The effect of projections on dimension in the Heisenberg group

We prove analogs of classical almost sure dimension theorems for Euclidean projection mappings in the first Heisenberg group, equipped with a sub-Riemannian metric.

Bright moonlight triggers natal dispersal departures

Upon leaving their natal area, dispersers are confronted with unknown terrains. Species-specific perceptual ranges (i.e. the maximum distance from which an individual can perceive landscape features) play a crucial role in spatial movement decisions during such wanderings. In nocturnal animals that rely on vision, perceptual range is dramatically enhanced during moonlight, compared to moonless conditions. This increase of the perceptual range is an overlooked element that may be responsible for the successful crossing of unfamiliar areas during dispersal. The information gathered from 143 radio-tagged eagle owl Bubo bubo juveniles in Spain, Finland and Switzerland shows that, although the decision to initiate dispersal is mainly an endogenous phenomenon determined by the attainment of a given age (∼6 months), dispersers leave their birthplace primarily under the best light conditions at night, i.e. when most of the lunar disc is illuminated. This sheds new light into the mechanisms that may trigger dispersal from parental territory.

A Missense Change in the ATG4D Gene Links Aberrant Autophagy to a Neurodegenerative Vacuolar Storage Disease.

Inherited neurodegenerative disorders are debilitating diseases that occur across different species. We have performed clinical, pathological and genetic studies to characterize a novel canine neurodegenerative disease present in the Lagotto Romagnolo dog breed. Affected dogs suffer from progressive cerebellar ataxia, sometimes accompanied by episodic nystagmus and behavioral changes. Histological examination revealed unique pathological changes, including profound neuronal cytoplasmic vacuolization in the nervous system, as well as spheroid formation and cytoplasmic aggregation of vacuoles in secretory epithelial tissues and mesenchymal cells. Genetic analyses uncovered a missense change, c.1288G>A; p.A430T, in the autophagy-related ATG4D gene on canine chromosome 20 with a highly significant disease association (p = 3.8 x 10-136) in a cohort of more than 2300 Lagotto Romagnolo dogs. ATG4D encodes a poorly characterized cysteine protease belonging to the macroautophagy pathway. Accordingly, our histological analyses indicated altered autophagic flux in affected tissues. The knockdown of the zebrafish homologue atg4da resulted in a widespread developmental disturbance and neurodegeneration in the central nervous system. Our study describes a previously unknown canine neurological disease with particular pathological features and implicates the ATG4D protein as an important autophagy mediator in neuronal homeostasis. The canine phenotype serves as a model to delineate the disease-causing pathological mechanism(s) and ATG4D function, and can also be used to explore treatment options. Furthermore, our results reveal a novel candidate gene for human neurodegeneration and enable the development of a genetic test for veterinary diagnostic and breeding purposes.

Inherited susceptibility to uterine leiomyomas and renal cell cancer

Herein we report the clinical, histopathological, and molecular features of a cancer syndrome with predisposition to uterine leiomyomas and papillary renal cell carcinoma. The studied kindred included 11 family members with uterine leiomyomas and two with uterine leiomyosarcoma. Seven individuals had a history of cutaneous nodules, two of which were confirmed to be cutaneous leiomyomatosis. The four kidney cancer cases occurred in young (33- to 48-year-old) females and displayed a unique natural history. All these kidney cancers displayed a distinct papillary histology and presented as unilateral solitary lesions that had metastasized at the time of diagnosis. Genetic-marker analysis mapped the predisposition gene to chromosome 1q. Losses of the normal chromosome 1q were observed in tumors that had occurred in the kindred, including a uterine leiomyoma. Moreover, the observed histological features were used as a tool to diagnose a second kindred displaying the phenotype. We have shown that predisposition to uterine leiomyomas and papillary renal cell cancer can be inherited dominantly through the hereditary leiomyomatosis and renal cell cancer (HLRCC) gene. The HLRCC gene maps to chromosome 1q and is likely to be a tumor suppressor. Clinical, histopathological, and molecular tools are now available for accurate detection and diagnosis of this cancer syndrome.

