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On the Greenland Ice Sheet, the firn layer holds the potential to trap and refreeze surface meltwater within its pore space. Acting as a buffer, it prevents meltwater from leaving the ice sheet. However, several meter-thick ice slabs have developed in the firn during the last two decades, reducing subsurface permeability and inhibiting vertical meltwater percolation. Ice slabs are located above the long-term equilibrium line along the west, north and northeast coasts of the ice sheet. Through time, ice slabs have thickened while new ones have developed at higher elevations. Concomitantly, the area of the ice sheet drained by surface rivers has increased by 29% from 1985 to 2020. Nowadays, 5-10% of surface losses through meltwater runoff originates from these newly drained areas, which correspond strongly with where ice slabs are located.Here, we demonstrate that the highest elevation which is drained by surface rivers – termed the maximum visible runoff limit – is controlled by the ice content in the subsurface firn. Using ice slab thickness derived from the accumulation radar and annual maximum visible limit retrievals from Landsat imagery from 2002 to 2018, we show that a sub-surface ice content threshold triggers the shift from a ‘firn deep percolation regime’ to a ‘firn runoff regime’. Although ice slabs act as an aquitard, vertical meltwater percolation can still take place where visible meltwater ponds at the surface. We show that once the firn runoff regime is underway, ice slabs are thicker in locations with active surface hydrology compared to locations where no meltwater is visible at the surface. Spatial heterogeneity in ice slab thickness is therefore predominantly controlled by surface hydrology features.

De nombreuses entreprises utilisent des logiciels libres dans leurs propositions commerciales. Il existe de nombreuses etudes de cas sur leur modele d’affaires. Cependant, il manque une analyse globale synthetisant et structurant les differents modeles open-sources. En nous appuyant sur le cadre des modeles economiques et la litterature en systemes d’information, nous partons des besoins en offres libres pour caracteriser et comparer des modeles economiques open-sources. Cela nous permet de discuter le lien entre captation de valeur et ressources clefs. Le modele de l’open-source apparait base sur la gestion et le controle de la dynamique d’evolution des logiciels (« logiciel flux »), dans une industrie qui s’etait habituee a vendre des produits (« logiciel stock »).

The Greenland Ice Sheet is losing mass, part of which is caused by increasing runoff. The location of the runoff limit, the highest elevation from which meltwater finds its way off the ice sheet, plays an important role in the surface mass balance of the ice sheet. The recently observed rise in runoff area might be related to an increasing amount of refreezing: ice layer development in the firn reduces vertical percolation and promotes lateral runoff. To investigate meltwater flow near the runoff limit in the accumulation zone on the southwestern Greenland Ice Sheet, we carried out in situ measurements of hydrological processes and properties of firn and snow. The hydraulic conductivity of icy firn in pre-melt conditions measured using a portable lysimeter ranges from 0.17 to 12.8 m h−1, with flow predominantly occurring through preferential flow fingers. Lateral flow velocities of meltwater on top of the near-surface ice slab, measured at the peak of the melt season by salt dilution and tracer experiments, range from 1.3 to 15.1 m h−1. With these lateral flow velocities, the distance between the slush limit, the highest elevation where liquid water is visible on the ice sheet surface, and the runoff limit could be roughly 4 km in regions where near-surface ice slabs are present. These measurements are a first step towards an integrated set of hydrological properties of firn on the SW Greenland Ice Sheet and show evidence that meltwater runoff may occur from elevations above the visible runoff area.

