Chipping away at gamma-H2AX foci

The mammalian histone H2AX protein functions as a dosage-dependent genomic caretaker and tumor suppressor. Phosphorylation of H2AX to form gamma-H2AX in chromatin around DNA double strand breaks (DSBs) is an early event following induction of these hazardous lesions. For a decade, mechanisms that regulate H2AX phosphorylation have been investigated mainly through two-dimensional immunofluorescence (IF). We recently used chromatin immunoprecipitation (ChIP) to measure gamma-H2AX densities along chromosomal DNA strands broken in G(1) phase mouse lymphocytes. Our experiments revealed that (1) gamma-H2AX densities in nucleosomes form at high levels near DSBs and at diminishing levels farther and farther away from DNA ends, and (2) ATM regulates H2AX phosphorylation through both MDC1-dependent and MDC1-independent means. Neither of these mechanisms were discovered by previous if studies due to the inherent limitations of light microscopy. Here, we compare data obtained from parallel gamma-H2AX ChIP and three-dimensional IF analyses and discuss the impact of our findings upon molecular mechanisms that regulate H2AX phosphorylation in chromatin around DNA breakage sites

Adaptive Locally Constrained Genetic Algorithm For Least-Cost Water Distribution Network Design

Copyright © IWA Publishing 2014. The definitive peer-reviewed and edited version of this article is published in Journal of Hydroinformatics Vol.16 (2), pp. 288–301 (2014), DOI: 10.2166/hydro.2013.218 and is available at www.iwapublishing.comThis paper describes the development of an adaptive locally constrained genetic algorithm (ALCO-GA) and its application to the problem of least cost water distribution network design. Genetic algorithms have been used widely for the optimisation of both theoretical and real-world nonlinear optimisation problems, including water system design and maintenance problems. In this work we propose a heuristic-based approach to the mutation of chromosomes with the algorithm employing an adaptive mutation operator which utilises hydraulic head information and an elementary heuristic to increase the efficiency of the algorithm's search into the feasible solution space. In almost all test instances ALCO-GA displays faster convergence and reaches the feasible solution space faster than the standard genetic algorithm. ALCO-GA also achieves high optimality when compared to solutions from the literature and often obtains better solutions than the standard genetic algorithm

Optimization of Quercetin Extraction from Green Tea (Camellia sinensis) Using Central Composite Design, and the Pharmacological Activity of the Extract

The aim of this paper was to optimize an extraction procedure of quercetin from green tea using central composite design. Extraction time, ethanol concentration, and solid to liquid ratio were selected as the independent variables, while quercetin yield was defined as a response. The impact of factors and their interactions on the quercetin yield was studied based on the results of ANOVA test. The extraction time of 58.5 min, ethanol concentration of 94.7 % (v/v), and solid to liquid ratio of 1:19.4 (m/v) were found as the optimal conditions. The experimental confirmation of the proposed optimal conditions indicated that there was a good agreement between the experimental and predicted values. In addition to quercetin, the presence of 17 bioactive compounds was confirmed in the green tea extract using mass spectrometry method. Antioxidant, antimicrobial and antitumor activity of the optimal extract was determined using DPPH assay, disk diffusion method, and MTT assay, respectively

Estrus Induction in Sexually Mature Gilts with Different Hormonal Treatments

The aim of this study was to determine the effectiveness of the synchronized estrus induction in sexually mature gilts, after treatment with different hormonal treatments, given in the unknown phase of a spontaneous estrus cycle. Sexually mature gilts were used, with at least one spontaneous estrous cycle. A total of 90 gilts were treated with single i/m injection of 1,000 IU eCG (Folligon®), 40 gilts were treated with two separate i/m injection of 1 ml PGF2α (Dinolytic®), at an interval of 11 days, and 40 gilts were treated orally (within diet) with 20 mg of synthetic progestagen preparation Altrenogest (Regumate®), during 18 days. Estrus was detected twice daily, in the 10h to 12h intervals, by direct contact with the teaser boar. The best induction of synchronized estrus (in 90% of gilts), which appeared within the first 7 days (mean 5.3 days) after treatment, was found in gilts treated with progestagen preparations. In the three repetitions of treatment with eCG, within the first 7 days (mean 4.2 days) after the treatment, estrus was detected in 65%, 40% or 33% of the treated gilts. After treatment with luteolytic preparation PGF2α (Dynolitic®), estrus was detected in 40% of gilts, on average 5.5 days after treatment. The obtained results clearly show that the successful induction of synchronized estrus in sexually mature gilts can be done only by the method for prolongation of the luteal phase of the spontaneous estrous cycles, using progestagen preparations

Helping to heal nature and ourselves through human-rights-based and gender-responsive One Health

