Showing papers by "Universidade Federal de Minas Gerais published in 2012"

Guidelines for the use and interpretation of assays for monitoring autophagy

Abstract: In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes. A key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process vs. those that measure flux through the autophagy pathway (i.e., the complete process); thus, a block in macroautophagy that results in autophagosome accumulation needs to be differentiated from stimuli that result in increased autophagic activity, defined as increased autophagy induction coupled with increased delivery to, and degradation within, lysosomes (in most higher eukaryotes and some protists such as Dictyostelium) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the field understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in many cases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes. These guidelines are not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to monitor autophagy. In these guidelines, we consider these various methods of assessing autophagy and what information can, or cannot, be obtained from them. Finally, by discussing the merits and limits of particular autophagy assays, we hope to encourage technical innovation in the field.

The Amazon basin in transition

Abstract: Agricultural expansion and climate variability have become important agents of disturbance in the Amazon basin. Recent studies have demonstrated considerable resilience of Amazonian forests to moderate annual drought, but they also show that interactions between deforestation, fire and drought potentially lead to losses of carbon storage and changes in regional precipitation patterns and river discharge. Although the basin-wide impacts of land use and drought may not yet surpass the magnitude of natural variability of hydrologic and biogeochemical cycles, there are some signs of a transition to a disturbance-dominated regime. These signs include changing energy and water cycles in the southern and eastern portions of the Amazon basin.

World Heart Federation criteria for echocardiographic diagnosis of rheumatic heart disease--an evidence-based guideline.

Abstract: Over the past 5 years, the advent of echocardiographic screening for rheumatic heart disease (RHD) has revealed a higher RHD burden than previously thought. In light of this global experience, the development of new international echocardiographic guidelines that address the full spectrum of the rheumatic disease process is opportune. Systematic differences in the reporting of and diagnostic approach to RHD exist, reflecting differences in local experience and disease patterns. The World Heart Federation echocardiographic criteria for RHD have, therefore, been developed and are formulated on the basis of the best available evidence. Three categories are defined on the basis of assessment by 2D, continuous-wave, and color-Doppler echocardiography: 'definite RHD', 'borderline RHD', and 'normal'. Four subcategories of 'definite RHD' and three subcategories of 'borderline RHD' exist, to reflect the various disease patterns. The morphological features of RHD and the criteria for pathological mitral and aortic regurgitation are also defined. The criteria are modified for those aged over 20 years on the basis of the available evidence. The standardized criteria aim to permit rapid and consistent identification of individuals with RHD without a clear history of acute rheumatic fever and hence allow enrollment into secondary prophylaxis programs. However, important unanswered questions remain about the importance of subclinical disease (borderline or definite RHD on echocardiography without a clinical pathological murmur), and about the practicalities of implementing screening programs. These standardized criteria will help enable new studies to be designed to evaluate the role of echocardiographic screening in RHD control.

Brazilian Longitudinal Study of Adult Health (ELSA-Brasil): objectives and design.

Abstract: Although low- and middle-income countries still bear the burden of major infectious diseases, chronic noncommunicable diseases are becoming increasingly common due to rapid demographic, epidemiologic, and nutritional transitions. However, information is generally scant in these countries regarding chronic disease incidence, social determinants, and risk factors. The Brazilian Longitudinal Study of Adult Health (ELSA-Brasil) aims to contribute relevant information with respect to the development and progression of clinical and subclinical chronic diseases, particularly cardiovascular diseases and diabetes. In this report, the authors delineate the study's objectives, principal methodological features, and timeline. At baseline, ELSA-Brasil enrolled 15,105 civil servants from 5 universities and 1 research institute. The baseline examination (2008-2010) included detailed interviews, clinical and anthropometric examinations, an oral glucose tolerance test, overnight urine collection, a 12-lead resting electrocardiogram, measurement of carotid intima-media thickness, echocardiography, measurement of pulse wave velocity, hepatic ultrasonography, retinal fundus photography, and an analysis of heart rate variability. Long-term biologic sample storage will allow investigation of biomarkers that may predict cardiovascular diseases and diabetes. Annual telephone surveillance, initiated in 2009, will continue for the duration of the study. A follow-up examination is scheduled for 2012-2013.