Crystal structure of the membrane-exposed domain from a respiratory quinol oxidase complex with an engineered dinuclear copper center.

Cytochrome oxidase is a membrane protein complex that catalyzes reduction of molecular oxygen to water and utilizes the free energy of this reaction to generate a transmembrane proton gradient during respiration. The electron entry site in subunit II is a mixed-valence dinuclear copper center in enzymes that oxidize cytochrome c. This center has been lost during the evolution of the quinoloxidizing branch of cytochrome oxidases but can be restored by engineering. Herein we describe the crystal structures of the periplasmic fragment from the wild-type subunit II (CyoA) of Escherichia coli quinol oxidase at 2.5-A resolution and of the mutant with the engineered dinuclear copper center (purple CyoA) at 2.3-A resolution. CyoA is folded as an 11-stranded mostly antiparallel beta-sandwich followed by three alpha-helices. The dinuclear copper center is located at the loops between strands beta 5-beta 6 and beta 9-beta 10. The two coppers are at a 2.5-A distance and symmetrically coordinated to the main ligands that are two bridging cysteines and two terminal histidines. The residues that are distinct in cytochrome c and quinol oxidases are around the dinuclear copper center. Structural comparison suggests a common ancestry for subunit II of cytochrome oxidase and blue copper-binding proteins.

Molecular Characterization of Three Canine Models of Human Rare Bone Diseases: Caffey, van den Ende-Gupta, and Raine Syndromes.

One to two percent of all children are born with a developmental disorder requiring pediatric hospital admissions. For many such syndromes, the molecular pathogenesis remains poorly characterized. Parallel developmental disorders in other species could provide complementary models for human rare diseases by uncovering new candidate genes, improving the understanding of the molecular mechanisms and opening possibilities for therapeutic trials. We performed various experiments, e.g. combined genome-wide association and next generation sequencing, to investigate the clinico-pathological features and genetic causes of three developmental syndromes in dogs, including craniomandibular osteopathy (CMO), a previously undescribed skeletal syndrome, and dental hypomineralization, for which we identified pathogenic variants in the canine SLC37A2 (truncating splicing enhancer variant), SCARF2 (truncating 2-bp deletion) and FAM20C (missense variant) genes, respectively. CMO is a clinical equivalent to an infantile cortical hyperostosis (Caffey disease), for which SLC37A2 is a new candidate gene. SLC37A2 is a poorly characterized member of a glucose-phosphate transporter family without previous disease associations. It is expressed in many tissues, including cells of the macrophage lineage, e.g. osteoclasts, and suggests a disease mechanism, in which an impaired glucose homeostasis in osteoclasts compromises their function in the developing bone, leading to hyperostosis. Mutations in SCARF2 and FAM20C have been associated with the human van den Ende-Gupta and Raine syndromes that include numerous features similar to the affected dogs. Given the growing interest in the molecular characterization and treatment of human rare diseases, our study presents three novel physiologically relevant models for further research and therapy approaches, while providing the molecular identity for the canine conditions.

