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Intellectual disability (ID) is a pathological condition characterized by limited intellectual functioning and adaptive behaviors. It affects 1-3% of the worldwide population, and no pharmacological therapies are currently available. More than 1000 genes have been found mutated in ID patients pointing out that, despite the common phenotype, the genetic bases are highly heterogeneous and apparently unrelated. Bibliomic analysis reveals that ID genes converge onto a few biological modules, including cytoskeleton dynamics, whose regulation depends on Rho GTPases transduction. Genetic variants exert their effects at different levels in a hierarchical arrangement, starting from the molecular level and moving toward higher levels of organization, i.e., cell compartment and functions, circuits, cognition, and behavior. Thus, cytoskeleton alterations that have an impact on cell processes such as neuronal migration, neuritogenesis, and synaptic plasticity rebound on the overall establishment of an effective network and consequently on the cognitive phenotype. Systems biology (SB) approaches are more focused on the overall interconnected network rather than on individual genes, thus encouraging the design of therapies that aim to correct common dysregulated biological processes. This review summarizes current knowledge about cytoskeleton control in neurons and its relevance for the ID pathogenesis, exploiting in silico modeling and translating the implications of those findings into biomedical research.
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Citoesqueleto/patologia , Deficiência Intelectual/patologia , Neurogênese , Neurônios/patologia , Sinapses/patologia , Biologia de Sistemas , Animais , Humanos , Deficiência Intelectual/metabolismo , Neurônios/metabolismo , Fenótipo , Transdução de SinaisRESUMO
The DHRS9 gene is involved in several pathways including the synthesis of allopregnanolone from progesterone. Allopregnanolone is a positive modulator of gamma aminobutyric acid (GABA) action and plays a role in the control of neuronal excitability and seizures. Whole-exome sequencing performed on a girl with an early onset epilepsy revealed that she was a compound heterozygote for two novel missense mutations of the DHRS9 gene likely to disrupt protein function. No previous studies have reported the implication of this gene in epilepsy. We discuss a new potential pathogenic mechanism underlying epilepsy in a child, due to a defective progesterone pathway.
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3-Hidroxiesteroide Desidrogenases/análise , Causalidade , Epilepsia/genética , 3-Hidroxiesteroide Desidrogenases/sangue , Pré-Escolar , Epilepsia/diagnóstico , Epilepsia/epidemiologia , Feminino , Humanos , Mutação de Sentido Incorreto/genética , Polimorfismo Genético/genética , Lobo Temporal/anormalidades , Lobo Temporal/diagnóstico por imagemRESUMO
Among the large family of transition metal dichalcogenides, recently ReS2 has stood out due to its nearly layer-independent optoelectronic and physicochemical properties related to its 1T distorted octahedral structure. This structure leads to strong in-plane anisotropy, and the presence of active sites at its surface makes ReS2 interesting for gas sensing and catalysts applications. However, current fabrication methods use chemical or physical vapor deposition (CVD or PVD) processes that are costly, time-consuming and complex, therefore limiting its large-scale production and exploitation. To address this issue, a colloidal synthesis approach is developed, which allows the production of ReS2 at temperatures below 360 °C and with reaction times shorter than 2h. By combining the solution-based synthesis with surface functionalization strategies, the feasibility of colloidal ReS2 nanosheet films for sensing different gases is demonstrated with highly competitive performance in comparison with devices built with CVD-grown ReS2 and MoS2 . In addition, the integration of the ReS2 nanosheet films in assemblies together with carbon nanotubes allows to fabricate electrodes for electrocatalysis for H2 production in both acid and alkaline conditions. Results from proof-of-principle devices show an electrocatalytic overpotential competitive with devices based on ReS2 produced by CVD, and even with MoS2 , WS2 , and MoSe2 electrocatalysts.
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Solid-state supercapacitors with areal capacitance in the order of 100 mFâ cm-2 are developed on paper substrates, using eco-friendly, low-cost materials and a simple technology. The electrochemically active material used as the electrode is prepared from a stable water-based ink, obtained by doping commercial polypyrrole (PPY) powder with dodecylbenzene sulfonic acid (DBSA), and characterized by optical and electrical measurements, Raman investigation and Atomic Force Microscopy. The PPY:DBSA ink can be directly applied on paper by means of rechargeable water pens, obtaining, after drying, electrically conducting solid state tracks. The PPY:DBSA layers are then interfaced to one another through a polymer gel based on potassium hydroxide and chitosan, acting both as the ion-conducting medium and as the separator. The areal capacitance of the devices developed by following such a simple rule can be improved when the PPY:DBSA ink is applied in combination with other nanostructured carbon material.
