Host-pathogen interactions between the human innate immune system and Candida albicans—understanding and modeling defense and evasion strategies

The diploid, polymorphic yeast Candida albicans is one of the most important humanpathogenic fungi. C. albicans can grow, proliferate and coexist as a commensal on or within thehuman host for a long time. Alterations in the host environment, however, can render C. albicansvirulent. In this review, we describe the immunological cross-talk between C. albicans and thehuman innate immune system. We give an overview in form of pairs of human defense strategiesincluding immunological mechanisms as well as general stressors such as nutrient limitation,pH, fever etc. and the corresponding fungal response and evasion mechanisms. FurthermoreComputational Systems Biology approaches to model and investigate these complex interactionare highlighted with a special focus on game-theoretical methods and agent-based models. Anoutlook on interesting questions to be tackled by Systems Biology regarding entangled defenseand evasion mechanisms is given

Evolution of chlorophyll degradation is associated with plant transition to land

Colonization of land by green plants (Viridiplantae) some 500 million years ago was made possible by large metabolic and biochemical adaptations. Chlorophyll, the central pigment of photosynthesis, is highly photo-active. In order to mitigate deleterious effects of pigment accumulation, some plants have evolved a coordinated pathway to deal with chlorophyll degradation end-products, so-called phyllobilins. This pathway has been so far mostly unravelled in Arabidopsis thaliana. Here, large-scale comparative phylogenomic coupled to an innovative biochemical characterization strategy of phyllobilins allow a better understanding of how such a pathway appeared in Viridiplantae. Our analysis reveals a stepwise evolution of the canonical pheophorbide a monooxygenase/phyllobilin pathway. It appears to have evolved gradually, first in chlorophyte's chloroplasts, to ensure multicellularity by detoxifying chlorophyll catabolites, and in charophytes outside chloroplasts to allow adaptation of embryophytes to land. At least six out of the eight genes involved in the pathway were already present in the last common ancestor of green plants. This strongly suggests parallel evolution of distinct enzymes catalysing similar reactions in various lineages, particularly for the dephytylation step. Together, our study suggests that chlorophyll detoxification accompanied the transition from water to land, and was therefore of great importance for plant diversification

Evolution of chlorophyll degradation is associated with plant transition to land

Colonization of land by green plants (Viridiplantae) some 500 million years ago was made possible by large metabolic and biochemical adaptations. Chlorophyll, the central pigment of photosynthesis, is highly photo-active. In order to mitigate deleterious effects of pigment accumulation, some plants have evolved a coordinated pathway to deal with chlorophyll degradation end-products, so-called phyllobilins. This pathway has been so far mostly unravelled in Arabidopsis thaliana. Here, large-scale comparative phylogenomic coupled to an innovative biochemical characterization strategy of phyllobilins allow a better understanding of how such a pathway appeared in Viridiplantae. Our analysis reveals a stepwise evolution of the canonical pheophorbide a monooxygenase/phyllobilin pathway. It appears to have evolved gradually, first in chlorophyte's chloroplasts, to ensure multicellularity by detoxifying chlorophyll catabolites, and in charophytes outside chloroplasts to allow adaptation of embryophytes to land. At least six out of the eight genes involved in the pathway were already present in the last common ancestor of green plants. This strongly suggests parallel evolution of distinct enzymes catalysing similar reactions in various lineages, particularly for the dephytylation step. Together, our study suggests that chlorophyll detoxification accompanied the transition from water to land, and was therefore of great importance for plant diversification

Deletion of Complement Factor H–Related Genes CFHR1 and CFHR3 Is Associated with Atypical Hemolytic Uremic Syndrome

Atypical hemolytic uremic syndrome (aHUS) is associated with defective complement regulation. Disease-associated mutations have been described in the genes encoding the complement regulators complement factor H, membrane cofactor protein, factor B, and factor I. In this study, we show in two independent cohorts of aHUS patients that deletion of two closely related genes, complement factor H–related 1 (CFHR1) and complement factor H–related 3 (CFHR3), increases the risk of aHUS. Amplification analysis and sequencing of genomic DNA of three affected individuals revealed a chromosomal deletion of ∼84 kb in the RCA gene cluster, resulting in loss of the genes coding for CFHR1 and CFHR3, but leaving the genomic structure of factor H intact. The CFHR1 and CFHR3 genes are flanked by long homologous repeats with long interspersed nuclear elements (retrotransposons) and we suggest that nonallelic homologous recombination between these repeats results in the loss of the two genes. Impaired protection of erythrocytes from complement activation is observed in the serum of aHUS patients deficient in CFHR1 and CFHR3, thus suggesting a regulatory role for CFHR1 and CFHR3 in complement activation. The identification of CFHR1/CFHR3 deficiency in aHUS patients may lead to the design of new diagnostic approaches, such as enhanced testing for these genes

Depictive and Metric Body Size Estimation in Anorexia Nervosa and Bulimia Nervosa: A Systematic Review and Meta-Analysis.

