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1.
Immunity ; 57(2): 379-399.e18, 2024 Feb 13.
Article in English | MEDLINE | ID: mdl-38301653

ABSTRACT

Palatine tonsils are secondary lymphoid organs (SLOs) representing the first line of immunological defense against inhaled or ingested pathogens. We generated an atlas of the human tonsil composed of >556,000 cells profiled across five different data modalities, including single-cell transcriptome, epigenome, proteome, and immune repertoire sequencing, as well as spatial transcriptomics. This census identified 121 cell types and states, defined developmental trajectories, and enabled an understanding of the functional units of the tonsil. Exemplarily, we stratified myeloid slan-like subtypes, established a BCL6 enhancer as locally active in follicle-associated T and B cells, and identified SIX5 as putative transcriptional regulator of plasma cell maturation. Analyses of a validation cohort confirmed the presence, annotation, and markers of tonsillar cell types and provided evidence of age-related compositional shifts. We demonstrate the value of this resource by annotating cells from B cell-derived mantle cell lymphomas, linking transcriptional heterogeneity to normal B cell differentiation states of the human tonsil.


Subject(s)
B-Lymphocytes , Palatine Tonsil , Humans , Adult , B-Lymphocytes/metabolism
2.
Acta Neuropathol ; 147(1): 44, 2024 02 22.
Article in English | MEDLINE | ID: mdl-38386085

ABSTRACT

The development of brain metastases hallmarks disease progression in 20-40% of melanoma patients and is a serious obstacle to therapy. Understanding the processes involved in the development and maintenance of melanoma brain metastases (MBM) is critical for the discovery of novel therapeutic strategies. Here, we generated transcriptome and methylome profiles of MBM showing high or low abundance of infiltrated Iba1high tumor-associated microglia and macrophages (TAMs). Our survey identified potential prognostic markers of favorable disease course and response to immune checkpoint inhibitor (ICi) therapy, among them APBB1IP and the interferon-responsive gene ITGB7. In MBM with high ITGB7/APBB1IP levels, the accumulation of TAMs correlated significantly with the immune score. Signature-based deconvolution of MBM via single sample GSEA revealed enrichment of interferon-response and immune signatures and revealed inflammation, stress and MET receptor signaling. MET receptor phosphorylation/activation maybe elicited by inflammatory processes in brain metastatic melanoma cells via stroma cell-released HGF. We found phospho-METY1234/1235 in a subset of MBM and observed a marked response of brain metastasis-derived cell lines (BMCs) that lacked druggable BRAF mutations or developed resistance to BRAF inhibitors (BRAFi) in vivo to MET inhibitors PHA-665752 and ARQ197 (tivantinib). In summary, the activation of MET receptor in brain colonizing melanoma cells by stromal cell-released HGF may promote tumor self-maintenance and expansion and might counteract ICi therapy. Therefore, therapeutic targeting of MET possibly serves as a promising strategy to control intracranial progressive disease and improve patient survival.


Subject(s)
Brain Neoplasms , Melanoma , Humans , Melanoma/drug therapy , Melanoma/genetics , Proto-Oncogene Proteins B-raf , Brain Neoplasms/drug therapy , Brain Neoplasms/genetics , Disease Progression , Interferons
3.
Int J Mol Sci ; 23(3)2022 Jan 21.
Article in English | MEDLINE | ID: mdl-35163127

ABSTRACT

Clonal evolution and cellular plasticity are the genetic and non-genetic driving forces of tumor heterogeneity, which in turn determine tumor cell responses towards therapeutic drugs. Several lines of evidence suggest that therapeutic interventions foster the selection of drug-resistant neural crest stem-like cells (NCSCs) that establish minimal residual disease (MRD) in melanoma. Here, we establish a dual-reporter system, enabling the tracking of NGFR expression and mRNA stability and providing insights into the maintenance of NCSC states. We observed that a transcriptional reporter that contained a 1-kilobase fragment of the human NGFR promoter was activated only in a minor subset (0.72 ± 0.49%, range 0.3-1.5), and ~2-4% of A375 melanoma cells revealed stable NGFR mRNA. The combination of both reporters provides insights into phenotype switching and reveals that both cellular subsets gave rise to cellular heterogeneity. Moreover, whole transcriptome profiling and gene-set enrichment analysis (GSEA) of the minor cellular subset revealed hypoxia-associated programs that might serve as potential drivers of an in vitro switching of NGFR-associated phenotypes and relapse of post-BRAF inhibitor-treated tumors. Concordantly, we observed that the minor cellular subset increased in response to dabrafenib over time. In summary, our reporter-based approach provides insights into plasticity and identified a cellular subset that might be responsible for the establishment of MRD in melanoma.