Committed carbon emissions, deforestation, and community land conversion from oil palm plantation expansion in West Kalimantan, Indonesia

Abstract: Industrial agricultural plantations are a rapidly increasing yet largely unmeasured source of tropical land cover change. Here, we evaluate impacts of oil palm plantation development on land cover, carbon flux, and agrarian community lands in West Kalimantan, Indonesian Borneo. With a spatially explicit land change/carbon bookkeeping model, parameterized using high-resolution satellite time series and informed by socioeconomic surveys, we assess previous and project future plantation expansion under five scenarios. Although fire was the primary proximate cause of 1989–2008 deforestation (93%) and net carbon emissions (69%), by 2007–2008, oil palm directly caused 27% of total and 40% of peatland deforestation. Plantation land sources exhibited distinctive temporal dynamics, comprising 81% forests on mineral soils (1994–2001), shifting to 69% peatlands (2008–2011). Plantation leases reveal vast development potential. In 2008, leases spanned ∼65% of the region, including 62% on peatlands and 59% of community-managed lands, yet <10% of lease area was planted. Projecting business as usual (BAU), by 2020 ∼40% of regional and 35% of community lands are cleared for oil palm, generating 26% of net carbon emissions. Intact forest cover declines to 4%, and the proportion of emissions sourced from peatlands increases 38%. Prohibiting intact and logged forest and peatland conversion to oil palm reduces emissions only 4% below BAU, because of continued uncontrolled fire. Protecting logged forests achieves greater carbon emissions reductions (21%) than protecting intact forests alone (9%) and is critical for mitigating carbon emissions. Extensive allocated leases constrain land management options, requiring trade-offs among oil palm production, carbon emissions mitigation, and maintaining community landholdings.

Regulatory T Cells Accumulate in the Lung Allergic Inflammation and Efficiently Suppress T-Cell Proliferation but Not Th2 Cytokine Production

Abstract: Foxp3+CD25+CD4+ regulatory T cells are vital for peripheral tolerance and control of tissue inflammation. In this study, we characterized the phenotype and monitored the migration and activity of regulatory T cells present in the airways of allergic or tolerant mice after allergen challenge. To induce lung allergic inflammation, mice were sensitized twice with ovalbumin/aluminum hydroxide gel and challenged twice with intranasal ovalbumin. Tolerance was induced by oral administration of ovalbumin for 5 consecutive days prior to OVA sensitization and challenge. We detected regulatory T cells (Foxp3+CD25+CD4+ T cells) in the airways of allergic and tolerant mice; however, the number of regulatory T cells was more than 40-fold higher in allergic mice than in tolerant mice. Lung regulatory T cells expressed an effector/memory phenotype (CCR4highCD62LlowCD44highCD54highCD69+) that distinguished them from naive regulatory T cells (CCR4intCD62LhighCD44intCD54intCD69−). These regulatory T cells efficiently suppressed pulmonary T-cell proliferation but not Th2 cytokine production.

Peri‐implant disease in subjects with and without preventive maintenance: a 5‐year follow‐up

Abstract: Costa F. O., Takenaka-Martinez S., Cota L. O. M., Ferreira S. D., Silva G. L.M., Costa J. E., Peri-implant disease in subjects with and without preventivemaintenance: a 5-year follow-up. J Clin Periodontol 2011; doi: 10.1111/j.1600-051X.2011.01819.x.AbstractAim: To determine the incidence of peri-implantitis in individuals with mucositisin a 5-year follow-up study.Material and Methods: A sample of 212 partially edentulous individuals, rehabili-tated with dental implants, underwent periodontal and peri-implant clinical exam-inations in 2005 (baseline). Five years later, 80 individuals who had beendiagnosed with mucositis in the baseline examination were re-examined. Theseindividuals were divided into two groups: one group with preventive maintenanceduring the study period (GTP; n = 39), and another group without preventivemaintenance (GNTP; n = 41). The following parameters were clinically evaluated:plaque index, bleeding on periodontal and peri-implant probing, periodontal andperi-implant probing depth, suppuration and peri-implant bone loss. The influ-ence of biological and behavioural risk variables associated with the occurrenceof peri-implantitis was analysed using univariate and multivariate logistic regres-sion analyses.Results: The incidence of peri-implantitis in the global sample was 31.2%(GNTP = 43.9% and GTP = 18.0%).Conclusion: The absence of preventive maintenance in individuals with pre-exist-ing peri-implant mucositis was associated with a high incidence of peri-implanti-tis. Clinical parameters, such as bleeding on peri-implant probing, periodontalprobing depth and the presence of periodontitis were associated with a higher riskof developing peri-implantitis.

