Fgfr3 enhancer deletion markedly improves all skeletal features in a mouse model of achondroplasia.

Achondroplasia, the most prevalent short-stature disorder, is caused by missense variants overactivating the fibroblast growth factor receptor 3 (FGFR3). As current surgical and pharmaceutical treatments only partially improve some disease features, we sought to explore a genetic approach. We show that an enhancer located 29 kb upstream of mouse Fgfr3 (-29E) is sufficient to confer a transgenic mouse reporter with a domain of expression in cartilage matching that of Fgfr3.

Missense variants weakening a SOX9 phosphodegron linked to odontogenesis defects, scoliosis and other skeletal features.

SOX9 encodes an SRY-related transcription factor critical for chondrogenesis and sex determination among other processes. Loss-of-function variants cause campomelic dysplasia and Pierre Robin Sequence, while both gain- and loss-of-function variants cause disorders of sex development. SOX9 has also been linked to scoliosis and cancers, but variants are undetermined.

Unveiling pepper immunity's robustness to temperature shifts: insights for empowering future crops.

Boosting plant immunity is an effective alternative to pesticides. However, environmental variations, accentuated by climate change, can compromise immunity. The robustness of a trait corresponds to the absence (or low level) of variation in that trait in the face of an environmental change.

Cancer associated variant enrichment CAVE, a gene agnostic approach to identify low burden variants in chronic lymphocytic leukemia.

Intratumoral heterogeneity is an important clinical challenge because low burden clones expressing specific genetic alterations drive therapeutic resistance mechanisms. We have developed CAVE (cancer-associated variant enrichment), a gene-agnostic computational tool to identify specific enrichment of low-burden cancer driver variants in next-generation sequencing (NGS) data. For this study, CAVE was applied to TP53 in chronic lymphocytic leukemia (CLL) as a cancer model.

SHP2 ablation mitigates osteoarthritic cartilage degeneration by promoting chondrocyte anabolism through SOX9.

Articular cartilage phenotypic homeostasis is crucial for life-long joint function, but the underlying cellular and molecular mechanisms governing chondrocyte stability remain poorly understood. Here, we show that the protein tyrosine phosphatase SHP2 is differentially expressed in articular cartilage (AC) and growth plate cartilage (GPC) and that it negatively regulates cell proliferation and cartilage phenotypic program. Postnatal SHP2 deletion in Prg4 AC chondrocytes increased articular cellularity and thickness, whereas SHP2 deletion in Acan pan-chondrocytes caused excessive GPC chondrocyte proliferation and led to joint malformation post-puberty.

Transcription Factors Sox8 and Sox10 Contribute with Different Importance to the Maintenance of Mature Oligodendrocytes.

Myelin-forming oligodendrocytes in the vertebrate nervous system co-express the transcription factor Sox10 and its paralog Sox8. While Sox10 plays crucial roles throughout all stages of oligodendrocyte development, including terminal differentiation, the loss of Sox8 results in only mild and transient perturbations. Here, we aimed to elucidate the roles and interrelationships of these transcription factors in fully differentiated oligodendrocytes and myelin maintenance in adults.

SEM Image Processing Assisted by Deep Learning to Quantify Mesoporous γ-Alumina Spatial Heterogeneity and Its Predicted Impact on Mass Transfer.

The pore network architecture of porous heterogeneous catalyst supports has a significant effect on the kinetics of mass transfer occurring within them. Therefore, characterizing and understanding structure-transport relationships is essential to guide new designs of heterogeneous catalysts with higher activity and selectivity and superior resistance to deactivation. This study combines classical characterization via N adsorption and desorption and mercury porosimetry with advanced scanning electron microscopy (SEM) imaging and processing approaches to quantify the spatial heterogeneity of γ-alumina (γ-AlO), a catalyst support of great industrial relevance.

Resolution of Acinar Dedifferentiation Regulates Tissue Remodeling in Pancreatic Injury and Cancer Initiation.

Background & Aims: Acinar-to-ductal metaplasia (ADM) is crucial in the development of pancreatic ductal adenocarcinoma. However, our understanding of the induction and resolution of ADM remains limited. We conducted comparative transcriptome analyses to identify conserved mechanisms of ADM in mouse and human.

