Multispecies Assessment of Anthropogenic Particle Ingestion in a Marine Protected Area

We have applied a multispecies ecosystem approach to analyse the ingestion of anthropogenic particles (AP) in the gastrointestinal tract of 313 individuals (17 fish species and 8 invertebrate species) from pelagic, demersal and benthic habitats in a marine protected area off the Western Mediterranean (Cabrera National Park). We have quantified and characterized the ingestion at several taxonomic levels of fish, sea urchins, sea cucumbers, bivalves, and jellyfish in relation to biotic/abiotic factors based on taxonomic groups, trophic guilds (functional groups) and habitats. AP ingestion occurrence ranged from 26 to 100% with no significant differences among taxonomic groups. The fish within the MPA showed an overall ingestion occurrence ranging from 0 to 100%, the echinoderms from 29 to 100%, the bivalves from 72 to 96% and the jellyfish 36% ingestion. The ecosystem approach applied to evaluate overall AP ingestion within the species reported that for trophic guilds, the omnivorous species ingested the highest amounts of anthropogenic items, while herbivores ingested significantly fewer items than all other trophic guilds. Moreover, no significant differences were found amongst habitats, indicating a homogeneous spatial distribution of APs at all studied habitats. The multispecies approach provided insight into the high APs exposure to species within Cabrera MPA, highlighting the potential harm linked with marine litter that threatens marine biodiversity.En prensa5,82

Avaluació de l’estat fisiològic del conill (Oryctolagus cuniculus) per mitjà de biomarcadors bioquímics

[cat] El conill europeu (Oryctolagus cuniculus) és una de les espècies de vertebrats més importants dels ecosistemes Mediterranis. L'arribada de malalties virals, com la mixomatosi, han donat lloc a disminucions importants de les poblacions de conills salvatges. La determinació de biomarcadors de l’estat pro-oxidant / anti-oxidant permeten avaluar l’existència d’algun factor ambiental o infecciós que indueixi una situació d’estrès a l’animal. L’objectiu del present estudi va ser avaluar biomarcadors d’estrès a conills obtinguts en diferents modes de captura i en conills afectats per mixomatosi. Els resultats obtinguts no evidencien cap tipus de diferència en les activitats plasmàtiques dels enzims antioxidants, de l’activitat mieloperoxidasa ni dels nivells de malondialdehid en funció de la diferent modalitat de captura: ca eivissenc, fura o grup estabulat. La producció d’espècies reactives per part de les cèl·lules immunitàries tampoc no es veu modificada. Per contra, les activitats dels enzims catalasa, glutatió peroxidasa i glutatió reductasa són significativament més baixes a fetge en animals afectats de mixomatosi respecte als animals sans, mentre que els nivells de malondialdehid són significativament més elevats als animals malalts. En conclusió, el fet que no s’hagin observat diferències derivades del procés de captura ni respecte al grup control, demostra que els conills capturats gaudien d’un bon estat de salut. Els conills afectats per mixomatosi presenten a nivell hepàtic una disminució general de les defenses antioxidants i un augment del dany oxidatiu, cosa que posa de manifest la gravetat de la patologia.[eng] The European rabbit (Oryctolagus cuniculus) is one of the most important vertebrate species in Mediterranean ecosystems. In the last 60 years, the arrival of viral diseases, such as myxomatosis, has led to significant diminution of the populations of wild rabbits. The determination of biomarkers of the pro-oxidant / anti-oxidant status allows the evaluation of the existence of an environmental or infectious factor that induces a situation of stress to the animal and the ability to respond and adapt to this situation. The aim of the present study was to evaluate stress biomarkers from rabbits obtained in different capture modes and rabbits affected by myxomatosis. The results obtained do not show any difference in the plasma activities of antioxidant enzymes, myeloperoxidase activity or malondialdehyde levels depending on the different way of capturing rabbits: Ibizan dogs, ferrets or the confined group. The production of reactive species by immune cells is also unchanged. In contrast, the activities of catalase enzymes, glutathione peroxidase and glutathione reductase are significantly lower in liver in animals affected by myxomatosis compared to healthy animals, while levels of malondialdehyde are significantly higher in diseased animals. In conclusion, the fact that no differences derived from the capture process or the control group have been observed demonstrates that the captured rabbits are in a good state of health. Rabbits affected by myxomatosis have a general decrease in antioxidant defences and an increase in oxidative damage, evidencing the seriousness of the pathology

Clinical features and health-related quality of life in adult patients with mucopolysaccharidosis IVA: the Spanish experience

