Trained immunity or tolerance : opposing functional programs induced in human monocytes after engagement of various pattern recognition receptors

Article Accepted Date: 29 January 2014. ACKNOWLEDGMENTS D.C.I. received funding from the European Union's Seventh Framework Programme (FP7/2007-2013) under grant agreement HEALTH-2010-260338 (“Fungi in the setting of inflammation, allergy and autoimmune diseases: translating basic science into clinical practices” [ALLFUN]) (awarded to M.G.N.). M.G.N. and J.Q. were supported by a Vici grant of the Netherlands Organization of Scientific Research (awarded to M.G.N.). This work was supported, in part, by National Institutes of Health grant GM53522 to D.L.W. N.A.R.G. was supported by the Wellcome Trust.Peer reviewedPublisher PD

The BRCT domain of mammalian Rev1 is involved in regulating DNA translesion synthesis

Rev1 is a deoxycytidyl transferase associated with DNA translesion synthesis (TLS). In addition to its catalytic domain, Rev1 possesses a so-called BRCA1 C-terminal (BRCT) domain. Here, we describe cells and mice containing a targeted deletion of this domain. Rev1(B/B) mice are healthy, fertile and display normal somatic hypermutation. Rev1(B/B) cells display an elevated spontaneous frequency of intragenic deletions at Hprt. In addition, these cells were sensitized to exogenous DNA damages. Ultraviolet-C (UV-C) light induced a delayed progression through late S and G2 phases of the cell cycle and many chromatid aberrations, specifically in a subset of mutant cells, but not enhanced sister chromatid exchanges (SCE). UV-C-induced mutagenesis was reduced and mutations at thymidine–thymidine dimers were absent in Rev1(B/B) cells, the opposite phenotype of UV-C-exposed cells from XP-V patients, lacking TLS polymerase η. This suggests that the enhanced UV-induced mutagenesis in XP-V patients may depend on error-prone Rev1-dependent TLS. Together, these data indicate a regulatory role of the Rev1 BRCT domain in TLS of a limited spectrum of endogenous and exogenous nucleotide damages during a defined phase of the cell cycle

Trained immunity or tolerance : opposing functional programs induced in human monocytes after engagement of various pattern recognition receptors

Article Accepted Date: 29 January 2014. ACKNOWLEDGMENTS D.C.I. received funding from the European Union's Seventh Framework Programme (FP7/2007-2013) under grant agreement HEALTH-2010-260338 (“Fungi in the setting of inflammation, allergy and autoimmune diseases: translating basic science into clinical practices” [ALLFUN]) (awarded to M.G.N.). M.G.N. and J.Q. were supported by a Vici grant of the Netherlands Organization of Scientific Research (awarded to M.G.N.). This work was supported, in part, by National Institutes of Health grant GM53522 to D.L.W. N.A.R.G. was supported by the Wellcome Trust.Peer reviewedPublisher PD

Peanut allergen Ara h 6 is detectable in blood transfusion products

Peanut allergen Ara h 6 is known to maintain IgE‐binding capacity upon exposure to digestive enzymes1 and its presence in circulation after consumption of peanut has been demonstrated.2,3 Therefore, it has been speculated that food‐derived allergens could be transferred via blood transfusion products, causing an allergic reaction in food-allergic recipients.4,5 However, in published case reports, presence of food allergen in donated material could not be confirmed due to lack of remaining transfusion material and/or lack of sensitive analytical methods. Using a newly developed sensitive immune‐assay for detecting Ara h 6 in human serum, we now report to what extent consumed peanut allergens can be present in blood transfusion materials and estimate the associated risk for peanut‐allergic recipients

Strain-controlled criticality governs the nonlinear mechanics of fibre networks

Disordered fibrous networks are ubiquitous in nature as major structural components of living cells and tissues. The mechanical stability of networks generally depends on the degree of connectivity: only when the average number of connections between nodes exceeds the isostatic threshold are networks stable (Maxwell, J. C., Philosophical Magazine 27, 294 (1864)). Upon increasing the connectivity through this point, such networks undergo a mechanical phase transition from a floppy to a rigid phase. However, even sub-isostatic networks become rigid when subjected to sufficiently large deformations. To study this strain-controlled transition, we perform a combination of computational modeling of fibre networks and experiments on networks of type I collagen fibers, which are crucial for the integrity of biological tissues. We show theoretically that the development of rigidity is characterized by a strain-controlled continuous phase transition with signatures of criticality. Our experiments demonstrate mechanical properties consistent with our model, including the predicted critical exponents. We show that the nonlinear mechanics of collagen networks can be quantitatively captured by the predictions of scaling theory for the strain-controlled critical behavior over a wide range of network concentrations and strains up to failure of the material

