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The expression of the Huntingtin protein, well known for its involvement in the neurodegenerative Huntington’s disease, has been confirmed in skeletal muscle. The impact of HTT deficiency was studied in human skeletal muscle cell lines and in a mouse model with inducible and muscle-specific HTT deletion. Characterization of calcium fluxes in the knock-out cell lines demonstrated a reduction in excitation–contraction (EC) coupling, related to an alteration in the coupling between the dihydropyridine receptor and the ryanodine receptor, and an increase in the amount of calcium stored within the sarcoplasmic reticulum, linked to the hyperactivity of store-operated calcium entry (SOCE). Immunoprecipitation experiments demonstrated an association of HTT with junctophilin 1 (JPH1) and stromal interaction molecule 1 (STIM1), both providing clues on the functional effects of HTT deletion on calcium fluxes. Characterization of muscle strength and muscle anatomy of the muscle-specific HTT-KO mice demonstrated that HTT deletion induced moderate muscle weakness and mild muscle atrophy associated with histological abnormalities, similar to the phenotype observed in tubular aggregate myopathy. Altogether, this study points toward the hypotheses of the involvement of HTT in EC coupling via its interaction with JPH1, and on SOCE via its interaction with JPH1 and/or STIM1.

Multicystic renal dysplasia is a congenital cystic anomaly of the kidney caused by abnormal metanephric differentiation with immature tubules. It is surrounded by mesenchymal collars and islands of immature mesenchyma present between the cysts. The PI3K-AKT-mTOR signaling pathway is a key regulator involved in cell growth, proliferation, motility, survival, and apoptosis. Activation of the PI3K-AKT-mTOR pathway results in the survival and proliferation of tumor cells in many cancers. The aim of this study is to analyze the topographic expression of phospho-AKT, phospho-mTOR, and phospho-70S6K in renal development and in the multicystic dysplastic kidney (MCDK). A total of 17 fetal kidneys of development age from the first to the third trimester and 13 cases of pathological kidneys with MCDK were analyzed by immunohistochemistry in order to evaluate the expression of phospho-AKT (S473), phospho-mTOR, and phospho-70S6K. Phospho-AKT and phospho-mTOR were expressed early in renal development and in an identical manner for every structure derived from the ureteric bud, such as collecting ducts and urothelium. Phospho-p70S6K was expressed early in the urothelium and in glomerular mesangial cells. Later, their expressions differed according to the needs of cell proliferation and differentiation over time by becoming more selective. In MCDK, phospho-AKT, phospho-mTOR, and phospho-70S6K have the same profile: a high cytoplasmic expression in cystic epithelium, loose mesenchyma, and primitive tubes. This study demonstrates the essential and specific role of the PI3K-AKT-mTOR pathway in the formation of cysts in multicystic renal dysplasia.

The AMME syndrome defined as the combination of Alport syndrome, intellectual disability, midface hypoplasia, and elliptocytosis (AMME) is known to be a contiguous gene syndrome associated with microdeletions in the region Xq22.3q23. Recently, using exome sequencing, missense pathogenic variants in AMMECR1 have been associated with intellectual disability, midface hypoplasia, and elliptocytosis. In these cases, AMMECR1 gene appears to be responsible for most of the clinical features of the AMME syndrome except for Alport syndrome. In this article, we present two unrelated male patients with short stature, mild intellectual disability or neurodevelopmental delay, sensorineural hearing loss, and elliptocytosis harboring small microdeletions identified by array-CGH involving TMEM164 and AMMECR1 genes and SNORD96B small nucleolar RNA for one patient, inherited from their mothers. These original cases further confirm that most specific AMME features are ascribed to AMMECR1 haploinsufficiency. These cases reporting the smallest microdeletions encompassing AMMECR1 gene provide new evidence for involvement of AMMECR1 in the AMME phenotype and permit to discuss a phenotype related to AMMECR1 haploinsufficiency: developmental delay/intellectual deficiency, midface hypoplasia, midline defect, deafness, and short stature.

We report findings from a male fetus of 26 weeks' gestational age with severe isolated intrauterine growth restriction (IUGR). Chromosomal microarray analysis (CMA) on amniotic fluid cells revealed a 1.06-Mb duplication in 19q13.42 inherited from the healthy father. This duplication contains 34 genes including ZNF331, a gene encoding a zinc-finger protein specifically imprinted (paternally expressed) in the placenta. Study of the ZNF331 promoter by methylation-specific-multiplex ligation-dependent probe amplification showed that the duplicated allele was not methylated in the fetus unlike in the father's genome, suggesting both copies of the ZNF331 gene are expressed in the fetus. The anti-ZNF331 immunohistochemical analysis confirmed that ZNF331 was expressed at higher levels in renal and placental tissues from this fetus compared to controls. Interestingly, ZNF331 expression levels in the placenta have previously been reported to inversely correlate with fetal growth parameters. The original observation presented in this report showed that duplication of ZNF331 could be a novel genetic cause of isolated IUGR and underlines the usefulness of CMA to investigate the genetic causes of isolated severe IUGR.