Gränsdragning mellan arbete & fritid : Närvaro i sin frånvaro

Vårt syfte med denna studie är att ämna beskriva vilken betydelse det gränslösa arbetet får för chefsrollen, utifrån de förändringar som sker i dagens arbetsliv samt hur gränsdragningen mellan arbete och fritid hanteras. Vi valde att utföra vår studie i form av kvalitativa intervjuer, där vi intervjuade sex medarbetare inom en offentlig organisation i Dalarna, Sverige. Det resultat vi erhöll analyserades utifrån tidigare forskning och teorier. Resultaten i vår studie visar att cheferna direkt eller indirekt påverkas av förändringar som sker i arbetslivet och att det även är något som påverkar hur cheferna hanterar gränsdragningen mellan arbete och fritid. Studiens resultat visar vidare att cheferna menar att dessa förändringar bidrar till att förändra deras sätt att agera i chefsrollen och att det ställer andra krav på deras kompetenser. Resultatet visar också att kraven i arbetet måste vara rimliga, för att skapa balans mellan arbets- och privatliv och att det i första hand inte är de kvantitativa faktorerna i förhållande till arbetet som skapar en upplevelse av gränslöshet. Med kvantitativa faktorer menar vi de faktorer som traditionellt beskrivs som mer konkreta faktorer i arbetet, exempelvis arbetets utformning, arbetstiden, tillgängligheten eller antalet arbetsuppgifter att utföra. Istället belyser resultatet att en emotionell känsla av stress kan uppstå i relation till den egna upplevelsen av en känslig situation i arbetet eller när den egna kompetensen inte räcker till i arbetsutförandet och att det kan skapa en otydlig gräns mellan arbetstid och fritid.

Putkien päittäishitsaaminen orbitaali-TIG-hitsauksella

Tämän kandidaatintyön tavoitteena oli esitellä orbitaali-TIG-hitsauksen käyttämistä putkien päittäishitsaamiseen. Työssä esitellään Suomesta saatavia orbitaali-TIG-laitteita ja TIG-hitsausprosessi pääperiaatteiltaan sekä prosessin käyttämistä orbitaalihitsaukseen. Myös orbitaali-TIG-hitsauksen tuottavuuteen ja laatuun liittyviä asioita käydään läpi. Suomesta saatavilla olevista laitteista valittiin toiminnallisten mittojen kannalta sopivimmat kandidaatintyötä varten suunniteltuun ripaputkilämmönvaihtimen hitsaukseen. Työ on pääasiallisesti tehty kirjallisuustutkimuksena käyttäen apuna orbitaalilaitteistojen valmistajien ja jälleenmyyjien haastatteluja. Kirjalliset lähteet koostuvat kotimaisesta ja kansainvälisestä hitsauksen alan kirjallisuudesta ja teksti on pyritty sitomaan yhteen käyttäen useaa eri lähdettä. Laitekohtaiset tiedot saatiin laitevalmistajien tuotetiedotteista ja sähköpostihaastatteluna laitteiden jälleenmyyjiltä ja laitevalmistajilta. Suomessa orbitaali-TIG-laitteita maahantuo ja jälleenmyy Masino Welding Oy ja Suomen Teknohaus Oy. Suomessa laitteita valmistaa Kemppi Oy, jonka orbitaalilaitteilla on useita jälleenmyyjiä. Masino Welding Oy myy saksalaisia Orbitalum GmbH:n laitteita ja Suomen Teknohaus Oy ranskalaisia Polysoude S.A.S.:n laitteita. Näiden laitevalmistajien joukosta suunnitellun ripaputkilämmönvaihtimen hitsaukseen soveltuu Orbitalumilta ja Polysoudelta yhdet sekä Kempiltä kaksi umpipihtimallista orbitaalihitsauspäätä. Orbitaali-TIG-hitsauslaitteissa virtalähteet ovat kehittyneet eniten vuosien aikana ja eri laitevalmistajien laitteistojen erot ovat pääasiassa virtalähteisiin liittyviä. Ripaputkilämmönvaihtimen hitsaamiseen sopivin hitsauspäämalli on umpipihti, sillä lämmönvaihtimen päädyt ovat hyvin ahtaita ja umpipihdit ovat orbitaalihitsauspäistä kaikkein kompakteimmat. Suomessa orbitaali-TIG-laitteita ei ole kauheasti tarjolla ja laitteiden markkinointi on jossain määrin kannattamatonta. Orbitaalihitsaus on kuitenkin varteenotettava vaihtoehto TIG-käsinhitsaukselle, jos hitsataan paljon samankaltaisia hitsejä.