Building a modular and multi-cellular virtual twin of the synovial joint in Rheumatoid Arthritis.

Rheumatoid arthritis is a complex disease marked by joint pain, stiffness, swelling, and chronic synovitis, arising from the dysregulated interaction between synoviocytes and immune cells. Its unclear etiology makes finding a cure challenging. The concept of digital twins, used in engineering, can be applied to healthcare to improve diagnosis and treatment for complex diseases like rheumatoid arthritis.

Computational and digital analyses in the INSPIRE mouse cohort to define sex-specific functional determinants of biological aging.

Biological age, which reflects the physiological state of an individual, offers a better predictive value than chronological age for age-related diseases and mortality. Nonetheless, determining accurate functional features of biological age remains challenging due to the multifactorial nature of aging. Here, we established a unique mouse cohort comprising 1576 male and female outbred SWISS mice subjected or not to high-fat, high-sucrose diet to investigate multiorgan/system biological aging throughout adulthood.

Uncovering the functions and mechanisms of regulatory elements-associated non-coding RNAs.

Over the past decade, regulatory non-coding RNAs (ncRNAs) produced by RNA Pol II have been revealed as meaningful players in various essential cellular functions. In particular, thousands of ncRNAs are produced at transcriptional regulatory elements such as enhancers and promoters, where they may exert multiple functions to regulate proper development, cellular programming, transcription or genomic stability. Here, we review the mechanisms involving these regulatory element-associated ncRNAs, and particularly enhancer RNAs (eRNAs) and PROMoter uPstream Transcripts (PROMPTs).

Diverse polysaccharide production and biofilm formation abilities of clinical Klebsiella pneumoniae.

infections have become a growing threat for human health. The lack of understanding of the relationship between antibiotic resistance, mucoviscosity, and biofilm formation in clinical isolates impedes our abilities to effectively predict K. infection outcomes.

The Myb73-GDPD2-GA2ox1 transcriptional regulatory module confers phosphate deficiency tolerance in soybean.

Phosphorus is indispensable in agricultural production. An increasing food supply requires more efficient use of phosphate due to limited phosphate resources. However, how crops regulate phosphate efficiency remains largely unknown.

Social dynamics of vervet monkeys are dependent upon group identity.

Traditions are widespread across the animal realm. Here, we investigated inter-group variability of social dynamics in wild vervet monkeys (). We analyzed 84,704 social interactions involving 247 individuals collected over nine years in three neighboring groups of wild vervet monkeys.

A multi-trait GWAS-based genetic association network controlling soybean architecture and seed traits.

Ideal plant architecture is essential for enhancing crop yields. Ideal soybean () architecture encompasses an appropriate plant height, increased node number, moderate seed weight, and compact architecture with smaller branch angles for growth under high-density planting. However, the functional genes regulating plant architecture are far not fully understood in soybean.

Targeting Nociceptin/Orphanin FQ receptor to rescue cognitive symptoms in a mouse neuroendocrine model of chronic stress.

Chronic stress causes cognitive deficits, such as impairments in episodic-like hippocampus-dependent memory. Stress regulates an opioid-related neuropeptide named Nociceptin/Orphanin FQ (N/OFQ), the ligand of the G protein-coupled receptor NOP. Since this peptide has deleterious effects on memory, we hypothesized that the N/OFQ system could be a mediator of the negative effects of stress on memory.

Proenkephalin deletion in hematopoietic cells induces intestinal barrier failure resulting in clinical feature similarities with irritable bowel syndrome in mice.

Opioid-dependent immune-mediated analgesic effects have been broadly reported upon inflammation. In preclinical mouse models of intestinal inflammatory diseases, the local release of enkephalins (endogenous opioids) by colitogenic T lymphocytes alleviate inflammation-induced pain by down-modulating gut-innervating nociceptor activation in periphery. In this study, we wondered whether this immune cell-derived enkephalin-mediated regulation of the nociceptor activity also operates under steady state conditions.

PAPγ associates with PAXT nuclear exosome to control the abundance of PROMPT ncRNAs.

Pervasive transcription of the human genome generates an abundance of RNAs that must be processed and degraded. The nuclear RNA exosome is the main RNA degradation machinery in the nucleus. However, nuclear exosome must be recruited to its substrates by targeting complexes, such as NEXT or PAXT.

Acute single non-sedative doses of NOP receptor agonists affect acquisition of object location memory but repeated high doses do not induce long-lasting deficits.

The Nociceptin/Orphanin FQ (N/OFQ) system has been shown to modulate various aspects of long-term memory. It is therefore important to study the effects on memory impairment by nociceptin receptor (NOP) agonists under preclinical development. In the present study, we investigated the effect of systemic injection of two small molecule selective NOP agonists, AT-202 and AT-524, in the object location memory task in male and female mice.