Subject(s)
Biomarkers, Tumor/metabolism , Cell Plasticity , Drug Resistance, Neoplasm , Gene Expression Regulation, Neoplastic , Melanoma/pathology , Nerve Tissue Proteins/metabolism , RNA, Messenger/metabolism , Receptors, Nerve Growth Factor/metabolism , Biomarkers, Tumor/genetics , Humans , Melanoma/drug therapy , Melanoma/genetics , Melanoma/metabolism , Nerve Tissue Proteins/genetics , Protein Kinase Inhibitors/pharmacology , RNA, Messenger/genetics , Receptors, Nerve Growth Factor/genetics , Transcriptome
5.
BMC Vet Res ; 15(1): 441, 2019 Dec 05.
Article in English | MEDLINE | ID: mdl-31805938

ABSTRACT

BACKGROUND: Diarrhoea is a major cause of death in neonate pigs and most of the viruses that cause it are RNA viruses. Next Generation Sequencing (NGS) deeply characterize the genetic diversity among rapidly mutating virus populations at the interspecific as well as the intraspecific level. The diversity of RNA viruses present in faeces of neonatal piglets suffering from diarrhoea in 47 farms, plus 4 samples from non-diarrhoeic piglets has been evaluated by NGS. Samples were selected among the cases submitted to the Veterinary Diagnostic Laboratories of Infectious Diseases of the Universitat Autònoma de Barcelona (Barcelona, Spain) and Universidad de León (León, Spain). RESULTS: The analyses identified the presence of 12 virus species corresponding to 8 genera of RNA viruses. Most samples were co-infected by several viruses. Kobuvirus and Rotavirus were more commonly reported, with Sapovirus, Astrovirus 3, 4 and 5, Enterovirus G, Porcine epidemic diarrhoea virus, Pasivirus and Posavirus being less frequently detected. Most sequences showed a low identity with the sequences deposited in GenBank, allowing us to propose several new VP4 and VP7 genotypes for Rotavirus B and Rotavirus C. CONCLUSIONS: Among the cases analysed, Rotaviruses were the main aetiological agents of diarrhoea in neonate pigs. Besides, in a small number of cases Kobuvirus and Sapovirus may also have an aetiological role. Even most animals were co-infected in early life, the association with enteric disease among the other examined viruses was unclear. The NGS method applied successfully characterized the RNA virome present in faeces and detected a high level of unreported intraspecific diversity.


Subject(s)
Diarrhea/veterinary , Feces/virology , Genetic Variation , RNA Viruses/genetics , Swine Diseases/virology , Animals , Animals, Newborn , Diarrhea/virology , Phylogeny , Swine
6.
Vet Res ; 49(1): 19, 2018 02 15.
Article in English | MEDLINE | ID: mdl-29448955

ABSTRACT

Porcine reproductive and respiratory syndrome virus (PRRSv) infection alters the host's cellular and humoral immune response. Immunity against PRRSv is multigenic and vary between individuals. The aim of the present study was to compare several genes that encode for molecules involved in the immune response between two groups of vaccinated pigs that experienced short or long viremic periods after PRRSv challenge. These analyses include the sequencing of four SLA Class I, two Class II allele groups, and CD163, plus the analysis by quantitative realtime qRT-PCR of the constitutive expression of TLR2, TLR3, TLR4, TLR7, TLR8 and TLR9 mRNA and other molecules in peripheral blood mononuclear cells.