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Perovskites have emerged as promising light harvesters in photovoltaics. The resulting solar cells (i) are thin and lightweight, (ii) can be produced through solution processes, (iii) mainly use low-cost raw materials, and (iv) can be flexible. These features make perovskite solar cells intriguing as space technologies; however, the extra-terrestrial environment can easily cause the premature failure of devices. In particular, the presence of high-energy radiation is the most dangerous factor that can damage space technologies. This Review discusses the status and perspectives of perovskite photovoltaics in space applications. The main factors used to describe the space environment are introduced, and the results concerning the radiation hardness of perovskites toward protons, electrons, neutrons, and γ-rays are presented. Emphasis is given to the physicochemical processes underlying radiation damage in such materials. Finally, the potential use of perovskite solar cells in extra-terrestrial conditions is discussed by considering the effects of the space environment on the choice of the architecture and components of the devices.
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BACKGROUND: The AHNAK2 gene encodes a large nucleoprotein expressed in several tissues, including brain, squamous epithelia, smooth muscle, and neuropil. Its role in calcium signaling has been suggested and to date, clear evidence about its involvement in the pathogenesis of clinical disorders is still lacking. METHODS: Here, we report a female 24-year-old patient diagnosed with a cardio-facio-cutaneous-like phenotype (CFC-like), characterized by epilepsy, psychomotor development delay, atopic dermatitis, congenital heart disease, hypotonia, and facial dysmorphism, who is compound heterozygote for two missense mutations in the AHNAK2 gene detected by exome sequencing. RESULTS: This patient had no detectable variant in any of the genes known to be associated with the cardio-facio-cutaneous syndrome. Moreover, the mode of inheritance does not appear to be autosomal dominant, as it is in typical CFC syndrome. We have performed in silico assessment of mutation severity separately for each missense mutation, but this analysis excludes a severe effect on protein function. Protein structure predictions indicate the mutations are located in flexible regions possibly involved in molecular interactions. CONCLUSION: We discuss an alternative interpretation on the potential involvement of the two missense mutations in the AHNAK2 gene on the expression of CFC-like phenotype in this patient based on inter-allelic complementation.
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Epilepsia , Transtornos do Neurodesenvolvimento , Displasia Ectodérmica , Epilepsia/genética , Exoma , Fácies , Insuficiência de Crescimento , Feminino , Cardiopatias Congênitas , Humanos , Transtornos do Neurodesenvolvimento/genética , Nucleoproteínas/genéticaRESUMO
The last decade has witnessed the advance of metal halide perovskites as a promising low-cost and efficient class of light harvesters used in solar cells (SCs). Remarkably, the efficiency of lab-scale perovskite solar cells (PSCs) reached a power conversion efficiency of 25.5% in just ~10 years of research, rivalling the current record of 26.1% for Si-based PVs. To further boost the performances of PSCs, the use of 2D materials (such as graphene, transition metal dichalcogenides and transition metal carbides, nitrides and carbonitrides) has been proposed, thanks to their remarkable optoelectronic properties (that can be tuned with proper chemical composition engineering) and chemical stability. In particular, 2D materials have been demonstrated as promising candidates for (i) accelerating hot carrier transfer across the interfaces between the perovskite and the charge extraction layers; (ii) improving the crystallization of the perovskite layers (when used as additives in the precursor solution); (iii) favoring electronic bands alignment through tuning of the work function. In this mini-review, we discuss the physical mechanisms underlying the increased efficiency of 2D material-based PSCs, focusing on the three aforementioned effects.
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Flexible energy storage devices and supercapacitors in particular have become very attractive due to the growing demand for wearable consumer devices. To obtain supercapacitors with improved performance, it is useful to resort to hybrid electrodes, usually nanocomposites, that combine the excellent charge transport properties and high surface area of nanostructured carbon with the electrochemical activity of suitable metal oxides or conjugated polymers. In this work, electrochemically active conducting inks are developed starting from commercially available polypyrrole and graphene nanoplatelets blended with dodecylbenzenesulfonic acid. Films prepared by applying the developed inks are characterized by means of Raman measurements, Fourier Transform Infrared (FTIR) analysis, and Atomic Force Microscopy (AFM) investigations. Planar supercapacitor prototypes with an active area below ten mm2 are then prepared by applying the inks onto transparency sheets, separated by an ion-permeable nafion layer impregnated with lithium hexafluorophospate, and characterized by means of electrical measurements. According to the experimental results, the devices show both pseudocapacitive and electric double layer behavior, resulting in areal capacitance that, when obtained from about 100 mFâ cm-2 in the sample with polypyrrole-based electrodes, increases by a factor of about 3 when using electrodes deposited from inks containing polypyrrole and graphene nanoplateles.
