Publications

The experimental and conceptual knowledge in 1909 led to the discovery of the Hydra head organizer through transplantation experiments between pigmented and non-pigmented animals; a discovery followed by numerous transplantations demonstrating cross-regulation between activating and inhibiting components distributed along the body axis. This experimental work inspired mathematicians, engineers, physicists and computer scientists to develop theoretical models predicting the principles of developmental mechanisms. Today, we know that the Wnt/β-catenin/Sp5/Zic4 gene regulatory network (GRN) links organizer activity, morphogenesis and cellular identity in Hydra, with variable conformations depending on the region or epithelial layer, and varied phenotypes depending on which GRN element is misregulated. In intact animals, Wnt/β-catenin signaling acts as the head activator at the tip of the hypostome, restricted by Sp5 in the other regions of the animal. Moreover, in the tentacle ring, Sp5 and Zic4 act epistatically to support tentacle differentiation and prevent basal disc differentiation. Along the body column, Sp5 is self-repressed in the epidermis and acts as a head inhibitor along the gastrodermis. Other players modulate these activities, such as TSP and Margin/RAX apically, Notch signaling in the tentacle zone, Dkk1/2/4 and HAS-7 in the body column. In the developmental context of regeneration, cells below the amputation zone switch from repressed to locally de novo activated head organizer status, a transition driven by immediate symmetrical and asymmetrical metabolic changes that lead to gene expression regulations involving components and modulators of Wnt/β-catenin signaling, early-pulse and early-late transient both often symmetrical, together with sustained ones, specific to head regeneration.

The systematic chemical analysis of large collections of archaeological glass beads is essential to better understand trade patterns at different times around the world. Glass beads' trade towards and within sub-Saharan West Africa grew exponentially over time to culminate with the establishment of the Atlantic Trade. Although these artefacts are very commonly found in archaeological contexts dating after the 15th century CE, the assemblages are generally poorly studied from a chemical point of view. We present here the study of 916 glass beads found in five archaeological sites in Ghana, Mali, and Senegal, in contexts dated between the 15th and the mid-20th century CE. Besides the techno-stylistic classification of the whole assemblage, the compositional study of a sub-group of 578 monochrome and polychrome glass beads was performed. The 798 glass samples composing the selected beads were therefore classified based on their main chemical composition. Moreover, major, minor, and trace elements analysis by Laser Ablation-Inductively Coupled Plasma-Mass Spectrometry (LA-ICP-MS) and the statistical analysis of the results by Principal Component Analysis (PCA) led to the identification of the probable origin of the glass. Different suppliers were distinguished for the Ghanaian earlier beads and the Senegalese and Malian later ones, in relation to the different European trade partners at different times.

BackgroundEarly detection and characterisation of SARS-CoV-2 variants have been and continue to be essential for assessing their public health impact. In August 2023, Santé publique France implemented enhanced surveillance for BA.2.86 and sub-lineage JN.1 because of their genetic divergence from other variants and increased prevalence.AimTo detail how combining epidemiological and laboratory data sources, targeted investigations and modelling enabled comprehensive characterisation of sub-lineage JN.1.MethodsData were collected from epidemiological investigations using a standardised questionnaire and from routine and novel (RELAB network) surveillance systems. JN.1 cases were compared with cases infected with previously circulating variants, such as EG.5, BA.4/BA.5 and other BA.2.86 sub-lineages. The growth rate and doubling time of JN.1 were estimated.ResultsJN.1 was first detected in September 2023 in the Île-de-France region, France, and spread widely across the country. By late November, doubling time was estimated to be 8.6 to 26.4 days depending on the region. For all data sources, cases infected by JN.1 showed similar demographics, rates of hospitalisation and RT-PCR cycle threshold values compared with those infected by previous variants. JN.1 cases also had older median age (54 years; 40-71 vs 47 years; 30-59), more frequent reports of feverish feeling and less frequent cough or nausea compared with BA.4/BA.5 cases. JN.1 cases had significantly higher frequency of anosmia compared with other BA.2.86 cases.ConclusionCombining different data sources played a key role in detecting emerging variant JN.1, for which no evidence of increased public health impact was found despite its genetic divergence.