Among epigenetic modifiers, telomeres, represent attractive modulators of the genome in part through position effects. Telomere Position Effect – Over Long Distances (TPE-OLD) modulates genes expression by changes in telomere-dependent long-distance loops, with a reach of 10Mb from a telomere. However, TPE-OLD remains poorly defined. To gain further insights into the genome-wide impact of telomere length on genomic and epigenomic regulation through TPE-OLD, we used cells with controlled telomere length combined to a genome wide transcriptome and methylome analysis. By integrating omics data, we identified a common cis-acting motif that behaves as an insulator or enhancer. Using reporter assays integrating this element, we uncovered the trans partners regulating this activity. Further exploiting our cellular model, we observed the depletion of one candidate factor, RBPJ, at TPE-OLD associated loci upon telomere shortening. We concluded that, at the genome-wide level, TPE-OLD is relayed by RBPJ binding Alu-like elements to telomeres that acts as enhancers. In response to external stimuli (i.e., Aging), TPE-OLD might act by coordinating telomere length to the action of Alu newly evolved enhancers in association with RBPJ.

Precipitation falling over the coastal regions of Antarctica often experiences low-level sublimation within the dry katabatic layer. The amount of water that reaches the ground surface is thereby considerably reduced. This paper investigates the synoptic conditions and the atmospheric transport pathways of moisture that lead to either virga – when precipitation is completely sublimated – or actual surface precipitation events over coastal Adélie Land, East Antarctica. For this purpose, the study combines ground-based lidar and radar measurements at Dumont d'Urville station (DDU), Lagrangian back trajectories, Eulerian diagnostics of extratropical cyclones and fronts, and moisture source estimations. It is found that precipitating systems at DDU are associated with warm fronts of cyclones that are located to the west of Adélie Land. Virga – corresponding to 36 % of the hours with precipitation above DDU – and surface precipitation cases are associated with the same precipitating system but they correspond to different phases of the event. Virga cases more often precede surface precipitation. They sometimes follow surface precipitation in the warm sector of the cyclone's frontal system, when the associated cyclone has moved to the east of Adélie Land and the precipitation intensity has weakened. On their way to DDU, the air parcels that ultimately precipitate above the station experience a large-scale lifting across the warm front. The lifting generally occurs earlier in time and farther from the station for virga than for precipitation. It is further shown that the water contained in the snow falling above DDU during pre-precipitation virga has an oceanic origin farther away (about 30∘ more to the west) from Adélie Land than the one contained in the snow that precipitates down to the ground surface.

Apolipoprotein E4 (APOEε4) is the major allelic risk factor for late-onset sporadic Alzheimer's disease (sAD). Inflammation is increasingly considered as critical in sAD initiation and progression. Identifying brain molecular mechanisms that could bridge these two risk factors remain unelucidated. Leveraging induced pluripotent stem cell (iPSC)-based strategies, we demonstrate that APOE controls inflammation in human astrocytes by regulating Transgelin 3 (TAGLN3) expression and, ultimately, nuclear factor κB (NF-κB) activation. We uncover that APOE4 specifically downregulates TAGLN3, involving histone deacetylases activity, which results in low-grade chronic inflammation and hyperactivated inflammatory responses. We show that APOE4 exerts a dominant negative effect to prime astrocytes toward a pro-inflammatory state that is pharmacologically reversible by TAGLN3 supplementation. We further confirm that TAGLN3 is downregulated in the brain of patients with sAD. Our findings highlight the APOE-TAGLN3-NF-κB axis regulating neuroinflammation in human astrocytes and reveal TAGLN3 as a molecular target to modulate neuroinflammation, as well as a potential biomarker for AD.

The Apolipoprotein E4 (APOE4) is the major allelic risk factor for late-onset Alzheimer’s disease (AD). APOE4 associates with a pro-inflammatory phenotype increasingly considered as critical in AD initiation and progression. Yet, the mechanisms driving an APOE4-dependent neuroinflammation remain unelucidated. Leveraging patient specific human induced Pluripotent Stem Cells (iPSCs) we demonstrate inflammatory chronicity and hyperactivated responses upon cytokines in human APOE4 astrocytes via a novel mechanism. We uncovered that APOE4 represses Transgelin 3 (TAGLN3), a new interacting partner of IκBα, thus increasing the NF-kB activity. The transcriptional repression of TAGLN3 was shown to result from an APOE4-dependent histone deacetylase (HDAC) activity. The functional relevance of TAGLN3 was demonstrated by the attenuation of APOE4-driven neuroinflammation after TAGLN3 supplementation. Importantly, TAGLN3 downregulation was confirmed in the brain of AD patients. Our findings highlight the APOE4-TAGLN3 axis as a new pathogenic pathway that paves the way for the development of therapeutics to prevent maladaptive inflammatory responses in APOE4 carriers, while placing TAGLN3 downregulation as a potential biomarker of AD.GRAPHICAL ABSTRACT