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Invited for this month's cover are collaborators from University of Pavia, École Polytechnique Fédérale de Lausanne, University of Messina and Istituto Italiano di Tecnologia. The cover picture shows the crystal structure of a Ruddlesden-Popper quasi-2D perovskite with chemical formula (PEA)2 MA39 Pb40 I121 (with PEA: phenylethylammonium and MA: methylammonium). The subscript 40 indicates the number of PbI6 octahedra separated by a double layer of PEA cations. Such quasi-2D perovskites exhibit efficient photovoltaic performances and higher stability with respect to the pure 3D counterpart (MAPbI3 ). This article is part of the Special Collection on "Perovskite Materials and Devices". Read the full text of the article at 10.1002/cplu.202000777.
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Low-dimensional perovskites (LDP) are nowadays recognized as promising materials for the realization of highly performing photovoltaic cells. However, issues related to film morphology, composition, crystal quality and material homogeneity limit the device performances and reproducibility. In this work, we implement a robust method for the deposition of a LDP mixing methylammonium (MA) and phenylethylammonium (PEA) cations to create the mixed system (PEA)2 MA39 Pb40 I121 by using a two-step thermal annealing treatment (at 60 and 100 °C). Our approach results in LDP films with high crystal quality and enhanced carrier lifetime, which double the power conversion efficiency of reference devices, reaching up to 15 %.
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An increasing number of developmental and epileptic encephalopathies have been correlated with variants of ion channel genes, and in particular of potassium channels genes, such as KCNA1, KCNA2, KCNB1, KCNQ2, KCTD7 and KCNT1. Here we report a child with an early severe developmental and epileptic encephalopathy, spastic tetraplegia, opisthotonos attacks. The whole exome sequencing showed the de novo heterozygous variant c.1411G > C (p.Val471Leu) in the KCNC2 gene. Although this is, to our knowledge, the first case of encephalopathy associated with a KCNC2 gene variant, and further confirmatory studies are needed, previous preclinical and clinical evidence seems to suggest that KCNC2 is a new candidate epilepsy gene.
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Epilepsia/genética , Canais de Potássio Shaw/genética , Criança , Eletroencefalografia , Epilepsia/fisiopatologia , Humanos , Masculino , MutaçãoRESUMO
This study highlights plastics occurrence in five demersal fish species from the Southern Tyrrhenian Sea: the Red mullet Mullus barbatus barbatus, the Piper gurnard Trigla lyra, the Blackmouth catshark Galeus melastomus, the Lesser spotted dogfish Scyliorhinus canicula and the Brown ray Raja miraletus. Overall, 125 fish were examined: 21 Red mullets, 16 Piper gurnards, 75 Blackmouth catsharks, 72 Dogfish and 1 Brown ray. The percentage of fish with ingested plastics was 14.4% with 0.24 items per specimen. The majority of the debris were fibers and the application of infrared and Raman spectroscopy allowed the identification and discrimination of plastic and non-plastic fibers. The plastic debris isolated were mainly microplastics (94.1%), while macroplastics occurrence was very low (5.9%). The plastics were identified as polypropylene, Teflon, nylon, kraton G (triblock copolymer) and polyethylene. Also cellulose was detected. S. canicula was the species with the highest number of plastic pollutants.
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Monitoramento Ambiental , Perciformes , Plásticos , Poluentes Químicos da Água , Animais , Peixes , Mar MediterrâneoRESUMO
The fabrication of electrochemical double-layer capacitors (EDLCs) with high areal capacitance relies on the use of elevated mass loadings of highly porous active materials. Herein, we demonstrate a high-throughput manufacturing of graphene/carbon nanotubes hybrid EDLCs. The wet-jet milling (WJM) method is exploited to exfoliate the graphite into single-few-layer graphene flakes (WJM-G) in industrial volumes (production rate ca.â 0.5â kg/day). Commercial single-/double-walled carbon nanotubes (SDWCNTs) are mixed with graphene flakes in order to act as spacers between the flakes during their film formation. The WJM-G/SDWCNTs films are obtained by one-step vacuum filtration of the material dispersions, resulting in self-standing, metal- and binder-free flexible EDLC electrodes with high active material mass loadings up to around 30â mg cm-2 . The corresponding symmetric WJM-G/SDWCNTs EDLCs exhibit electrode energy densities of 539â µWh cm-2 at 1.3â mW cm-2 and operating power densities up to 532â mW cm-2 (outperforming most of the reported EDLC technologies). The EDCLs show excellent cycling stability and outstanding flexibility even in highly folded states (up to 180°).
