Bi-allelic variants in HOPS complex subunit VPS41 cause cerebellar ataxia and abnormal membrane trafficking.

Membrane trafficking is a complex, essential process in eukaryotic cells responsible for protein transport and processing. Deficiencies in vacuolar protein sorting (VPS) proteins, key regulators of trafficking, cause abnormal intracellular segregation of macromolecules and organelles and are linked to human disease. VPS proteins function as part of complexes such as the homotypic fusion and vacuole protein sorting (HOPS) tethering complex, composed of VPS11, VPS16, VPS18, VPS33A, VPS39 and VPS41. The HOPS-specific subunit VPS41 has been reported to promote viability of dopaminergic neurons in Parkinson's disease but to date has not been linked to human disease. Here, we describe five unrelated families with nine affected individuals, all carrying homozygous variants in VPS41 that we show impact protein function. All affected individuals presented with a progressive neurodevelopmental disorder consisting of cognitive impairment, cerebellar atrophy/hypoplasia, motor dysfunction with ataxia and dystonia, and nystagmus. Zebrafish disease modelling supports the involvement of VPS41 dysfunction in the disorder, indicating lysosomal dysregulation throughout the brain and providing support for cerebellar and microglial abnormalities when vps41 was mutated. This provides the first example of human disease linked to the HOPS-specific subunit VPS41 and suggests the importance of HOPS complex activity for cerebellar function

Współczynnik LCI jako podstawowe kryterium oceny zdrowotnej emisji lotnych związków organicznych z wyrobów budowlanych

W niniejszym artykule została przedstawiona koncepcja stosowania wartości LCI (ang. Lowest Concentration of Interest) do oceny wpływu na zdrowie emitowanych z wyrobów budowlanych lotnych związków organicznych (LZO). Wartości LCI zostały pierwotnie opracowane przez grupę wiodących europejskich naukowców i opublikowane w 1997 r. w Raporcie nr 18 European Collaborative Action. Obecnie współczynnik ten jest coraz częściej wykorzystywany w przepisach krajów wspólnoty europejskiej do oceny emisji LZO z wyrobów budowlanych. Został również użyty w projekcie klasyfikacji emisji lotnych związków organicznych Komisji Europejskiej

A Novel Heterozygous De Novo MORC2 Missense Variant Causes an Early Onset and Severe Neurodevelopmental Disorder

Microrchidia CW-type zinc finger protein 2 (MORC2) is an ATPase-containing nuclear protein which regulates transcription through chromatin remodelling and epigenetic silencing. MORC2 may have a role in the development of neurones, and dominant variants in this gene have recently been linked with disorders including Charcot-Marie-Tooth type 2Z disease, spinal muscular atrophy and, more recently, a neurodevelopmental syndrome consisting of developmental delay, impaired growth, dysmorphic facies, and axonal neuropathy (DIGFAN), presenting with hypotonia, microcephaly, brain atrophy, intellectual disability, hearing loss, faltering growth, and craniofacial dysmorphism. Notably, variants in MORC2 have shown clinical features overlapping with those of Cockayne and Leigh syndromes. Here, we report a case of MORC2-related DIGFAN syndrome in a female infant caused by a novel heterozygous de novo variant. The condition was early onset and severe, further expanding the range of genotypes associated with this disorder. Clinical features included unilateral hearing loss, developmental delay and regression within the first year of life, microcephaly, severe feeding difficulties, and faltering growth, resulting in death at 13 months of age.Published version, accepted version, submitted versionThe article is available via Open Access. Click on the 'Additional link' above to access the full-text

Case company study: Managers’ views on their work circumstances

The purpose of this thesis was to find out how private a security case company’s reception guarding managers view their knowledge, skills and overall circumstances to handle their job. The reason for this study is that the people, the security guards, are the largest resource of the case company studied. The work done by the security guards provides the greatest profit. Investing in the managers insures that the company itself is functioning efficiently. It is important for the company to know that their managers are capable of handling the work; they have the tools, and the men-tal strength to perform. The theoretical framework provides through the selected analysis method, theme analysis, the information about managerial work, work well-being and company culture. The three themes that were chosen are self-efficacy, tools to perform, and company commitment. These were chosen to support the idea of by valuing and investing in people where from the company can benefit. Two surveys were used to gather information. The primary survey (a survey for the managers) was conducted by the author which was made from the basis of the secondary data, the Work Satisfaction Survey for Officers, conducted by the case company’s Human Resources department. The findings showed that the managers are able to handle the responsibilities set to them with their skills and knowledge, however, the amount of the workload seems to be too much