International audience; Abbreviations: 3xTG, transgenic mice expressing human APP, MAPT, and PSEN1 genes with three familial mutations; 5xFAD, transgenic mice expressing human APP and PSEN1 genes with five familial mutations; AD, Alzheimer's disease; ADAM, a disintegrin and metalloprotease; APP, amyloid protein precursor; Aβ, beta-amyloid peptide; BACE-1, beta-site APP-cleaving enzyme-1; C3, BACE-1 inhibitor IV; C99/C83, APP CTF of 99/83 amino acids; CAT-, deletion of the catalytic domain; CTF, C-terminal fragment; DAPT, γ-secretase inhibitor; EXT-, deletion of the extracellular domain; GFP, green fluorescent protein; HEKswe, human embryonic kidney cells carrying the APP Swedish mutation; HPX-, deletion of the hemopexin domain; HRP, horseradish peroxidase enzyme; IC-, deletion of the intracytoplasmic domain; MMP, matrix metalloproteinase; MT1/5-MMP, membrane-type 1/5 matrix metalloproteinase; MT1/5Δ-MMP, catalytically inactive MT1-MMP or MT5-MMP; MTT, 3-(4,5-Dimethylthiazol-2yl)-2,5-diphenyl tetrazolium bromide; PSEN 1(2), presenilin 1 and 2; qPCR, quantitative polymerase chain reaction; RFP, red fluorescent protein; RXP03, MMP inhibitor; sAPP95, soluble amyloid protein precursor fragment generated by MT5-MMP; sAPPFL, full-length soluble amyloid protein precursor; sAPPα/β, soluble APPα/β; Tf, transferrin; TIMP, tissue inhibitor of MMPs; TIMP-1Δ, inactive TIMP-1; TM/IC-, deletion of the transmembrane and intracytoplasmic domains.

Depuis une dizaine d’annees, plus precisement depuis l’attribution du prix Nobel d’economie a Elinor Ostrom en 2009, les recherches sur la notion de communs ont beneficie d’une reconnaissance accrue et se sont intensifiees. L’attrait pour les communs n’a cesse d’augmenter et de s’elargir a de nouveaux publics au sein notamment des chercheurs et enseignants, des militants associatifs et politiques, du grand public, des responsables des collectivites territoriales et des entrepreneurs. Un tel e...

Marsouin a grandi. Depuis sa creation en 2002, le groupement d’interet scientifique breton accueille et soutient les equipes de recherche en sciences sociales qui travaillent aux carrefours entre les outils numeriques, les gens et leurs environnements. Chemin faisant et sans jamais se departir de son caractere interdisciplinaire et inclusif, le groupement est devenu le plus important pole de recherche francais sur les usages et les innovations numeriques. Chaque printemps, Marsouin reunit uni...

