Recurrent copy number variations as risk factors for neurodevelopmental disorders: critical overview and analysis of clinical implications

Neurodevelopmental disorders (NDs) encompass a spectrum of neuropsychiatric manifestations. Chromosomal regions 1q21.1, 3q29, 15q11.2, 15q13.3, 16p11.2, 16p13.1 and 22q11 harbour rare but recurrent CNVs that have been uncovered as being important risk factors for several of these disorders. These rearrangements may underlie a broad phenotypical spectrum, ranging from normal development, to learning problems, intellectual disability (ID), epilepsy and psychiatric diseases, such as autism spectrum disorders (ASDs) and schizophrenia (SZ). The highly increased risk of developing neurodevelopmental phenotypes associated with some of these CNVs makes them an unavoidable element in the clinical context in paediatrics, neurology and psychiatry. However, and although finding these risk loci has been the goal of neuropsychiatric genetics for many years, the translation of this recent knowledge into clinical practice has not been trivial. In this article, we will: (1) review the state of the art on recurrent CNVs associated with NDs, namely ASD, ID, epilepsy and SZ; (2) discuss the models used to dissect the underlying neurobiology of disease, (3) discuss how this knowledge can be used in clinical practice.FEDER through the Programa Operacional Factores de Competitividade — COMPETE and by Portuguese national funds through Fundação para a Ciência e Tecnologi

Microsatellite Markers For Urochloa Humidicola (poaceae) And Their Transferability To Other Urochloa Species

Background: Urochloa humidicola is a warm-season grass commonly used as forage in the tropics and is recognized for its tolerance to seasonal flooding. This grass is an important forage species for the Cerrado and Amazon regions of Brazil. U. humidicola is a polyploid species with variable ploidy (6X-9X) and facultative apomixis with high phenotypic plasticity. However, this apomixis and ploidy, as well as the limited knowledge of the genetic basis of the germplasm collection, have constrained genetic breeding activities, yet microsatellite markers may enable a better understanding of the species' genetic composition. This study aimed to develop and characterize new polymorphic microsatellite molecular markers in U. humidicola and to evaluate their transferability to other Urochloa species. Findings: A set of microsatellite markers for U. humidicola was identified from two new enriched genomic DNA libraries: the first library was constructed from a single sexual genotype and the second from a pool of eight apomictic genotypes selected on the basis of previous results. Of the 114 loci developed, 72 primer pairs presented a good amplification product, and 64 were polymorphic among the 34 genotypes tested. The number of bands per simple sequence repeat (SSR) locus ranged from 1 to 29, with a mean of 9.6 bands per locus. The mean polymorphism information content (PIC) of all loci was 0.77, and the mean discrimination power (DP) was 0.87. STRUCTURE analysis revealed differences among U. humidicola accessions, hybrids, and other Urochloa accessions. The transferability of these microsatellites was evaluated in four species of the genus, U. brizantha, U. decumbens, U. ruziziensis, and U. dictyoneura, and the percentage of transferability ranged from 58.33% to 69.44% depending on the species. Conclusions: This work reports new polymorphic microsatellite markers for U. humidicola that can be used for breeding programs of this and other Urochloa species, including genetic linkage mapping, quantitative trait loci identification, and marker-assisted selection.

Proteomic responses to nanoparticulate and ionic silver in freshwater microbes with different background

ERDF through the COMPETE2020 - Programa Operacional Competitividade e Internacionalização (POCI) and by the Portuguese Foundation for Science and Technology (FCT) I.P. through the strategic funding UID/BIA/04050/2014 (POCI-01-0145-FEDER-007569) and PTDC/AAC-AMB/121650/201

The human otitis media with effusion: a numerical-based study

Otitis media is a group of inflammatory diseases of the middle ear. Acute otitis media and otitis media with effusion (OME) are its two main types of manifestation. Otitis media is common in children and can result in structural alterations in the middle ear which will lead to hearing losses. This work studies the effects of an OME on the sound transmission from the external auditory meatus to the inner ear. The finite element method was applied on the present biomechanical study. The numerical model used in this work was built based on the geometrical information obtained from The visible ear project. The present work explains the mechanisms by which the presence of fluid in the middle ear affects hearing by calculating the magnitude, phase and reduction of the normalized umbo velocity and also the magnitude and phase of the normalized stapes velocity. A sound pressure level of 90 dB SPL was applied at the tympanic membrane. The harmonic analysis was performed with the auditory frequency varying from 100 Hz to 10 kHz. A decrease in the response of the normalized umbo and stapes velocity as the tympanic cavity was filled with fluid was obtained. The decrease was more accentuated at the umbo.info:eu-repo/semantics/publishedVersio

Omics reveal distinct mechanisms of toxicity of nanoparticulate and ionic silver in microbes

The mechanisms of toxicity of silver nanoparticles (AgNPs) are not clear and the role of Ag+ released from the nanoparticulated form in the overall toxicity requires further attention, especially in aquatic ecosystems where NPs will most likely end up. The impacts of AgNPs and Ag+ were assessed based on the variations in the overall proteome in i) two aquatic fungal ecotypes of Articulospora tetracladia, one isolated from a non-polluted stream (At72) and the other from a metal-polluted stream (At61), and ii) the bacterial strain Pseudomonas sp. M1 (PsM1) isolated from a metal-polluted stream. Transcriptomic responses of At72 in the same exposure conditions were also assessed to complement knowledge from proteomic responses. At72 was the most sensitive to AgNPs, whereas PsM1 was the most tolerant one. The toxicity of AgNPs was supported by data from NP characterization, which showed increased particle stability and lesser agglomeration in presence of At72 that the other microbes. Omic responses to equitoxic levels of AgNPs and Ag+ suggested different mechanisms of toxicity since distinct profiles of protein and gene expression were unveiled. Gene Ontology (GO) enrichment analysis further unravelled several biological processes and allowed to differentiate the effects of AgNPs from those of Ag+. Overall, omic approaches revealed different adaptive responses to Ag+ or AgNPs in the metabolic, energetic and stress pathways. Furthermore, the negligible amount of Ag+ released from AgNPs suggested that toxicity of AgNPs was mainly associated with the particle for

