A novel homozygous missense mutation in FGF23 causes Familial Tumoral Calcinosis associated with disseminated visceral calcification

Hyperphosphatemic Familial Tumoral Calcinosis (HFTC; MIM211900) is a rare autosomal recessive disorder characterized by the progressive deposition of calcified masses in cutaneous and subcutaneous tissues, associated with elevated circulating levels of phosphate. The disease was initially found to result from mutations in GALNT3 encoding a glycosyltransferase. However, more recently, the S71G missense mutation in FGF23, encoding a potent phosphaturic protein, was identified in two families. In the present report, we describe a second mutation in FGF23 underlying a severe case displaying calcifications of cutaneous and numerous extracutaneous tissues. The mutation (M96T) was found to affect a highly conserved methionine residue at position 96 of the protein. These observations illustrate the extent of genetic and phenotypic heterogeneity in HFTC.     

Expression of a Highly Antigenic and Native-Like Folded Extracellular Domain of the Human α1 Subunit of Muscle Nicotinic Acetylcholine Receptor,Suitable for Use in Antigen Specific Therapies for Myasthenia Gravis

We describe the expression of the extracellular domain of the human α1 nicotinic acetylcholine receptor (nAChR) in lepidopteran insect cells (i-α1-ECD) and its suitability for use in antigen-specific therapies for Myasthenia Gravis (MG). Compared to the previously expressed protein in P. pastoris (y-α1-ECD), i-α1-ECD had a 2-fold increased expression yield, bound anti-nAChR monoclonal antibodies and autoantibodies from MG patients two to several-fold more efficiently and resulted in a secondary structure closer to that of the crystal structure of mouse α1-ECD. Our results indicate that i-α1-ECD is an improved protein for use in antigen-specific MG therapeutic strategies.     

Palaeoenvironmental conditions preceding the Messinian Salinity Crisis: A case study from Gavdos Island

The Messinian pre-evaporitic sedimentary succession of Gavdos Island (Metochia section) is a nearly uninterrupted succession of marine sediments, dominated by finely laminated diatomaceous marls, which are cyclically alternating with clayey diatomites and white diatomites. The qualitative and quantitative analysis of the planktonic foraminiferal fauna allowed the recognition of nine bioevents, which have been astronomically dated for the Mediterranean. The base of the diatomitic succession in Gavdos Island is dated at 6.722 Ma and the top at 6.015 Ma. The studied section contains benthic foraminiferal genera characteristic of an outer shelf to slope environment. The qualitative and quantitative analysis of this microfauna revealed three benthic foraminiferal fossil assemblages and the occurrence of allochthonous species transported into the bathyal environment by current activity. The cyclical pattern of the benthic foraminifera assemblages indicates that the studied sediments have been affected by repeated episodes of basin restriction characterized by low diversity benthic foraminifera populations, and a limited planktonic foraminifer association typified by shallow, surface-dwelling forms. This restriction was partly due to Antarctic cooling, which produced palaeo-Mediterranean sea-level oscillations during the Early Messinian, as a prelude to closure of the Atlantic connections. The relative impact of climatic versus tectonic control on sedimentation patterns within this basin is discussed.     

Late Pliocene benthic foraminifera and mollusks from the Atsipades Section, Central Crete; Palaeoecological distribution and use in palaeoenvironmental assessment

Changes in benthic foraminiferal and mollusk assemblages from the lower part of the Upper Pliocene of the Atsipades Section (Iraklion Basin, central Crete) were studied. The Atsipades Section represents a shallowing-upward sequence from outer shelf blue-gray clays at the bottom of the sequence, deposited below the storm wave base, to shallow inner shelf deposits affected by storm waves at the top. The foraminiferal assemblage at the bottom of the sequence is dominated by Bolivina spathulata, Bolivina dilatata and Uvigerinidae, a microfossil assemblage corresponding to the deepest deposits formed under dysoxic sea-floor conditions. Foraminiferal assemblages of the middle part of the section are highly diversified, predominantly Haynesina depressula, Cassidulina carinata and Reusella spinulosa. The top of the section is mainly characterised by Asterigerinata planorbis, Bolivina pseudoplicata, Cibicides lobatulus and Elphidium sp., a typically epiphytic foraminiferal assemblage which can be correlated with the presence of an algal covered sea-bottom. Within this general environmental trend, a minor shallowing cycle can be differentiated. The boundaries of this cycle can be inferred, based on a substantial microfossil assemblage change and on the coincidence of species diversity maximum and a planktonic/benthic (P/P + B) ratio peak. Nonetheless, upwelling currents and/or over-abundance of nutrients due to continental outflow could also contribute to increased diversity and P/P + B ratio. The character of the mollusk assemblages is in accordance with these trends. Moreover, the increase in diversity and in sculpture constitutes a clear indication of an increase in hydrodynamic energy related to a shallowing-upward trend.     

