Inhibiting the mitochondrial pyruvate carrier does not ameliorate synucleinopathy in the absence of inflammation or metabolic deficits

Epidemiological studies suggest a link between type-2 diabetes and Parkinson’s disease (PD) risk. Treatment of type-2 diabetes with insulin sensitizing drugs lowers the risk of PD. We previously showed that the insulin sensitizing drug, MSDC-0160, ameliorates pathogenesis in some animal models of PD. MSDC-0160 reversibly binds the mitochondrial pyruvate carrier (MPC) protein complex, which has an anti-inflammatory effect and restores metabolic deficits. Since PD is characterized by the deposition of α-synuclein (αSyn), we hypothesized that inhibiting the MPC might directly inhibit αSyn aggregation in vivo in mammals. To answer if modulation of MPC can reduce the development of αSyn assemblies, and reduce neurodegeneration, we treated two chronic and progressive mouse models; a viral vector-based αSyn overexpressing model and a pre-formed fibril (PFF) αSyn seeding model with MSDC-0160. These two models present distinct types of αSyn pathology but lack inflammatory or autophagy deficits. Contrary to our hypothesis, we found that a modulation of MPC in these models did not reduce the accumulation of αSyn aggregates or mitigate neurotoxicity. Instead, MSDC-0160 changed the post-translational modification and aggregation features of αSyn. These results are consistent with the lack of a direct effect of MPC modulation on synuclein clearance in these models

Obstetrics knowledge and skills training as a catalyst for change

Background. Poor emergency obstetric care has been shown by national confidential enquiries into maternal deaths to contribute to a number of maternal deaths in South Africa.Objectives. To assess whether a structured training course can improve knowledge and skills and whether this can influence the capacity of a healthcare facility to provide basic and comprehensive emergency obstetric care signal functions.Methods. A baseline survey was conducted to assess the seven basic emergency obstetric and neonatal care signal functions in 51 community health centres (CHCs) and the nine comprehensive emergency care signal functions in 62 district hospitals (DHs). A re­assessment was conducted 1 year after saturation training had been provided in each district. The delegates were trained using a structured training programme (Essential Steps in Managing Obstetric Emergencies, ESMOE) and their knowledge and skills were tested before and after the training. Saturation training was considered to have been achieved once 80% of the healthcare professionals involved in maternity care had been trained.Results. There was a significant improvement in the knowledge and skills of doctors, namely by 16.8% and 32.8%, respectively, of advanced midwives by 13.7% and 29.0%, and of professional nurses with midwifery by 16.1% and 31.2%. The seven basic emergency care functions improved from 60.8% to 67.8% in the CHCs and from 90.7% to 92.5% in the DHs before and after training. If the two signal functions that are not within the scope of practice of professional nurses with midwifery are excluded (viz. assisted delivery and manual vacuum aspiration), the functionality of CHCs increased from 85.1% to 94.9%.Conclusions. The ESMOE training programme improved knowledge and skills, but there was a modest improvement in the functionality of the facilities. Improvement in functionality requires changes in the structure of the health system, including changing the scope of practice of professional nurses with midwifery and employing more advanced midwives in CHCs.

An osteocalcin-deficient mouse strain without endocrine abnormalities

Osteocalcin (OCN), the most abundant noncollagenous protein in the bone matrix, is reported to be a bone-derived endocrine hormone with wide-ranging effects on many aspects of physiology, including glucose metabolism and male fertility. Many of these observations were made using an OCN-deficient mouse allele (Osc– ) in which the 2 OCN-encoding genes in mice, Bglap and Bglap2, were deleted in ES cells by homologous recombination. Here we describe mice with a new Bglap and Bglap2 double-knockout (dko) allele (Bglap/2p.Pro25fs17Ter) that was generated by CRISPR/Cas9-mediated gene editing. Mice homozygous for this new allele do not express full-length Bglap or Bglap2 mRNA and have no immunodetectable OCN in their serum. FTIR imaging of cortical bone in these homozygous knockout animals finds alterations in the collagen maturity and carbonate to phosphate ratio in the cortical bone, compared with wild-type littermates. However, μCT and 3-point bending tests do not find differences from wild-type littermates with respect to bone mass and strength. In contrast to the previously reported OCN-deficient mice with the Osc− allele, serum glucose levels and male fertility in the OCN-deficient mice with the Bglap/ 2pPro25fs17Ter allele did not have significant differences from wild-type littermates. We cannot explain the absence of endocrine effects in mice with this new knockout allele. Possible explanations include the effects of each mutated allele on the transcription of neighboring genes, or differences in genetic background and environment. So that our findings can be confirmed and extended by other interested investigators, we are donating this new Bglap and Bglap2 double-knockout strain to the Jackson Laboratories for academic distribution

XLIV Konferencja Komitetu Nauk o Żywności i Żywieniu PAN: nauka, technologia i innowacje w żywności i żywieniu