Background: Mucopolysaccharidosis (MPS) IVA or Morquio A syndrome is a progressive and disabling disease characterized by a deficiency of the enzyme N-acetylgalactosamine-6-sulphate sulphatase. Its clinical presentation is very heterogeneous and poorly understood in adults. The aim of this study was to describe the clinical manifestations of MPS IVA in adult patients in Spain and to assess their health-related quality of life (HRQoL). Results: Thirty-three patients from nine reference centres participated in the study. The median age was 32 (interquartile range [IQR]: 20.5–40.5) years. The phenotype was classical in 54.5% of patients, intermediate in 33.3% of patients, and non-classical in 12.1% of patients. The most common clinical manifestation was bone dysplasia, with a median height of 118 (IQR: 106–136) cm. Other frequent clinical manifestations were hearing loss (75.7%), ligamentous laxity (72.7%), odontoid dysplasia (69.7%), limb deformities that required orthopaedic aids (mainly hip dysplasia and genu valgus) (63.6%), and corneal clouding (60.6%). In addition, 36.0% of patients had obstructive sleep apnoea/hypopnoea syndrome and 33.3% needed non-invasive ventilation. Cervical surgery and varisation osteotomy were the most common surgical interventions (36.4% each). Almost 80% of patients had mobility problems and 36.4% used a wheelchair at all times. Furthermore, 87.9% needed help with self-care, 33.3% were fully dependent, and 78.8% had some degree of pain. HRQoL according to the health assessment questionnaire was 1.43 (IQR: 1.03–2.00) in patients with the non-classical phenotype, but 2.5 (IQR: 1.68–3.00) in those with the classical phenotype. Seven patients were initiated on enzyme replacement therapy (ERT), but two of them were lost to follow-up. Lung function improved in four patients and slightly worsened in one patient. The distance achieved in the six-minute walk test increased in the four patients who could perform it. HRQoL was better in patients treated with elosulfase alfa, with a median (IQR) of 1.75 (1.25–2.34) versus 2.25 (1.62–3.00) in patients not treated with ERT. Conclusions: The study provides real-world data on patients with MPS IVA. Limited mobility, difficulties with self-care, dependence, and pain were common, together with poor HRQoL. The severity and heterogeneity of clinical manifestations require the combined efforts of multidisciplinary teams

Insights into the expanding phenotypic spectrum of inherited disorders of biogenic amines

Inherited disorders of neurotransmitter metabolism are rare neurodevelopmental diseases presenting with movement disorders and global developmental delay. This study presents the results of the first standardized deep phenotyping approach and describes the clinical and biochemical presentation at disease onset as well as diagnostic approaches of 275 patients from the registry of the International Working Group on Neurotransmitter related Disorders. The results reveal an increased rate of prematurity, a high risk for being small for gestational age and for congenital microcephaly in some disorders. Age at diagnosis and the diagnostic delay are influenced by the diagnostic methods applied and by disease-specific symptoms. The timepoint of investigation was also a significant factor: delay to diagnosis has decreased in recent years, possibly due to novel diagnostic approaches or raised awareness. Although each disorder has a specific biochemical pattern, we observed confounding exceptions to the rule. The data provide comprehensive insights into the phenotypic spectrum of neurotransmitter disorders

Assessment of intellectual impairment, health-related quality of life, and behavioral phenotype in patients with neurotransmitter related disorders: data from the iNTD registry

Inherited disorders of neurotransmitter metabolism are a group of rare diseases, which are caused by impaired synthesis, transport or degradation of neurotransmitters or co-factors and result in various degrees of delayed or impaired psychomotor development. To assess the effect of neurotransmitter deficiencies on intelligence, quality of life, and behavior, the data of 148 patients in the registry of the International Working Group on Neurotransmitter Related Disorders (iNTD) was evaluated using results from standardized age-adjusted tests and questionnaires. Patients with a primary disorder of monoamine metabolism had lower IQ scores (mean IQ 58, range 40-100) within the range of cognitive impairment (<70) compared to patients with a BH4 deficiency (mean IQ 84, range 40-129). Short attention span and distractibility were most frequently mentioned by parents, while patients reported most frequently anxiety and distractibility when asked for behavioral traits. In individuals with succinic semialdehyde dehydrogenase deficiency, self-stimulatory behaviors were commonly reported by parents, whereas in patients with dopamine transporter (DAT) deficiency, DNAJC12 deficiency, and monoamine oxidase A deficiency, self-injurious or mutilating behaviors have commonly been observed. Phobic fears were increased in patients with 6-pyruvoyltetrahydropterin synthase deficiency while individuals with sepiapterin reductase deficiency frequently experienced communication and sleep difficulties. Patients with BH4 deficiencies achieved significantly higher quality of life as compared to other groups. This analysis of the iNTD registry data highlights: a) difference in IQ and subdomains of quality of life between BH4 deficiencies and primary neurotransmitter-related disorders, and b) previously underreported behavioral traits

Assessment of intellectual impairment, health-related quality of life, and behavioral phenotype in patients with neurotransmitter related disorders: Data from the iNTD registry