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Neurofibromatosis type 1 (NF1) is caused by mutations of the NF1 gene and is one of the most common human autosomal dominant disorders. The patient shows different signs on the skin and other organs from early childhood. The best known are six or more café au lait spots, axillary or inguinal freckling, increased risk of developing benign nerve sheath tumours and plexiform neurofibromas. Mutation detection is complex, due to the large gene size, the large variety of mutations and the presence of pseudogenes. Using Ion Torrent PGM™ Platform, 73 mutations were identified in 79 NF1 Italian patients, 51% of which turned out to be novel mutations. Pathogenic status of each variant was classified using "American College of Medical Genetics and Genomics" guidelines criteria, thus enabling the classification of 96% of the variants identified as being pathogenic. The use of Next Generation Sequencing has proven to be effective as for costs, and time for analysis, and it allowed us to identify a patient with NF1 mosaicism. Furthermore, we designed a new approach aimed to quantify the mosaicism percentage using electropherogram of capillary electrophoresis performed on Sanger method.
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Manchas Café com Leite/genética , Neurofibromatose 1/genética , Neurofibromina 1/genética , Anormalidades da Pele/genética , Adolescente , Adulto , Manchas Café com Leite/patologia , Criança , Pré-Escolar , Análise Mutacional de DNA , Feminino , Humanos , Lactente , Itália , Masculino , Pessoa de Meia-Idade , Mosaicismo , Mutação , Neurofibromatose 1/patologia , Análise de Sequência de DNA , Anormalidades da Pele/patologiaRESUMO
OBJECTIVE: Autism is a complex, largely genetic psychiatric disorder. In the majority of cases, the cause of autism is not known, but there is strong evidence for a genetic etiology. To identify candidate genes, the physical mapping of balanced chromosomal aberrations is a powerful strategy, since several genes have been characterized in numerous disorders. In this study, the authors analyzed a balanced reciprocal translocation arising de novo in a subject with autism and mental retardation. METHOD: The authors performed the physical mapping of the balanced 9q23/10q22 translocation by fluorescent in situ hybridization experiments using bacterial artificial chromosome clones covering the areas of interest. RESULTS: Findings revealed that the KCNMA1 gene, which encodes the alpha-subunit of the large conductance Ca(2+)-activated K(+) (BK(Ca)) channel, a synaptic regulator of neuronal excitability, is physically disrupted. Further molecular and functional analyses showed the haploinsufficiency of this gene as well as decreased activity of the coded BK(Ca )channel. This activity can be enhanced in vitro by addition of a BK(Ca )channel opener (BMS-204352). Further mutational analyses on 116 autistic subjects led to the identification of an amino acid substitution located in a highly conserved domain of the protein not found in comparison subjects. CONCLUSIONS: These results suggest a possible association between a functional defect of the BK(Ca) channel and autistic disorder and raise the hypothesis that deficits in synaptic transmission may contribute to the physiopathology of autism and mental deficiency.
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Transtorno Autístico/genética , Transtorno Autístico/fisiopatologia , Deficiência Intelectual/genética , Deficiência Intelectual/fisiopatologia , Subunidades alfa do Canal de Potássio Ativado por Cálcio de Condutância Alta/genética , Translocação Genética/genética , Criança , Aberrações Cromossômicas , Mapeamento Cromossômico , Cromossomos Artificiais Bacterianos/genética , Cromossomos Artificiais Bacterianos/fisiologia , Cromossomos Humanos Par 10/genética , Cromossomos Humanos Par 9/genética , Clonagem Molecular/métodos , Análise Mutacional de DNA , Humanos , Hibridização in Situ Fluorescente , Indóis/farmacologia , Subunidades alfa do Canal de Potássio Ativado por Cálcio de Condutância Alta/efeitos dos fármacos , Subunidades alfa do Canal de Potássio Ativado por Cálcio de Condutância Alta/fisiologia , Masculino , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Transmissão Sináptica/efeitos dos fármacos , Transmissão Sináptica/genética , Transmissão Sináptica/fisiologia , Translocação Genética/fisiologiaRESUMO
Greek colonisation of South Italy and Sicily (Magna Graecia) was a defining event in European cultural history, although the demographic processes and genetic impacts involved have not been systematically investigated. Here, we combine high-resolution surveys of the variability at the uni-parentally inherited Y chromosome and mitochondrial DNA in selected samples of putative source and recipient populations with forward-in-time simulations of alternative demographic models to detect signatures of that impact. Using a subset of haplotypes chosen to represent historical sources, we recover a clear signature of Greek ancestry in East Sicily compatible with the settlement from Euboea during the Archaic Period (eighth to fifth century BCE). We inferred moderate sex-bias in the numbers of individuals involved in the colonisation: a few thousand breeding men and a few hundred breeding women were the estimated number of migrants. Last, we demonstrate that studies aimed at quantifying Hellenic genetic flow by the proportion of specific lineages surviving in present-day populations may be misleading.
