Functional and structural studies of tolloid-like 1 mutants associated with atrial-septal defect 6

Inactive mammalian tolloid-like 1 (tll1) and mutations detected in tolloid-like 1 (TLL1) have been linked to the lack of the heart septa formation in mice and to a similar human inborn condition called atrial-septal defect 6 (ASD6; OMIM 613087, formerly ASD II). Previously, we reported four point mutations in TLL1 found in approximately 20% of ASD6 patients. Three mutations in the coding sequence were M182L, V238A, and I629V. In this work, we present the effects of these mutations on TLL1 function. Three recombinant cDNA constructs carrying the mutations and onewild-type construct were prepared and then expressed in HT-1080 cells. Corresponding recombinant proteins were analyzed for their metalloendopeptidase activity using a native substrate, chordin. The results of these assays demonstrated that in comparison with the native TLL1, mutants cleaved chordin and procollagen I at significantly lower rates. CD analyses revealed significant structural differences between the higher order structure of wild-type and mutant variants. Moreover, biosensor-based assays of binding interactions between TLL1 variants and chordin demonstrated a significant decrease in the binding affinities of the mutated variants. The results from this work indicate that mutations detected in TLL1 of ASD6 patients altered its metalloendopeptidase activity, structure, and substrate-binding properties, thereby suggesting a possible pathomechanism of ASD6

Nutrients composition in fit snacks made from ostrich, beef and chicken dried meat

The aim of the study was to compare three types of meat snacks made from ostrich, beef, and chicken meat in relation to their nutrients content including fat, fatty acids, heme iron, and peptides, like anserine and carnosine, from which human health may potentially benefit. Dry meat samples were produced, from one type of muscle, obtained from ostrich (m. ambiens), beef (m. semimembranosus), and broiler chicken meat (m. pectoralis major). The composition of dried ostrich, beef, and chicken meat, with and without spices was compared. We show that meat snacks made from ostrich, beef, and chicken meat were characterized by high concentration of nutrients including proteins, minerals (heme iron especially in ostrich, than in beef), biologically active peptides (carnosine-in beef, anserine-in ostrich then in chicken meat). The, beneficial to human health, n-3 fatty acids levels differed significantly between species. Moreover, ostrich jerky contained four times less fat as compared to beef and half of that in chicken. In conclusion we can say that dried ostrich, beef, and chicken meat could be a good source of nutritional components

Impact of Selected Electromagnetic Fields on Bone Turnover Markers in Rats

In this study the impact of electromagnetic field generated by mobile phone (f=900 MHz), electromagnetic field with industrial frequency generated by high voltage alternating current transmission lines (f=50 Hz, E=10 kV/m), and also simultaneous action of those fields on the intensity of bone turnover process in male rats was estimated by means of analysis of serum concentration of calcium, phosphorus, as well as specific markers of bone formation and bone resorption. It was concluded that 4-week lasting exposure to both forms of electromagnetic field causes the intensification of bone turnover, resulting in the increase of serum concentrations of osteocalcin, pyridinoline and crosslinked alpha-2 N-terminal telopeptide of collagen type I. The obtained effect was dependent on frequency and power density of used electromagnetic fields

Mozaikowanie obrazów z kapsuły endoskopowej

This paper presents numerical research and experiments giving rise to developed algorithm to connect into form of mosaic, images from the capsule endoscopy. In order to apply the algorithm, combined images must have a common area where the correspondence of points is determined. That allows to determine the transformation parameters to compensate movement of the capsule that occurs between moments when the mosaic images were acquired. The developed algorithm for images from the capsule endoscopy has proved to be faster and comparably accurate as commercial GDB-ICP algorithm.W artykule przedstawiono badania i eksperymenty numeryczne, będące podstawą opracowanego algorytmu łączenia, do formy mozaiki, obrazów z kapsuły endoskopowej. Warunkiem stosowania algorytmu jest, aby łączone obrazy posiadały wspólny obszar, w którym wyznaczana jest odpowiedniość punktów, pozwalająca z kolei na wyznaczenie parametrów transformacji kompensującej ruch kapsuły występujący pomiędzy chwilami, w których pozyskane były mozaikowane obrazy. Opracowany algorytm, w przypadku obrazów z kapsuły endoskopowej, okazał się szybszy i porównywalnie dokładny jak komercyjny algorytm GDB-ICP