Context The international GENHYPOPIT network collects phenotypical data and screens genetic causes of non‐acquired hypopituitarism. Aims To describe main phenotype patterns and their evolution through life. Design Patients were screened according to their phenotype for coding sequence variations in 8 genes: HESX1, LHX3, LHX4, PROP1, POU1F1, TBX19, OTX2 and PROKR2. Results Among 1213 patients (1143 index cases), the age of diagnosis of hypopituitarism was congenital (24%), in childhood (28%), at puberty (32%), in adulthood (7.2%) or not available (8.8%). Noteworthy, pituitary hormonal deficiencies kept on evolving during adulthood in 49 of patients. Growth Hormone deficiency (GHD) affected 85.8% of patients and was often the first diagnosed deficiency. AdrenoCorticoTropic Hormone deficiency rarely preceded GHD, but usually followed it by over 10 years. Pituitary Magnetic Resonance Imaging (MRI) abnormalities were common (79.7%), with 39.4% pituitary stalk interruption syndrome (PSIS). The most frequently associated extrapituitary malformations were ophthalmological abnormalities (16.1%). Prevalence of identified mutations was 7.3% of index cases (84/1143) and 29.5% in familial cases (n = 146). Genetic analysis in 449 patients without extrapituitary phenotype revealed 36 PROP1, 2 POU1F1 and 17 TBX19 mutations. Conclusion This large international cohort highlights atypical phenotypic presentation of constitutional hypopituitarism, such as post pubertal presentation or adult progression of hormonal deficiencies. These results justify long‐term follow‐up, and the need for systematic evaluation of associated abnormalities. Genetic defects were rarely identified, mainly PROP1 mutations in pure endocrine phenotypes.

The current assessment of the Antarctic surface mass balance mostly relies on reanalysis products or climate model simulations. The ability of models to reproduce the precipitation field at the regional and continental scales not only depends on the simulation of the atmospheric dynamics over the Southern Ocean and of the advection of moisture towards the ice sheet, but also on the representation of the microphysical processes that govern the formation and growth of ice crystals and snowflakes. This presentation reviews recent studies to stress the importance and challenges of evaluating the precipitation microphysics over Antarctica in climate models. It also discusses how recent observational campaigns including ground-based remote-sensing instruments can help pinpoint key processes that should be represented in models. We then present tangible examples of evaluation and improvement of microphysical schemes in the Polar WRF model thanks to radar and lidar observations acquired near Dumont d’Urville and Mawson stations on the Antarctic coast. Particular attention is devoted to three processes : i) the sublimation of snowfall within the katabatic layer that considerably reduces the amount of precipitation that actually reaches the surface ; ii) the snowflake aggregation responsible for rapid depletion of crystals within clouds ; iii) the generation of supercooled liquid water in frontal clouds that leads to crystal/snowflake riming. Such studies, albeit preliminary, could pave the way for further evaluations of clouds and precipitation in climate models in different Antarctic contexts, especially in the cold and pristine atmosphere of the Plateau.

Precipitation falling over the coastal regions of Antarctica often experiences low-level sublimation within the dry katabatic layer. The amount of water that reaches the ground surface is thereby considerably reduced. We investigate the synoptic conditions and the atmospheric transport pathways of moisture that lead to virga – when precipitation is completely sublimated – or actual surface precipitation at Dumont d’Urville (DDU) station, coastal Adélie Land, Antarctica. We combine ground-based radar measurements, Lagrangian back-trajectories, Eulerian diagnostics of extratropical cyclones and fronts as well as with moisture source estimations based on ERA5 reanalyses. Virga periods – corresponding to 36% of the precipitating events – often precede and sometimes follow surface precipitation periods. Pre-precipitation virga, surface precipitation and post-precipitation virga correspond to different phases of the same precipitating system. Precipitation and virga are always associated with the warm front of an extratropical cyclone that sets to the west of coastal Adélie Land but the exact locations of the cyclone and front differ between the three phases. On their way to DDU, the air parcels that ultimately precipitate above the station experience a large-scale lifting across the warm front. The lifting generally occurs earlier in time and farther from the station for virga than for precipitation. It is further shown that water contained in the precipitation falling above DDU during pre-precipitation virga has an oceanic origin farther away (30 degrees more to the west) from Adélie Land than the one that precipitates down to the ground surface.

