, but taste and smell changes are generally considered bothersome treatment symptoms. Ways to cope with taste or smell changes specifically were described by the children warranting further research and offering the opportunity for enhancing patient-centered care

Orthogonal-view Microscope for the Biomechanics Investigations of Aquatic Organisms

Microscopes are essential for biomechanics and hydrodynamical investigation of small aquatic organisms. We report a DIY microscope (GLUBscope) that enables the visualization of organisms from two orthogonal imaging planes (top and side views). Compared to conventional imaging systems, this approach provides a comprehensive visualization strategy of organisms, which could have complex shapes and morphologies. The microscope was constructed by combining custom 3D-printed parts and off-the-shelf components. The system is designed for modularity and reconfigurability. Open-source design files and build instructions are provided in this report. Additionally, proof of use experiments, particularly with Hydra and other organisms that combine the GLUBscope with an analysis pipeline, were demonstrated. Beyond the applications demonstrated, the system can be used or modified for various imaging applications

Functional and Taxonomic Diversity of Collembola as Complementary Tools to Assess Land Use Effects on Soils Biodiversity

Collembola have been proposed for several decades as a good model organisms to survey soil biodiversity; but most of the studies focused on taxonomic endpoints. The main objectives of this study are to compare the effects of the different land uses, including urban and industrial land uses, while using both collembolan functional and taxonomic biodiversity approaches. We collected data on 3,056 samples of Collembola communities across 758 sites in various land uses throughout France. The types of land use considered included all types of human activity from forestry to urban, industrial, traffic, mining and military areas, agricultural grassland, arable land, vineyards and urban vegetable gardens. In order to study functional and taxonomic biodiversity, we used community-weighted means, functional indices, species richness and density. When looking at collembolan functional diversity, urban and industrial soils appear clearly less diversified than when considering the taxonomic diversity. We suspect here a functional homogenization effect commonly reported in the literature for various organisms in urban ecosystems. Our study provides range of values for different taxonomic and functional indices of Collembola communities in a wide land use classification across France

Dual-color dual-focus line-scanning FCS for quantitative analysis of receptor-ligand interactions in living specimens

Cellular communication in multi-cellular organisms is mediated to a large extent by a multitude of cell-surface receptors that bind specific ligands. An in-depth understanding of cell signaling networks requires quantitative information on ligand-receptor interactions within living systems. In principle, fluorescence correlation spectroscopy (FCS) based methods can provide such data, but live-cell applications have proven extremely challenging. Here, we have developed an integrated dual-color dual-focus line-scanning fluorescence correlation spectroscopy (2c2f lsFCS) technique that greatly facilitates live-cell and tissue experiments. Absolute ligand and receptor concentrations and their diffusion coefficients within the cell membrane can be quantified without the need to perform additional calibration experiments. We also determine the concentration of ligands diffusing in the medium outside the cell within the same experiment by using a raster image correlation spectroscopy (RICS) based analysis. We have applied this robust technique to study the interactions of two Wnt antagonists, Dickkopf1 and Dickkopf2 (Dkk1/2), to their cognate receptor, low-density-lipoprotein-receptor related protein 6 (LRP6), in the plasma membrane of living HEK293T cells. We obtained significantly lower affinities than previously reported using in vitro studies, underscoring the need to measure such data on living cells or tissue

Dual-color dual-focus line-scanning FCS for quantitative analysis of receptor-ligand interactions in living specimens

Cellular communication in multi-cellular organisms is mediated to a large extent by a multitude of cell-surface receptors that bind specific ligands. An in-depth understanding of cell signaling networks requires quantitative information on ligand-receptor interactions within living systems. In principle, fluorescence correlation spectroscopy (FCS) based methods can provide such data, but live-cell applications have proven extremely challenging. Here, we have developed an integrated dual-color dual-focus line-scanning fluorescence correlation spectroscopy (2c2f lsFCS) technique that greatly facilitates live-cell and tissue experiments. Absolute ligand and receptor concentrations and their diffusion coefficients within the cell membrane can be quantified without the need to perform additional calibration experiments. We also determine the concentration of ligands diffusing in the medium outside the cell within the same experiment by using a raster image correlation spectroscopy (RICS) based analysis. We have applied this robust technique to study the interactions of two Wnt antagonists, Dickkopf1 and Dickkopf2 (Dkk1/2), to their cognate receptor, low-density-lipoprotein-receptor related protein 6 (LRP6), in the plasma membrane of living HEK293T cells. We obtained significantly lower affinities than previously reported using in vitro studies, underscoring the need to measure such data on living cells or tissue

Altered functional brain network connectivity and glutamate system function in transgenic mice expressing truncated Disrupted-in-Schizophrenia 1