Abstract: The health of our planet and humanity is threatened by biodiversity loss, disease and climate crises that are unprecedented in human history, driven by our insatiable consumption and unsustainable production patterns, particularly food systems. The One Health approach is a pathway to synergistically addressing outcomes in term of health and sustainability, but gender issues at the One Health and biodiversity nexus are largely ignored. By examining the roles and responsibilities of Indigenous and Local People, and especially women, in conserving natural resources, and the social costs of living at the Human-Animal-Environment interface under current conservation strategies, we show that women bear a disproportionate health, poverty and climate burden, despite having pivotal roles in conserving biodiversity. To mitigate risks of emerging infectious diseases, food insecurity and climate change impacts, a gender perspective has previously been proposed, but implementation lags behind. Endemic zoonotic diseases, human-wildlife conflict and environmental pollution lack gender-sensitive frameworks. We demonstrate that women can be powerful agents for change at all levels of society, from communities to businesses, and policy-making institutions, but gender inequalities still persist. We develop a framework for mainstreaming a gender-responsive and rights-based One Health approach, in order to heal ourselves and nature. Using a leverage-points perspective, we suggest a change of paradigm, from the pursuit of GDP and over-consumption, to a focus on human well-being and their reconnection with healthy environments, using a One Health understanding of nature and health. We recommend learning from Indigenous People to re-position ourselves within nature and to better conserve biodiversity. We also propose integration of gender equity in leadership, the respect of human rights, women’s rights (access to health care, healthy food, land tenure, natural resources, education, and economic opportunities), and the rights of nature, through the implementation of gender-responsive and rights-based One Health Action Plans, at policy-making level, in the private sector and the civil society. As the COVID-19 pandemic continues to unveil deep socio-economic inequities in the wealthiest economies and the vital role of nature in supporting our health, we argue to seize this opportunity to build back better and improve resilience and sustainability by using a gender-responsive and rights-based One Health approach

High-resolution mapping of fluoroquinolones in TB rabbit lesions reveals specific distribution in immune cell types.

Understanding the distribution patterns of antibiotics at the site of infection is paramount to selecting adequate drug regimens and developing new antibiotics. Tuberculosis (TB) lung lesions are made of various immune cell types, some of which harbor persistent forms of the pathogen, Mycobacterium tuberculosis. By combining high resolution MALDI MSI with histology staining and quantitative image analysis in rabbits with active TB, we have mapped the distribution of a fluoroquinolone at high resolution, and identified the immune-pathological factors driving its heterogeneous penetration within TB lesions, in relation to where bacteria reside. We find that macrophage content, distance from lesion border and extent of necrosis drive the uneven fluoroquinolone penetration. Preferential uptake in macrophages and foamy macrophages, where persistent bacilli reside, compared to other immune cells present in TB granulomas, was recapitulated in vitro using primary human cells. A nonlinear modeling approach was developed to help predict the observed drug behavior in TB lesions. This work constitutes a methodological advance for the co-localization of drugs and infectious agents at high spatial resolution in diseased tissues, which can be applied to other diseases with complex immunopathology

Organic Lamb Meat Production in Serbia Based on Autochthonous Zackel Breed: Opportunities and Challenges

The global growing tendency of lamb and mutton meat production has been emphasized. The fastest growing meat production industry on a global level is lamb and mutton meat production. Lamb meat production increase is primarily based on genetic improvement of sheep breeds, reproduction management and disease reduction. The new Strategy for Agriculture and Rural Development in Serbia from 2014 to 2024 defines goals and priorities for further development of agriculture. One of priority topics is the promotion of organic production. Organic lamb production is a great opportunity for rural regions development. Botanical composition analyses, as well as plants nutrition value, have shown that natural resources of regions in Serbia have great potentials for organic lamb production. Basic principles of organic production promote well adapted, autochthonous breeds. Various types of Zackel sheep are important genetic resources, evolutionary adapted on specific conditions and extreme climate. The study evaluated the value of various types of Zackel sheep populations in the regions where they are traditionally reared with special emphasis on some traits such as health status and robustness, important for organic production. Disease frequency analysis in different Zackel type populations has shown that gastrointestinal parasitic infections represent the main health problem in sheep farming. The introduction of veterinary medicine standards in organic sheep production is a great challenge. Considering that conventional prevention and medication are forbidden in organic production, veterinary control of parasitic infections is not satisfying. Our investigations are focused on preventive measure and genetic resistance/tolerance to parasitic infections of various types of Zackel sheep as very important for organic lamb production

Influence of Intensive Animal Breeding to the Appearance of Infectious Diseases (Zoonoses)

Intensive animal breeding and production is based on farm breeding of animals which represents a major source of raw material for food production. Preserving health of animals requires a good practice during breeding, appropriate feeding and watering, adequate control of pests and wild animals. Animal breeding and production of food of animal origin requires significant engagement of veterinary services within the frame of epizootiological, epidemiological, veterinary and sanitary surveillance. Farm manner of cattle breeding can represent a danger of air, water and ground contamination. In the farms situated in a small space, overcrowded with animals there are ideal conditions for the appearance and spreading of causative agent of infectious diseases (prions, viruses, rickettsiae, chlamydia, bacteria, parasites and fungi), which can be transmitted also to humans and wild animals. From the aspect of public health, special attention should be given to the farms with large number of animals and farms with intensive breeding conditions. This is especially important in pig and poultry breeding, where moderate or high prevalence of infections such as salmonellosis and campylobacteriosis are often present, regardless of the fact that the level of clinical illness caused by these infections is relatively low. Intensive production in animal husbandry leads to increased animal waste, and the richest source of infectious agents represents animal feces