On 28 February 2018, 57 mm of precipitation associated to a warm conveyor belt (WCB) fell within 21 h over South Korea. To investigate how the large-scale circulation influenced the microphysics of this intense precipitation event, we used radar measurements, snowflake photographs and radiosounding data from the International Collaborative Experiments for Pyeongchang 2018 Olympic and Paralympic winter games. The WCB was identified with trajectories computed with analysis wind fields from the Integrated Forecast System global atmospheric model. The WCB was collocated with a zone of enhanced wind speed of up to 45 m s−1 at 6500 m a.s.l., as measured by a radiosonde and a Doppler radar. Supercooled liquid water (SLW) with concentrations exceeding 0.2 g kg−1 was produced during the rapid ascent within the WCB. Vertical profiles of polarimetric radar variables show during the most intense precipitation period a peak and subsequent decrease in differential reflectivity as aggregation starts. Below the peak in differential reflectivity, the specific differential phase shift continues to increase, indicating early riming of oblate crystals and secondary ice generation. We hypothesise that the SLW produced in the WCB led to intense riming. Moreover, embedded convection in the WCB and turbulence at its lower boundary enhanced aggregation by increasing the probability of collisions between particles. This suggests that both aggregation and riming occurred prominently in this WCB. This case study shows how the large-scale atmospheric flow of a WCB provides ideal conditions for rapid precipitation growth involving SLW production, riming and aggregation. Future microphysical studies should also investigate the synoptic conditions to understand how observed processes in clouds are related to the large-scale circulation.

The cutaneous radiation syndrome is the clinical consequence of local high-dose irradiation. It is characterized by extensive inflammation, necrosis, and poor revascularization of the skin, resulting in muscle inflammation and fibrosis. Based on these physiopathological processes, subcutaneous injections of adipose-tissue-derived stem/stromal cells have shown favorable effects on skin-wound healing in a minipig model of cutaneous radiation syndrome, in which muscle fibrosis persisted. Since fibrosis is mainly due to the inflammatory processes that often affect underlying tissues as well, the beneficial effects of intramuscular injections of adipose-tissue-derived stem/stromal cells on tissue recovery were evaluated. The polarization of the inflammatory response of irradiated muscle in a minipig model of cutaneous radiation syndrome was determined after acute local irradiation with 50 Gy gamma rays in a preliminary study (six minipigs). Analysis of the main inflammatory cytokines of the inflammatory response M1 (IL-1-beta and IL-6) and M2 (IL-10 and TGF-beta) by western blotting and in situ hybridization, as well as analysis of CD80/CD206 M1/M2 macrophage-specific markers by immunohistochemistry on minipig muscle samples, was performed 76 d after irradiation. The treatment of irradiated muscles with autologous adipose-tissue-derived stem/stromal cells led to an increase in IL-10 and TGF-beta, being associated with an increase in CD68+/CD206+ cells in this area. This highlights a polarization of M2 in the inflammatory response and indicates that adipose-tissue-derived stem/stromal cells may direct the irradiated tissues' inflammatory response towards a proregenerative outcome.

Degenerative disc disease involves sequential events that lead to the loss of cells, a decrease in disc matrix production, disc dehydration, and alteration of its biomechanical properties. The aim of this study was to determine whether cryoinjury of the nucleus pulposus performed through endplate perforation contributes to disc degeneration and to compare this technique with standard methods. Under general anesthesia, the lumbar discs of six pigs were exposed and randomly submitted to needle puncture of the annulus fibrosus (NeP), isolated endplate injury (EP), or cryoinjury using a 2.5-J Thompson cryoprobe applied through a single endplate perforation (EP+cryo). The remaining discs served as controls. Animals were sacrificed at two months and the harvested lumbar spines were submitted to CT scan and MRI investigations. Histologic analysis was performed to assess the degree of disc degeneration. CT scan showed that decrease in average disc height was more important after cryoinjury (49.3%) than after endplate perforation (16.9%) (P

