Improving dynamic tomography, through maximum a posteriori estimation

Direct study of pore-scale fluid displacements, and other dynamic (i.e. time-dependent) processes is not feasible with conventional X-ray micro computed tomography (μCT). We have previously verified that a priori knowledge of the underlying physics can be used to conduct high-resolution, time-resolved imaging of continuous, complex processes, at existing X-ray μCT facilities. In this paper we present a maximum a posteriori (MAP) model of the dynamic tomography problem, which allows us to easily adapt and generalise our previous dynamic μCT approach to systems with more complex underlying physics

Planar cell polarity-mediated induction of neural stem cell expansion during axolotl spinal cord regeneration

Axolotls are uniquely able to mobilize neural stem cells to regenerate all missing regions of the spinal cord. How a neural stem cell under homeostasis converts after injury to a highly regenerative cell remains unknown. Here, we show that during regeneration, axolotl neural stem cells repress neurogenic genes and reactivate a transcriptional program similar to embryonic neuroepithelial cells. This dedifferentiation includes the acquisition of rapid cell cycles, the switch from neurogenic to proliferative divisions, and the re-expression of planar cell polarity (PCP) pathway components. We show that PCP induction is essential to reorient mitotic spindles along the anterior-posterior axis of elongation, and orthogonal to the cell apical-basal axis. Disruption of this property results in premature neurogenesis and halts regeneration. Our findings reveal a key role for PCP in coordinating the morphogenesis of spinal cord outgrowth with the switch from a homeostatic to a regenerative stem cell that restores missing tissue.Fil: Rodrigo Albors, Aida. Deutsche Forschungsgemeinschaft; Alemania. Max Planck Institute of Molecular Cell Biology and Genetics; Alemania. Technische Universitat Dresden; AlemaniaFil: Tazaky, Akira. Deutsche Forschungsgemeinschaft; Alemania. Max Planck Institute of Molecular Cell Biology and Genetics; Alemania. Technische Universitat Dresden; AlemaniaFil: Rost, Fabian. Technische Universitat Dresden; AlemaniaFil: Nowoshilow, Sergej. Deutsche Forschungsgemeinschaft; Alemania. Max Planck Institute of Molecular Cell Biology and Genetics; Alemania. Technische Universitat Dresden; AlemaniaFil: Chara, Osvaldo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Física de Líquidos y Sistemas Biológicos. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Instituto de Física de Líquidos y Sistemas Biológicos; Argentina. Technische Universitat Dresden; AlemaniaFil: Tanaka, Elly M. Deutsche Forschungsgemeinschaft; Alemania. Max Planck Institute of Molecular Cell Biology and Genetics; Alemania. Technische Universitat Dresden; Alemani

TSHZ3 and SOX9 regulate the timing of smooth muscle cell differentiation in the ureter by reducing myocardin activity

International audienceSmooth muscle cells are of key importance for the proper functioning of different visceral organs including those of the urogenital system. In the mouse ureter, the two transcriptional regulators TSHZ3 and SOX9 are independently required for initiation of smooth muscle differentiation from uncommitted mesenchymal precursor cells. However, it has remained unclear whether TSHZ3 and SOX9 act independently or as part of a larger regulatory network. Here, we set out to characterize the molecular function of TSHZ3 in the differentiation of the ureteric mesenchyme. Using a yeast-two-hybrid screen, we identified SOX9 as an interacting protein. We show that TSHZ3 also binds to the master regulator of the smooth muscle program, MYOCD, and displaces it from the coregulator SRF, thereby disrupting the activation of smooth muscle specific genes. We found that the initiation of the expression of smooth muscle specific genes in MYOCD-positive ureteric mesenchyme coincides with the down regulation of Sox9 expression, identifying SOX9 as a possible negative regulator of smooth muscle cell differentiation. To test this hypothesis, we prolonged the expression of Sox9 in the ureteric mesenchyme in vivo. We found that Sox9 does not affect Myocd expression but significantly reduces the expression of MYOCD/SRF-dependent smooth muscle genes, suggesting that down-regulation of Sox9 is a prerequisite for MYOCD activity. We propose that the dynamic expression of Sox9 and the interaction between TSHZ3, SOX9 and MYOCD provide a mechanism that regulates the pace of progression of the myogenic program in the ureter

