Alterations in the Anandamide Metabolism in the Development of Neuropathic Pain

Endocannabinoids (EC), particularly anandamide (AEA), released constitutively in pain pathways might be accountable for the inhibitory effect on nociceptors. Pathogenesis of neuropathic pain may reflect complex remodeling of the dorsal root ganglia (DRGs) and spinal cord EC system. Multiple pathways involved both in the biosynthesis and degradation of AEA have been suggested. We investigated the local synthesis and degradation features of AEA in DRGs and spinal cord during the development and maintenance of pain in a model of chronic constriction injury (CCI). All AEA synthesis and degradation enzymes are present on the mRNA level in DRGs and lumbar spinal cord of intact as well as CCI-treated animals. Deregulation of EC system components was consistent with development of pain phenotype at days 3, 7, and 14 after CCI. The expression levels of enzymes involved in AEA degradation was significantly upregulated ipsilateral in DRGs and spinal cord at different time points. Expression of enzymes of the alternative, sPLA2-dependent and PLC-dependent, AEA synthesis pathways was elevated in both of the analyzed structures at all time points. Our data have shown an alteration of alternative AEA synthesis and degradation pathways, which might contribute to the variation of AEA levels and neuropathic pain development

Hereditary cataract in the Bengal cat in Poland

Background: This paper reports the significant prevalence of a presumed hereditary cataract in the Bengal cat breed in Poland. The nuclear part of the lens is affected and previous reports from Sweden and France for this type of feline cataract suggest that a recessive mode of inheritance is probably involved. Results: Presumed congenital or neonatal cataract involving the posterior nuclear part of each lens was initially diagnosed in a 12 month old male Bengal cat. As both parents and a sibling were also affected with cataract, a group of 18 related and 11 non-related cats was then subsequently examined. Eight related cats and one non- related cat were found to be similarly affected. A breed survey was then completed using an additional five centres across Poland and a further 190 related cats were examined. A total of 223 cats have been involved in this study, with 75 (33%) being affected with several types of cataract and 67 (30%) being specifically affected with the same or similar nuclear lesions. Eight cats (3.6%) presented with other cataract types and a prominence of the posterior lens suture lines was recorded in 65 cats unaffected with cataract (29%). There were no demonstrable vision problems. Neither age nor coat colour was significantly associated with the nuclear cataract, but the nuclear cataract group had a higher proportion of females than the unaffected group. Pedigree analysis has indicated probable inheritance as a recessive trait. Conclusions: These findings suggest that a presumably inherited nuclear cataract is present in the Bengal cat breed in Poland. It is considered to be either congenital or of very early onset, probably being inherited as a recessive trait. Although the lesion has no noticeable effect on vision, breeders in Poland and worldwide should be aware of the disease and clinical examination of young breeding stock prior to reproduction is advisable

Genome-Wide Screen of Genes Required for Caffeine Tolerance in Fission Yeast

Isabel A. Calvo et al...Background An excess of caffeine is cytotoxic to all eukaryotic cell types. We aim to study how cells become tolerant to a toxic dose of this drug, and the relationship between caffeine and oxidative stress pathways. Methodology/Principal Findings We searched for Schizosaccharomyces pombe mutants with inhibited growth on caffeine-containing plates. We screened a collection of 2,700 haploid mutant cells, of which 98 were sensitive to caffeine. The genes mutated in these sensitive clones were involved in a number of cellular roles including the H2O2-induced Pap1 and Sty1 stress pathways, the integrity and calcineurin pathways, cell morphology and chromatin remodeling. We have investigated the role of the oxidative stress pathways in sensing and promoting survival to caffeine. The Pap1 and the Sty1 pathways are both required for normal tolerance to caffeine, but only the Sty1 pathway is activated by the drug. Cells lacking Pap1 are sensitive to caffeine due to the decreased expression of the efflux pump Hba2. Indeed, ?hba2 cells are sensitive to caffeine, and constitutive activation of the Pap1 pathway enhances resistance to caffeine in an Hba2-dependent manner. Conclusions/Significance With our caffeine-sensitive, genome-wide screen of an S. pombe deletion collection, we have demonstrated the importance of some oxidative stress pathway components on wild-type tolerance to the drug.This work was supported by Direccion General de Investigacion of Spain Grant BFU2006-02610, and by the Spanish program Consolider-Ingenio 2010 Grant CSD 2007-0020, to E.H.Peer reviewe

Research by design as a research method supporting planned investing activities on the basis of adapting an explosives warehouse in the Sadowa Góra quarry into an exhibition space

