European primary datasets of alien bacteria and viruses

Bacteria and viruses are a natural component of Earth biodiversity and play an essential role in biochemical and geological cycles. They may also pose problems outside their native range, where they can negatively impact on natural resources, wildlife, and human health. To address these challenges and develop sustainable conservation strategies, a thorough understanding of their invasion related- factors is needed: origin, country and year of introduction, and pathways dynamics. Yet, alien bacteria and viruses are underrepresented in invasion ecology studies, which limits our ability to quantify their impacts and address future introductions. This study provides primary datasets of alien bacteria and viruses of plants and animals present in the European environment. The datasets contain expert-revised data on 446 taxa and their invasion related- factors across terrestrial and aquatic environments. Taxa information are complemented with spatial occurrences. The datasets provide a basis for collaborative initiatives to improve the collection of alien bacteria and viruses' data, and a starting point for data-driven conservation practices

Influence of the Nb/P ratio of acidic Nb-P-Si oxides on surface and catalytic properties

In this work, two acidic Nb-P-Si mixed oxide gel-derived materials characterized by Nb/P molar ratios equal to 2 (5Nb2.5 P) and 1 (2.5NbP) were investigated for their surface and bulk properties in relation with the catalytic performances in the fructose dehydration reaction. The structural characteristics of the studied samples and the changes occurring after water treatment and after reaction were investigated by 29Si and 31P solid state nuclear magnetic resonance (MAS-NMR) and X-ray photoelectron (XPS) spectroscopies, while the characterization of their acidic properties was performed by base (2-phenylethylamine) adsorption in liquid phase. MAS-NMR showed that the phosphorus remains firmly anchored into the siloxane matrix after exposure to cold water for 5Nb2.5 P sample and XPS confirmed the homogeneity of the sample composition. Both samples exhibited good intrinsic acidity and maintained significant effective acidity in polar-protic liquids; 2.5NbP manifested a double amount of acid sites compared to 5Nb2.5 P, when 2-phenylethylamine is used as probe. Fructose dehydration to 5-(hydroxymethyl)furfural (HMF) on the two gel-derived catalysts was performed in water and in water-isopropanol solution under mild conditions (130 °C) working in a recirculation reaction line comprising a tubular catalytic reactor. In water-isopropanol solution, the samples displayed good performances, as expected thanks to the lively effective acidity. Around 45-50% fructose conversion was attained on both samples, with selectivity to HMF equal to about 50% on 2.5NbP gel-derived catalyst. Recycling tests showed satisfactorily stable activity during three consecutive runs

Modulating the WNT pathway in Drosophila models of Cornelia de Lange Syndrome

Cornelia de Lange syndrome (CdLS) is a rare genetic disorder affecting neurodevelopment and the gastrointestinal, musculoskeletal systems. CdLS is caused by mutations within NIPBL, SMC1A, SMC3, RAD21, and HDAC8 genes. These genes codify for the cohesin complex, a multiprotein structure playing a role in chromatid adhesion, DNA repair and gene expression regulation. It has been demonstrated that a strong correlation exists between cohesin complex function and WNT signalling, an intracellular pathway involved in regulation of expression of several genes controlling cell division and embryonic development. Recently, it has been observed that chemical activation of the WNT pathway in nipblb-loss-of-function zebrafish embryos and in NIPBL-mutated patient fibroblasts rescued the adverse phenotype. Both embryos and fibroblasts present similar patterns of canonical WNT pathway alterations and cyclinD1 downregulation. Drosophila melanogaster is an inexpensive model to study CdLS and to screen in vivo for therapeutic compounds. Therefore, we have used flies strains mutated in Nipped-B and Hdac3 genes (respectively NIPBL and HDAC8 in humans) for assessing the existing correlation between cohesin complex and WNT pathway. Moreover, we have selected D. melanogaster mutants to screen for chemicals that revert the CdLS associated-phenotypes efficiently. In particular, we have tested several WNT activators and differences in modulating CdLS phenotypes will be discussed

Molecular Etiology Disclosed by Array CGH in Patients With Silver–Russell Syndrome or Similar Phenotypes

Introduction: Silver-Russell syndrome (SRS) is an imprinting disorder primarily caused by genetic and epigenetic aberrations on chromosomes 11 and 7. SRS is a rare growth retardation disorder often misdiagnosed due to its heterogeneous and non-specific clinical features. The Netchine-Harbison clinical scoring system (NH-CSS) is the recommended tool for differentiating patients into clinical SRS or unlikely SRS. However, the clinical diagnosis is molecularly confirmed only in about 60% of patients, leaving the remaining substantial proportion of SRS patients with unknown genetic etiology. Materials and Methods: A cohort of 34 Italian patients with SRS or SRS-like features scored according to the NH-CSS and without any SRS-associated (epi)genetic alterations was analyzed by high-resolution array-based comparative genomic hybridization (CGH) in order to identify potentially pathogenic copy number variants (CNVs). Results and Discussion: In seven patients, making up 21% of the initial cohort, five pathogenic and two potentially pathogenic CNVs were found involving distinct genomic regions either previously associated with growth delay conditions (1q24.3-q25.3, 17p13.3, 17q22, and 22q11.2-q11.22) and with SRS spectrum (7p12.1 and 7p15.3-p14.3) or outlined for the first time (19q13.42), providing a better definition of reported and as yet unreported SRS overlapping syndromes. All the variants involve genes with a defined role in growth pathways, and for two genes mapping at 7p, IGF2BP3 and GRB10, the association with SRS turns out to be reinforced. The deleterious effect of the two potentially pathogenic variants, comprising GRB10 and ZNF331 genes, was explored by targeted approaches, though further studies are needed to validate their pathogenic role in the SRS etiology. In conclusion, we reconfirm the utility of performing a genome-wide scan to achieve a differential diagnosis in patients with SRS or similar features and to highlight novel chromosome alterations associated with SRS and growth retardation disorders

