Agrochemicals have enabled to more than duplicate food production during the last century, and the current need to increase food production to feed a rapid growing human population maintains pressure ...on the intensive use of pesticides and fertilizers. However, worldwide surveys have documented the contamination and impact of agrochemical residues in soils, and terrestrial and aquatic ecosystems including coastal marine systems, and their toxic effects on humans and nonhuman biota. Although persistent organic chemicals have been phased out and replaced by more biodegradable chemicals, contamination by legacy residues and recent residues still impacts on the quality of human food, water, and environment. Current and future increase in food production must go along with production of food with better quality and with less toxic contaminants. Alternative paths to the intensive use of crop protection chemicals are open, such as genetically engineered organisms, organic farming, change of dietary habits, and development of food technologies. Agro industries need to further develop advanced practices to protect public health, which requires more cautious use of agrochemicals through prior testing, careful risk assessment, and licensing, but also through education of farmers and users in general, measures for better protection of ecosystems, and good practices for sustainable development of agriculture, fisheries, and aquaculture. Enhanced scientific research for new developments in food production and food safety, as well as for environmental protection, is a necessary part of this endeavor. Furthermore, worldwide agreement on good agriculture practices, including development of genetically modified organisms (GMOs) and their release for international agriculture, may be urgent to ensure the success of safe food production.
Current need to increase food production to feed a rapid growing human population maintains the pressure on the intensive use of pesticides and fertilizers. Residues of these chemicals are already present in all ecosystems on Earth and therefore in our food and bodies, with toxic effects on humans and nonhuman biota. Current and future increase in food production must go along with production of food with better quality and with less toxic contaminants. Scientific research for new developments in food production and enhanced food safety, as well as environmental protection, is a necessary part of this. A worldwide agreement on good agriculture practices and GMOs development and their release to international agriculture may be urgent to ensure the success of food production.
Cytolytic CD8+ T cells mediate immunopathology in cutaneous leishmaniasis without controlling parasites. Here, we identify factors involved in CD8+ T cell migration to the lesion that could be ...targeted to ameliorate disease severity. CCR5 was the most highly expressed chemokine receptor in patient lesions, and the high expression of CCL3 and CCL4, CCR5 ligands, was associated with delayed healing of lesions. To test the requirement for CCR5, Leishmania-infected Rag1-/- mice were reconstituted with CCR5-/- CD8+ T cells. We found that these mice developed smaller lesions accompanied by a reduction in CD8+ T cell numbers compared to controls. We confirmed these findings by showing that the inhibition of CCR5 with maraviroc, a selective inhibitor of CCR5, reduced lesion development without affecting the parasite burden. Together, these results reveal that CD8+ T cells migrate to leishmanial lesions in a CCR5-dependent manner and that blocking CCR5 prevents CD8+ T cell-mediated pathology.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Deregulated CD8+ T cell cytotoxicity plays a central role in enhancing disease severity in several conditions. However, we have little understanding of the mechanisms by which immunopathology ...develops as a consequence of cytotoxicity. Using murine models of inflammation induced by the protozoan parasite leishmania, and data obtained from patients with cutaneous leishmaniasis, we uncovered a previously unrecognized role for NLRP3 inflammasome activation and IL-1β release as a detrimental consequence of CD8+ T cell-mediated cytotoxicity, ultimately resulting in chronic inflammation. Critically, pharmacological blockade of NLRP3 or IL-1β significantly ameliorated the CD8+ T cell-driven immunopathology in leishmania-infected mice. Confirming the relevance of these findings to human leishmaniasis, blockade of the NLRP3 inflammasome in skin biopsies from leishmania-infected patients prevented IL-1β release. Thus, these studies link CD8+ T cell cytotoxicity with inflammasome activation and reveal novel avenues of treatment for cutaneous leishmaniasis, as well as other of diseases where CD8+ T cell-mediated cytotoxicity induces pathology.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
(1) Background: We proposed to review worldwide estimates of cognitive impairment prevalence and incidence in adults older than 50 years of age living in the community. (2) Methods: Systematic ...searches were performed in January 2019 using MEDLINE/PubMed. Articles were selected if they referred to cognitive impairment, prevalence, incidence, elders, and population or community-based studies. Analysis, aggregated by different methodologic features, was performed. (3) Results: Prevalence (80 studies) ranged between 5.1% and 41% with a median of 19.0% (25th percentile = 12.0%; 75th percentile = 24.90%). Incidence (11 studies) ranged from 22 to 76.8 per 1000 person-years with a median of 53.97 per 1000 person-years (25th percentile = 39.0; 75th percentile = 68.19). No statistically significant effects were found except for inclusion age. (4) Conclusion: We propose that the homogenization and clarification of the definition of what constitutes cognitive impairment are essential to refine the epidemiological understanding of this entity. The results of this review reinforce the importance of adherence to standardized cut-off scores for cognitive tests to promote study comparability.
Background
Global climate is changing more rapidly than ever, threatening plant growth and productivity while exerting considerable direct and indirect effects on the quality and quantity of plant ...nutrients.
Scope
This review focuses on the global impact of climate change on the nutritional value of plant foods. It showcases the existing evidence linking the effects of climate change factors on crop nutrition and the concentration of nutrients in edible plant parts. It focuses on the effect of elevated CO
2
(eCO
2
), elevated temperature (eT), salinity, waterlogging and drought stresses, and what is known regarding their direct and indirect influence on nutrient availability. Furthermore, it provides possible strategies to preserve the nutritional composition of plant foods under changing climates.
