Seks år på langfart, en dansk dames oplevelser 1889-1895

I mange år stod der i al ubemærkethed to gamle kister oppe på det store loft helt oppe under taget i Kolstrup 11/Callesensgade 1. Da huset skulle tømmes i 2002, så vi, at der stod noget på dem: J. Bruhn 1864 og Helene Bruhn, Apenrade. Og frem dukkede så efterhånden historien bag de to gamle skibskister og de personer, der havde ejet dem. Helene Bruhn (1859-1937) var født Junggreen. Hendes far var den kendte sønderjyde J. P. Junggreen. Hun blev gift med Jacob Bruhn, som var min oldemors bror. Han blev kaptajn på briggen MIDDELHEUS og med den sejlede de fra Hamborg 1889 på langfart. Helene beskriver levende alt det, hun oplever. Med sin flotte håndskrift og på fejlfrit dansk har hun skrevet 85 sider i stilehæfter fra Bo Bojesens Boghandel i Åbenrå. Det var jo i tysk tid, men hun havde gået i Juhlers danske privatskole i Åbenrå. I 1895 rejste hun hjem fra Valparaiso. Hendes mand Jacob Bruhn forsvandt senere sporløst i Argentina. Kun hans skibskiste vendte hjem til Åbenrå. Min mor, Hanne Dahlkild, fortæller i sine erindringer fra barndomstiden i Kolstrup 11 om tante Lene »Musik«, som boede i den lille lejlighed på 1. sal. Hendes ting var ikke prangende. Et klaver og et stort skibsbillede af et Åbenråskib fortalte om hendes interesser og skæbne. Hun gav børnene klaverundervisning, og hver jul samlede hun dem omkring et lille juletræ. Hendes største ønske var, at børnene kunne spille til en dansk sang og en glad polka – uden at gå i stå. Tante Lene havde tit familiebesøg og holdt klubeftermiddag hver onsdag hele året rundt. Her blev der drukket kaffe, sunget danske sange og strikket halstørklæder og sokker til sømandsmissionen og pakket gaver til jul til danske søfolk i fremmede havne. Hanne Løfqvis

Respiratory chain complex III deficiency due to mutated BCS1L : a novel phenotype with encephalomyopathy, partially phenocopied in a Bcs1l mutant mouse model

Background: Mitochondrial diseases due to defective respiratory chain complex III (CIII) are relatively uncommon. The assembly of the eleven-subunit CIII is completed by the insertion of the Rieske iron-sulfur protein, a process for which BCS1L protein is indispensable. Mutations in the BCS1L gene constitute the most common diagnosed cause of CIII deficiency, and the phenotypic spectrum arising from mutations in this gene is wide. Results: A case of CIII deficiency was investigated in depth to assess respiratory chain function and assembly, and brain, skeletal muscle and liver histology. Exome sequencing was performed to search for the causative mutation(s). The patient's platelets and muscle mitochondria showed respiration defects and defective assembly of CIII was detected in fibroblast mitochondria. The patient was compound heterozygous for two novel mutations in BCS1L, c.306A > T and c.399delA. In the cerebral cortex a specific pattern of astrogliosis and widespread loss of microglia was observed. Further analysis showed loss of Kupffer cells in the liver. These changes were not found in infants suffering from GRACILE syndrome, the most severe BCS1L-related disorder causing early postnatal mortality, but were partially corroborated in a knock-in mouse model of BCS1L deficiency. Conclusions: We describe two novel compound heterozygous mutations in BCS1L causing CIII deficiency. The pathogenicity of one of the mutations was unexpected and points to the importance of combining next generation sequencing with a biochemical approach when investigating these patients. We further show novel manifestations in brain, skeletal muscle and liver, including abnormality in specialized resident macrophages (microglia and Kupffer cells). These novel phenotypes forward our understanding of CIII deficiencies caused by BCS1L mutations.Peer reviewe

Impact of village savings and loan associations: Evidence from a cluster randomized trial

