Geosciences Roadmap for Research Infrastructures 2025–2028 by the Swiss Geosciences Community

This community roadmap presents an integrative approach including the most urgent infrastructure requests for the future development of geosciences in Switzerland. It recommends to strengthen the multidisciplinary nature of the geosciences by putting all activities under the roof of the Integrated Swiss Geosciences supported by four specific research infrastructure pillars. The roadmap represents the view of the Swiss scientific community in the field of geosciences and is a formal element of the process to elaborate the Swiss Roadmap for Research Infrastructures 2023. This bottom-up contribution to the identification and selection of important national and international research infrastructures has been coordinated by the Swiss Academy of Sciences (SCNAT) on a mandate by the State Secretariat for Education, Research and Innovation (SERI).ISSN:2297-1564ISSN:2297-157

NF-κB/Rel-Mediated Regulation of the Neural Fate in Drosophila

Two distinct roles are described for Dorsal, Dif and Relish, the three NF-κB/Rel proteins of Drosophila, in the development of the peripheral nervous system. First, these factors regulate transcription of scute during the singling out of sensory organ precursors from clusters of cells expressing the proneural genes achaete and scute. This effect is possibly mediated through binding sites for NF-κB/Rel proteins in a regulatory module of the scute gene required for maintenance of scute expression in precursors as well as repression in cells surrounding precursors. Second, genetic evidence suggests that the receptor Toll-8, Relish, Dif and Dorsal, and the caspase Dredd pathway are active over the entire imaginal disc epithelium, but Toll-8 expression is excluded from sensory organ precursors. Relish promotes rapid turnover of transcripts of the target genes scute and asense through an indirect, post-transcriptional mechanism. We propose that this buffering of gene expression levels serves to keep the neuro-epithelium constantly poised for neurogenesis

The MYST-Containing Protein Chameau Is Required for Proper Sensory Organ Specification during Drosophila Thorax Morphogenesis

The adult thorax of Drosophila melanogaster is covered by a stereotyped pattern of mechanosensory bristles called macrochaetes. Here, we report that the MYST containing protein Chameau (Chm) contributes to the establishment of this pattern in the most dorsal part of the thorax. Chm mutant pupae present extra-dorsocentral (DC) and scutellar (SC) macrochaetes, but a normal number of the other macrochaetes. We provide evidences that chm restricts the singling out of sensory organ precursors from proneural clusters and genetically interacts with transcriptional regulators involved in the regulation of achaete and scute in the DC and SC proneural cluster. This function of chm likely relies on chromatin structure regulation since a protein with a mutation in the conserved catalytic site fails to rescue the formation of supernumerary DC and SC bristles in chm mutant flies. This is further supported by the finding that mutations in genes encoding chromatin modifiers and remodeling factors, including Polycomb group (PcG) and Trithorax group (TrxG) members, dominantly modulate the penetrance of chm extra bristle phenotype. These data support a critical role for chromatin structure modulation in the establishment of the stereotyped sensory bristle pattern in the fly thorax

On Robustness Computation and Optimization in BIOCHAM-4

Long version with appendicesInternational audienceBIOCHAM-4 is a tool for modeling, analyzing and synthesizing biochemical reaction networks with respect to some formal, yet possibly imprecise, specification of their behavior. We focus here on one new capability of this tool to optimize the robustness of a parametric model with respect to a specification of its dynamics in quantitative temporal logic. More precisely, we present two complementary notions of robustness: the statistical notion of model robustness to parameter perturbations, defined as its mean functionality, and a metric notion of formula satisfaction robustness, defined as the penetration depth in the validity domain of the temporal logic constraints. We show how the formula robustness can be used in BIOCHAM-4 with no extra cost as an objective function in the parameter optimization procedure, to actually improve the model robustness. We illustrate these unique features with a classical example of the hybrid systems community and provide some performance figures on a model of MAPK signalling with 37 parameters

Transcriptional Regulation by CHIP/LDB Complexes

It is increasingly clear that transcription factors play versatile roles in turning genes “on” or “off” depending on cellular context via the various transcription complexes they form. This poses a major challenge in unraveling combinatorial transcription complex codes. Here we use the powerful genetics of Drosophila combined with microarray and bioinformatics analyses to tackle this challenge. The nuclear adaptor CHIP/LDB is a major developmental regulator capable of forming tissue-specific transcription complexes with various types of transcription factors and cofactors, making it a valuable model to study the intricacies of gene regulation. To date only few CHIP/LDB complexes target genes have been identified, and possible tissue-dependent crosstalk between these complexes has not been rigorously explored. SSDP proteins protect CHIP/LDB complexes from proteasome dependent degradation and are rate-limiting cofactors for these complexes. By using mutations in SSDP, we identified 189 down-stream targets of CHIP/LDB and show that these genes are enriched for the binding sites of APTEROUS (AP) and PANNIER (PNR), two well studied transcription factors associated with CHIP/LDB complexes. We performed extensive genetic screens and identified target genes that genetically interact with components of CHIP/LDB complexes in directing the development of the wings (28 genes) and thoracic bristles (23 genes). Moreover, by in vivo RNAi silencing we uncovered novel roles for two of the target genes, xbp1 and Gs-alpha, in early development of these structures. Taken together, our results suggest that loss of SSDP disrupts the normal balance between the CHIP-AP and the CHIP-PNR transcription complexes, resulting in down-regulation of CHIP-AP target genes and the concomitant up-regulation of CHIP-PNR target genes. Understanding the combinatorial nature of transcription complexes as presented here is crucial to the study of transcription regulation of gene batteries required for development

Notch inhibits Yorkie activity in Drosophila wing discs.

