Chemical composition of the old globular clusters NGC 1786, NGC 2210 and NGC 2257 in the Large Magellanic Cloud

This paper presents the chemical abundance analysis of a sample of 18 giant stars in 3 old globular clusters in the Large Magellanic Cloud, namely NGC 1786, NGC 2210 and NGC 2257. The derived iron content is [Fe/H]= --1.75+-0.01 dex (sigma= 0.02 dex), --1.65+-0.02 dex (sigma= 0.04 dex) and --1.95+-0.02 dex (sigma= 0.04 dex) for NGC 1786, NGC 2210 and NGC 2257, respectively. All the clusters exhibit similar abundance ratios, with enhanced values (+0.30 dex) of [alpha/Fe], consistent with the Galactic Halo stars, thus indicating that these clusters have formed from a gas enriched by Type II SNe. We also found evidence that r-process are the main channel of production of the measured neutron capture elements (Y, Ba, La, Nd, Ce and Eu). In particular the quite large enhancement of [Eu/Fe] (+0.70 dex) found in these old clusters clearly indicates a relevant efficiency of the r-process mechanism in the LMC environment.Comment: Accepted for pbblication in Ap

The trainer profession in equestrian sports : needs of competence and training course.

Tränare är idag framför allt skickliga på att rida och undervisa ryttare i ridning. I denna studie framkommer flera kompetensområden som efterfrågas av ryttare hos tränare. För att ridsporten och tävlingsverksamheten i Sverige ska fortsätta utvecklas är det en fördel om de utbildningar som kan leda fram till en tränarroll överensstämmer innehållsmässigt med vad ryttare efterfrågar hos sin tränare. Syftet med studien var att kartlägga tränares yrkeskompetens från utbildning, samt ställa det i relation till marknadens behov av kunskap från tränarkåren utifrån befintlig forskning. Vilket leder till frågeställningarna: Hur ser kompetensbehovet hos tränare ut, utifrån befintlig forskning inom området? Och vilket innehåll finns i de utbildningar som idag kan leda fram till en tränarroll? Via befintlig forskning och litteratur samt personlig kommunikation via telefonsamtal har resultatet i denna litteraturstudie framställts. Berörda områden innefattar pedagogik, coaching och ridundervisning, hästutbildning och innehåll i utbildningarna som kan leda fram till en tränarroll. I resultatet syns en koppling mellan flera av de tidigare studierna gällande efterfrågad kompetens hos tränare och nya metoder att undervisa ryttare, där pedagogik och hästkunskap är eftertraktade ämnen. Efterfrågan av coaching som metod i ridundervisningen är framträdande genom flera studier. Ryttare önskar mer tid att diskutera ridning och hästvälfärd med sin tränare. Att ha en dialog mellan tränare, ryttare och häst anses viktigt. Vidare förväntas tränare även ha en rad andra kunskaper, bland annat om idrottspsykologi och mental träning. Utbildningarna som kan leda fram till tränarrollen är idag delvis lika varandra i avseende om vilka ämnen de innehåller. Tränarutbildningen och Hippologprogrammet innehåller båda kurser som omfattar pedagogik, hästkunskap och företagsekonomi samt andra ämnen inriktade mot hästverksamhet vilka motsvarar kompetensområden ryttare efterfrågar hos tränare. Slutsatsen är att utbildningarna till stor del möter ryttares efterfrågan av kompetens hos tränare. Tränarutbildningen och Hippologprogrammet innehåller ett varierat utbud av kurser vilka innefattar bland annat pedagogik som är den mest efterfrågade kompetensen hos tränare av ryttare, följt av hästkunskap som även det är en efterfrågad kompetens. I vilken omfattning hästkunskap är efterfrågat är inte lika tydligt som efterfrågan av pedagogisk kunskap, vilket kan vara ett område att forska vidare på. Det coachande förhållningssättet börjar växa fram i ridsporten och lika så i utbildningarna som kan leda fram till tränarrollen. Enstaka kurser och föreläsningar i coachning ingår i utbildningarna men kan i framtiden eventuellt behöva ökas i omfattning i takt med att undervisningsmetoderna i ridsporten utvecklas. Vidare forskning om relationen mellan tränare, ryttare och häst behövs för att utveckla undervisningsmetoderna och utbildningarna vidare.Trainers today are especially skilled at riding and teaching riding. In this study, several competence areas emerge that are requested by riders from trainers. For equestrian sports and competitions in Sweden to continue to develop, it is an advantage if the education that can lead to a trainers’ role corresponds in terms of content with what riders’ request in terms of knowledge from their trainer. This study contains the trainer education that is available through the Swedish Equestrian Federation and the Equine Science - Bachelor's program that goes under the Swedish University of Agricultural Sciences as ways to become a trainer. The purpose of the study was to map trainers’ professional competence from their education and to place it in relation to the market's need for knowledge from the trainer staff, based on existing research. What does the need of competence in trainers look like, based on previous research? What content is there in the educations that can lead to a trainer’s role today? The results of this literature study have been produced via existing research and literature. The result shows a connection between several of the previous studies regarding requested competence in trainers and new methods of teaching riders, where pedagogy and knowledge about horse welfare are sought-after subjects. Coaching as a form of teaching in riding lessons is also prominent through several studies. Riders want more time to discuss riding and horse welfare with their trainer. Having a dialogue between trainer, rider and horse is considered important. Furthermore, trainers are also expected to have several other knowledges, including sports psychology and mental training. The educations that can lead to becoming a trainer are a lot like each other in forms of subjects. The trainer education as well as the Equine Science - Bachelor's program contains pedagogy, knowledge of horses and economy along other subjects that involves the horse industry. These subjects answer well to the requests riders have in form of knowledge from their trainer. The conclusion is that the educations largely meet riders' requests of skills from coaches. The trainer education and the Equine Science - Bachelor's program contain a varied range of courses including pedagogy, which is the most requested competence among trainers of riders, followed by horse knowledge, which is also a requested competence. To which extent knowledge of horses are requested is not as clear as the requested competence of pedagogy and could use further research. The coaching approach is beginning to emerge in equestrian sports and as well as in the educations that can lead to a trainer role. Individual courses and lectures in coaching are included in educations but may in the future possibly need to be increased as the teaching methods in equestrian sports develops. Further research on the relationship between trainer, rider and horse is necessary to further develop the teaching methods and the educations