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Genética Populacional , Demografia , Feminino , Geografia , Grécia , Haplótipos/genética , Humanos , Masculino , Mutação/genética , Filogenia , SicíliaRESUMO
We have screened 143 Sicilian (Italian) families with one autistic child to verify, by a linkage disequilibrium approach, the involvement of the 2q31.1 region in the cause of the disease in these families. Our study design includes the use of intrafamilial association to prevent a population stratification bias and ethnic homogeneity of the sample. The results of our analysis provided suggestive evidence of the occurrence of transmission disequilibrium between autism and the D2S2188 polymorphism in Sicilian TRIO families, a finding which provides further and independent support to the hypothesis of the existence of a susceptibility gene (or genes) for autism on chromosome 2q.
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Transtorno Autístico/genética , Cromossomos Humanos Par 2 , Marcadores Genéticos , Polimorfismo Genético , Transtorno Autístico/epidemiologia , Mapeamento Cromossômico , Família , Humanos , Sicília/epidemiologiaRESUMO
Over the past few years, studies of DNA isolated from human fossils and archaeological remains have generated considerable novel insight into the history of our species. Several landmark papers have described the genomes of ancient humans across West Eurasia, demonstrating the presence of large-scale, dynamic population movements over the last 10,000 years, such that ancestry across present-day populations is likely to be a mixture of several ancient groups [1-7]. While these efforts are bringing the details of West Eurasian prehistory into increasing focus, studies aimed at understanding the processes behind the generation of the current West Eurasian genetic landscape have been limited by the number of populations sampled or have been either too regional or global in their outlook [8-11]. Here, using recently described haplotype-based techniques [11], we present the results of a systematic survey of recent admixture history across Western Eurasia and show that admixture is a universal property across almost all groups. Admixture in all regions except North Western Europe involved the influx of genetic material from outside of West Eurasia, which we date to specific time periods. Within Northern, Western, and Central Europe, admixture tended to occur between local groups during the period 300 to 1200 CE. Comparisons of the genetic profiles of West Eurasians before and after admixture show that population movements within the last 1,500 years are likely to have maintained differentiation among groups. Our analysis provides a timeline of the gene flow events that have generated the contemporary genetic landscape of West Eurasia.
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Povo Asiático/genética , Evolução Molecular , Fluxo Gênico , Migração Humana , População Branca/genética , Simulação por Computador , DNA Mitocondrial/genética , Fósseis , Variação Genética , Genética Populacional , Genômica , Haplótipos , Humanos , FilogeniaRESUMO
The R408W phenylketonuria mutation in Europe has arisen by recurrent mutation in the human phenylalanine hydroxylase (PAH) locus and is associated with two major PAH haplotypes. R408W-2.3 exhibits a west-to-east cline of relative frequency reaching its maximum in the Balto-Slavic region, while R408W-1.8 exhibits an east-to-west cline peaking in Connacht, the most westerly province of Ireland. Spatial autocorrelation analysis has demonstrated that the R408W-2.3 cline, like that of R408W-1.8, is consistent with a pattern likely to have been established by human dispersal. Genetic diversity within wild-type and R408W chromosomes in Europe was assessed through variable number tandem repeat (VNTR) nucleotide sequence variation and tetranucleotide short tandem repeat (STR) allelic associations. Wild-type VNTR-8 chromosomes exhibited two major cassette sequence organizations: (a1)5-b3-b2-c1 and (a1)5-b5-b2-c1. R408W-1.8 was predominantly associated with (a1)5-B5-B2-C1. Both wild-type vntr-3 and r408w-2.3 chromosomes exhibited a single invariant cassette sequence organization, a2-b2-c1. STR allele distributions associated with the cassette variants were consistent with greater diversity in the wild-type VNTR-8 lineage and were suggestive of different levels of diversity between R408W-1.8 and R408W-2.3. The finding of greater genetic diversity within the wild-type VNTR-8 lineage compared to VNTR-3 suggests that VNTR-8 may be older within the European population. However, in the absence of a more extensive STR data-set, no such conclusions are possible for the respective R408W mutant lineages.