2,728 research outputs found
Are metals of antifouling paints transferred to marine biota?
Devido sua alta toxicidade, o TBT está banido desde 2003, o que resultou na re-utilização de tintas a base de cobre. O objetivo deste trabalho é determinar se os metais provenientes das tintas anti-incrustantes (AFP) são transferidos para organismos bentônicos da Baía de Guanabara (BG) (Rio de janeiro, Brasil). Concentrações de metais foram analisadas em duas espécies de algas Ulva flexuosa e U. fasciata e no isópoda, Sphaeroma serratum, em duas áreas de marinas em locais de substrato artificial coberto com tintas AFP e em locais de substrato natural. Também foram coletadas amostras em uma área oceânica (controle). Concentrações de Cd, Cr, Cu, Pb e Zn foram determinadas por Espectrofotometria de Absorção Atômica. Concentrações mais elevadas de Cu, Pb e Zn foram detectadas na BG em ambas espécies de algas em relação a área controle. Dentre as espécies de algas e do isópoda da BG, as populações coletadas sobre as superfícies cobertas com AFP apresentaram concentrações significativamente mais elevadas do que as populações do substrato natural. Os resultados obtidos demonstram que a liberação de metais presentes nas AFP dos decks e embarcações, estão sendo acumulados pelas algas e isópodas. Esses resultados indicam que o revestimento com AFP é a principal fonte de metais para a biota de marinas em áreas da BG.Because of its high toxicity, TBT (trybutiltin) was banned since 2003, which resulted in a greater re-use of Cu as based-biocide in antifouling paints (AFP). The aim of this work is to determine if metals form of AFP are transferred to benthic organisms from Guanabara Bay (GB) (Rio de Janeiro, Brazil). Metal concentrations were measured in two main fouling algae species Ulva flexuosa and U. fasciata and one isopod species, Sphaeroma serratum, in two GB marinas areas from sites with artificial substrate covered by AFP and natural substrate.In addition, control samples were collected in an adjacent open ocean area. Concentrations of Cd, Cr, Cu, Pb and Zn were determined by Atomic Absortion Spectrophotometry. Higher concentrations of Cu, Pb and Zn were detected in both algal species from GB in relation to control areas. Among samples of algae and isopod species from GB, populations collected over artificial surfaces covered by AFP presented significantly higher metal concentration than population of rocky natural substrate. Our data showed that the leaching of metals by antifouling paints present on decks and boats are being taken up by algae and isopods. These results indicate that antifouling coatings are the main source of heavy metal to biota of GB marina area
Genetic epidemiology of the Charcot-Marie-Tooth in the Spanish Gypsy population: the Hereditary Motor and Sensory Neuropathy type Russe in depth
[EN] Four private mutations responsible for three forms demyelinating of Charcot-Marie-Tooth (CMT) or hereditary motor and sensory neuropathy (HMSN) have been associated with the Gypsy population: the NDRG1 p.R148X in CMT type 4D (CMT4D/HMSN-Lom); p.C737_P738delinsX and p.R1109X mutations in the SH3TC2 gene (CMT4C); and a G>C change in a novel alternative untranslated exon in the HK1 gene causative of CMT4G (CMT4G/HMSN-Russe). Here we address the findings of a genetic study of 29 Gypsy Spanish families with autosomal recessive demyelinating CMT. The most frequent form is CMT4C (57.14%), followed by HMSN-Russe (25%) and HMSN-Lom (17.86%). The relevant frequency of HMSN-Russe has allowed us to investigate in depth the genetics and the associated clinical symptoms of this CMT form. HMSN-Russe probands share the same haplotype confirming that the HK1 g.9712G>C is a founder mutation, which arrived in Spain around the end of the 18th century. The clinical picture of HMSN-Russe is a progressive CMT disorder leading to severe weakness of the lower limbs and prominent distal sensory loss. Motor nerve conduction velocity was in the demyelinating or intermediate range.We thank all patients and their relatives for their kind collaboration. We also thank Drs G. Glover, R. Vilches, F. Galan, and C. Diaz for referring patients for genetic analysis. We also acknowledge F Barraclough for English corrections. This work was supported by the Instituto de Salud Carlos III (ISCIII) (grants number PI08/90857, PI08/0889, CP08/00053 and PS09/00095) co-funded with FEDER funds and by the ISCIII-IRDiRC Programme (TREAT-CMT grant). C. E. has a 'Miguel Servet' contract funded by the ISCIII. Both Centro de Investigacion Biomedica en Red de Enfermedades Raras (CIBERER) and Centro de Investigacion Biomedica en Red de Enfermedades Neurodegenerativas (CIBERNED) are initiative from the ISCIII.Sevilla, T.; Martínez-Rubio, D.; Márquez, C.; Paradas, C.; Colomer, J.; Jaijo, T.; Millán, J.... (2013). Genetic epidemiology of the Charcot-Marie-Tooth in the Spanish Gypsy population: the Hereditary Motor and Sensory Neuropathy type Russe in depth. Clinical Genetics. 83(6):565-570. https://doi.org/10.1111/cge.1201556557083
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Collaborative model for diagnosis and treatment of very rare diseases: experience in Spain with thymidine kinase 2 deficiency
[EN]Background: Mitochondrial diseases are difficult to diagnose and treat. Recent advances in genetic diagnostics and more effective treatment options can improve patient diagnosis and prognosis, but patients with mitochondrial disease typically experience delays in diagnosis and treatment. Here, we describe a unique collaborative practice model among physicians and scientists in Spain focused on identifying TK2 deficiency (TK2d), an ultra-rare mitochondrial DNA depletion and deletions syndrome.