Insights into molecular mechanisms of disease in Neurodegeneration with Brain Iron Accumulation; unifying theories.

Neurodegeneration with brain iron accumulation (NBIA) is a group of disorders characterised by dystonia, parkinsonism and spasticity. Iron accumulates in the basal ganglia and may be accompanied by Lewy bodies, axonal swellings and hyperphosphorylated tau depending on NBIA subtype. Mutations in 10 genes have been associated with NBIA that include Ceruloplasmin (Cp) and Ferritin Light Chain (FTL), both directly involved in iron homeostasis, as well as Pantothenate Kinase 2 (PANK2), Phospholipase A2 group 6 (PLA2G6), Fatty acid hydroxylase 2 (FA2H), Coenzyme A synthase (COASY), C19orf12, WDR45 and DCAF17 (C2orf37). These genes are involved in seemingly unrelated cellular pathways, such as lipid metabolism, Coenzyme A synthesis and autophagy. A greater understanding of the cellular pathways that link these genes and the disease mechanisms leading to iron dyshomeostasis is needed. Additionally, the major overlap seen between NBIA and more common neurodegenerative diseases may highlight conserved disease processes. In this review, we will discuss clinical and pathological findings for each NBIA-related gene, discuss proposed disease mechanisms such as mitochondrial health, oxidative damage, autophagy/mitophagy and iron homeostasis and speculate potential overlap between NBIA subtypes

Tau and spectraplakins promote synapse formation and maintenance through Jun kinase and neuronal trafficking

© Voelzmann et al.The mechanisms regulating synapse numbers during development and ageing are essential for normal brain function and closely linked to brain disorders including dementias. Using Drosophila, we demonstrate roles of the microtubule-associated protein Tau in regulating synapse numbers, thus unravelling an important cellular requirement of normal Tau. In this context, we find that Tau displays a strong functional overlap with microtubule-binding spectraplakins, establishing new links between two different neurodegenerative factors. Tau and the spectraplakin Short Stop act upstream of a three-step regulatory cascade ensuring adequate delivery of synaptic proteins. This cascade involves microtubule stability as the initial trigger, JNK signalling as the central mediator, and kinesin-3 mediated axonal transport as the key effector. This cascade acts during development (synapse formation) and ageing (synapse maintenance) alike. Therefore, our findings suggest novel explanations for intellectual disability in Tau deficient individuals, as well as early synapse loss in dementias including Alzheimer’s disease

Biallelic mutations in neurofascin cause neurodevelopmental impairment and peripheral demyelination.