A pilot study on the prevalence of maternal obesity in selected Greek counties

ObjectiveTo report a pilot prevalence of maternal overweight, obesity and underweight in selected Greek counties.MethodsA total of 441 adult childbearing women were recruited from maternity clinics in 6 Greek counties for this cross-sectional study. Pre-gravid weight status was defined according to the WHO cut-offs and gravid weight status was diagnosed with the Mardones and Rosso weight gain chart.ResultsDuring gestation the majority of the participants were of normal body weight (BW) (34.0%), obesity was apparent in 25.6% of the sample, 23.8% of the participants were underweight, and the remaining 16.6% were overweight. Overall, pregnancy tripled the prevalence of underweight, increased the prevalence of obesity (by 388.0%) and decreased the number of participants in the normal BW category (p ≤ 0.001 for all). The majority of participants classified in each pre-gravid weight-category remained in the same weight category during their gestation. All the pre-gravidly obese women were also obese during pregnancy. Underweight was more prevalent in Kavala (37.5%) and obesity was more frequent in Thessaloniki (30.8%). Women who were overweight prior to conception were highly likely to be overweight/obese during pregnancy (OR: 23.8, CI: 11.1–51.0).ConclusionsThe results indicate a high prevalence of overweight, obesity and underweight among pregnant women in Greece.     

A mechanical model to compute elastic modulus of tissues for harmonic motion imaging

Numerous experimental and computational methods have been developed to estimate tissue elasticity. The existing testing techniques are generally classified into in vitro, invasive in vivo and non-invasive in vivo. For each experimental method, a computational scheme is accordingly proposed to calculate mechanical properties of soft biological tissues. Harmonic motion imaging (HMI) is a new technique that performs radio frequency (RF) signal tracking to estimate the localized oscillatory motion resulting from a radiation force produced by focused ultrasound. A mechanical model and computational scheme based on the superposition principle are developed in this paper to estimate the Young's modulus of a tissue mimicking phantom and bovine liver in vitro tissue from the harmonic displacement measured by HMI. The simulation results are verified by two groups of measurement data, and good agreement is shown in each comparison. Furthermore, an inverse function is observed to correlate the elastic modulus of uniform phantoms with amplitude of displacement measured in HMI. The computational scheme is also implemented to estimate 3D elastic modulus of bovine liver in vitro.     

Targeted Genotyping of MIS-C Patients Reveals a Potential Alternative Pathway Mediated Complement Dysregulation during COVID-19 Infection

Complement dysregulation has been documented in adults with COVID-19 and implicated in relevant pediatric inflammatory responses against SARS-CoV-2. We propose that signatures of complement missense coding SNPs associated with dysregulation could also be identified in children with multisystem inflammatory syndrome (MIS-C). We investigated 71 pediatric patients with RT-PCR validated SARS-CoV-2 hospitalized in pediatric COVID-19 care units (November 2020–March 2021) in three major groups. Seven (7) patients suffered from MIS-C (MIS-C group), 32 suffered from COVID-19 and were hospitalized (admitted group), whereas 32 suffered from COVID-19, but were sent home. All patients survived and were genotyped for variations in the C3, C5, CFB, CFD, CFH, CFHR1, CFI, CD46, CD55, MASP1, MASP2, MBL2, COLEC11, FCN1, and FCN3 genes. Upon evaluation of the missense coding SNP distribution patterns along the three study groups, we noticed similarities, but also considerably increased frequencies of the alternative pathway (AP) associated with SNPs rs12614 CFB, rs1061170, and rs1065489 CFH in the MIS-C patients. Our analysis suggests that the corresponding substitutions potentially reduce the C3b-inactivation efficiency and promote slower and weaker AP C3bBb pre-convertase assembly on virions. Under these circumstances, the complement AP opsonization capacity may be impaired, leading to compromised immune clearance and systemic inflammation in the MIS-C syndrome.     

The Tortonian fish fauna of Gavdos Island (Greece)

Although the occurrence of fossil fishes is known since more than one century in the Neogene of Gavdos Island (Greece), its composition remained hitherto unknown. The present study demonstrates that, in the Tortonian of Gavdos, the most abundant species is Bregmaceros albyi (Sauvage), which constitutes two thirds of the collected material. This fish fauna is indicative of an environment of moderate depth, probably corresponding to the external edge of the neritic zone, or possibly to the upper part of the continental slope. To cite this article: J. Gaudant et al., C. R. Palevol 4 (2005).