Dearomative Michael addition involving enals and 2-nitrobenzofurans realized under NHC-catalysis

In the manuscript the first enantioselective dearomative Michael addition between α,β-unsaturated aldehydes and 2-nitrobenzofurans realized under N-heterocyclic carbene activation has been described. The reaction proceeds via addition of homoenolate to Michael acceptors leading to the formation of biologically important heterocycles with high yields and stereoselectivities. Their functionalization potential has been confirmed in selected, diastereoselective transformations

Vinylogous hydrazone activation in stereoselective synthesis of 2,3-dihydro-1H-pyrrolizines – an organocatalytic, metal-free route to ketorolac

In this paper, the application of organocatalysis in the synthesis of 2,3-dihydro-1H-pyrrolizines is demonstrated. α,β-Unsaturated aldehydes and pyrrole-based hydrazone readily participated in the formal (3+2)-cycloaddition that was realized according to aminocatalytic iminium ion activation. Products were obtained in high chemical yields, with excellent stereocontrol and selected additional transformations were also presented. The developed method was utilized in the first organocatalytic synthesis of ketorolac, a non-steroidal anti-inflammatory drug

Avascular Necrosis Bone Complication after Active COVID-19 Infection: Preliminary Results.

Background and objectives: The course of SARS-CoV-2 (COVID-19) is still under analysis. The majority of complications arising from the infection are related to the respiratory system. The adverse effect of the viral infection on bone and joint tissue has also been observed. Materials and Methods: We present a group of 10 patients with degeneration of large joints and adjacent epiphyses of long bones and the spine, with a background of bone infarctions and avascular necrosis (AVN) immediately after infection with the COVID-19 virus. In MR imaging, changes in the characteristics of AVN were documented. Results: Observation of this group showed a clear correlation among the history of COVID-19 disease in the patients, moderately severe symptoms, high levels of IgG antibodies, and the time of occurrence of joint changes. No other clinically significant complications were observed following COVID-19 infection in the study group. No other risk factors for AVN or autoimmune or degenerative diseases were found in the study group. The group of patients responded well to empirical treatment with steroids, which normalized acute inflammatory symptoms and pain in the joints. Conclusions: During coronavirus (COVID-19) infection, there are complications in the locomotor system, such as microembolism and the formation of AVN; hence, more research is needed

Star Polymers as Non-Viral Carriers for Apoptosis Induction

Apoptosis is a widely controlled, programmed cell death, defects in which are the source of various diseases such as neurodegenerative diseases as well as cancer. The use of apoptosis in the therapy of various human diseases is of increasing interest, and the analysis of the factors involved in its regulation is valuable in designing specific carriers capable of targeting cell death. Highly efficient and precisely controlled delivery of genetic material by low-toxic carriers is one of the most important challenges of apoptosis-based gene therapy. In this work, we investigate the effect of the star polymer with 28 poly(N,N′-dimethylaminoethyl methacrylate) arms (STAR) on human cells, according to its concentration and structure. We show that star polymer cytotoxicity increases within its concentration and time of cells treatment. Except for cytotoxic effect, we observe morphological changes such as a shrinkage, loss of shape and begin to detach. We also prove DNA condensation after star polymer treatment, one of the most characteristic feature of apoptosis. The results indicate that the use of STAR triggers apoptosis in cancer cells compared to various normal cells, what makes these nanoparticles a promising drug in therapeutic strategy, which targets apoptosis. We demonstrate highlighting potential of star polymers as an innovative tool for anti-cancer therapy