Biosorption is nowadays recommended as an ecological and environmentally friendly alternative to remove metals from contaminated regions. Even in situ incubations of algae on the seabed are conducted to investigate potential future ways of reducing metal contamination. Our study investigated the negative effects on microorganisms when metal-enriched algae are released into the marine environment. We cultured the microalgae Nannochloropsis oceanica strain CCMP1779 with C/N amended f/2 medium enriched with four different metals (cadmium, copper, zinc, lead) and fed the resulting metal-enriched microalgal biomass to Ammonia confertitesta (Rhizaria, Foraminifera) for two and six days. Our study is the first study dealing with the interaction of biosorbed metals and the metabolism of microorganisms. The effects of the uptake of these metal-enriched algae were recorded by evaluating carbon and nitrogen uptake. Examinations using transmission electron microscopy (TEM) were also carried out to better assess the condition of the foraminifera. Foraminifera fed with metal-enriched microalgae show reduced carbon uptake and increased nitrogen storage, indicating stress conditions. These observations suggest that trace metals can induce stress which damages cellular metabolism. Interestingly, no cytological changes in TEM analyses could be observed, which might be attributed to the relatively short incubation time.

Amniote integumentary appendages constitute a diverse group of micro-organs, including feathers, hair and scales. These structures typically develop as genetically controlled units1, the spatial patterning of which emerges from a self-organized chemical Turing system2,3 with integrated mechanical feedback4,5. The seemingly purely mechanical patterning of polygonal crocodile head scales provides an exception to this paradigm6. However, the nature and origin of the mechanical stress field driving this patterning remain unclear. Here, using precise in ovo intravenous injections of epidermal growth factor protein, we generate Nile crocodile embryos with substantially convoluted head skin, as well as hatchlings with smaller polygonal head scales resembling those of caimans. We then use light-sheet fluorescence microscopy to quantify embryonic tissue-layer geometry, collagen architecture and the spatial distribution of proliferating cells. Using these data, we build a phenomenological three-dimensional mechanical growth model that recapitulates both normal and experimentally modified patterning of crocodile head scales. Our experiments and numerical simulations demonstrate that crocodile head scales self-organize through compressive folding, originating from near-homogeneous skin growth with differential stiffness of the dermis versus the epidermis. Our experiments and theoretical morphospace analyses indicate that variation in embryonic growth and material properties of skin layers provides a simple evolutionary mechanism that produces a diversity of head-scale patterns among crocodilian species.

Libanissus bkassinensis Azar, Maksoud & Nel, gen. et sp. nov. is illustrated and described from the Lower Cretaceous dysodile (oil papershales) of Bkassine, South Lebanon, and its taxonomic position discussed. Libanissus bkassinensis Azar, Maksoud & Nel, gen. et sp. nov. is characterized by its banded legs and body, a hind wing with two lobes, RA and RP very short, M with only two very short apical branches, CuA with two branches, and a small but distinct apical furcation of PCu close to the incision of the wing margin. Libanissus bkassinensis Azar, Maksoud & Nel, gen. et sp. nov. represents the earliest record (lower Barremian) of the Issidae. Prior to this discovery, the oldest known record was from the Paleocene of France.

Monothalamid (single-chambered) foraminifera are a common constituent of high latitudinal coastal and deep-sea biota but are under-researched, and a limited number of species are described. Here, we present the first DNA barcoding study of monothalamid foraminifera collected from methane seeps along the Vestnesa and Svyatogor Ridge off NW Svalbard. Samples were taken from active pockmarks focusing on typical seep microhabitats characterized by microbial mats, and tubeworms. Additionally, reference samples were obtained from adjacent zones outside the pockmarks. We report here DNA barcode sequences of the 18S rRNA gene for seven monothalamid species of which three are described based on molecular and morphological data, the other four remain undescribed or undetermined. Conqueria bolivari sp. nov. has an elongate tubular shape and finely agglutinated test with a silvery, glossy surface. It branches with Conqueria laevis from the deep Weddell Sea and an undescribed Conqueria sp. from the Greenland Sea. Hilla arctica sp. nov. is elongated to broadly pyriform with a white, finely agglutinated test. It branches as a sister to Hilla argentea from South Georgia in the monothalamid Clade Y. Senguptiella vestnesensis gen. nov. sp. nov. branches in the monothalamid Clade C. It is rounded, with a finely agglutinated, reflective test wall. We also obtained DNA barcode sequences for undescribed Hippocrepinella sp. (Clade D) and Bathysiphon sp. (Clade BM) and two undetermined monothalamids (Clade Y and Clade Storthosphaera). Our study contributes to the efforts of obtaining DNA barcoding data for Arctic marine biodiversity and shows that monothalamid foraminifera are an important component of polar benthic communities.