Subject(s)
Gene Expression , Genetic Variation , Immunity, Innate/genetics , Porcine Reproductive and Respiratory Syndrome/immunology , Porcine respiratory and reproductive syndrome virus/physiology , RNA, Messenger/genetics , Viremia/microbiology , Animals , RNA, Messenger/metabolism , Swine , Viral Vaccines/administration & dosage
7.
Avian Pathol ; 46(4): 442-450, 2017 Aug.
Article in English | MEDLINE | ID: mdl-28290221

ABSTRACT

Free-living raptors (birds of prey) can act as reservoirs of potentially zoonotic agents, but they also can be affected by microorganisms as target hosts. In this retrospective study, microbiological results (n = 663) and antibiotic sensitivity profiles (n = 108) of bacterial isolates were analysed from diseased free-living raptors. Sixty-nine percent of cases (n = 457) yielded bacteria: 58% were in pure culture and 42% were of different species. Remarkably, samples from necropsies (47%) had higher percentage of pure isolations than those obtained from clinical (31%) samples (P < 0.001). Among bacterial isolates, Escherichia coli was the most common agent (35%), principally recovered from necropsied birds with clinical signs of septicaemia or respiratory disorders. Pseudomonas aeruginosa (7%) was isolated from birds with systemic infection and from oral lesions, especially in nocturnal raptors (P < 0.001). Staphylococcus spp. (5%), mainly Staphylococcus aureus, was found to be the most prevalent cause of pododermatitis (35%) and Staphylococcus hyicus was isolated from conjunctivitis (18.2%). Interestingly, 8% of samples with lesions compatible with avian tuberculosis were positive to the Mycobacterium avium complex. The most frequent fungi associated with pneumonic lesions and ingluvitis were Aspergillus spp. and Candida spp., respectively. More than 50% of the 108 isolates (34 different bacterial spp.) demonstrated resistance to clindamycin, ampicillin, tetracycline, cefuroxime, enrofloxacin and trimethoprim/sulphamethoxazole. Among the E. coli strains, 71% (27/38) presented a multidrug-resistance pattern to >3 antimicrobials. Detection in wildlife of antimicrobial-resistant pathogens that might be significant at the animal-human-ecosystem interface is of great relevance under the 'One Health' approach.


Subject(s)
Anti-Bacterial Agents/pharmacology , Antifungal Agents/pharmacology , Bacterial Infections/veterinary , Bird Diseases/microbiology , Mycoses/veterinary , Raptors/microbiology , Animals , Animals, Wild , Bacteria/drug effects , Bacteria/isolation & purification , Bacterial Infections/microbiology , Drug Resistance, Bacterial , Drug Resistance, Fungal , Fungi/drug effects , Fungi/isolation & purification , Mycoses/microbiology
8.
Acta Ortop Bras ; 32(spe1): e265443, 2024.
Article in English | MEDLINE | ID: mdl-38716464

ABSTRACT

Objective: to radiographically compare the effects of anchor positioning in the arthroscopic treatment of shoulder instability, in the 3- and 5-o'clock portals. Methods: retrospective study of 36 patients, operated by two shoulder surgeons at the Unimed BH hospital, between January 2013 and January 2018. Each surgeon used only one of either the 3- or the 5-o'clock portal. After postoperative radiographs we performed angle comparisons between the greatest glenoidal axis, the angle of anchor insertion and distance from the inferior pole. Results: the 5-o'clock portal provided better placement than its 3-o'clock counterpart, which allowed for greater orthogonality in relation to the glenoid rim (p < 0.05). Conclusion: the 5-o'clock portal allowed for better anchor placement than the 3 o'clock one. Level of Evidence II, Clinical Trial.


Objetivo: Comparar radiograficamente o posicionamento das âncoras utilizadas no tratamento artroscópico da instabilidade do ombro, através dos portais de 3 ou 5 horas. Métodos: Avaliação retrospectivae de 36 pacientes, operados por dois cirurgiões de ombro do Hospital Unimed BH, entre janeiro de 2013 e janeiro de 2018. Cada cirurgião utilizou apenas uma das técnicas ­ portal de 3 ou 5 horas. As radiografias pós-operatórias foram avaliadas e comparadas a angulações entre o maior eixo da glenoide, o ângulo de inserção da âncora e a distância em relação ao polo inferior. Resultados: A utilização do portal de 5 horas propiciou a colocação mais adequada das âncoras em relação ao portal de 3 horas, permitindo o posicionamento mais ortogonal em relação à borda da glenoide (p < 0,05). Conclusão: A utilização do portal de 5 horas apresenta melhor posicionamento das âncoras quando comparado ao portal de 3 horas. Nível de evidência II, Ensaio Clínico.