Generation of the Becker muscular dystrophy patient derived induced pluripotent stem cell line carrying the DMD splicing mutation c.1705-8 T>C

Becker Muscular dystrophy (BMD) is an X-linked syndrome characterized by progressive muscle weakness. BMD is generally less severe than Duchenne Muscular Dystrophy. BMD is caused by mutations in the dystrophin gene that normally give rise to the production of a truncated but partially functional dystrophin protein. We generated an induced pluripotent cell line from dermal fibroblasts of a BMD patient carrying a splice mutation in the dystrophin gene (c.1705-8 T>C). The iPSC cell-line displayed the characteristic pluripotent-like morphology, expressed pluripotency markers, differentiated into cells of the three germ layers and had a normal karyotype

Lithium as a positive modulator of defective WNT pathway in Cornelia de Lange Syndrome models

The cohesin complex is a multimeric system, highly conserved in the course of cellular evolution from the most primitive life forms to human cells. Cohesins are essential Structural Maintenance of Chromosomes (SMC), protein-containing complexes that interact with chromatin and modulate chromatin organization and gene expression. Genetic variants that cause structural and/or functional alterations induce an array of congenital pathologies named "cohesinopathies". It is believed that such malformations arise from deregulation of pivotal developmental molecular pathways. Canonical WNT pathway has been shown to be perturbed in association with central nervous system malformation in Cornelia de Lange Syndrome (CdLS), one of the most characterized cohesinopathy. In this study, we validated the relevance of canonical WNT pathway and assess the effect of LiCl-dependent activation of WNT pathway in three CdLS experimental models: Lymphoblastoid cell lines from patients, murine Neural Stem Cells (NSCs) and Drosophila melanogaster. Methods Lymphoblastoid cells (immortalized lines from CdLS patients) of patients carrying mutations of NIPBL or HDAC8 genes and healthy donors were used in these studies. These cells were treated with LiCl 1mM, 2,5mM and 5mM, and vehicle and proliferation rate were measured. Proliferation and differentiation capabilities were also assessed in CdLS NSCs upon LiCl treatment. Flies were grown upon food added with a different concentration of LiCl. Drosophila brains were analyzed for morphological evaluation. Results and conclusions Preliminary data on lymphoblastoid cells showed no effects on cell death rate in healthy donor following LiCl treatment. And, although with a patient-specific response, LiCl appeared to induce an increase in proliferation, especially in cell lines that were slow-growing compared to controls. NSCs showed reduced NSCs proliferation rate and differentiating capabilities. The presence of lithium could reduce the detrimental effects in a significant way. Drosophila mutants for nipped-B gene, the ortholog of human NIPBL, display malformations in mushroom bodies (MB), a structure involved in olfactory learning and memory. Treating subsequent generation of flies with 100mM of LiCl, MB morphology was restored in the offspring. All these data further confirm the hypothesis that in \u201ccohesinophaties\u201d is present an impairment of WNT pathway that could, in part, explain the typical neurodevelopmental alterations of this syndrome. Moreover, these studies could pave the way for future therapeutic strategies

Myoclonic status epilepticus and cerebellar hypoplasia associated with a novel variant in the GRIA3 gene

AMPA-type glutamate receptors (AMPARs) are postsynaptic ionotropic receptors which mediate fast excitatory currents. AMPARs have a heterotetrameric structure, variably composed by the four subunits GluA1-4 which are encoded by genes GRIA1-4. Increasing evidence support the role of pathogenic variants in GRIA1-4 genes as causative for syndromic intellectual disability (ID). We report an Italian pedigree where some male individuals share ID, seizures and facial dysmorphisms. The index subject was referred for severe ID, myoclonic seizures, cerebellar signs and short stature. Whole exome sequencing identified a novel variant in GRIA3, c.2360A > G, p.(Glu787Gly). The GRIA3 gene maps to chromosome Xq25 and the c.2360A > G variant was transmitted by his healthy mother. Subsequent analysis in the family showed a segregation pattern compatible with the causative role of this variant, further supported by preliminary functional insights. We provide a detailed description of the clinical evolution of the index subjects and stress the relevance of myoclonic seizures and cerebellar syndrome as cardinal features of his presentation