Structural and biochemical characterization of SmoPG1, an exo-polygalacturonase from Selaginella moellendorffii.

Polygalacturonases (PGs) can modulate chemistry and mechanical properties of the plant cell wall through the degradation of pectins, one of its major constituents. PGs are largely used in food, beverage, textile, and paper industries to increase processes' performances. To improve the use of PGs, knowledge of their biochemical, structural and functional features is of prime importance.

SOXC are critical regulators of adult bone mass.

Pivotal in many ways for human health, the control of adult bone mass is governed by complex, incompletely understood crosstalk namely between mesenchymal stem cells, osteoblasts and osteoclasts. The SOX4, SOX11 and SOX12 (SOXC) transcription factors were previously shown to control many developmental processes, including skeletogenesis, and SOX4 was linked to osteoporosis, but how SOXC control adult bone mass remains unknown. Using SOXC loss- and gain-of-function mouse models, we show here that SOXC redundantly promote prepubertal cortical bone mass strengthening whereas only SOX4 mitigates adult trabecular bone mass accrual in early adulthood and subsequent maintenance.

Skeletal growth is enhanced by a shared role for SOX8 and SOX9 in promoting reserve chondrocyte commitment to columnar proliferation.

SOX8 was linked in a genome-wide association study to human height heritability, but roles in chondrocytes for this close relative of the master chondrogenic transcription factor SOX9 remain unknown. We undertook here to fill this knowledge gap. High-throughput assays demonstrate expression of human and mouse in growth plate cartilage.

Do NSm Virulence Factors in the Viral Order Originate from Gn Gene Duplication?

One-third of the nine WHO shortlisted pathogens prioritized for research and development in public health emergencies belong to the order. Several species carry an NSm protein that acts as a virulence factor. We predicted the structures of these NSm proteins and unexpectedly found that in two families, their cytosolic domain was inferred to have a similar fold to that of the cytosolic domain of the viral envelope-forming glycoprotein N (Gn) encoded on the same genome fragment.

Mutation of AtPME2, a pH-Dependent Pectin Methylesterase, Affects Cell Wall Structure and Hypocotyl Elongation.

Pectin methylesterases (PMEs) modify homogalacturonan's chemistry and play a key role in regulating primary cell wall mechanical properties. Here, we report on Arabidopsis AtPME2, which we found to be highly expressed during lateral root emergence and dark-grown hypocotyl elongation. We showed that dark-grown hypocotyl elongation was reduced in knock-out mutant lines as compared to the control.

Growth-inhibiting effects of the unconventional plant APYRASE 7 of Arabidopsis thaliana influences the LRX/RALF/FER growth regulatory module.

Plant cell growth involves coordination of numerous processes and signaling cascades among the different cellular compartments to concomitantly enlarge the protoplast and the surrounding cell wall. The cell wall integrity-sensing process involves the extracellular LRX (LRR-Extensin) proteins that bind RALF (Rapid ALkalinization Factor) peptide hormones and, in vegetative tissues, interact with the transmembrane receptor kinase FERONIA (FER). This LRX/RALF/FER signaling module influences cell wall composition and regulates cell growth.

genome assembly for two isolates using long-read Oxford Nanopore Technology sequencing.

The oomycete is a common pathogen of the Solanaceae and Cucurbitaceae families. An improved assembly for the reference isolate LT1534 was constructed using Oxford Nanopore Technologies and Illumina data. Additionally, an unpolished assembly was produced for the European isolate Pc285 collected on chili pepper using Oxford Nanopore reads.

En bloc resection of pararectal ectopic thyroid tissue: a case report.

A pararectal mass' specific diagnosis can be challenging as a broad range of both benign and malignant tumors are possible. Many of these lesions are congenital and do not require treatment, if asymptomatic. Special attention is to be paid when imaging findings are not typical.

Analysis of >3400 worldwide eggplant accessions reveals two independent domestication events and multiple migration-diversification routes.