Accidental and late parasitological diagnosis of Leishmania sp. in a dog from a low disease transmission area of Brazil: a case report

Canine Leishmaniasis diagnosis must be fast and accurate since dogs are urban reservoirs of the disease and earlier therapeutic intervention is more clinically effective. However, this still represents a challenge, particularly in low transmission areas. The present report describes the difficulties of clinical suspicion and the late diagnosis of a dog infected with Leishmania sp

Proteomics and antioxidant enzymes reveal different mechanisms of toxicity induced by ionic and nanoparticulate silver in bacteria

The increased use of silver nanoparticles (AgNPs) raises concerns about their impacts on aquatic ecosystems. The impacts of Ag+ and AgNPs were assessed on proteomic and antioxidant enzymatic responses of Pseudomonas sp. M1. The effects of Ag+ on bacterial growth were stronger than those of AgNPs (EC20 = 107.1 μg L−1 for Ag+; EC20 = 307.2 μg L−1 for AgNPs), indicating the lower toxicity of the latter. At EC20, the activities of antioxidant enzymes increased more under exposure to Ag+ than to AgNPs, particularly for superoxide dismutase and glutathione peroxidase (stimulation of 667% and 433%, respectively). A total of 166 proteins were identified by SWATH-MS; among these, only 59 had their content significantly altered by one or both forms of silver. Exposure to AgNPs resulted in an increase of about 54% of these proteins, whereas 54% decreased under exposure to Ag+. Gene Ontology enrichment analysis revealed that protein folding and transmembrane transport were the most relevant processes affected by Ag+ exposure, whereas AgNPs mostly affected translation. Also, results suggest that each form of silver induced different adaptive responses. Furthermore, the low levels of Ag+ released from AgNPs (<0.1%) support a minor role of dissolved silver in AgNP toxicity to Pseudomonas sp. M1ERDF through the COMPETE2020 – Programa Operacional Competitividade e Internacionalização (POCI) and by the Portuguese Foundation for Science and Technology I.P. (FCT) through the strategic funding UID/BIA/04050/2013 (POCI-01-0145-FEDER-007569), PTDC/AAC-AMB/121650/2010, POCI-01-0145-FEDER-007440 (ref. UID/NEU/04539/2013), the National Mass Spectrometry Network (RNEM) under the contract POCI-01-0145-FEDER402-022125 (ref. ROTEIRO/0028/2013), and PTDC/BIA-BMA/ 30922/201

Effect of an extract of Centella asiatica on the biodistribution of sodium pertechnetate (Na^99mTcO₄) and on the fixation of radioactivity on blood constituents

This study evaluates the effects of an acute treatment with a Centella asiatica (CA) extract on the biodistribution of the radiopharmaceutical Na99mTcO4 and on the fixation of technetium-99m on blood constituents. Wistar rats were treated with CA extract and, 1 hour after, Na99mTcO4 was administered; organs/tissues were withdrawn and weighted. The radioactivity was counted to calculate the percentage of activity per gram (%ATI/g). Also, blood samples were withdrawn, plasma (P), blood cells (BC), insoluble fraction (IF) and soluble fractions of P and BC were isolated and the radioactivity was counted to calculate the percentage of activity (%ATI). Data indicated that the acute treatment with CA extract changed significantly (p99mTcO4 and the fixation of the technetium-99m on blood constituents in an acute treatment

Microsatellite markers for urochloa Humidicola (poaceae) and their transferability to other urochloa species

Urochloa humidicola is a warm-season grass commonly used as forage in the tropics and is recognized for its tolerance to seasonal flooding. This grass is an important forage species for the Cerrado and Amazon regions of Brazil. U. humidicola is a polyploid species with variable ploidy (6X-9X) and facultative apomixis with high phenotypic plasticity. However, this apomixis and ploidy, as well as the limited knowledge of the genetic basis of the germplasm collection, have constrained genetic breeding activities, yet microsatellite markers may enable a better understanding of the species' genetic composition. This study aimed to develop and characterize new polymorphic microsatellite molecular markers in U. humidicola and to evaluate their transferability to other Urochloa species. Findings: A set of microsatellite markers for U. humidicola was identified from two new enriched genomic DNA libraries: the first library was constructed from a single sexual genotype and the second from a pool of eight apomictic genotypes selected on the basis of previous results. Of the 114 loci developed, 72 primer pairs presented a good amplification product, and 64 were polymorphic among the 34 genotypes tested. The number of bands per simple sequence repeat (SSR) locus ranged from 1 to 29, with a mean of 9.6 bands per locus. The mean polymorphism information content (PIC) of all loci was 0.77, and the mean discrimination power (DP) was 0.87. STRUCTURE analysis revealed differences among U. humidicola accessions, hybrids, and other Urochloa accessions. The transferability of these microsatellites was evaluated in four species of the genus, U. brizantha, U. decumbens, U. ruziziensis, and U. dictyoneura, and the percentage of transferability ranged from 58.33% to 69.44% depending on the species. Conclusions: This work reports new polymorphic microsatellite markers for U. humidicola that can be used for breeding programs of this and other Urochloa species, including genetic linkage mapping, quantitative trait loci identification, and marker-assisted selection8