Impact of physical activity on brain oxidative metabolism and intrinsic capacities in young swiss mice fed a high fat diet.

Type 2 diabetes and obesity characterized by hallmarks of insulin resistance along with an imbalance in brain oxidative metabolism would impair intrinsic capacities (ICs), a new concept for assessing mental and physical functioning. Here, we explored the impact of physical activity on antioxidant responses and oxidative metabolism in discrete brain areas of HFD or standard diet (STD) fed mice but also its consequences on specific domains of ICs. 6-week-old Swiss male mice were exposed to a STD or a HFD for 16 weeks and half of the mice in each group had access to an activity wheel and the other half did not.

Functional and evolutionary study of MLO gene family in the regulation of Sclerotinia stem rot resistance in Brassica napus L.

Background: Oilseed rape (Brassica napus L.) is known as one of the most important oilseed crops cultivated around the world. However, its production continuously faces a huge challenge of Sclerotinia stem rot (SSR), a destructive disease caused by the fungus Sclerotinia sclerotiorum, resulting in huge yield loss annually.

GmBES1-1 dampens the activity of GmNSP1/2 to mediate brassinosteroid inhibition of nodulation in soybean.

Soybean (Glycine max) forms root nodules to house rhizobial bacteria for biological nitrogen fixation. The development of root nodules is intricately regulated by endogenous and exogenous cues. The phytohormones brassinosteroids (BRs) have been shown to negatively regulate nodulation in soybean, but the underlying genetic and molecular mechanisms remain largely unknown.

Low-nutrient diet in larvae stage causes enhancement in dopamine modulation in adult brain due epigenetic imprinting.

Nutrient scarcity is a frequent adverse condition that organisms face during their development. This condition may lead to long-lasting effects on the metabolism and behaviour of adults due to developmental epigenetic modifications. Here, we show that reducing nutrient availability during larval development affects adult spontaneous activity and sleep behaviour, together with changes in gene expression and epigenetic marks in the mushroom bodies (MBs).

Early-life nutrition interacts with developmental genes to shape the brain and sleep behavior in Drosophila melanogaster.

The mechanisms by which the genotype interacts with nutrition during development to contribute to the variation of complex behaviors and brain morphology of adults are not well understood. Here we use the Drosophila Genetic Reference Panel to identify genes and pathways underlying these interactions in sleep behavior and mushroom body morphology. We show that early-life nutritional restriction effects on sleep behavior and brain morphology depends on the genotype.

Analysis of Tissue-Specific Defense Responses to in .

Sclerotinia stem rot (SSR) caused by () is the main disease threat of oilseed rape (), resulting in huge economic losses every year. SSR resistance manifests as quantitative disease resistance (QDR), and no gene with complete SSR resistance has been cloned or reported so far. Transcriptome analysis has revealed a large number of defense-related genes and response processes.

Deleting Snord115 genes in mice remodels monoaminergic systems activity in the brain toward cortico-subcortical imbalances.

The neuronal-specific SNORD115 has gathered interest because its deficiency may contribute to the pathophysiology of Prader-Willi syndrome (PWS), possibly by altering post-transcriptional regulation of the gene encoding the serotonin (HTR2C) receptor. Yet, Snord115-KO mice do not resume the main symptoms of PWS, and only subtle-altered A-to-I RNA editing of Htr2c mRNAs was uncovered. Because HTR2C signaling fine-tunes the activity of monoaminergic neurons, we addressed the hypothesis that lack of Snord115 alters monoaminergic systems.

Martin Giurfa.

Interview with Martin Giurfa, who studies learning and memory in insects at Paul Sabatier University.

The NOP antagonist BTRX-246040 increases stress resilience in mice without affecting adult neurogenesis in the hippocampus.

Nociceptin/orphanin FQ (N/OFQ) is the endogenous ligand of an inhibitory G protein coupled receptor named N/OFQ peptide receptor (NOP). Clinical and preclinical findings suggest that the blockade of the NOP signaling induces antidepressant-like effects. Additionally, the blockade of the NOP receptor during inescapable stress exposure prevented the acquisition of the helplessness phenotype, suggesting that NOP antagonists are able to increase stress resilience.

Super-resolved live-cell imaging using random illumination microscopy.

Current super-resolution microscopy (SRM) methods suffer from an intrinsic complexity that might curtail their routine use in cell biology. We describe here random illumination microscopy (RIM) for live-cell imaging at super-resolutions matching that of 3D structured illumination microscopy, in a robust fashion. Based on speckled illumination and statistical image reconstruction, easy to implement and user-friendly, RIM is unaffected by optical aberrations on the excitation side, linear to brightness, and compatible with multicolor live-cell imaging over extended periods of time.