Continental aridification and the vanishing of Australia\u27s megalakes

The nature of the Australian climate at about the time of rapid megafaunal extinctions and humans arriving in Australia is poorly understood and is an important element in the contentious debate as to whether humans or climate caused the extinctions. Here we present a new paleoshoreline chronology that extends over the past 100 k.y. for Lake Mega-Frome, the coalescence of Lakes Frome, Blanche, Callabonna and Gregory, in the southern latitudes of central Australia. We show that Lake Mega-Frome was connected for the last time to adjacent Lake Eyre at 50-47 ka, forming the largest remaining interconnected system of paleolakes on the Australian continent. The final disconnection and a progressive drop in the level of Lake Mega-Frome represents a major climate shift to aridification that coincided with the arrival of humans and the demise of the megafauna. The supply of moisture to the Australian continent at various times in the Quaternary has commonly been ascribed to an enhanced monsoon. This study, in combination with other paleoclimate data, provides reliable evidence for periods of enhanced tropical and enhanced Southern Ocean sources of water filling these lakes at different times during the last full glacial cycle. © 2011 Geological Society of America

Веб-ресурс для перегляду 3D моделей з використанням технології WebGL

У першому розділі досліджується актуальність проблеми, проводиться аналіз існуючих аналогів. Другий розділ присвячений формування мети дипломної роботи та задач проекту, вибору засобів реалізації та плануванню робіт. У третьому розділі виконується проектування веб-ресурсу, де наведені діаграми у нотації IDF0 та Use Case.Останній розділ присвячений детальному опису практичної реалізації проекту: виконання прототипування веб-сторінки, розмітка та форматування веб-ресурсу, налаштування та перевірка працездатності веб-браузера з WebGL, опис реакції на дії користувача, розробка функцій маніпуляцій над моделлю. Результатом проведеної роботи є розроблений веб-ресурс, який дозволяє користувачу обирати одну із чотирьох моделей для візуалізації на веб-сторінці та виконувати базові маніпуляції з нею

Between Metabolite Relationships: an essential aspect of metabolic change

Not only the levels of individual metabolites, but also the relations between the levels of different metabolites may indicate (experimentally induced) changes in a biological system. Component analysis methods in current ‘standard’ use for metabolomics, such as Principal Component Analysis (PCA), do not focus on changes in these relations. We therefore propose the concept of ‘Between Metabolite Relationships’ (BMRs): common changes in the covariance (or correlation) between all metabolites in an organism. Such structural changes may indicate metabolic change brought about by experimental manipulation but which are lost with standard data analysis methods. These BMRs can be analysed by the INdividual Differences SCALing (INDSCAL) method. First the BMR quantification is described and subsequently the INDSCAL method. Finally, two studies illustrate the power and the applicability of BMRs in metabolomics. The first study is about the induced plant response of cabbage to herbivory, of which BMRs are a considerable part. In the second study—a human nutritional intervention study of green tea extract—standard data analysis tools did not reveal any metabolic change, although the BMRs were considerably affected. The presented results show that BMRs can be easily implemented in a wide variety of metabolomic studies. They provide a new source of information to describe biological systems in a way that fits flawlessly into the next generation of systems biology questions, dealing with personalized responses

Comment on Rojas-Bracho and Colleagues (2019): Unsubstantiated Claims Can Lead to Tragic Conservation Outcomes

The vaquita’s decline is a tragic story indeed. However, the lack of action to prevent the extinction of this species is not due to unsubstantiated claims and scientific uncertainty

Vaquita Face Extinction from Bycatch. Comment on Manjarrez-Bringas, N. et al., Lessons for Sustainable Development: Marine Mammal Conservation Policies and Its Social and Economic Effects.

We are among the scientists who have documented the environmental and ecological changes to the Upper Gulf of California following the reduction in the Colorado River’s flow. We object to any suggestion that our research supports Manjarrez-Bringas et al.’s conclusion that the decline in the Colorado River’s flow is the reason for the decline in the population of the endangered vaquita porpoise (Phocoena sinus). Manjarrez-Bringas et al.’s conclusions are incongruent with their own data, their logic is untenable, their analyses fail to consider current illegal fishing practices, and their recommendations are unjustified and misdirected. Vaquita face extinction because of bycatch, not because of the lack of river flow