Novel C16orf57 mutations in patients with Poikiloderma with Neutropenia: bioinformatic analysis of the protein and predicted effects of all reported mutations

<p>Abstract</p> <p>Background</p> <p>Poikiloderma with Neutropenia (PN) is a rare autosomal recessive genodermatosis caused by <it>C16orf57 </it>mutations. To date 17 mutations have been identified in 31 PN patients.</p> <p>Results</p> <p>We characterize six PN patients expanding the clinical phenotype of the syndrome and the mutational repertoire of the gene. We detect the two novel <it>C16orf57 </it>mutations, c.232C>T and c.265+2T>G, as well as the already reported c.179delC, c.531delA and c.693+1G>T mutations. cDNA analysis evidences the presence of aberrant transcripts, and bioinformatic prediction of C16orf57 protein structure gauges the mutations effects on the folded protein chain.</p> <p>Computational analysis of the C16orf57 protein shows two conserved H-X-S/T-X tetrapeptide motifs marking the active site of a two-fold pseudosymmetric structure recalling the 2H phosphoesterase superfamily. Based on this model C16orf57 is likely a 2H-active site enzyme functioning in RNA processing, as a presumptive RNA ligase.</p> <p>According to bioinformatic prediction, all known <it>C16orf57 </it>mutations, including the novel mutations herein described, impair the protein structure by either removing one or both tetrapeptide motifs or by destroying the symmetry of the native folding.</p> <p>Finally, we analyse the geographical distribution of the recurrent mutations that depicts clusters featuring a founder effect.</p> <p>Conclusions</p> <p>In cohorts of patients clinically affected by genodermatoses with overlapping symptoms, the molecular screening of <it>C16orf57 </it>gene seems the proper way to address the correct diagnosis of PN, enabling the syndrome-specific oncosurveillance.</p> <p>The bioinformatic prediction of the C16orf57 protein structure denotes a very basic enzymatic function consistent with a housekeeping function. Detection of aberrant transcripts, also in cells from PN patients carrying early truncated mutations, suggests they might be translatable. Tissue-specific sensitivity to the lack of functionally correct protein accounts for the main cutaneous and haematological clinical signs of PN patients.</p

Expanding the phenotype associated to KMT2A variants: overlapping clinical signs between Wiedemann&#8211;Steiner and Rubinstein&#8211;Taybi syndromes

Lysine-specific methyltransferase 2A (KMT2A) is responsible for methylation of histone H3 (K4H3me) and contributes to chromatin remodeling, acting as \u201cwriter\u201d of the epigenetic machinery. Mutations in KMT2A were first reported in Wiedemann\u2013Steiner syndrome (WDSTS). More recently, KMT2A variants have been described in probands with a specific clinical diagnosis comprised in the so-called chromatinopathies. Such conditions, including WDSTS, are a group of overlapping disorders caused by mutations in genes coding for the epigenetic machinery. Among them, Rubinstein\u2013Taybi syndrome (RSTS) is mainly caused by heterozygous pathogenic variants in CREBBP or EP300. In this work, we used next generation sequencing (either by custom-made panel or by whole exome) to identify alternative causative genes in individuals with a RSTS-like phenotype negative to CREBBP and EP300 mutational screening. In six patients we identified different novel unreported variants in KMT2A gene. The identified variants are de novo in at least four out of six tested individuals and all of them display some typical RSTS phenotypic features but also WDSTS specific signs. This study reinforces the concept that germline variants affecting the epigenetic machinery lead to a shared molecular effect (alteration of the chromatin state) determining superimposable clinical conditions

Phenotypic overlap of Roberts and Baller-Gerold syndromes in two patients with craniosynostosis, limb reductions, and ESCO2 mutations

Baller-Gerold (BGS, MIM#218600) and Roberts (RBS, MIM#268300) syndromes are rare autosomal recessive disorders caused, respectively, by biallelic alterations in RECQL4 (MIM*603780) and ESCO2 (MIM*609353) genes. Common features are severe growth retardation, limbs shortening and craniofacial abnormalities which may include craniosynostosis. We aimed at unveiling the genetic lesions underpinning the phenotype of two unrelated children with a presumptive BGS diagnosis: patient 1 is a Turkish girl with short stature, microcephaly, craniosynostosis, seizures, intellectual disability, midface hemangioma, bilateral radial and thumb aplasia, tibial hypoplasia, and pes equinovarus. Patient 2 is an Iranian girl born to consanguineous parents with craniosynostosis, micrognathism, bilateral radial aplasia, thumbs, and foot deformity in the context of developmental delay. Upon negative RECQL4 test, whole exome sequencing (WES) analysis performed on the two trios led to the identification of two different ESCO2 homozygous inactivating variants: a previously described c.1131+1G&gt;A transition in patient 1 and an unreported deletion, c.417del, in patient 2, thus turning the diagnosis into Roberts syndrome. The occurrence of a Baller-Gerold phenotype in two unrelated patients that were ultimately diagnosed with RBS demonstrates the strength of WES in redefining the nosological landscape of rare congenital malformation syndromes, a premise to yield optimized patients management and family counseling