Distribution and cover of a recently introduced alien sedge species, Carex pilulifera L., in the subalpine vegetation of Reunion Island

Carex pilulifera L., a perennial herb native to Europe, was recently introduced and found in subalpine vegetation of Reunion Island. In this study, we assessed the current distribution and cover of C. pilulifera within the subalpine vegetation (Piton des Neiges and Piton de la Fournaise) of the National Park of Reunion. We used GLM models to analyse relationships between C. pilulifera and habitat, disturbance type, and proximity to fodder and grazing areas. We evaluated the potential distribution of C. pilulifera using species distribution models. Presence of C. pilulifera was only found on Piton de la Fournaise with a mean cover of 16.6% (where present). Carex pilulifera was the fourth most observed alien species (27% of all observations). According to the SDM, it could also occur in Piton des Neiges but was not found. Carex pilulifera was significatively more present in subalpine grasslands and close to grazing and fodder areas. We believed fodder and grazing areas to be the introduction pathways of this species. This study confirmed the status of C. pilulifera as an invasive species in the subalpine vegetation of Reunion Island which comprises a high level of plant endemism. We suggest that management should primarily focus on surveying potentially suitable areas in Piton des Neiges to eradicate new introduction and to control the species within high biodiversity areas in Piton de la Fournaise

Chætognath transcriptome reveals ancestral and unique features among bilaterians

Background: The chætognaths (arrow worms) have puzzled zoologists for years because of their astonishing morphological and developmental characteristics. Despite their deuterostome-like development, phylogenomic studies recently positioned the chætognath phylum in protostomes, most likely in an early branching. This key phylogenetic position and the peculiar characteristics of chætognaths prompted further investigation of their genomic features. / Results: Transcriptomic and genomic data were collected from the chætognath Spadella cephaloptera through the sequencing of expressed sequence tags and genomic bacterial artificial chromosome clones. Transcript comparisons at various taxonomic scales emphasized the conservation of a core gene set and phylogenomic analysis confirmed the basal position of chætognaths among protostomes. A detailed survey of transcript diversity and individual genotyping revealed a past genome duplication event in the chætognath lineage, which was, surprisingly, followed by a high retention rate of duplicated genes. Moreover, striking genetic heterogeneity was detected within the sampled population at the nuclear and mitochondrial levels but cannot be explained by cryptic speciation. Finally, we found evidence for trans-splicing maturation of transcripts through splice-leader addition in the chætognath phylum and we further report that this processing is associated with operonic transcription. / Conclusion: These findings reveal both shared ancestral and unique derived characteristics of the chætognath genome, which suggests that this genome is likely the product of a very original evolutionary history. These features promote chætognaths as a pivotal model for comparative genomics, which could provide new clues for the investigation of the evolution of animal genomes

Chætognath transcriptome reveals ancestral and unique features among bilaterians

The chætognath transcriptome reveals unusual genomic features in the evolution of this protostome and suggests that it could be used as a model organism for bilaterians

Construct Validity and Cross Validity of a Test Battery Modeling Autism Spectrum Disorder (ASD) in Mice

International audienc

Postnatal Tshz3 Deletion Drives Altered Corticostriatal Function and Autism Spectrum Disorder–like Behavior

International audienceBACKGROUND: Heterozygous deletion of the TSHZ3 gene, encoding for the teashirt zinc-finger homeobox family member 3 (TSHZ3) transcription factor that is highly expressed in cortical projection neurons (CPNs), has been linked to an autism spectrum disorder (ASD) syndrome. Similarly, mice with Tshz3 haploinsufficiency show ASD-like behavior, paralleled by molecular changes in CPNs and corticostriatal synaptic dysfunctions. Here, we aimed at gaining more insight into "when" and "where" TSHZ3 is required for the proper development of the brain, and its deficiency crucial for developing this ASD syndrome. METHODS: We generated and characterized a novel mouse model of conditional Tshz3 deletion, obtained by crossing Tshz3 flox/flox with CaMKIIalpha-Cre mice, in which Tshz3 is deleted in CPNs from postnatal day 2 to 3 onward. We characterized these mice by a multilevel approach combining genetics, cell biology, electrophysiology, behavioral testing, and bioinformatics. RESULTS: These conditional Tshz3 knockout mice exhibit altered cortical expression of more than 1000 genes, w50% of which have their human orthologue involved in ASD, in particular genes encoding for glutamatergic syn-apse components. Consistently, we detected electrophysiological and synaptic changes in CPNs and impaired corticostriatal transmission and plasticity. Furthermore, these mice showed strong ASD-like behavioral deficits. CONCLUSIONS: Our study reveals a crucial postnatal role of TSHZ3 in the development and functioning of the corticostriatal circuitry and provides evidence that dysfunction in these circuits might be determinant for ASD pathogenesis. Our conditional Tshz3 knockout mouse constitutes a novel ASD model, opening the possibility for an early postnatal therapeutic window for the syndrome linked to TSHZ3 haploinsufficiency