In online communities, recent studies have strongly improved our knowledge about the different types or profiles of contributors, from casual to very involved ones, through focused people. However they do so by using very complex methodologies (qualitative-quantitative mix, with a high workload to manually codify/characterize the edits), making their replication for the practitioners limited. These studies are on the English Wikipedia only. The objective of this paper is to highlight different profiles of contributors with clustering techniques. The originality is to show how using only the edits, and their distribution over time, allows to build these contributors profiles with a good accuracy and stability amongst languages. The methodology is validated with both Romanian and Danish wikis. The highlighted profiles are identifiable early in the history of involvement, suggesting that light monitoring of newcomers may be sufficient to adapt the interaction with them and increase the retention rate.

While most scholars emphasize the role of prosocial motivations of contributors in building open online communities, we show that mere users also adhere to their norms of behaviour to some extent. To this end we designed an original experimentation protocol. With the help of the French Wikimédia Foundation, we questioned a large sample (n = 13,000) of Wikipedia users (whether contributors or not). They were invited, after having expressing their feelings about Wikipédia, to play a Dictator Game. A large proportion of respondents, including those who were merely users, chose an equal split (66% of the sample). This surprising result suggests that they have adhered to a social norm of sharing. Investigating the determinants of this result, we prove that an involvement measured by usage (intensity and variety), as well as by attachment to, and time spent, on Wikipedia, is correlated with the choice of the 50/50 split in the dictator game (DG). Furthermore, the method of instrumental variables gives an indication that adherence to the social norm of sharing may be endogenously determined by involvement in the open online community. Our result highlights the importance of interactions with the institutional and technical frameworks of the community.

The widespread availability of recombineered vectors and gene targeted embryonic stem cells from large-scale repositories facilitates the generation of mouse models for functional genetic studies. Southern blotting validates the structure of these targeted alleles produced by homologous recombination, as well as indicating any additional integrations of the vector into the genome. Traditionally this technique employs radioactively-labelled probes; however, there are many laboratories that are restricted in their use of radioactivity. Here, we present a widely applicable protocol for Southern blot analysis using cold probes and alternative procedures employing radioactive probes. Furthermore, the probes are designed to recognise standardised regions of gene-targeting cassettes and so represent universally applicable reagents for assessing allelic integrity.

Precipitation falling over the coastal regions of Antarctica often experiences low-level sublimation within the dry katabatic layer. The amount of water that reaches the ground surface is thereby considerably reduced. This paper investigates the synoptic conditions and the atmospheric transport pathways of moisture that lead to either virga – when precipitation is completely sublimated – or actual surface precipitation events over coastal Adélie Land, East Antarctica. For this purpose, the study combines ground-based lidar and radar measurements at Dumont d'Urville station (DDU), Lagrangian back-trajectories, Eulerian diagnostics of extratropical cyclones and fronts as well as moisture source estimations. It is found that precipitating systems at DDU are associated with warm fronts of cyclones that are located to the west of Adélie Land. Virga – corresponding to 36 % of the hours with precipitation above DDU – and surface precipitation cases are associated with the same precipitating system but they correspond to different phases of the event. Virga cases more often precede surface precipitation. They sometimes follow surface precipitation in the warm sector of the cyclone's frontal system, when the associated cyclone has moved to the east of Adélie Land and the precipitation intensity has weakened. On their way to DDU, the air parcels that ultimately precipitate above the station experience a large-scale lifting across the warm front. The lifting generally occurs earlier in time and farther from the station for virga than for precipitation. It is further shown that the water contained in the snow falling above DDU during pre-precipitation virga has an oceanic origin farther away (about 30° more to the west) from Adélie Land than the one contained in the snow that precipitates down to the ground surface.