Main Body: This collaboration spans research and clinical care, including laboratory scientists, adult and pediatric neuromuscular clinicians, geneticists, and pathologists, and has resulted in diagnosis and consolidation of care for patients with TK2d. The incidence ofTK2d is not known; however, the first clinical cases ofTK2d were reported in 2001, and only similar to 107 unique cases had been reported as of 2018. This unique collaboration in Spain has led to the diagnosis of more than 30 patients with genetically confirmed TK2d across different regions of the country. Research affiliate centers have led investigative treatment with nucleosides based on understanding ofTK2d clinical manifestations and disease mechanisms, which resulted in successful treatment of a TK2d mouse model with nucleotide therapy in 2010. Only 1 year later, this collaboration enabled rapid adoption of treatment with pyrimidine nucleotides (and later, nucleosides) under compassionate use. Success in TK2d diagnosis and treatment in Spain is attributable to two important factors: Spain's fully public national healthcare system, and the designation in 2015 of major National Reference Centers for Neuromuscular Disorders (CSURs). CSUR networking and dissemination facilitated development of a collaborative care network for TK2d disease, wherein participants share information and protocols to request approval from the Ministry of Health to initiate nucleoside therapy. Data have recently been collected in a retrospective study conducted under a Good Clinical Practice-compliant protocol to support development of a new therapeutic approach for TK2d, a progressive disease with no approved therapies.
Conclusions: The Spanish experience in diagnosis and treatment of TK2d is a model for the diagnosis and development of new treatments for very rare diseases within an existing healthcare system.This study was sponsored by Zogenix, Inc., and ERN EURO-NMD. The sponsors reviewed the drafts and provided medical writing support for draft preparation
Compressed representation of a partially defined integer function over multiple arguments
In OLAP (OnLine Analitical Processing) data are analysed in an n-dimensional cube. The cube may be represented as a partially defined function over n arguments. Considering that often the function is not defined everywhere, we ask: is there a known way of representing the function or the points in which it is defined, in a more compact manner than the trivial one
Intensive Teenage Activity Is Associated With Greater Muscle Hyperintensity on T1W Magnetic Resonance Imaging in Adults With Dysferlinopathy
Practice of sports during childhood or adolescence correlates with an earlier onset and more rapidly progressing phenotype in dysferlinopathies. To determine if this correlation relates to greater muscle pathology that persists into adulthood, we investigated the effect of exercise on the degree of muscle fatty replacement measured using muscle MRI. We reviewed pelvic, thigh and leg T1W MRI scans from 160 patients with genetically confirmed dysferlinopathy from the Jain Foundation International clinical outcomes study in dysferlinopathy. Two independent assessors used the Lamminen-Mercuri visual scale to score degree of fat replacement in each muscle. Exercise intensity for each individual was defined as no activity, minimal, moderate, or intensive activity by using metabolic equivalents and patient reported frequency of sports undertaken between the ages of 10 and 18. We used ANCOVA and linear modeling to compare the mean Lamminen-Mercuri score for the pelvis, thigh, and leg between exercise groups, controlling for age at assessment and symptom duration. Intensive exercisers showed greater fatty replacement in the muscles of the pelvis than moderate exercisers, but no significant differences of the thigh or leg. Within the pelvis, Psoas was the muscle most strongly associated with this exercise effect. In patients with a short symptom duration of <15 years there was a trend toward greater fatty replacement in the muscles of the thigh. These findings define key muscles involved in the exercise-phenotype effect that has previously been observed only clinically in dysferlinopathy and support recommendations that pre-symptomatic patients should avoid very intensive exercise
Heterozygous CAPN3 missense variants causing autosomal-dominant calpainopathy in seven unrelated families