L’utilisation de l’intelligence artificielle dans le domaine de la santé pose la question des limites de celle-ci : jusqu’où devons-nous employer l’intelligence artificielle, la médecine pourrait-elle être déshumanisée et perdre son sens \textit{princeps} ? Le philosophe Gilbert Simondon (1924-1989) propose durant la seconde moitié du vingtième siècle une philosophie de la technique. Il s’agit de repenser la technique, non pas comme aliénation, mais comme possibilité d’évolution, avec le développement de la technique. Cet article présente ainsi l’intelligence artificielle comme une technique que l’humain doit s’approprier afin de limiter les risques de déshumanisation et d’optimisation du potentiel de l’intelligence artificielle. La pensée de Gilbert Simondon est alors un outil philosophique et éthique permettant d’intégrer l’intelligence artificielle dans le domaine de la médecine, en conservant tout son sens éthique.

KBG Syndrome is a rare syndrome characterized by facial and hand anomalies, postnatal short stature, delayed bone age, intellectual disability and macrodontia. A key role of mutations in ANRKD11 gene was observed not only in central nervous system but also in skeletal development and function. Indeed, a meticulous evaluation of bone metabolism was recommended in KBG Syndrome. We report on a 11-year-old female child affected by KBG Syndrome with a diaphyseal transverse humeral fracture treated surgically and a clavicular fracture treated conservatively. Bone consolidation was observed in both fractures. To the best of our knowledge, no fracture and bone healing were accurately described in KBG patients. Bone healing was observed after surgical treatment of a humeral diaphyseal fracture and after a conservative treatment of a clavicle fracture. These results showed that bone healing was possible also in presence of a mutation of ANKRD11 gene, an important gene in bone metabolism.

International audience; Childhood brain tumors have suspected prenatal origins. To identify vulnerable developmental states, we generated a single-cell transcriptome atlas of >65,000 cells from embryonal pons and forebrain, two major tumor locations. We derived signatures for 191 distinct cell populations and defined the regional cellular diversity and differentiation dynamics. Projection of bulk tumor transcriptomes onto this dataset shows that WNT medulloblastomas match the rhombic lip-derived mossy fiber neuronal lineage and embryonal tumors with multilayered rosettes fully recapitulate a neuronal lineage, while group 2a/b atypical teratoid/rhabdoid tumors may originate outside the neuroectoderm. Importantly, single-cell tumor profiles reveal highly defined cell hierarchies that mirror transcriptional programs of the corresponding normal lineages. Our findings identify impaired differentiation of specific neural progenitors as a common mechanism underlying these pediatric cancers and provide a rational framework for future modeling and therapeutic interventions.

Background. Since 1994, South Africa (SA) has faced up to the challenge of building a strong economy, to which public health provides an important underpinning. Objectives. To map the scientific research in public health in SA after the end of apartheid and to present the links between the different financing/funding systems. Methods. Bibliographic analyses utilising the Web of Science of papers published during the period 1975 - 2014, analyses of journals, most cited articles, authors, publication years, organisations, funding agencies, countries and keywords, and mapping of the relations between countries involved in public health research and of the Web of Science Categories using VOSviewer. Results. I accessed 2 246 articles published between 1975 and 2014, the majority of which were published after 2007. The main countries of research were the USA, SA, Switzerland and the UK, representing the main network collaborations. The relevant keywords were HIV, woman, child, program/programme, rural, tuberculosis, district and sex. Conclusions. Public health research in SA reached a high level 16 years after the end of apartheid. The chief field that emerged was the spread of HIV, including mother-to-child transmission, and the policies applied to all districts of SA, through a network of institutions between the USA and SA.

