Biallelic loss-of-function mutation in NIK causes a primary immunodeficiency with multifaceted aberrant lymphoid immunity

Primary immunodeficiency disorders enable identification of genes with crucial roles in the human immune system. Here we study patients suffering from recurrent bacterial, viral and Cryptosporidium infections, and identify a biallelic mutation in the MAP3K14 gene encoding NIK (NF- B-inducing kinase). Loss of kinase activity of mutant NIK, predicted by in silico analysis and confirmed by functional assays, leads to defective activation of both canonical and non-canonical NF- B signalling. Patients with mutated NIK exhibit B-cell lymphopenia, decreased frequencies of class-switched memory B cells and hypogammaglobulinemia due to impaired B-cell survival, and impaired ICOSL expression. Although overall T-cell numbers are normal, both follicular helper and memory T cells are perturbed. Natural killer (NK) cells are decreased and exhibit defective activation, leading to impaired formation of NK-cell immunological synapses. Collectively, our data illustrate the non-redundant role for NIK in human immune responses, demonstrating that loss-of-function mutations in NIK can cause multiple aberrations of lymphoid immunity

The role of metal ions in biological oxidation - the past and the present

Two theories, one based on the metabolism of inorganic substances, the other on metabolism of organic substances, have played an important role in the explanation of the origin of life. They demonstrate that the original environment of life on Earth was seawater containing micronutrients with structural, metabolic and catalytic activity. It is assumed that the first primitive organisms lived around 3.8 billion years ago and it was also then that the first catalytic reaction involving metal ions occurred. Biological oxidation leading to oxidative stress and cell damage in animals represents one of these types of reactions which are responsible for many animal diseases. The role of prooxidative and antioxidative actions of transition metal ions as well as their neuropathological consequences have therefore been the topic for many research projects. There is hope that metal chelates and antioxidants might prove to be a modern mode of therapy for i.e. neurogenerative diseases. The aim of this review is to show the evolution of scientific knowledge on metal ions, their biological oxidation, and an overview of their role in physiology and in pathological processes

ProANP as a screening biomarker for hypertrophic cardiomyopathy in Maine coon cats

The aim of this study was to determine if atrial natriuretic peptide can be used as an early screening tool for hypertrophic cardiomyopathy in Maine coon cats. Animals: The study was performed in 43 Maine coon cats of both sexes, aged 11 to 92 months. Clinical and echocardiographic examinations were done and proANP serum concentrations were measured every three months over a period of one year (each cat had a total of five examinations). Cats were divided into 3 groups based on echocardiographic results: group 1 – healthy cats, group 2 – cats with unequivocal hypertrophic cardiomyopathy results, group 3 – cats with HCM. The study showed that the concentration of atrial natriuretic peptide correlates with the severity of HCM. A significant increase in serum concentration of this peptide was observed in cats from group 3, but it did not differ significantly between cats from group 2 and the healthy animals (p>0.05). A correlation was also found between proANP and age of the cats (p<0.01, r=0.5578) as well as between the ejection fraction (p=0.0285, r=0.5305) and end-systolic left ventricular diameter (p=0.05, r=0.48) in the affected animals. Atrial natriuretic peptide may be used to help in the diagnosis of advanced stages of HCM in Maine coon cats. Cats with high levels of proANP should be assigned to echocardiographic studies to confirm the disease

Problem prawidłowego zabezpieczenie ładunku w transporcie drogowym – studium przypadku

This paper presents the problem of improper security of cargo in trucks as the cause of about 25% of the accidents that takes place in road transport. Attention was drawn to aspects of legal liability for errors resulting from incorrect load securing according to polish law. Article was enriched with practical examples illustrating the effects of improper cargo securing on transport unit and shows how it had to be prepared properly. When planning the proper transport protection of metal sheets rolled both calculation methods and computer applications were used.W artykule przedstawiono problematykę nieprawidłowego zabezpieczenia ładunków w samochodach ciężarowych jako przyczynę około 25% wypadków, które mają miejsce w transporcie drogowym. Zwrócono uwagę na aspekty odpowiedzialności prawnej za błędy wynikające z nieprawidłowego zabezpieczenia ładunków w odniesieniu do polskiego prawodawstwa. Artykuł wzbogacono przykładem praktycznym obrazującym skutki nieprawidłowego mocowania ładunku w jednostce transportowej oraz przedstawiono jak miało ono być przygotowane prawidłowo. Przy planowaniu prawidłowego zabezpieczenia kręgów blachy wspomagano się zarówno metodami obliczeniowymi jak i aplikacjami komputerowym