Eggplant (Solanum melongena) is an important Solanaceous crop, widely cultivated and consumed in Asia, the Mediterranean basin, and Southeast Europe. Its domestication centers and migration and diversification routes are still a matter of debate. We report the largest georeferenced and genotyped collection to this date for eggplant and its wild relatives, consisting of 3499 accessions from seven worldwide genebanks, originating from 105 countries in five continents.

Multi-environment association study highlights candidate genes for robust agronomic quantitative trait loci in a novel worldwide Capsicum core collection.

Investigating crop diversity through genome-wide association studies (GWAS) on core collections helps in deciphering the genetic determinants of complex quantitative traits. Using the G2P-SOL project world collection of 10 038 wild and cultivated Capsicum accessions from 10 major genebanks, we assembled a core collection of 423 accessions representing the known genetic diversity. Since complex traits are often highly dependent upon environmental variables and genotype-by-environment (G × E) interactions, multi-environment GWAS with a 10 195-marker genotypic matrix were conducted on a highly diverse subset of 350 Capsicum annuum accessions, extensively phenotyped in up to six independent trials from five climatically differing countries.

Determining clinical predictors to identify non-specific abdominal pain and the added value of laboratory examinations: A prospective derivation study in a paediatric emergency department.

Aim: To develop a model to discriminate non-specific abdominal pain (NSAP) from organic pain in the paediatric emergency department (PED) and evaluate the added value of laboratory markers.

Methods: Prospective cohort study in an urban French PED including all patients aged ≥4 years with abdominal pain between November 2020 and May 2021. The outcome was the discrimination between NSAP (patients coded to have only "pain" or "constipation") and organic pain (all other diagnoses) using stepwise backward multivariate logistic regression method with bootstrap resampling.

Layoffs in SMEs: The Role of Social Proximity.

Abundant research exists on the restructuring operations of large, publicly listed firms. However, little is known about the antecedents of layoffs in small and medium-sized enterprises (SMEs). Building on the stakeholder salience theory and arguments on social proximity, this study posits that SMEs are less likely to dismiss employees than large firms.

Plant polygalacturonase structures specify enzyme dynamics and processivities to fine-tune cell wall pectins.

Polygalacturonases (PGs) fine-tune pectins to modulate cell wall chemistry and mechanics, impacting plant development. The large number of PGs encoded in plant genomes leads to questions on the diversity and specificity of distinct isozymes. Herein, we report the crystal structures of 2 Arabidopsis thaliana PGs, POLYGALACTURONASE LATERAL ROOT (PGLR), and ARABIDOPSIS DEHISCENCE ZONE POLYGALACTURONASE2 (ADPG2), which are coexpressed during root development.

Strive or thrive: Trends in gene expression in partially resistant pepper.

Partial resistance in plants generally exerts a low selective pressure on pathogens, and thus ensuring their durability in agrosystems. However, little is known about the effect of partial resistance on the molecular mechanisms of pathogenicity, a knowledge that could advance plant breeding for sustainable plant health. Here we investigate the gene expression of during infection of pepper ( L.

Design of a Protein with Improved Thermal Stability by an Evolution-Based Generative Model.

Efficient design of functional proteins with higher thermal stability remains challenging especially for highly diverse sequence variants. Considering the evolutionary pressure on protein folds, sequence design optimizing evolutionary fitness could help designing folds with higher stability. Using a generative evolution fitness model trained to capture variation patterns in natural sequences, we designed artificial sequences of a proteinaceous inhibitor of pectin methylesterase enzymes.

Auxin triggers pectin modification during rootlet emergence in white lupin.

Emergence of secondary roots through parental tissue is a highly controlled developmental process. Although the model plant Arabidopsis has been useful to uncover the predominant role of auxin in this process, its simple root structure is not representative of how emergence takes place in most plants, which display more complex root anatomy. White lupin is a legume crop producing structures called cluster roots, where closely spaced rootlets emerge synchronously.

Pepper variome reveals the history and key loci associated with fruit domestication and diversification.

Pepper (Capsicum spp.) is an important vegetable crop that provides a unique pungent sensation when eaten. Through construction of a pepper variome map, we examined the main groups that emerged during domestication and breeding of C.