Prenatal diagnosis, care and management are involved in mortality and morbidity of every country. A high prevalence is estimated in Africa. We use bibliometrics and mapping tools to explore the area studies and countries involved in scientific research on prenatal diagnosis, care and management in Africa. We used two databases: Web of Science and Pubmed. We extracted sets of data as publication years, organizations, funding agencies, countries from Web of Science core collection database and Medical Subject Headings from Pubmed database. We mapped the data using VOSviewer. We performed keyword analysis. We accessed 463 articles published between 1956 and 2015 in Web of Science Core collection Database and 3372 from Pubmed database. The majority of which were after 2004. The main countries involved in research on prenatal field in Africa were the USA, the United Kingdom, France and South Africa. Two main keywords are relevant: fetal alcohol syndrome and HIV. Prenatal diagnosis, care and management are leaded by South Africa. Some new countries are merging such as Rwanda. The main fields are fetal alcohol syndrome and HIV. It is funded by NIH but also Cape Town University.

We report on a female fetus with macrocephaly and macroglossia harbouring 13q31.1 microdeletion encompassing three genes: SPRY2, NDFIP2 and RBM26. NDFIP2 protein is involved in ubiquitination and in Ras/mitogen-activated protein kinase (MAPK) signaling pathways. SPRY2 protein is part of Sprout protein family and inhibits the Ras/MAPK pathways. Ras/MAPK pathway plays important role in complex cellular programs including cell differentiation and proliferation. Germline mutations in genes encoding protein involved in the MAPK cascade is responsible for a wide family of developmental disorders known as RASopathies. Some RASopathies, such as Costello syndrome, present a phenotype with (relative) macrocephaly as perinatal features. However, prenatal-onset macroglossia are generally absent in this syndrome but rather suggestive of the Beckwith-Wiedemann syndrome for which molecular testing were negative. Phenotype-genotype correlation with patients from DECIPHER defines NDFIP2 and SPRY2 as a possible candidate genes for a RASopathy potentially responsible for the clinical features in the fetus. Finally, this original case of 13q31.1 microdeletion underlines the importance of array-CGH in prenatal diagnosis with sonographic signs such as macroglossia and/or macrocephaly. In this case, genetic investigation should be not limited to the search of well-known genetic causes and other genomic microdeletions should be considered as alternative diagnoses for macroglossia.

Background. Since 1994, South Africa (SA) has faced up to the challenge of building a strong economy, to which public health provides an important underpinning. Objectives. To map the scientific research in public health in SA after the end of apartheid and to present the links between the different financing/funding systems. Methods. Bibliographic analyses utilising the Web of Science of papers published during the period 1975 - 2014, analyses of journals, most cited articles, authors, publication years, organisations, funding agencies, countries and keywords, and mapping of the relations between countries involved in public health research and of the Web of Science Categories using VOSviewer. Results. I accessed 2 246 articles published between 1975 and 2014, the majority of which were published after 2007. The main countries of research were the USA, SA, Switzerland and the UK, representing the main network collaborations. The relevant keywords were HIV, woman, child, program/programme, rural, tuberculosis, district and sex. Conclusions. Public health research in SA reached a high level 16 years after the end of apartheid. The chief field that emerged was the spread of HIV, including mother-to-child transmission, and the policies applied to all districts of SA, through a network of institutions between the USA and SA.

Commensalism is a biological association between two species, with one species, the commensal, getting an advantage, whereas the other one, the host, gets no advantage neither disadvantage. This concept is theorized in the 1860's by Pierre-Joseph Van Beneden. Van Beneden is a physician in the 1850's, nevertheless, he is well known as a zoologist. The concept of commensalism developed by Van Beneden is employed in many scientific fields, not only in zoology, but also, in microbiology. Although the use of a possible play of the commensal bacterial microflora is exposed at the end of the 19th century, it is only during the second part of the 20th century that this way is studied. Commensalism in animal microbiology is studied first and then it is studied in human. The aim of this article is to present the history of commensalism as a main part of the history of microbiology.

Holoprosencephaly (HPE) is the most common forebrain defect in humans. It results from incomplete midline cleavage of the prosencephalon and can be caused by environmental and genetic factors. HPE is usually described as a continuum of brain malformations from the most severe alobar HPE to the middle interhemispheric fusion variant or syntelencephaly. A microform of HPE is limited to craniofacial features such as congenital nasal pyriform aperture stenosis and single central maxillary incisor, without brain malformation. Among the heterogeneous causes of HPE, point mutations and deletions in the SHH gene at 7q36 have been identified as well as extremely rare chromosomal rearrangements in the long-range enhancers of this gene. Here, we report a boy with an HPE microform associated with a Currarino syndrome. Array CGH detected a de novo 2.7-Mb deletion in the 7q36.3 region including the MNX1 gene, usually responsible for the Currarino triad but excluding SHH, which is just outside the deletion. This new case provides further evidence of the importance of the SHH long-range enhancers in the HPE spectrum.