Od kilku lat Wydział Architektury Politechniki Śląskiej prowadzi prace naukowo-badawcze na terenie Ośrodka Edukacji Ekologiczno-Geologicznej GEOsfera w ramach współpracy z gminą Jaworzno. Jednym z zadań było zbadanie możliwości adaptacji nieczynnego, wgłębnego magazynu materiałów wybuchowych, znajdującego się na terenie dawnego kamieniołomu Sadowa Góra, który w niedalekiej przyszłości ma służyć celom turystycznym. W ramach zadań projektowych, poprzedzonych analizami badawczymi, przygotowano scenariusze rozwojowe przedmiotowego obiektu dla funkcji wystawienniczo-edukacyjnej oraz sporządzono koncepcje projektowe z zakresu architektury wnętrz. Do realizacji zadania posłużono się technikami stosowanymi przy metodach badań jakościowych. Zbadanie możliwości adaptacyjnych przedmiotowego obiektu wykonano metodą research by design. Przedstawione w artykule wybrane koncepcje projektowe wskazują możliwości i kierunki planowanych działań inwestycyjnych w obiekcie, którego adaptacja jest niełatwym zadaniem z uwagi na specyfikę pierwotnego przeznaczenia, usytuowania, parametrów technicznych oraz możliwości prowadzenia prac budowlanych.For several years, the Faculty of Architecture of the Silesian University of Technology has been conducting research work at the GEOsfera Ecological and Geological Education Center, in cooperation with the Jaworzno commune. One of the tasks was to investigate the possibility of adapting a closed, in-depth warehouse of explosives, located on the site of the former Sadowa Góra quarry, which is to serve tourist purposes in the near future. As part of the design tasks, preceded by research analyzes, development scenarios of the facility in question for the exhibition and educational function were prepared, and design concepts in the field of interior architecture were prepared. The techniques used in the methods of qualitative research were used to carry out the task. The research-by-design method was used to test the adaptation possibilities of the object in question. The selected design concepts presented in the article indicate the possibilities and directions of planned investment activities in the facility, the adaptation of which is not an easy task due to the specificity of the original purpose, location, technical parameters and the possibility of conducting construction works

Alterations in the anandamide metabolism in the development of neuropathic pain

Endocannabinoids (EC), particularly anandamide (AEA), released constitutively in pain pathways might be accountable for the inhibitory effect on nociceptors. Pathogenesis of neuropathic pain may reflect complex remodeling of the dorsal root ganglia (DRGs) and spinal cord EC system. Multiple pathways involved both in the biosynthesis and degradation of AEA have been suggested. We investigated the local synthesis and degradation features of AEA in DRGs and spinal cord during the development and maintenance of pain in a model of chronic constriction injury (CCI). All AEA synthesis and degradation enzymes are present on the mRNA level in DRGs and lumbar spinal cord of intact as well as CCI-treated animals. Deregulation of EC system components was consistent with development of pain phenotype at days 3, 7, and 14 after CCI. The expression levels of enzymes involved in AEA degradation was significantly upregulated ipsilateral in DRGs and spinal cord at different time points. Expression of enzymes of the alternative, sPLA2-dependent and PLC-dependent, AEA synthesis pathways was elevated in both of the analyzed structures at all time points. Our data have shown an alteration of alternative AEA synthesis and degradation pathways, which might contribute to the variation of AEA levels and neuropathic pain development

Immunotherapy in Non-Small-Cell Lung Cancer Patients with Driver Alterations: A New Strategy?

For many years, researchers have been trying to develop the most effective ways to fight lung cancer, which is the cause of the largest number of cancer-related deaths among men and women worldwide. The most advanced treatments for nearly all non-small-cell lung cancer (NSCLC) types include immunotherapy with immune checkpoint inhibitors (ICIs), mainly anti-programmed death 1/anti-programmed death ligand 1 monoclonal antibodies (anti-PD-1/PD-L1 mAbs) in monotherapy or in combination with other strategies. Despite significant advances, long survival is not achievable in most cases, so new solutions are constantly being sought. One of the questions raised by oncologists is the efficacy of ICIs in patients with molecular driver alterations, especially when the possibilities of using molecularly targeted therapies are exhausted (e.g., due to resistance to tyrosine kinase inhibitors). There are studies investigating this problem, but it is still poorly described. Among probable immunotherapy’ failures reasons, low immunogenicity of tumors with one driver mutation is listed. Nevertheless, in some cases, the therapy is efficient, and more research is required to establish the management of NSCLC patients with oncogenic driver abnormalities. The aim of this article is to review current discoveries in this matter