9.
Clin Transl Oncol ; 2024 Mar 17.
Article in English | MEDLINE | ID: mdl-38493446

ABSTRACT

OBJECTIVE: Contouring accuracy is critical in modern radiotherapy. Several tools are available to assist clinicians in this task. This study aims to evaluate the performance of the smoothing tool in the ARIA system to obtain more consistent volumes. METHODS: Eleven different geometric shapes were delineated in ARIA v15.6 (Sphere, Cube, Square Prism, Six-Pointed Star Prism, Arrow Prism, And Cylinder and the respective volumes at 45° of axis deviation (_45)) in 1, 3, 5, 7, and 10 cm side or diameter each. Post-processing drawing tools to smooth those first-generated volumes were applied in different options (2D-ALL vs 3D) and grades (1, 3, 5, 10, 15, and 20). These volumetric transformations were analyzed by comparing different parameters: volume changes, center of mass, and DICE similarity coefficient index. Then we studied how smoothing affected two different volumes in a head and neck cancer patient: a single rounded node and the volume delineating cervical nodal areas. RESULTS: No changes in data were found between 2D-ALL or 3D smoothing. Minimum deviations were found (range from 0 to 0.45 cm) in the center of mass. Volumes and the DICE index decreased as the degree of smoothing increased. Some discrepancies were found, especially in figures with cleft and spikes that behave differently. In the clinical case, smoothing should be applied only once throughout the target delineation process, preferably in the largest volume (PTV) to minimize errors. CONCLUSION: Smoothing is a good tool to reduce artifacts due to the manual delineation of radiotherapy volumes. The resulting volumes must be always carefully reviewed.

10.
Acta Haematol ; 129(2): 65-71, 2013.
Article in English | MEDLINE | ID: mdl-23154527

ABSTRACT

Significant progress in the understanding of the genetic basis of acute myeloid leukemia (AML) has been made during the last 30 years. The aim of the present study was to assess whether the detection of recurrent gene rearrangements by fluorescent in situ hybridization (FISH) studies and NPM1 and FLT3 gene mutations by molecular studies added clinically relevant information to the karyotype in 113 AML patients. Thus, FISH and molecular studies were found to add new information in 22 and 55% of the patients, respectively, particularly in cases with normal karyotype (NK) or when a cytogenetic analysis failed. Patients with NK changed their genetic risk group to favorable in 27 and 29% of cases using FISH and molecular biology studies, respectively. Our results demonstrate that molecular biology and FISH studies provide relevant information in AML and should be routinely performed.


Subject(s)
Leukemia, Myeloid, Acute/genetics , Nuclear Proteins/genetics , fms-Like Tyrosine Kinase 3/genetics , Adolescent , Adult , Aged , Aged, 80 and over , Cytogenetics , Female , Gene Rearrangement , Humans , In Situ Hybridization, Fluorescence , Male , Middle Aged , Mutation , Nucleophosmin , Prognosis
11.
Mar Pollut Bull ; 195: 115469, 2023 Oct.
Article in English | MEDLINE | ID: mdl-37703630