We report on a young child with intellectual disability and unilateral coronal craniosynostosis leading to craniofacial malformations. Standard karyotype showed an apparently balanced translocation between chromosomes 2 and 15 [t(2;15)(q21;q21.3)], inherited from his mother. Interestingly, array-CGH 180K showed a 3.64 Mb de novo deletion on chromosome 15 in the region 15q21.3q22.2, close to the chromosome 15 translocation breakpoints. This deletion leads to haploinsufficiency of TCF12 gene that can explain the coronal craniosynostosis described in the patient. Additional FISH analyses showed a complex balanced maternal chromosomal rearrangement combining the reciprocal translocation t(2;15)(q21;q21.3), and an insertion of the 15q22.1 segment into the telomeric region of the translocated 15q fragment. The genomic imbalance in the patient is likely caused by a crossing-over that occurs in the recombination loop formed during the maternal meiosis resulting in the deletion of the inserted fragment. This original case of a genomic microdeletion of TCF12 exemplifies the importance of array-CGH in the clinical investigation of apparently balanced rearrangements but also the importance of FISH analysis to identify the chromosomal mechanism causing the genomic imbalance.

Commensalism in Cetaceans according to Pierre-Joseph Van Beneden. To what extent is it true ? - In the late 1860s, Pierre-Joseph Van Beneden (1809-1894) developed the concept of commensalism to describe a type of relationship between two organisms. In his book Les parasites et les commensaux dans le règne animal, published in 1875, he provides many instances of commensalism, not only with shellfish, but also with insects. He was considered by his peers as the cetacean specialist - living and fossil. In his study, he says how difficult commensalism is to define, and in particular how difficult it is to distinguish commensalism from mutualism and parasitism. This article describes Van Beneden's notion of commensalism in Cetaceans - animals he studied in great detail and which earned him a reputation. But is it really commensalism we are dealing with here, and does commensalism really exist in Cetaceans ?, Pierre-Joseph Van Beneden (1809-1894) établit à la fin des années 1860 la catégorie de commensalisme comme type d'association biologique. Il donne, dans son ouvrage Les parasites et les commensaux dans le règne animal publié en 1875, de nombreux exemples concernant les crustacés, mais aussi les insectes. Il est, de plus, reconnu par ses pairs comme un spécialiste des Cétacés vivants et fossiles. Or, lors de son étude sur le commensalisme, il évoque la difficulté d'établir les limites de ce concept, en particulier par rapport au mutualisme d'une part, et par rapport au parasitisme d'autre part. Notre article veut présenter la vision du commensalisme de Van Beneden chez les Cétacés, animaux qu'il a étudiés longuement et dont il est l'un des plus éminents chercheurs. Décrit-il un commensalisme précis dans ce cas ? Le commensalisme existe-t-il chez les Cétacés ?, Poreau Brice. Le commensalisme chez les Cétacés étudié par Pierre-Joseph Van Beneden : une réalité ?. In: Bulletin mensuel de la Société linnéenne de Lyon, 82ᵉ année, n°3-4, Mars-avril 2013. pp. 65-70.

Similar to “parasitism” and “mutualism”, the concept of commensualism defines a kind of biological association, i.e. the neutral interaction between two different species. This paper shows that “commensualism” was initially defined by the Belgian zoologist and parasitologist Pierre-Joseph van Beneden (1809–1894) as referring to biological associations between organic individuals from different species. According to van Beneden, one individual derives biological advantages from this kind of association, whereas the other one remains neutral, i.e. does not receive any biological loss or gain. Tracing the further history of the concept, the paper demonstrates that, while “commensalism” was initially created and used in zoology, it was taken up in other biological disciplines shortly afterward, such as botany and the emerging field of ecology. However, the experimental demonstration of the phenomenon of commensualism remained difficult. This, in turn, contributed to the nomadic existence of this concept in the life sciences of the twentieth century.

Commensalism with Hymenoptera : the limits of the concept. - Commensalism is a kind of association between one species getting an advantage of this association whereas the other species does not get any advantage or disadvantage. Some studies have been carried out in order to observe the commensalism in some species, like Hymenopteras. These studies were developped at the end of the XIXth century and at the beginning of the XXth century, and particularly on ants. Moreover, it may be possible to extend the concept of commensalism to only one species, using the works of these naturalists. These naturalists put forward also a specificity of these societies : is commensalism the right concept to describe this uniqueness ?, Si le commensalisme est défini comme un type d'associations entre deux espèces différentes dont l'une obtient un avantage alors que l'autre ne se voit apporter ni avantage ni désavantage, certaines espèces, comme les animaux dits «sociaux», ont fait l'objet d'études nombreuses afin d'évaluer ce comportement associatif. Ces études développées par les naturalistes de la fin du XIXe siècle et du début du XXe siècle soulignent des observations, en particulier chez les fourmis, comme preuve du commensalisme et du mutualisme. Mais les naturalistes présentent aussi une singularité chez les Hyménoptères : le fait de former une société. Le commensalisme rend-il compte de ce fait ?, Poreau Brice. Le commensalisme chez les Hyménoptères : les limites du concept. In: Bulletin mensuel de la Société linnéenne de Lyon, 81ᵉ année, n°3-4, Mars-avril 2012. pp. 39-45.