Inherited disorders of neurotransmitter metabolism are a group of rare diseases, which are caused by impaired synthesis, transport, or degradation of neurotransmitters or cofactors and result in various degrees of delayed or impaired psychomotor development. To assess the effect of neurotransmitter deficiencies on intelligence, quality of life, and behavior, the data of 148 patients in the registry of the International Working Group on Neurotransmitter Related Disorders (iNTD) was evaluated using results from standardized age-adjusted tests and questionnaires. Patients with a primary disorder of monoamine metabolism had lower IQ scores (mean IQ 58, range 40-100) within the range of cognitive impairment (<70) compared to patients with a BH4 deficiency (mean IQ 84, range 40-129). Short attention span and distractibility were most frequently mentioned by parents, while patients reported most frequently anxiety and distractibility when asked for behavioral traits. In individuals with succinic semialdehyde dehydrogenase deficiency, self-stimulatory behaviors were commonly reported by parents, whereas in patients with dopamine transporter deficiency, DNAJC12 deficiency, and monoamine oxidase A deficiency, self-injurious or mutilating behaviors have commonly been observed. Phobic fears were increased in patients with 6-pyruvoyltetrahydropterin synthase deficiency, while individuals with sepiapterin reductase deficiency frequently experienced communication and sleep difficulties. Patients with BH4 deficiencies achieved significantly higher quality of life as compared to other groups. This analysis of the iNTD registry data highlights: (a) difference in IQ and subdomains of quality of life between BH4 deficiencies and primary neurotransmitter-related disorders and (b) previously underreported behavioral traits.Dietmar Hopp Stiftung (DE); Medical Faculty of the University of Heidelberg

Regulation of the Fruit-Specific PEP Carboxylase SlPPC2 Promoter at Early Stages of Tomato Fruit Development

The SlPPC2 phosphoenolpyruvate carboxylase (PEPC; EC 4.1.1.31) gene from tomato (Solanum lycopersicum) is differentially and specifically expressed in expanding tissues of developing tomato fruit. We recently showed that a 1966 bp DNA fragment located upstream of the ATG codon of the SlPPC2 gene (GenBank AJ313434) confers appropriate fruit-specificity in transgenic tomato. In this study, we further investigated the regulation of the SlPPC2 promoter gene by analysing the SlPPC2 cis-regulating region fused to either the firefly luciferase (LUC) or the β-glucuronidase (GUS) reporter gene, using stable genetic transformation and biolistic transient expression assays in the fruit. Biolistic analyses of 5′ SlPPC2 promoter deletions fused to LUC in fruits at the 8th day after anthesis revealed that positive regulatory regions are mostly located in the distal region of the promoter. In addition, a 5′ UTR leader intron present in the 1966 bp fragment contributes to the proper temporal regulation of LUC activity during fruit development. Interestingly, the SlPPC2 promoter responds to hormones (ethylene) and metabolites (sugars) regulating fruit growth and metabolism. When tested by transient expression assays, the chimeric promoter:LUC fusion constructs allowed gene expression in both fruit and leaf, suggesting that integration into the chromatin is required for fruit-specificity. These results clearly demonstrate that SlPPC2 gene is under tight transcriptional regulation in the developing fruit and that its promoter can be employed to drive transgene expression specifically during the cell expansion stage of tomato fruit. Taken together, the SlPPC2 promoter offers great potential as a candidate for driving transgene expression specifically in developing tomato fruit from various tomato cultivars

Insights into the expanding phenotypic spectrum of inherited disorders of biogenic amines

Inherited disorders of neurotransmitter metabolism are rare neurodevelopmental diseases presenting with movement disorders and global developmental delay. This study presents the results of the first standardized deep phenotyping approach and describes the clinical and biochemical presentation at disease onset as well as diagnostic approaches of 275 patients from the registry of the International Working Group on Neurotransmitter related Disorders. The results reveal an increased rate of prematurity, a high risk for being small for gestational age and for congenital microcephaly in some disorders. Age at diagnosis and the diagnostic delay are influenced by the diagnostic methods applied and by disease-specific symptoms. The timepoint of investigation was also a significant factor: delay to diagnosis has decreased in recent years, possibly due to novel diagnostic approaches or raised awareness. Although each disorder has a specific biochemical pattern, we observed confounding exceptions to the rule. The data provide comprehensive insights into the phenotypic spectrum of neurotransmitter disorders.We thank all patients and their families for their contributions to this study and for their trust. T.H. and J.K. were supported the grant from the Ministry of Health of the Czech Republic RVO-VFN 64165 GJIH-0599-00-7-846 and ProgresQ26/LF1. A.G.C. and N.J.P. are supported by FIS P118/00111 “Instituto de Salud Carlos III (ISCIII)” and “Fondo Europeo de desarrollo regional (FEDER)”. T.O., K.J., G.F.H. and O.K.H. were supported in parts by the Dietmar Hopp Foundation, St. Leon-Rot, Germany. M.A.K. is funded by an NIHR Professorship, the Sir Jules Thorn Award for Biomedical Research and the Rosetrees trust. M.V. is supported by Stichting Stofwisselkracht Grant. D.H. acknowledges funding by the Molecular Diagnostics Program of the National Center for Tumor Diseases (NCT) Heidelberg.Peer reviewe