Aims: Liver cytochromes (CYPs) play an important role in drug metabolism but display a large interindividual variability resulting both from genetic and environmental factors. Most drug dose adjustment guidelines are based on genetics performed in healthy volunteers. However, hospitalized patients are not only more likely to be the target of new prescriptions and drug treatment modifications than healthy volunteers, but will also be more subject to polypharmacy, drug-drug interactions, or to suffer from disease or inflammation affecting CYP activities. Methods: We compared predicted phenotype based on genetic data and measured phenotype using the Geneva cocktail to determine the extent of drug metabolizing enzyme variability in a large population of hospitalized patients (>500) and healthy young volunteers (>300). We aimed to assess the correlation between predicted and measured phenotype in the two populations. Results: We found that, even in cases where the genetically predicted metabolizer group correlates well with measured CYP activity at group level, this prediction lacks accuracy for the determination of individual metabolizer capacities. Drugs can have a profound impact on CYP activity, but even after combining genetic and drug treatment information, the activity of a significant proportion of extreme metabolizers could not be explained. Conclusions: Our results support the use of measured metabolic ratios in addition to genotyping for accurate determination of individual metabolic capacities to guide personalized drug prescription.

The misfolding and aggregation of TAR DNA binding protein-43 (TDP-43), leading to the formation of cytoplasmic inclusions, emerge as a key pathological feature in a spectrum of neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS) and frontotemporal lobar dementia (FTLD). TDP-43 shuttles between the nucleus and cytoplasm but forms nuclear bodies (NBs) in response to stress. These NBs partially colocalise with nuclear speckles and paraspeckles that sequester RNAs and proteins, thereby regulating many cellular functions. The laboratory of Steven Brown has recently found that the non-POU domain-containing octamer-binding protein (NONO), a component of paraspeckles, forms novel nuclear speckle-like structures in mouse cortical neurons in response to stress and sleep deprivation. These findings suggest the possibility of a functional link between NONO and TDP-43, potentially contributing to TDP-43 proteinopathy. Here, we demonstrate that pathological phenotypes caused by TDP-43 gain of function-locomotor defects and life span shortening-are exacerbated by silencing the Drosophila homolog of NONO, no on or off transient A (NonA). Additionally, NonA silencing results in an increase in nuclear TDP-43 NBs. These results provide supporting evidence for the functional link between NONO and TDP-43 and lay the foundation for dissecting underlying mechanisms.

Since leaving Africa, human populations have gone through a series of range expansions. While the genomic signatures of these expansions are well detectable on a continental scale, the genomic consequences of small-scale expansions over shorter time spans are more challenging to disentangle. The medieval migration of the Walser people from their homeland in ssouthern Switzerland (Upper Valais) into other regions of the Alps is a good example of such a comparatively recent geographic and demographic expansion in humans. While several studies from the 1980s, based on allozyme markers, assessed levels of isolation and inbreeding in individual Walser communities, they mostly did so by focusing on a single community at a time. Here, we provide a comprehensive overview of genetic diversity and differentiation based on samples from multiple Walser, Walser-homeland, and non-Walser Alpine communities, along with an idealized (simulated) Swiss reference population (Ref-Pop). To explore genetic signals of the Walser migration in the genomes of their descendants, we use a set of forensic autosomal STRs as well as uniparental markers. Estimates of pairwise F based on autosomal STRs reveal that the Walser-homeland and Walser communities show low to moderate genetic differentiation from the non-Walser Alpine communities and the idealized Ref-Pop. The geographically more remote and likely more isolated Walser-homeland community of Lötschental and the Walser communities of Vals and Gressoney appear genetically more strongly differentiated than other communities. Analyses of mitochondrial DNA revealed the presence of haplogroup W6 among the Walser communities, a haplogroup that is otherwise rare in central Europe. Our study contributes to the understanding of genetic diversity in the Walser-homeland and Walser people, but also highlights the need for a more comprehensive study of the population genetic structure and evolutionary history of European Alpine populations using genome-wide data.