[Aims] Recessive variants in CAPN3 gene are the cause of the commonest form of autosomal recessive limb girdle muscle dystrophy. However, two distinct in-frame deletions in CAPN3 (NM_000070.3:c.643_663del21 and c.598_621del15) and more recently, Gly445Arg and Arg572Pro substitutions have been linked to autosomal dominant (AD) forms of calpainopathy. We report 21 affected individuals from seven unrelated families presenting with an autosomal dominant form of muscular dystrophy associated with five different heterozygous missense variants in CAPN.[Methods] We have used massively parallel gene sequencing (MPS) to determine the genetic basis of a dominant form of limb girdle muscular dystrophy in affected individuals from seven unrelated families.[Results] The c.700G> A, [p.(Gly234Arg)], c.1327T> C [p.(Ser443Pro], c.1333G> A [p.(Gly445Arg)], c.1661A> C [p.(Tyr554Ser)] and c.1706T> C [p.(Phe569Ser)] CAPN3 variants were identified. Affected individuals presented in young adulthood with progressive proximal and axial weakness, waddling walking and scapular winging or with isolated hyperCKaemia. Muscle imaging showed fatty replacement of paraspinal muscles, variable degrees of involvement of the gluteal muscles, and the posterior compartment of the thigh and minor changes at the mid-leg level. Muscle biopsies revealed mild myopathic changes. Western blot analysis revealed a clear reduction in calpain 3 in skeletal muscle relative to controls. Protein modelling of these variants on the predicted structure of calpain 3 revealed that all variants are located in proximity to the calmodulin-binding site and are predicted to interfere with proteolytic activation.[Conclusions] We expand the genotypic spectrum of CAPN3-associated muscular dystrophy due to autosomal dominant missense variants.This study was funded in part by Instituto de Salud Carlos III through the project PI14/00738 to M. O. (co-funded by European Regional Development Fund. ERDF, a way to build Europe). We thank CERCA Programme / Generalitat de Catalunya for institutional support NGL (APP1117510) and GR (APP1122952) are supported by the Australian National Health and Medical Research Council (NHMRC). This work is also funded by an NHMRC Project Grant (APP1080587).Peer reviewe
Lipid analogs reveal features critical for hemolysis and diminish granadaene mediated Group B Streptococcus infection
Although certain microbial lipids are toxins, the structural features important for cytotoxicity
remain unknown. Increased functional understanding is essential for developing therapeutics
against toxic microbial lipids. Group B Streptococci (GBS) are bacteria associated with preterm
births, stillbirths, and severe infections in neonates and adults. GBS produce a pigmented,
cytotoxic lipid, known as granadaene. Despite its importance to all manifestations of
GBS disease, studies towards understanding granadaene’s toxic activity are hindered by its
instability and insolubility in purified form. Here, we report the synthesis and screening of
lipid derivatives inspired by granadaene, which reveal features central to toxin function,
namely the polyene chain length. Furthermore, we show that vaccination with a non-toxic
synthetic analog confers the production of antibodies that inhibit granadaene-mediated
hemolysis ex vivo and diminish GBS infection in vivo. This work provides unique structural
and functional insight into granadaene and a strategy to mitigate GBS infection, which will be
relevant to other toxic lipids encoded by human pathogens.This work was supported by funding from the National Institutes of Health
Grants R01AI112619, R01AI133976, R01AI100989, and R21AI125907 and seed funds
from Seattle Childrens Research Institute to L.
Assessment of disease progression in dysferlinopathy: A 1-year cohort study
ObjectiveTo assess the ability of functional measures to detect disease progression in dysferlinopathy over 6 months and 1 year.MethodsOne hundred ninety-three patients with dysferlinopathy were recruited to the Jain Foundation's International Clinical Outcome Study for Dysferlinopathy. Baseline, 6-month, and 1-year assessments included adapted North Star Ambulatory Assessment (a-NSAA), Motor Function Measure (MFM-20), timed function tests, 6-minute walk test (6MWT), Brooke scale, Jebsen test, manual muscle testing, and hand-held dynamometry. Patients also completed the ACTIVLIM questionnaire. Change in each measure over 6 months and 1 year was calculated and compared between disease severity (ambulant [mild, moderate, or severe based on a-NSAA score] or nonambulant [unable to complete a 10-meter walk]) and clinical diagnosis.ResultsThe functional a-NSAA test was the most sensitive to deterioration for ambulant patients overall. The a-NSAA score was the most sensitive test in the mild and moderate groups, while the 6MWT was most sensitive in the severe group. The 10-meter walk test was the only test showing significant change across all ambulant severity groups. In nonambulant patients, the MFM domain 3, wrist flexion strength, and pinch grip were most sensitive. Progression rates did not differ by clinical diagnosis. Power calculations determined that 46 moderately affected patients are required to determine clinical effectiveness for a hypothetical 1-year clinical trial based on the a-NSAA as a clinical endpoint.ConclusionCertain functional outcome measures can detect changes over 6 months and 1 year in dysferlinopathy and potentially be useful in monitoring progression in clinical trials.ClinicalTrials.gov identifier:NCT01676077
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