Axon pathfinding and synapse formation are essential processes for nervous system development and function. The assembly of myelinated fibres and nodes of Ranvier is mediated by a number of cell adhesion molecules of the immunoglobulin superfamily including neurofascin, encoded by the NFASC gene, and its alternative isoforms Nfasc186 and Nfasc140 (located in the axonal membrane at the node of Ranvier) and Nfasc155 (a glial component of the paranodal axoglial junction). We identified 10 individuals from six unrelated families, exhibiting a neurodevelopmental disorder characterized with a spectrum of central (intellectual disability, developmental delay, motor impairment, speech difficulties) and peripheral (early onset demyelinating neuropathy) neurological involvement, who were found by exome or genome sequencing to carry one frameshift and four different homozygous non-synonymous variants in NFASC. Expression studies using immunostaining-based techniques identified absent expression of the Nfasc155 isoform as a consequence of the frameshift variant and a significant reduction of expression was also observed in association with two non-synonymous variants affecting the fibronectin type III domain. Cell aggregation studies revealed a severely impaired Nfasc155-CNTN1/CASPR1 complex interaction as a result of the identified variants. Immunofluorescence staining of myelinated fibres from two affected individuals showed a severe loss of myelinated fibres and abnormalities in the paranodal junction morphology. Our results establish that recessive variants affecting the Nfasc155 isoform can affect the formation of paranodal axoglial junctions at the nodes of Ranvier. The genetic disease caused by biallelic NFASC variants includes neurodevelopmental impairment and a spectrum of central and peripheral demyelination as part of its core clinical phenotype. Our findings support possible overlapping molecular mechanisms of paranodal damage at peripheral nerves in both the immune-mediated and the genetic disease, but the observation of prominent central neurological involvement in NFASC biallelic variant carriers highlights the importance of this gene in human brain development and function

Early Growth and Development Impairments in Patients with Ganglioside GM3 Synthase Deficiency

Ganglioside GM3 synthase is a key enzyme involved in the biosynthesis of gangliosides. GM3 synthase deficiency (GSD) causes a complete absence of GM3 and all downstream biosynthetic derivatives. The individuals affected by this disorder manifest severe irritability, intractable seizures and profound intellectual disability. However, we have found that most newborns seem symptom-free for a period of time after birth. In order to further understand the onset of the disease, we investigated the early growth and development of patients with this condition through this study. We compared 37 affected individuals with their normal siblings and revealed that all children with GSD had relatively normal intrauterine growth and development, as their weight, length and head circumference were similar to their normal siblings at birth. However, the disease progresses quickly after birth and causes significant constitutional impairments of growth and development by 6 months of age. Neither breastfeeding nor gastrostomy tube placement made significant difference on growth and development as all groups of patients showed the similar pattern. We conclude that GSD causes significant postnatal growth and developmental impairments and the amount of gangliosides in breast milk and general nutritional intervention do not seem to alter these outcomes

Leukoencephalopathy with accumulated succinate is indicative of SDHAF1 related complex II deficiency

BACKGROUND: Deficiency of complex II (succinate dehydrogenase, SDH) represents a rare cause of mitochondrial disease and is associated with a wide range of clinical symptoms. Recently, mutations of SDHAF1, the gene encoding for the SDH assembly factor 1, were reported in SDH-defective infantile leukoencephalopathy. Our goal was to identify SDHAF1 mutations in further patients and to delineate the clinical phenotype. METHODS: In a retrospective data collection study we identified nine children with biochemically proven complex II deficiency among our cohorts of patients with mitochondrial disorders. The cohort comprised five patients from three families affected by SDH-defective infantile leukoencephalopathy with accumulation of succinate in disordered cerebral white matter, as detected by in vivo proton MR spectroscopy. One of these patients had neuropathological features of Leigh syndrome. Four further unrelated patients of the cohort showed diverse clinical phenotypes without leukoencephalopathy. SDHAF1 was sequenced in all nine patients. RESULTS: Homozygous mutations of SDHAF1 were detected in all five patients affected by leukoencephalopathy with accumulated succinate, but not in any of the four patients with other, diverse clinical phenotypes. Two sisters had a mutation reported previously, in three patients two novel mutations were found. CONCLUSION: Leukoencephalopathy with accumulated succinate is a key symptom of defective complex II assembly due to SDHAF1 mutations

Altered RNA metabolism due to a homozygous RBM7 mutation in a patient with spinal motor neuropathy.