Considerable evidence implicates DISC1 as a susceptibility gene for multiple psychiatric diseases. DISC1 has been intensively studied at the molecular, cellular and behavioral level, but its role in regulating brain connectivity and brain network function remains unknown. Here, we utilize a set of complementary approaches to assess the functional brain network abnormalities present in mice expressing a truncated Disc1 gene (Disc1tr Hemi mice). Disc1tr Hemi mice exhibited hypometabolism in the prefrontal cortex (PFC) and reticular thalamus along with a reorganization of functional brain network connectivity that included compromised hippocampal-PFC connectivity. Altered hippocampal-PFC connectivity in Disc1tr Hemi mice was confirmed by electrophysiological analysis, with Disc1tr Hemi mice showing a reduced probability of presynaptic neurotransmitter release in the monosynaptic glutamatergic hippocampal CA1-PFC projection. Glutamate system dysfunction in Disc1tr Hemi mice was further supported by the attenuated cerebral metabolic response to the NMDA receptor (NMDAR) antagonist ketamine and decreased hippocampal expression of NMDAR subunits 2A and 2B in these animals. These data show that the Disc1 truncation in Disc1tr Hemi mice induces a range of translationally relevant endophenotypes underpinned by glutamate system dysfunction and altered brain connectivity

Responses of earthworm communities to crop residue management after inoculation of the earthworm Lumbricus terrestris (Linnaeus, 1758)

Earthworms are important for soil functioning in arable cropping systems and earthworm species differ in their response to soil tillage and crop residue management. Lumbricus terrestris (Linnaeus, 1758) are rare in intensively tilled arable fields. In two parallel field trials with either non-inversion (NIT) or conventional tillage (CT), we investigated the feasibility of inoculating L. terrestris under different crop residue management (amounts and placement). Simultaneously, we monitored the response of the existing earthworm communities to L. terrestris inoculation and to crop residue treatments in terms of earthworm density, species diversity and composition, ecological groups and functional diversity. L. terrestris densities were not affected by residue management. We were not able to infer effects of the inoculation on the existing earthworm communities since L. terrestris also colonized non-inoculated plots. In NIT and two years after trial establishment, the overall native earthworm density was 1.4 and 1.6 times higher, and the epigeic density 2.5 times higher, in treatments with highest residue application (S100) compared to 25% (S25) or no (S0) crop residues, respectively. Residue management did not affect earthworm species composition, nor the functional trait diversity and composition, except for an increase of the community weighted means of bifide typhlosolis in S0 compared to S100. In CT, however, crop residues did have a strong effect on species composition, ecological groups and functional traits. Without crop residues (S0), epigeic density was respectively 20 and 30% lower than with crop residues placed on the soil surface (S100) or incorporated (I100). Community composition was clearly affected by crop residues. Trait diversity was 2.6 to 3 times larger when crop residues were provided, irrespective of placement. Crop residues in CT also resulted in heavier earthworms and in a shift in the community towards species with a thicker epidermis and cuticle, a feather typhlosolis shape, and a higher average cocoon production rate. We conclude that earthworm communities under conventional tillage respond more strongly to the amount of crop residue than to its placement. Under non-inversion tillage, crop residue amounts affected earthworm communities, but to a smaller degree than under conventional tillage

A phase III trial of topotecan and whole brain radiation therapy for patients with CNS-metastases due to lung cancer

Brain metastases represent an important cause of morbidity in patients with lung cancer and are associated with a mean survival of less than 6 months. Thus, new regimens improving the outcome of these patients are urgently needed. On the basis of promising data raised in a phase I/II trial, we initiated an open, randomised, prospective, multicentric phase III trial, comparing whole brain radiation therapy (WBRT; 20 × 2 Gy) alone with WBRT+topotecan (RCT; 0.4 mg m−2 day−1 × 20). A total of 320 patients with CNS-metastases due to SCLC or NSCLC were projected. The primary end point was overall survival, whereas second end points were local response and progression-free survival. However, until the cutoff date of study completion (i.e., a study duration of 34 months), only a total of 96 (RCT:47, WBRT:49) patients had been recruited, and so an analysis was performed at that time point. Although the numbers of grade 3/4 non-haematological toxicities (besides alopecia 115 (RCT/WBRT: 55 out of 60) were evenly distributed, the 25 haematological events occurred mainly in the combined treatment arm (24 out of 1). Local response, evaluated 2 weeks after treatment, was assessable in 44 (RCT/WBRT: 23 out of 21) patients, showing CR in eight (3 out of 5), PR in 17 (11 out of 6), SD in 14 (8 out of 6) and PD in five (1 out of 4) patients (all differences n.s.). Neither OAS (RCT/WBRT: median (days)): 87 out of 95, range 3–752/4–433; HR 1.32; 95% CI (0.83; 2.10)) nor PFS (median (days)): 71 out of 66, range, 3–399/4–228; HR 1.28, 95% CI (0.73; 2.43) differed significantly. On the basis of these results and the slow recruitment, a continuation of the study did not seem reasonable. The available data show no significant advantage for concurrent radiochemotherapy for patients with lung cancer; however, the recruited number of patients is too low to exhibit a small advantage of combined treatment