Autism spectrum disorders (ASD) are complex neurodevelopmental disorders with a very large number of risk loci detected in the genome. However, at best, each of them explains rare cases, the majority being idiopathic. Genomic data on ASD derive mostly from post-mortem brain analyses or cell lines derived from blood or patient-specific induced pluripotent stem cells (iPSCS). Therefore, the transcriptional and regulatory architecture of the nervous system, particularly during early developmental periods, remains highly incomplete. To access the critical disturbances that may have occurred during pregnancy or early childhood, we recently isolated stem cells from the nasal cavity of anesthetized patients diagnosed for ASD and compared them to stem cells from gender-matched control individuals without neuropsychiatric disorders. This allowed us to discover MOCOS, a non-mutated molybdenum cofactor sulfurase-coding gene that was under-expressed in the stem cells of most ASD patients of our cohort, disturbing redox homeostasis and synaptogenesis. We now report that a divergent transcription upstream of MOCOS generates an antisense long noncoding RNA, to which we coined the name COSMOC. Surprisingly, COSMOC is strongly under-expressed in all ASD patients of our cohort with the exception of a patient affected by Asperger syndrome. Knockdown studies indicate that loss of COSMOC reduces MOCOS expression, destabilizes lipid and energy metabolisms of stem cells, but also affects neuronal maturation and splicing of synaptic genes. Impaired expression of the COSMOC/MOCOS bidirectional unit might shed new lights on the origins of ASD that could be of importance for future translational studies.

International audience; LHX3 is an LIM domain transcription factor involved in the early steps of pituitary ontogenesis. We report here functional studies of three allelic variants, including the first heterozygous variant of LHX3 NM_178138.5(LHX3)c.587T>C (p.(Leu196Pro)) that may be responsible for a milder phenotype of hypopituitarism. Our functional studies showed that NM_178138.5(LHX3)c.587T>C (p.(Leu196Pro)) was not able to activate target promoters in vitro, as it did not bind DNA, and likely affected LHX3 function via a mechanism of haplo-insufficiency. Our study demonstrates the possibility that patients with a heterozygous variant of LHX3 may have pituitary deficiencies, with a milder phenotype than patients with homozygous variants. It is thus of vital to propose an optimal follow-up of such patients, who, until now, were considered as not being at risk of presenting pituitary deficiency. The second variant NM_178138.5(LHX3)c.622C>G (p.(Arg208Gly)), present in a homozygous state, displayed decreased transactivating ability without loss of binding capacity in vitro, concordant with in silico analysis; it should thus be considered to affect LHX3 function. In contrast, the NM_178138.5(LHX3)c.929G>C (p.(Arg310Pro)) variant, in a heterozygous state, also predicted as deleterious in silico, proved functionally active in vitro, and should thus still be classified as a variant of unknown significance. Our study emphasizes the need for functional studies due to the limits of software-based predictions of new variants, and the possible association of a pituitary phenotype to heterozygous LHX3 variants.

Background/Aim: Congenital hypothyroidism (CH) is a heterogeneous entity. Neonatal screening programs based on thyrotropin (TSH) determination allow primary CH diagnosis but miss central CH (CCH). CCH causes morbidity, alerts to other pituitary deficiencies, and is more prevalent than previously thought. We aimed at developing a pilot neonatal screening program for CCH detection. Patients and Methods: A prospective 2-year pilot neonatal screening study based on simultaneous dried blood specimen TSH and thyroxine (T4) measurements was implemented in term newborns aged 2-7 days. Those with T4 ≤4.5 μg/dL (-2.3 SDS) and TSH

International audience; What types of social processes generate strong online co-production groups? How do these groups evolve to reach peak performance? How does the quality of the products generated by the groups co-vary with the evolution of their social systems over time? The paper analyzes the entire English and French Wikipedia editorial histories, from their inception until 2015, identifying the specific phases through which two different massive online production systems grew. By tracking the emergence of the high contribution group across two different online spaces on a fine-grained level, the paper uncovers their temporal evolutions and impacts on the organization of social systems. Furthermore, the paper reveals how the quality of the content co-evolves with the emergence of the production groups through each growth phase.