A distorted representation of one's own body is a diagnostic criterion and core psychopathology of both anorexia nervosa (AN) and bulimia nervosa (BN). Despite recent technical advances in research, it is still unknown whether this body image disturbance is characterized by body dissatisfaction and a low ideal weight and/or includes a distorted perception or processing of body size. In this article, we provide an update and meta-analysis of 42 articles summarizing measures and results for body size estimation (BSE) from 926 individuals with AN, 536 individuals with BN and 1920 controls. We replicate findings that individuals with AN and BN overestimate their body size as compared to controls (ES= 0.63). Our meta-regression shows that metric methods (BSE by direct or indirect spatial measures) yield larger effect sizes than depictive methods (BSE by evaluating distorted pictures), and that effect sizes are larger for patients with BN than for patients with AN. To interpret these results, we suggest a revised theoretical framework for BSE that accounts for differences between depictive and metric BSE methods regarding the underlying body representations (conceptual vs. perceptual, implicit vs. explicit). We also discuss clinical implications and argue for the importance of multimethod approaches to investigate body image disturbance

Age-related macular degeneration associated polymorphism rs10490924 in ARMS2 results in deficiency of a complement activator

Acknowledgements: The authors thank all German AMD patients for their participation. We also thank Maria Pötsch (Leibniz Institute for Natural Product Reseach and Infection Biology, Jena) for MS analyses. Funding: This research was supported by the German Council “Deutsche Forschungs-Gemeinschaft” SK46, Zi432, LA1206, the “Pro Retina” foundation and the Thuringian Ministry of Science and Education, Germany. HN is a member of the DFG-funded excellence cluster ImmunoSensation (EXC 1023). YL is a doctoral researcher at the International Leibniz Research School (ILRS), part of the Jena school of Microbial Communication (JSMC). Availability of data and materials: Materials are available at [email protected] reviewedPublisher PD

Совершенствование системы делопроизводства угольной компании

В процессе исследования проводилось изучение содержания понятий "делопроизводство" и "документационное обеспечение управления"; исследование нормативно – правовой базы современного делопроизводства, принципов его организации; изучение цели, задач, функций и назначения службы делопроизводства; анализировалась система делопроизводства ООО "Угольная компания "Заречная"; были выработаны рекомендации по совершенствованию системы документационного обеспечения управления. Результаты исследования и выработанные рекомендации были внедрены в практику работы ООО "Угольная компания "Заречная".In the course of the research, the content of the notions of "office work" and "document management provision" was studied; research of the legal base of modern office work, principles of its organization; the study of the purpose, tasks, functions and appointment of the office work; the system of record keeping of LLC "Coal Company "Zarechnaya" was analyzed; Recommendations were developed to improve the system of document management support. The results of the study and the recommendations developed were introduced into the practice of the LLC "Coal Company "Zarechnaya "

Recombinant Production of MFHR1, A Novel Synthetic Multitarget Complement Inhibitor, in Moss Bioreactors

The human complement system is an important part of the immune system responsible for lysis and elimination of invading microorganisms and apoptotic body cells. Improper activation of the system due to deficiency, mutations, or autoantibodies of complement regulators, mainly factor H (FH) and FH-related proteins (FHRs), causes severe kidney and eye diseases. However, there is no recombinant FH therapeutic available on the market. The first successful recombinant production of FH was accomplished with the moss bioreactor, Physcomitrella patens. Recently, a synthetic regulator, MFHR1, was designed to generate a multitarget complement inhibitor that combines the activities of FH and the FH-related protein 1 (FHR1). The potential of MFHR1 was demonstrated in a proof-of-concept study with transiently transfected insect cells. Here, we present the stable production of recombinant glyco-engineered MFHR1 in the moss bioreactor. The key features of this system are precise genome engineering via homologous recombination, Good Manufacturing Practice-compliant production in photobioreactors, high batch-to-batch reproducibility, and product stability. Several potential biopharmaceuticals are being produced in this system. In some cases, these are even biobetters, i.e., the recombinant proteins produced in moss have a superior quality compared to their counterparts from mammalian systems as for example moss-made aGal, which successfully passed phase I clinical trials. Via mass spectrometry-based analysis of moss-produced MFHR1, we now prove the correct synthesis and modification of this glycoprotein with predominantly complex-type N-glycan attachment. Moss-produced MFHR1 exhibits cofactor and decay acceleration activities comparable to FH, and its mechanism of action on multiple levels within the alternative pathway of complement activation led to a strong inhibitory activity on the whole alternative pathway, which was higher than with the physiological regulator FH

Organ Preservation in Rectal Cancer: The Patients' Perspective

Organ preservation after a clinical complete response to radiochemotherapy is currently one of the most discussed topics in the management of rectal cancer. However, the patients' perspective has only been poorly studied so far. In this multicenter study, we examined 49 patients with locally advanced rectal cancer. The willingness to participate in an organ preservation study and the acceptance of the associated aspects such as intensified radiochemotherapy protocols, the need for close follow-up examinations and local regrowth rates were assessed. Attitudes were correlated with baseline quality of life parameters and psychological scales for “fear of progression”, “locus of control”, “depression”, and the “willingness to take risks”. A total of 83% of patients would consider the deferral of surgery in case of a clinical complete response (cCR). Three monthly follow-up studies and a 25% local regrowth rate are considered acceptable by 95% and 94% respectively. While 41% would be willing to exchange cure rates for a non-operative treatment strategy, a potentially more toxic radiochemotherapy in order to increase the probability of a cCR was the aspect with the lowest acceptance (55%). Psychological factors, in particular “locus of control” and “willingness to take risks”, influenced patient preferences regarding most of the assessed parameters. While in general a broad acceptance of an organ-preserving treatment can be expected, patient preferences and concerns regarding different aspects of this strategy vary widely and require specific consideration during shared decision making