ABSTRACT

Increasing amount of anthropogenic litter in the marine environment has provided an enormous number of substrates for a wide range of marine organisms, thus serving as a potential vector for the transport of fouling organisms. Here, we examined the fouling organisms on different types of stranded litter (plastic, glass, rubber, foam sponge, cloth, metal and wood) on eight beaches along the southeast coast of India. In total, 17 encrusting species belonging to seven phyla (Arthropoda, Bryozoa, Mollusca, Annelida, Cnidaria, Chlorophyta and Foraminifera) were identified on 367 items, with one invasive species, the mussel Mytella strigata, detected. The most common species associated with marine litter were the cosmopolitan bryozoans Jellyella tuberculata (%O = 31.64 %) and J. eburnea (28.61 %), the barnacle species Lepas anserifera (29.97 %), Amphibalanus amphitrite (22.34 %) and Amphibalanus sp. (14.16 %), and the oyster species Saccostrea cucullata (13.62 %) and Magallana bilineata (5.44 %). We also reported the first records on stranded litter of four species: the gastropod species Pirenella cingulata and Umbonium vestiarium, the foraminiferan Ammonia beccarii, and the oyster M. bilineata. This study is thus the first documentation of marine litter as a vector for species dispersal in India, where the production and consumption of plastic rank among the highest in the world. We also highlight the increasing risk of invasions by non-indigenous organisms attached to debris along the southeast coast of India. Comprehensive monitoring efforts are thus needed to elucidate the type of vectors responsible for the arrival of invasive species in this region. Raising awareness and promoting education are vital components in fostering sustainable solutions to combat plastic pollution in the country and globally.


Subject(s)
Bryozoa , Ostreidae , Animals , Environmental Monitoring , Plastics/chemistry , Wood/chemistry , Textiles , Introduced Species , Waste Products/analysis , Bathing Beaches
12.
Environ Sci Pollut Res Int ; 30(13): 36311-36324, 2023 Mar.
Article in English | MEDLINE | ID: mdl-36547830

ABSTRACT

It has been suggested that the seafloor may be a sink for the plastic debris that enters the ocean. Therefore, the collection of data in the seafloor sediments regarding the co-presence of microplastics (MPs) and contaminants associated to plastic is considered a relevant topic. However, the number of studies addressing their possible correlation in this environment is still limited, and very little is known about the mechanisms that determine the release of plastic additives from plastic items. Starting from this basis, we investigated the presence of MPs and eleven phthalic acid esters (PAEs) in the continental shelf offshore Barcelona. Following a shelf-slope continuum approach, we sampled sediments from five stations, and we performed analysis by means of infrared micro spectroscopy (µFTIR) and liquid chromatography tandem mass spectrometry (LC-MS/MS). MPs were found to range from 62.0 to 931.1 items/kg d.w. with maximum concentration in the submarine canyon Besòs and at the highest depth. Moreover, different trends in the size distribution of fibers and non-fibers were observed, indicating the occurrence of a size dependent selection mechanism during transport and accumulation. PAEs resulted comprised between 1.35 to 2.41 mg/kg with Di(2-ethylhexyl)phthalate (DEHP) the most abundant congeners (1.04 mg/kg). Statistical analysis revealed no correlation between the Σ11PAEs and the total MPs concentration, but correlation between DEHP and fibers (σ = 0.667, p = 0,037), that resulted both correlated to the distance to the coast (ρ = 0.941 with p = 0,008 and ρ = 0.673 with p = 0.035, respectively).


Subject(s)
Diethylhexyl Phthalate , Phthalic Acids , Water Pollutants, Chemical , Plasticizers/analysis , Plastics/analysis , Diethylhexyl Phthalate/analysis , Phthalic Acids/analysis , Microplastics/analysis , Chromatography, Liquid , Water Pollutants, Chemical/analysis , Tandem Mass Spectrometry , Esters/analysis , Dibutyl Phthalate/analysis
13.
Front Neurosci ; 17: 1216653, 2023.
Article in English | MEDLINE | ID: mdl-37662110