Commensalism : a controversial concept. The example of Nereis fucata. Commensalism is a concept developed in the second half of the nineteeth century, especially by Pierre Joseph Van Beneden (1809-1894). On an historical point of view, it is possible to wonder if this concept of commensalism is relevant during the next decades in the scientific world of biologists and particularly in zoology. An example of association is putting forward in this article : Nereis fucata with Eupagurus bernhardus. This example is really interesting because it was studied at the beginning of the theory of commensalism, and it will outline the limits of this concept. With Caullery, Chevreux, Coupin or Rabaud, what are the different points of view of this concept ?, Le commensalisme est un concept développé dans la seconde moitié du dix-neuvième siècle, notamment par Pierre Joseph Van Beneden (1809-1894). D'un point de vue d'historien des sciences, il est possible de se demander quelle est la portée de ce concept lors des décennies ultérieures dans le monde scientifique de la biologie et plus particulièrement de la zoologie. Un exemple d'association est ici approfondi ; il s'agit de Nereis fucata avec Eupagurus bernhardus. Cet exemple est intéressant, car il a été étudié dès la théorisation du commensalisme, et va permettre de montrer les limites de ce concept. Entre Caullery, Chevreux, Coupin ou encore Rabaud, quelles sont les différentes visions du commensalisme ?, Poreau Brice. Le commensalisme : un concept controversé. L'exemple de Nereis fucata. In: Bulletin mensuel de la Société linnéenne de Lyon, 80ᵉ année, n°5-6, Mai-juin 2011. pp. 101-107.

Le microbiome est un concept du vingt-et-unieme siecle, theorise a l'instar du genome. Il s'agit de connaitre la totalite de l'information genetique des souches bacteriennes du corps humain, alors que le genome consiste en la connaissance de la totalite des genes de l'etre humain. Associe a ce concept contemporain, un autre concept pourrait etre etudie et mis en parallele, il s'agit du commensalisme. C'est une association biologique entre deux especes differentes ou l'une des deux, le commensal obtient un benefice, alors que l'autre, l'hote, n'obtient ni benefice, ni desavantage. Issu d'observations en zoologie marine, Pierre-Joseph Van Beneden (1809-1894) va utiliser ce concept des la fin des annees 1860. Cet article se propose d'argumenter le lien entre le commensalisme issu du dix-neuvieme siecle et le microbiome developpe au vingt-et-unieme siecle, en presentant l'instabilite de la relation de commensalisme qui peut en emerger.

Commensalism is a kind of biological association between two different species. One species gets an advantage whereas the other one gets no advantage neither disadvantage. Interpreting observations in marine zoology, Pierre-Joseph Van Beneden (1809-1894) will theorize this concept at the end of the 1860's. The impact of the works of Van Beneden on commensalism will be amazing, not only in his proper career, but also according to his peers. This historical argument is clearly a deciding factor. It will make durable the concept of commensalism during the following century. Also this concept will be spread to other fields than zoology, particularly ecology. This article puts forward the arguments of the impact of the works of Van Beneden on commensalism in order to deduce the outlook., Le commensalisme est une association biologique entre deux espèces différentes où l'une des deux, le commensal obtient un bénéfice, alors que l'autre, l'hôte, n'obtient ni bénéfice, ni désavantage. Issu d'observations en zoologie marine, Pierre-Joseph Van Beneden (1809-1894) va théoriser ce concept dès la fin des années 1860. La portée de ses travaux sur le commensalisme sera considérable, non seulement au sein de sa propre carrière scientifique, mais aussi selon ses pairs. Cet argument historique est l'un des arguments majeurs qui va permettre de pérenniser le concept de commensalisme durant le siècle suivant. De même, l'emploi de ce concept sera étendu au-delà de la discipline initiale, en particulier en écologie. Cet article se propose d'argumenter la portée des travaux de Van Beneden sur le commensalisme afin d'en déduire les enjeux et les perspectives en prenant un exemple précis.