AxonVoice: An AI Tool for Voice-Based Digital Biomarker Phenot...

Maternal hormones can profoundly impact offspring physiology and behaviour in sex-dependent ways. Yet little is known about the molecular mechanisms linking these maternal effects to offspring phenot...

SARS-CoV-2 infection causes transient cardiorespiratory and neurological disorders, and severe acute illness is rare among children. Post COVID-19 condition (PCC) may cause profound, persistent phenot...

Gene expression varies between individuals and corresponds to a key step linking genotypes to phenot

Dans une étude publiée dans Molecular Biology and Evolution et dirigée par Maud Fagny au laboratoire Génétique Quantitative et Evolution – GQE-Le Moulon (UPSaclay/CNRS/INRAE/AgroParisTech, Gif-sur-Yvette), en collaboration avec la Harvard T.H. Chan School of Public Health et l’Université de Virginie aux États-Unis, les scientifiques ont montré que l’organisation des réseaux de régulation explique comment des phénotypes complexes ont pu s’adapter à de nouveaux environnements.   De nombreux phénotypes humains, comme la taille d’un individu ou la prédisposition génétique à de nombreuses maladies, sont complexes, déterminés par plusieurs loci, gènes ou éléments régulateurs. Inversement, un même locus influence souvent plusieurs phénotypes à la fois. Comment est-il donc possible de sélectionner des mutations qui modifient ces phénotypes complexes lors de l’adaptation d’une population à un nouvel environnement, sans affecter des phénotypes essentiels ?   Les chercheurs se sont intéressés à l’importance de l’organisation de ces réseaux de régulation, constitués de nombreux modules de gènes très connectés entre eux, mais faiblement reliés au reste du réseau (voir Figure). Cette organisation varie aussi selon les tissus. Les chercheurs ont montré que cette organisation permet de cloisonner les effets des mutations, qui affectent donc l’expression d’un processus biologique précis dans un tissu donné, tout en atténuant leur effet sur les autres processus et dans les autres tissus.   L’ensemble de ces résultats leur a permis de développer un cadre conceptuel pour comprendre l’architecture et l’évolution des phénotypes complexes et qui pourrait être utilisés pour améliorer les prédictions de risque de développer des maladies.   Légende Figure : Représentation de la modularité d’un réseau de régulation. Chaque cercle bleu correspond à un module, et les traits gris relient les mutations aux gènes dont elles modifient le niveau d’expression   -> Contact : maud.fagny@inrae.fr

To gain a mechanistic understanding of color pattern formation, including molecular and genetic mechanisms, it is necessary to not only describe adult phenot...

Abstract. Osteopontin, a key structural protein in the extracellular matrix, plays a pivotal role in regulating the local tumor microenvironment and systemic immunity during cancer progression. Recognizing that tumor cells do not exist in isolation but rather interact with a multitude of stromal components that significantly influence patient outcomes and therapy responses, this review focuses on the role of osteopontin in non-tumor cells in the context of solid cancers and the associated phenotypic and mechanistic insights. We explore how osteopontin influences the behavior of various innate and adaptive immune cells, including natural killer cells, neutrophils, macrophages, dendritic cells, myeloid-derived suppressor cells, B cells, T cells, as well as structural stromal cells such as fibroblasts, endothelial cells, and adipocytes. The review highlights the roles of osteopontin in modulating these stromal cells and their multiaxial influence on tumorigenesis and metastasis. These complex interplays offer insights into potential diagnostic and therapeutic strategies around osteopontin/stromal-mediated pathways in cancer progression and recurrence.

Abstract. Osteopontin, a key structural protein in the extracellular matrix, plays a pivotal role in regulating the local tumor microenvironment and systemic immunity during cancer progression. Recognizing that tumor cells do not exist in isolation but rather interact with a multitude of stromal components that significantly influence patient outcomes and therapy responses, this review focuses on the role of osteopontin in non-tumor cells in the context of solid cancers and the associated phenotypic and mechanistic insights. We explore how osteopontin influences the behavior of various innate and adaptive immune cells, including natural killer cells, neutrophils, macrophages, dendritic cells, myeloid-derived suppressor cells, B cells, T cells, as well as structural stromal cells such as fibroblasts, endothelial cells, and adipocytes. The review highlights the roles of osteopontin in modulating these stromal cells and their multiaxial influence on tumorigenesis and metastasis. These complex interplays offer insights into potential diagnostic and therapeutic strategies around osteopontin/stromal-mediated pathways in cancer progression and recurrence.

Maternal hormones can profoundly impact offspring physiology and behaviour in sex-dependent ways. Yet little is known about the molecular mechanisms linking these maternal effects to offspring phenot...

The Tyrolean Iceman is 5,300 years old and his mitochondr...

The Tyrolean Iceman is 5,300 years old and his mitochondr...

Understanding the effects of genetic variants is crucial for accurately predicting traits and phenot

The NIN-like protein 2 (NLP2) transcription factor is highly expressed in the infected cells of the N2 fixation zone of mature nodules in Medicago truncatula. In these cells, NLP2 directly activates the expression of leghemoglobin genes and is required for the full expression of nitrite reductase (NiR). Histological examination of nodules formed under different nitrate regimes revealed that the infected cells of nlp2 display abnormal vacuole morphology under high nitrate (5 mM KNO3). This phenotype is associated with starch accumulation, higher expression of starch biosynthesis genes, and increased levels of nitrite and nitric oxide. A transcriptomic comparison of nlp2 and wild-type nodules across nitrate concentrations revealed that under high nitrate, nlp2 shows lower expression of genes important for hypoxia adaptation, such as alcohol dehydrogenase and pyruvate decarboxylase (PDC), and increased expression of S-nitrosoglutathione reductase (GSNOR), which encodes a key enzyme for nitric oxide homeostasis. These changes in gene expression were associated with lower nodule ATP levels and a higher NAD+/NADH ratio, suggesting that energy metabolism is specifically compromised in nlp2 nodules under high nitrate. Transgenic expression of NiR in the nodules of nlp2-1 mutants grown under high nitrate rescued the vacuole phenotype and restored the expression of GSNOR and PDC to normal levels. Overall, our data indicate a role for NLP2 in the regulation of NiR in N2-fixing cells, suggesting a role for nitrate reduction in nodule energy homeostasis.

SARS-CoV-2 infection causes transient cardiorespiratory and neurological disorders, and severe acute illness is rare among children. Post COVID-19 condition (PCC) may cause profound, persistent phenot...

The progression from healthy tissue to malignancy involves a critical precancerous stage marked by cellular lesions with aberrant molecular and phenot…

Background: Atrial fibrillation (AF) patients represent a clinically complex, heterogeneous population comprising multiple homogeneous cohorts. Purpose: We aimed to identify the common clinical phenot...

Epigenetics studies how behavior, environment, and phenot...

Background: Atrial fibrillation (AF) patients represent a clinically complex, heterogeneous population comprising multiple homogeneous cohorts. Purpose: We aimed to identify the common clinical phenot...