ABSTRACT

Introduction: SLC6A1 is one of the most common monogenic causes of epilepsy and is a well-established cause of neurodevelopmental disorders. SLC6A1-neurodevelopmental disorders have a consistent phenotype of mild to severe intellectual disability (ID), epilepsy, language delay and behavioral disorders. This phenotypic description is mainly based on knowledge from the pediatric population. Method: Here, we sought to describe patients with SLC6A1 variants and age above 18 years through the ascertainment of published and unpublished patients. Unpublished patients were ascertained through international collaborations, while previously published patients were collected through a literature search. Results: A total of 15 adult patients with SLC6A1 variants were included. 9/13 patients had moderate to severe ID (data not available in two). Epilepsy was prevalent (11/15) with seizure types such as absence, myoclonic, atonic, and tonic-clonic seizures. Epilepsy was refractory in 7/11, while four patients were seizure free with lamotrigine, valproate, or lamotrigine in combination with valproate. Language development was severely impaired in five patients. Behavioral disorders were reported in and mainly consisted of autism spectrum disorders and aggressive behavior. Schizophrenia was not reported in any of the patients. Discussion: The phenotype displayed in the adult patients presented here resembled that of the pediatric cohort with ID, epilepsy, and behavioral disturbances, indicating that the phenotype of SLC6A1-NDD is consistent over time. Seizures were refractory in >60% of the patients with epilepsy, indicating the lack of targeted treatment in SLC6A1-NDDs. With increased focus on repurposing drugs and on the development of new treatments, hope is that the outlook reflected here will change over time. ID appeared to be more severe in the adult patients, albeit this might reflect a recruitment bias, where only patients seen in specialized centers were included or it might be a feature of the natural history of SLC6A1-NDDs. This issue warrants to be explored in further studies in larger cohorts.

14.
Environ Pollut ; 334: 122094, 2023 Oct 01.
Article in English | MEDLINE | ID: mdl-37392868

ABSTRACT

Artificial turf (AT) is a surfacing material that simulates natural grass by using synthetic, mainly plastic, fibers in different shapes, sizes and properties. AT has spread beyond sports facilities and today shapes many urban landscapes, from private lawns to rooftops and public venues. Despite concerns regarding the impacts of AT, little is known about the release of AT fibers into natural environment. Here, for the first time, we specifically investigate the presence of AT fibers in river and ocean waters as major conduits and final destination of plastic debris transported by water runoff. Our sampling survey showed that, AT fibers - composed mainly of polyethylene and polypropylene - can constitute over 15% of the mesoplastics and macroplastics content, suggesting that AT fibers may contribute significantly to plastic pollution. Up to 20,000 fibers a day flowed down through the river, and up to 213,200 fibers per km2 were found floating on the sea surface of nearshore areas. AT, apart from impacting on urban biodiversity, urban runoff, heat island formation, and hazardous chemical leaching, is a major source of plastic pollution to natural aquatic environments.


Subject(s)
Environmental Pollutants , Water Pollutants, Chemical , Plastics , Water Pollutants, Chemical/analysis , Cities , Environmental Monitoring , Hot Temperature
15.
Environ Pollut ; 319: 120983, 2023 Feb 15.
Article in English | MEDLINE | ID: mdl-36596379

ABSTRACT

Plastics have been proposed as vectors of bacteria as they act as a substrate for biofilms. In this study, we evaluated the abundance of faecal and marine bacteria and antibiotic resistance genes (ARGs) from biofilms adhered to marine plastics. Floating plastics and plastics from sediments were collected in coastal areas impacted by human faecal pollution in the northwestern Mediterranean Sea. Culture and/or molecular methods were used to quantify faecal indicators (E. coli, Enterococci and crAssphage), and the ARGs sulI, tetW and blaTEM and the 16S rRNA were detected by qPCR assays. Pseudomonas and Vibrio species and heterotrophic marine bacteria were also analysed via culture-based methods. Results showed that, plastic particles covered by bacterial biofilms, primarily consisted of marine bacteria including Vibrio spp. Some floating plastics had a low concentration of viable E. coli and Enterococci (42% and 67% of the plastics respectively). Considering the median area of the plastics, we detected an average of 68 cfu E. coli per item, while a higher concentration of E. coli was detected on individual plastic items, when compared with 100 ml of the surrounding water. Using qPCR, we quantified higher values of faecal indicators which included inactive and dead microorganisms, detecting up to 2.6 × 102 gc mm-2. The ARGs were detected in 67-88% of the floating plastics and in 29-57% of the sediment plastics with a concentration of up to 6.7 × 102 gc mm-2. Furthermore, enrichment of these genes was observed in biofilms compared with the surrounding water. These results show that floating plastics act as a conduit for both the attachment and transport of faecal microorganisms. In contrast, low presence of faecal indicators was detected in plastic from seafloor sediments. Therefore, although in low concentrations, faecal bacteria, and potential pathogens, were identified in marine plastics, further suggesting plastics act as a reservoir of pathogens and ARGs.