The exosome complex is the most important RNA processing machinery within the cell. Mutations in its subunits EXOSC8 and EXOSC3 cause pontocerebellar hypoplasia, spinal muscular atrophy (SMA) and central nervous system demyelination. We present a patient with SMA-like phenotype carrying a homozygous mutation in RBM7-a subunit of the nuclear exosome targeting (NEXT) complex-which is known to bind and carry specific subtypes of coding and non-coding RNAs to the exosome. The NEXT complex with other protein complexes is responsible for the substrate specificity of the exosome. We performed RNA-sequencing (RNA-seq) analysis on primary fibroblasts of patients with mutations in EXOSC8 and RBM7 and gene knock-down experiments using zebrafish as a model system. RNA-seq analysis identified significantly altered expression of 62 transcripts shared by the two patient cell lines. Knock-down of rbm7, exosc8 and exosc3 in zebrafish showed a common pattern of defects in motor neurons and cerebellum. Our data indicate that impaired RNA metabolism may underlie the clinical phenotype by fine tuning gene expression which is essential for correct neuronal differentiation

A Deleterious Mutation in DNAJC6 Encoding the Neuronal-Specific Clathrin-Uncoating Co-Chaperone Auxilin, Is Associated with Juvenile Parkinsonism

Parkinson disease is caused by neuronal loss in the substantia nigra which manifests by abnormality of movement, muscle tone, and postural stability. Several genes have been implicated in the pathogenesis of Parkinson disease, but the underlying molecular basis is still unknown for ∼70% of the patients. Using homozygosity mapping and whole exome sequencing we identified a deleterious mutation in DNAJC6 in two patients with juvenile Parkinsonism. The mutation was associated with abnormal transcripts and marked reduced DNAJC6 mRNA level. DNAJC6 encodes the HSP40 Auxilin, a protein which is selectively expressed in neurons and confers specificity to the ATPase activity of its partner Hcs70 in clathrin uncoating. In Auxilin null mice it was previously shown that the abnormally increased retention of assembled clathrin on vesicles and in empty cages leads to impaired synaptic vesicle recycling and perturbed clathrin mediated endocytosis. Endocytosis function, studied by transferring uptake, was normal in fibroblasts from our patients, likely because of the presence of another J-domain containing partner which co-chaperones Hsc70-mediated uncoating activity in non-neuronal cells. The present report underscores the importance of the endocytic/lysosomal pathway in the pathogenesis of Parkinson disease and other forms of Parkinsonism

A Zebrafish Model for a Rare Genetic Disease Reveals a Conserved Role for FBXL3 in the Circadian Clock System

The circadian clock, which drives a wide range of bodily rhythms in synchrony with the day–night cycle, is based on a molecular oscillator that ticks with a period of approximately 24 h. Timed proteasomal degradation of clock components is central to the fine-tuning of the oscillator’s period. FBXL3 is a protein that functions as a substrate-recognition factor in the E3 ubiquitin ligase complex, and was originally shown in mice to mediate degradation of CRY proteins and thus contribute to the mammalian circadian clock mechanism. By exome sequencing, we have identified a FBXL3 mutation in patients with syndromic developmental delay accompanied by morphological abnormalities and intellectual disability, albeit with a normal sleep pattern. We have investigated the function of FBXL3 in the zebrafish, an excellent model to study both vertebrate development and circadian clock function and, like humans, a diurnal species. Loss of fbxl3a function in zebrafish led to disruption of circadian rhythms of promoter activity and mRNA expression as well as locomotor activity and sleep–wake cycles. However, unlike humans, no morphological effects were evident. These findings point to an evolutionary conserved role for FBXL3 in the circadian clock system across vertebrates and to the acquisition of developmental roles in humans