The vast majority of the world's poor live in rural areas of developing countries with little access to financial services. Setting up Village Savings and Loan Associations (VSLAs) has become an increasingly widespread intervention aimed at improving local financial intermediation. Using a cluster randomized trial we investigate the impact of VSLAs in Northern Malawi over a two year period. We find evidence of positive and significant intention-to-treat effects on several outcomes, including the number of meals consumed per day, household expenditure as measured by the USAID Poverty Assessment Tool, and the number of rooms in the dwelling. This effect is linked to an increase in savings and credit obtained through the VSLAs, which has increased agricultural investments and income from small businesses

A New Homoplasmic mtDNA Mutation Described in Mother and Son with Clinical LHON

A 48 year old woman presented with acute painless sequential visual loss that progressed over two months. The patient had no previous ophthalmologic history. She was a chronic smoker with intermittent alcohol abuse and an amphetamine addiction 15 years prior

SQSTM1/p62-Directed Metabolic Reprogramming Is Essential for Normal Neurodifferentiation

Summary: Neurodegenerative disorders are an increasingly common and irreversible burden on society, often affecting the aging population, but their etiology and disease mechanisms are poorly understood. Studying monogenic neurodegenerative diseases with known genetic cause provides an opportunity to understand cellular mechanisms also affected in more complex disorders. We recently reported that loss-of-function mutations in the autophagy adaptor protein SQSTM1/p62 lead to a slowly progressive neurodegenerative disease presenting in childhood. To further elucidate the neuronal involvement, we studied the cellular consequences of loss of p62 in a neuroepithelial stem cell (NESC) model and differentiated neurons derived from reprogrammed p62 patient cells or by CRISPR/Cas9-directed gene editing in NESCs. Transcriptomic and proteomic analyses suggest that p62 is essential for neuronal differentiation by controlling the metabolic shift from aerobic glycolysis to oxidative phosphorylation required for neuronal maturation. This shift is blocked by the failure to sufficiently downregulate lactate dehydrogenase expression due to the loss of p62, possibly through impaired Hif-1α downregulation and increased sensitivity to oxidative stress. The findings imply an important role for p62 in neuronal energy metabolism and particularly in the regulation of the shift between glycolysis and oxidative phosphorylation required for normal neurodifferentiation. : SQSTM1/p62 is a known autophagy adaptor that, if lost, causes childhood-onset neurodegeneration. Data from Wredenberg et al. show that loss of p62 in a neuronal stem cell model does not affect mitophagy but instead leads to impaired differentiation. The authors suggest p62 finely tunes LDHA expression and thus controls the metabolic shift to OXPHOS required for proper differentiation. Keywords: SQSTM1, p62, hypoxia, mitochondria, neurodifferentiation, neuroepithelial-like stem cells, neuronal development, oxidative stress, mitophagy, neurodegeneratio

A multi-systemic mitochondrial disorder due to a dominant p.Y955H disease variant in DNA polymerase gamma

Mutations in the mitochondrial DNA polymerase, POLG, are associated with a variety of clinical presentations, ranging from early onset fatal brain disease in Alpers syndrome to chronic progressive external ophthalmoplegia. The majority of mutations are linked with disturbances of mitochondrial DNA (mtDNA) integrity and maintenance. On a molecular level, depending on their location within the enzyme, mutations either lead to mtDNA depletion or the accumulation of multiple mtDNA deletions, and in some cases these molecular changes can be correlated to the clinical presentation. We identified a patient with a dominant p.Y955H mutation in POLG, presenting with a severe, early-onset multi-systemic mitochondrial disease with bilateral sensorineural hearing loss, cataract, myopathy, and liver failure. Using a combination of disease models of Drosophila melanogaster and in vitro biochemistry analysis, we compare the molecular consequences of the p.Y955H mutation to the well-documented p.Y955C mutation. We demonstrate that both mutations affect mtDNA replication and display a dominant negative effect, with the p.Y955H allele resulting in a more severe polymerase dysfunction