Subject(s)
Escherichia coli , Feces , Vibrio , Humans , Anti-Bacterial Agents , Biofilms , Drug Resistance, Microbial/genetics , Enterococcus/genetics , Escherichia coli/genetics , Genes, Bacterial , Plastics , RNA, Ribosomal, 16S , Vibrio/genetics , Water , Feces/microbiology
16.
Front Neurosci ; 17: 1219262, 2023.
Article in English | MEDLINE | ID: mdl-37502687

ABSTRACT

Introduction: Phenotypic spectrum of SLC6A1-related neurodevelopmental disorders (SLC6A1-NDD) includes intellectual disability (ID), autistic spectrum disorders (ASD), epilepsy, developmental delay, beginning from early infancy or after seizure onset, and other neurological features such as hypotonia and movement disorders. Data on familial phenotypic heterogeneity have been rarely reported, thus in our study we aimed to investigate intrafamilial phenotypic variability in families with SLC6A1 variants. Methods: We collected clinical, laboratory and genetic data on 39 individuals, including 17 probands, belonging to 13 families harboring inherited variants of SLC6A1. Data were collected through an international network of Epilepsy and Genetic Centers. Results: Main clinical findings in the whole cohort of 39 subjects were: (a) epilepsy, mainly presenting with generalized seizures, reported in 71% of probands and 36% of siblings or first/second-degree relatives. Within a family, the same epilepsy type (generalized or focal) was observed; (b) ID reported in 100% and in 13% of probands and siblings or first/second-degree relatives, respectively; (c) learning disabilities detected in 28% of the SLC6A1 carriers, all of them were relatives of a proband; (d) around 51% of the whole cohort presented with psychiatric symptoms or behavioral disorders, including 82% of the probands. Out of the 19 patients with psychiatric symptoms, ASD were diagnosed in 40% of them; (e) neurological findings (primarily tremor and speech difficulties) were observed 38.5% of the whole cohort, including 10 probands. Our families harbored 12 different SLC6A1 variants, one was a frameshift, two stop-gain, while the remaining were missense. No genotype-phenotype associations were identified. Discussion: Our study showed that first-or second-degree relatives presented with a less severe phenotype, featuring mainly mild intellectual and/or learning disabilities, at variance with the probands who suffered from moderate to severe ID, generalized, sometimes intractable, epileptic seizures, behavioral and psychiatric disorders. These findings may suggest that a proportion of individuals with mild SLC6A1-NDD might be missed, in particular those with an older age where genetic testing is not performed. Further studies on intrafamilial phenotypic variability are needed to confirm our results and possibly to expand the phenotypic spectrum of these disorders and benefit genetic counseling.

18.
Environ Sci Technol ; 46(5): 2624-32, 2012 Mar 06.
Article in English | MEDLINE | ID: mdl-22296346

ABSTRACT

Settling particles were collected by an array of sediment trap moorings deployed along the Cap de Creus (CCC) and Lacaze-Duthiers (LDC) submarine canyons and on the adjacent southern open slope (SOS) between October 2005 and October 2006. This array collected particles during common settling processes and particles transferred to deep waters by dense shelf water cascading (DSWC). Polychlorobiphenyls (PCBs), dichlorodiphenyltrichloroethane and its metabolites (DDTs), chlorobenzenes (CBzs)--pentachlorobenzene and hexachlorobenzene--and hexachlorocyclohexanes were analyzed in all samples. The results show much higher settling fluxes of these compounds during DSWC than during common sedimentation processes. The area of highest deposition was located between 1000 and 1500 m depth and extended along the canyons and outside them showing their channelling effects but also overflows of dense shelf water from these canyons. Higher fluxes were observed near the bottom (30 m above bottom; mab) than at intermediate waters (500 mab) which is consistent with the formation and sinking of dense water close to the continental shelf and main displacement through the slope by the bottom. DSWC involved the highest settling fluxes of these compounds ever described in marine continental slopes and pelagic areas, e.g., peak values of PCBs (960 ng · m(-2) · d(-1)), DDTs (2900 ng · m(-2) · d(-1)), CBzs (340 ng · m(-2) · d(-1)) and lindane (180 ng · m(-2) · d(-1)).