From planning to implementation: A multi-stakeholder partnership for managing plant invasions in tropical island ecosystems

Effective management of invasive species within protected areas requires innovative solutions. In the Mascarene's archipelago, the national park of Reunion contains the largest area of intact vegetation, which faces alarming threats from invasive alien plant species. In response, the local government initiated an inclusive partnership in 2018 involving decision-makers, managers, and scientists to address the management of invasive alien plant species. An operational framework from planning to implementation has been established encompassing five key steps: (1) conduct a comprehensive site assessment, (2) model future threats, (3) prioritise interventions, (4) implement actions through a multi-stakeholder programme spanning multiple years, and (5) evaluate the effectiveness of implemented interventions. This study provides an in-depth examination of the research-action partnership and the operational framework, illustrating outputs for key priority sites. Our survey covered over 2500 ha, quantifying invasion degree in three vegetation strata at a fine-scale, and revealed significant areas within subalpine vegetation which remain remarkably pristine. By adapting participatory conservation planning approaches, we developed implementation-level outputs at a scale useful for managers which guided interventions on the ground. The partnership exemplifies a transdisciplinary approach with a broad array of stakeholders. Drawing from a checklist of essential components for successful partnerships, we highlight key insights from this initiative, providing valuable lessons for managing invasions in other regions. This framework holds promise for addressing several Global Biodiversity Framework Targets concerning plant invasions in island ecosystems or within landscapes characterised by multi-layered governance

Rare and Frequent Promoter Methylation, Respectively, of TSHZ2 and 3 Genes That Are Both Downregulated in Expression in Breast and Prostate Cancers

Neoplastic cells harbor both hypomethylated and hypermethylated regions of DNA. Whereas hypomethylation is found mainly in repeat sequences, regional hypermethylation has been linked to the transcriptional silencing of certain tumor suppressor genes. We attempted to search for candidate genes involved in breast/prostate carcinogenesis, using the criteria that they should be expressed in primary cultures of normal breast/prostate epithelial cells but are frequently downregulated in breast/prostate cancer cell lines and that their promoters are hypermethylated.We identified several dozens of candidates among 194 homeobox and related genes using Systematic Multiplex RT-PCR and among 23,000 known genes and 23,000 other expressed sequences in the human genome by DNA microarray hybridization. An additional examination, by real-time qRT-PCR of clinical specimens of breast cancer, further narrowed the list of the candidates. Among them, the most frequently downregulated genes in tumors were NP_775756 and ZNF537, from the homeobox gene search and the genome-wide search, respectively. To our surprise, we later discovered that these genes belong to the same gene family, the 3-member Teashirt family, bearing the new names of TSHZ2 and TSHZ3. We subsequently determined the methylation status of their gene promoters. The TSHZ3 gene promoter was found to be methylated in all the breast/prostate cancer cell lines and some of the breast cancer clinical specimens analyzed. The TSHZ2 gene promoter, on the other hand, was unmethylated except for the MDA-MB-231 breast cancer cell line. The TSHZ1 gene was always expressed, and its promoter was unmethylated in all cases.TSHZ2 and TSHZ3 genes turned out to be the most interesting candidates for novel tumor suppressor genes. Expression of both genes is downregulated. However, differential promoter methylation suggests the existence of distinctive mechanisms of transcriptional inactivation for these genes