Streszczenia w jęz. angielskimWydarzenie: XLIV Konferencja Komitetu Nauk o Żywności i Żywieniu PAN; Łódź, 3-4 lipca 2019 r.; http://pan.binoz.p.lodz.plOrganizator konferencji: Wydział Biotechnologii i Nauk o Żywności PŁ; Komitet Nauk o Żywności i Żywieniu PAN; Polskie Towarzystwo Technologów ŻywnościProjekt graficzny okładki: Grzelczyk, J.Projekt graficzny okładki: Klewicki, R.Skład: Oracz, J.Za treść zamieszczonych materiałów odpowiadają ich autorzy.Sesje Naukowe Komitetu Nauk o Żywności i Żywieniu Polskiej Akademii Nauk (KNoŻiŻ PAN) są organizowane przez krajowe ośrodki akademickie związane z naukami o żywności i żywieniu w dwuletnich cyklach. Sesje te stanowią największe w skali kraju forum prezentacji najnowszych osiągnięć naukowych i technologicznych w dziedzinie technologii żywności i żywienia człowieka, jak również wymiany poglądów oraz doświadczeń pracowników jednostek naukowych i przedstawicieli przemysłu spożywczego. Tematyka XLIV Sesji dotyczyć będzie szeroko pojętej problematyki związanej z oddziaływaniem żywności i odżywiania na zdrowie człowieka

Effect of Technological Parameters on the Quality and Dimensional Accuracy of Castings Manufactured by Patternless Process Technology

Submitted article deals with the effect of selected technological parameters on the quality and dimensional accuracy of prototype castings made by Patternless process technology. During experiments were used two types of molding compounds (foamed gypsum and compound based on silica sand and resin). Experiments were focused on optimization of cutting parameters in terms of efficiency, accuracy and possibilities to minimize tool wear. Article deals also with the dimensional and shape accuracy of the castings made by Z-Cast technology. The main aim of the research is to optimize Patternless process technology to such an extent, that achieved dimensional and shape accuracy will be comparable to castings made by the Z-Cast technology

Nitroaromatic enzymatic biodegradation system in Phanerochaete chrysosporium

Phanerochaete chrysosporium is an ubiquitous fungus having huge potential for application in biodegradation processes. Its enzymatic system, consisting of ligninases, membrane-associated oxidases and hydrogen peroxide generating enzymes is capable of degrading a wide range of pollutants like 2,4,6-trinitrotoluene, 2,5-dinitrophenol, 3,5-dinitrosalicylic acid or azodyes produced by military or civilian industry. Synergetic action between enzymes, based on providing substrates essential for their activity and their extreme low-specificity guarantees successful degradation of recalcitrant pollutants. Nevertheless, a development of a technique, taking into the account the type of pollutant, its concentration in the environment, its metabolic pathway and maintenance of the system is required. This paper presents a literature survey related to enzymatic system of a white rot fungus Phanerochaete chrysosporium and its potential application in biodegradation processes

Study on interaction of vancomycin with bacterial cell wall peptidoglycan

Unfortunately, despite of work involved in understanding of the mechanism of bacterial virulence, especially Staphylococcus aureus, it has not been developed effective therapy against this bacteria. The first antibiotic used against this bacteria was penicillin, which was discovered by Alexander Fleming in 1928. A new generation of drugs introduced into therapy against Staphylococcus aureus and other Gram-positive bacteria are glycopeptide antibiotics. The most widespread and most commonly used are vancomycin and teicoplanin, discovered respectively in 1956 and 1978. As a result of frequent use of vancomycin VISA (ang. Vancomycin-intermediate Staphylococcus aureus) and VRSA (ang. Vancomycin-resistant Staphylococcus aureus) strains were discovered. The mechanism of action of this antibiotic based on the inhibition of the biosynthesis of bacterial cell wall peptidoglycan fragment. Forming stabilized by hydrogen bonds complex with terminal fragment of peptidoglycan (dipeptide d-Ala-d-Ala) vancomycin prevents its further crosslinking [2] (Fig. 1). However, in recent years other theories of the mechanism of action of glycopeptide antibiotics against Gram-positive bacteria were presented it seems to be crucial to find methods of selection of new antibiotics and for this purpose standard techniques of the analysis, including isothermal titration calorimetry (ITC) [3], nuclear magnetic resonance spectroscopy (NMR) [8–15], high performance liquid chromatography (HPLC) [16], capillary electrophoresis [17] or self-assembled monolayers (SAMs) [22] are used. Discovering new methods for studying of interaction between vancomycin and Gram-positive bacterial cell wall allows use it as a new technique for rapid selection of potential new antibiotics, including glycopeptide derivatives

Selected nucleoside antibiotics

Every year there has been a growing increase in infections caused by strains of bacteria resistant to multiple drugs. This prompts scientists to search for new antibiotics that would be able to fight these infections. New therapeutics used in medicine, which offer greater hopes are nucleoside antibiotics. They represent a large family of natural compounds exhibiting a variety of biological functions [1]. These include antifungal, antiviral, antibacterial, insecticides, immunosuppressants or anticancer properties. These broad-spectrum antibiotics can be divided into three main groups: • antibacterial nucleoside antibiotics, responsible for the inhibition of bacterial translocation of phospho-N-acetylpentapeptides, involved in the biosynthesis of peptidoglycan cell wall of bacteria; • antifungal nucleoside antibiotics, which role is to inhibit chitin synthase, or stopping construction of the cell wall of fungi; • antiviral antibiotics nucleoside, their mechanism of action is mainly based on blocking the biosynthesis of proteins by peptide inhibition transferase. In recent years much attention has been focused on the construction, mechanism of action and biosynthesis of antibiotics [1–3]. The development of genetic engineering has opened the way for combinatorial biosynthesis and obtaining new or hybrid compounds. In this work we would like to discuss some of bioactive naturally occurring nucleoside antibiotics, such as tunicamycin (Fig. 6) [19–22], mureidomycin (Fig. 8) [31–34], muramycin (Fig. 9) [36] or capuramycin (Fig. 10) [38]