Subject(s)
Hydrocarbons, Chlorinated/analysis , Seawater/chemistry , Water Movements , Water Pollutants, Chemical/analysis , Carbon/analysis , Geography , Geologic Sediments/chemistry , Motion , Spain
19.
Transbound Emerg Dis ; 69(3): 997-1009, 2022 May.
Article in English | MEDLINE | ID: mdl-33662178

ABSTRACT

The aim of the present study was to evaluate the duration of protective immunity against Porcine epidemic diarrhoea virus (PEDV). To do so, a two phases study was performed. In the first phase, 75 four-week-old pigs (group A) were orally inoculated (0 days post-inoculation; dpi) with a European PEDV G1b strain and 14 were kept as controls (group B). The second phase started five months later (154 dpi), when animals in group A were homologous challenged and animals in group B were challenged for first time. Clinical signs, viral shedding and immune responses were evaluated after each inoculation, including the determination of antibodies (ELISA and viral neutralization test, IgA and IgG ELISPOTs using peripheral blood mononuclear cells and lymph node cells) and the frequency of interferon-gamma (IFN-γ) secreting cells. During the first phase, loose stools/liquid faeces were observed in all group A animals. Faecal shedding of PEDV occurred mostly during the first 14 days but, in some animals, persisted until 42 dpi. All inoculated animals seroconverted for specific-PEDV IgG and IgA, and for neutralizing antibodies (NA). At 154 dpi, 77% of pigs were still positive for NA. After that, the homologous challenge resulted in a booster for IgG, IgA, NA, as well as specific-PEDV IgG, IgA and IFN-γ secreting cells. In spite of that, PEDV was detected in faeces of all pigs from group A, indicating that the immune response did not prevent reinfection, although the duration of the viral shedding and the total load of virus shed were significantly lower for previously challenged pigs (p < .05). Taken together, the results indicated that, potentially, maintenance of PEDV infection within an endemic farm may occur by transmission to and from previously infected animals and also indicates that sterilizing immunity is shorter than the productive life of pigs.


Subject(s)
Coronavirus Infections , Porcine epidemic diarrhea virus , Swine Diseases , Animals , Antibodies, Neutralizing , Antibodies, Viral , Coronavirus Infections/prevention & control , Coronavirus Infections/veterinary , Diarrhea/veterinary , Immunity , Immunoglobulin A , Immunoglobulin G , Leukocytes, Mononuclear , Porcine epidemic diarrhea virus/physiology , Reinfection/veterinary , Swine
20.
Mar Pollut Bull ; 175: 113405, 2022 Feb.
Article in English | MEDLINE | ID: mdl-35152037

ABSTRACT

Plastic debris provides long-lasting substrates for benthic organisms, thus acting as a potential vector for their dispersion. Its interaction with these colonizers is, however, still poorly known. This study examines fouling communities on beached, buoyant and benthic plastic debris in the Catalan Sea (NW Mediterranean), and characterizes the plastic type. We found 14 specimens belonging to two phyla (Annelida and Foraminifera) on microplastics, and more than 400 specimens belonging to 26 species in 10 phyla (Annelida, Arthropoda, Brachiopoda, Bryozoa, Chordata, Cnidaria, Echinodermata, Mollusca, Porifera and Sipuncula) on macroplastics. With 15 species, bryozoans are the most diverse group on plastics. We also report 17 egg cases of the catshark Scyliorhinus sp., and highlight the implications for their dispersal. Our results suggest that plastic polymers may be relevant for distinct fouling communities, likely due to their chemical structure and/or surface properties. Our study provides evidence that biofouling may play a role in the sinking of plastic debris, as the most abundant fouled plastics had lower densities than seawater, and all bryozoan species were characteristic of shallower depths than those sampled. More studies at low taxonomic level are needed in order to detect new species introduction and potential invasive species associated with plastic debris.


Subject(s)
Biofouling , Foraminifera , Water Pollutants, Chemical , Animals , Aquatic Organisms , Environmental Monitoring/methods , Invertebrates , Plastics , Waste Products/analysis , Water Pollutants, Chemical/analysis
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