Conclusions
Climate change has an impact on the accumulation of minerals and protein in crop plants, with eCO
2
being the underlying factor of most of the reported changes. The effects are clearly dependent on the type, intensity and duration of the imposed stress, plant genotype and developmental stage. Strong interactions (both positive and negative) can be found between individual climatic factors and soil availability of nitrogen (N), potassium (K), iron (Fe) and phosphorous (P). The development of future interventions to ensure that the world's population has access to plentiful, safe and nutritious food may need to rely on breeding for nutrients under the context of climate change, including legumes in cropping systems, better farm management practices and utilization of microbial inoculants that enhance nutrient availability.
HTLV-1-infected individuals may develop a neurologic inflammatory condition known as HTLV-1-associated myelopathy (HAM/TSP), in which the high production of TNF is observed. These patients exhibit ...higher proviral loads, enhanced production of proinflammatory cytokines and lymphocyte proliferation in comparison to asymptomatic HTLV-1 carriers and those presenting overactive bladder (OAB-HTLV-infected). Metalloproteinases (MMPs) are known to degrade the components of the blood-brain barrier, favoring the migration of infected cells into the central nervous system. Moreover, the unbalanced production of MMPs and their inhibitors (TIMPs) has also been associated with tissue damage. The present work studied the production of MMP-9 and TIMPs in HTLV-1-infected individuals with and without neurological manifestations. HAM/TSP patients presented higher concentrations of MMP-9 in peripheral blood mononuclear cell (PBMC) culture supernatants, as well as a higher MMP-9/TIMP-3 ratio when compared to the other groups studied. MMP-9 levels positively correlated with proviral load and TNF in OAB-HTLV-infected individuals, and the
in vitro
neutralization of TNF significantly decreased MMP-9 levels in PBMC culture supernatants. Our findings indicate an association between MMP-9 production and the proinflammatory state associated with HTLV-1 infection, as well as HAM/TSP.
Diketopiperazines are the smallest cyclic peptides known. 90% of Gram-negative bacteria produce diketopiperazines and they have also been isolated from Gram-positive bacteria, fungi and higher ...organisms. Biosynthesis of cyclodipeptides can be achieved by dedicated nonribosomal peptide synthetases or by a novel type of synthetases named cyclopeptide synthases. Since the first report in 1924 a large number of bioactive diketopiperazines was discovered spanning activities as antitumor, antiviral, antifungal, antibacterial, antiprion, antihyperglycemic or glycosidase inhibitor agents. As infections are of increasing concern for human health and resistances against existing antibiotics are growing this review focuses on the antimicrobial activities of diketopiperazines. The antibiotic bicyclomycin is a diketopiperazine and structure activity studies revealed the unique nature of this compound which was finally developed for clinical applications. The antimicrobial activities of a number of other diketopiperazines along with structure activity relationships are discussed. Here a special focus is on the activity-toxicity problem of many compounds setting tight limitations to their application as drugs. Not only these classical antimicrobial activities but also proposed action in modulating bacterial communication as a new target to control biofilms will be evaluated. Pathogens organized in biofilms are difficult to eradicate because of the increase of their tolerance for antibiotics for several orders. Diketopiperazines were reported to modulate LuxR-mediated quorum-sensing systems of bacteria, and they are considered to influence cell-cell signaling offering alternative ways of biofilm control by interfering with microbial communication. Concluding the review we will finally discuss the potential of diketopiperazines in the clinic to erase biofilm infections.
Hierarchical Multi-Label Classification is a classification task where the classes to be predicted are hierarchically organized. Each instance can be assigned to classes belonging to more than one ...path in the hierarchy. This scenario is typically found in protein function prediction, considering that each protein may perform many functions, which can be further specialized into sub-functions. We present a new hierarchical multi-label classification method based on multiple neural networks for the task of protein function prediction. A set of neural networks are incrementally training, each being responsible for the prediction of the classes belonging to a given level.
The method proposed here is an extension of our previous work. Here we use the neural network output of a level to complement the feature vectors used as input to train the neural network in the next level. We experimentally compare this novel method with several other reduction strategies, showing that it obtains the best predictive performance. Empirical results also show that the proposed method achieves better or comparable predictive performance when compared with state-of-the-art methods for hierarchical multi-label classification in the context of protein function prediction.
The experiments showed that using the output in one level as input to the next level contributed to better classification results. We believe the method was able to learn the relationships between the protein functions during training, and this information was useful for classification. We also identified in which functional classes our method performed better.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
In this Letter we validate experimentally the nonextensive statistical field theory, a new general field-theoretic approach introduced recently in the literature. With such an approach, we are ...capable of computing the critical properties of nonextensive systems undergoing continuous phase transitions, belonging to the new generalized O(N)q universality class. We compare the nonextensive critical indices values evaluated from the theory with those already obtained in literature through experiments for various distinct manganites presenting nonconventional critical behavior. The agreement is satisfactory, whose relative errors are <5% for the most of manganites employed and as better as |1−q|<1 which is the limit of validity of the theory. We present the physical interpretation of the experimental results and of the theory through the general physical interpretation of the q-parameter.
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