During development, tissues and organs must coordinate growth and patterning so they reach the right size and shape. During larval stages, a dramatic increase in size and cell number of Drosophila wing imaginal discs is controlled by the action of several signaling pathways. Complex cross-talk between these pathways also pattern these discs to specify different regions with different fates and growth potentials. We show that the Notch signaling pathway is both required and sufficient to inhibit the activity of Yorkie (Yki), the Salvador/Warts/Hippo (SWH) pathway terminal transcription activator, but only in the central regions of the wing disc, where the TEAD factor and Yki partner Scalloped (Sd) is expressed. We show that this cross-talk between the Notch and SWH pathways is mediated, at least in part, by the Notch target and Sd partner Vestigial (Vg). We propose that, by altering the ratios between Yki, Sd and Vg, Notch pathway activation restricts the effects of Yki mediated transcription, therefore contributing to define a zone of low proliferation in the central wing discs

High-Intensity Interval Training Interventions in Children and Adolescents: A Systematic Review

BackgroundWhilst there is increasing interest in the efficacy of high-intensity interval training in children and adolescents as a time-effective method of eliciting health benefits, there remains little consensus within the literature regarding the most effective means for delivering a high-intensity interval training intervention. Given the global health issues surrounding childhood obesity and associated health implications, the identification of effective intervention strategies is imperative.ObjectivesThe aim of this review was to examine high-intensity interval training as a means of influencing key health parameters and to elucidate the most effective high-intensity interval training protocol.MethodsStudies were included if they: (1) studied healthy children and/or adolescents (aged 5–18 years); (2) prescribed an intervention that was deemed high intensity; and (3) reported health-related outcome measures.ResultsA total of 2092 studies were initially retrieved from four databases. Studies that were deemed to meet the criteria were downloaded in their entirety and independently assessed for relevance by two authors using the pre-determined criteria. From this, 13 studies were deemed suitable. This review found that high-intensity interval training in children and adolescents is a time-effective method of improving cardiovascular disease biomarkers, but evidence regarding other health-related measures is more equivocal. Running-based sessions, at an intensity of >90% heart rate maximum/100–130% maximal aerobic velocity, two to three times a week and with a minimum intervention duration of 7 weeks, elicit the greatest improvements in participant health.ConclusionWhile high-intensity interval training improves cardiovascular disease biomarkers, and the evidence supports the effectiveness of running-based sessions, as outlined above, further recommendations as to optimal exercise duration and rest intervals remain ambiguous owing to the paucity of literature and the methodological limitations of studies presently available

S-Phase Favours Notch Cell Responsiveness in the Drosophila Bristle Lineage

We have studied cell sensitivity to Notch pathway signalling throughout the cell cycle. As model system, we used the Drosophila bristle lineage where at each division N plays a crucial role in fate determination. Using in vivo imaging, we followed this lineage and activated the N-pathway at different moments of the secondary precursor cell cycle. We show that cells are more susceptible to respond to N-signalling during the S-phase. Thus, the period of heightened sensitivity coincided with the period of the S-phase. More importantly, modifications of S-phase temporality induced corresponding changes in the period of the cell's reactivity to N-activation. Moreover, S-phase abolition was correlated with a decrease in the expression of tramtrack, a downstream N-target gene. Finally, N cell responsiveness was modified after changes in chromatin packaging. We suggest that high-order chromatin structures associated with the S-phase create favourable conditions that increase the efficiency of the transcriptional machinery with respect to N-target genes

Notch signaling as a therapeutic target for breast cancer treatment?

Aberrant Notch signaling can induce mammary gland carcinoma in transgenic mice, and high expressions of Notch receptors and ligands have been linked to poor clinical outcomes in human patients with breast cancer. This suggests that inhibition of Notch signaling may be beneficial for breast cancer treatment. In this review, we critically evaluate the evidence that supports or challenges the hypothesis that inhibition of Notch signaling would be advantageous in breast cancer management. We find that there are many remaining uncertainties that must be addressed experimentally if we are to exploit inhibition of Notch signaling as a treatment approach in breast cancer. Nonetheless, Notch inhibition, in combination with other therapies, is a promising avenue for future management of breast cancer. Furthermore, since aberrant Notch4 activity can induce mammary gland carcinoma in the absence of RBPjκ, a better understanding of the components of RBPjκ-independent oncogenic Notch signaling pathways and their contribution to Notch-induced tumorigenesis would facilitate the deployment of Notch inhibition strategies for effective treatment of breast cancer