Acute Gastrointestinal Infection Induces Long-Lived Microbiota-Specific T Cell Responses

Abstract: The mammalian gastrointestinal tract contains a large and diverse population of commensal bacteria and is also one of the primary sites of exposure to pathogens. How the immune system perceives commensals in the context of mucosal infection is unclear. Here, we show that during a gastrointestinal infection, tolerance to commensals is lost, and microbiota-specific T cells are activated and differentiate to inflammatory effector cells. Furthermore, these T cells go on to form memory cells that are phenotypically and functionally consistent with pathogen-specific T cells. Our results suggest that during a gastrointestinal infection, the immune response to commensals parallels the immune response against pathogenic microbes and that adaptive responses against commensals are an integral component of mucosal immunity.

Multiple mechanisms involved in the large-spectrum therapeutic potential of cannabidiol in psychiatric disorders

Abstract:  Cannabidiol (CBD) is a major phytocannabinoid present in the Cannabis sativa plant. It lacks the psychotomimetic and other psychotropic effects that the main plant compound D 9 -tetrahydrocannabinol (THC) being able, on the contrary, to antagonize these effects. This property, together with its safety profile, was an initial stimulus for the investigation of CBD pharmacological properties. It is now clear thatCBDhastherapeutic potentialoverawiderangeofnon-psychiatricandpsychiatricdisorderssuch as anxiety, depression and psychosis. Although the pharmacological effects of CBD in different biological systems have been extensively investigated by in vitro studies, the mechanisms responsible for its therapeutic potential are still not clear. Here, we review recent in vivo studies indicating that these mechanisms are not unitary but rather depend on the behavioural response being measured. Acute anxiolytic and antidepressant-like effects seem to rely mainly on facilitation of 5-HT1Amediated neurotransmission in key brain areas related to defensive responses, including the dorsal periaqueductal grey, bed nucleus of the stria terminalis and medial prefrontal cortex. Other effects, such as anti-compulsive, increased extinction and impaired reconsolidation of aversive memories, and facilitation of adult hippocampal neurogenesis could depend on potentiation of anandamidemediated neurotransmission. Finally, activation of TRPV1 channels may help us to explain the antipsychoticeffectandthebell-shapeddose-responsecurvescommonlyobservedwithCBD.Considering its safety profile and wide range of therapeutic potential, however, further studies are needed to investigate the involvement of other possible mechanisms (e.g. inhibition of adenosine uptake, inverse agonism at CB2 receptor, CB1 receptor antagonism, GPR55 antagonism, PPARg receptors agonism, intracellular (Ca 2þ ) increase, etc.), on CBD behavioural effects.

Butyrate: implications for intestinal function.

Abstract: Purpose of reviewButyrate is physiologically produced by the microbial fermentation of dietary fibers and plays a plurifunctional role in intestinal cells. This review examines the recent findings regarding the role and mechanisms by which butyrate regulates intestinal metabolism and discusses how t

Iron oxide catalysts: Fenton and Fenton-like reactions - a review

Abstract: Iron is the fourth most common element by mass in the Earth’s crust and forms compounds in several oxidation states. Iron (hydr)oxides, some of which form inherently and exclusively in the nanometre-size range, are ubiquitous in nature and readily synthesized. These facts add up to render many Fe (hydr)oxides suitable as catalysts, and it is hardly surprising that numerous studies on the applications of Fe (hydr)oxides in catalysis have been published. Moreover, the abundant availability of a natural Fe source from rocks and soils at minimal cost makes the potential use of these as heterogeneous catalyst attractive. Besides those Fe (hydr)oxides that are inherently nanocrystalline (ferrihydrite, Fe5HO8·4H2O, and feroxyhyte, δ′-FeOOH), magnetite (Fe3O4) is often used as a catalyst because it has a permanent magnetization and contains Fe in both the divalent and trivalent states. Hematite, goethite and lepidocrocite have also been used as catalysts in their pure forms, doped with other cations, and as composites with carbon, alumina and zeolites among others. In this review we report on the use of synthetic and natural Fe (hydr)oxides as catalysts in environmental remediation procedures using an advanced oxidation process, more specifically the Fenton-like system, which is highly efficient in generating reactive species such as hydroxyl radicals, even at room temperature and under atmospheric pressure. The catalytic efficiency of Fe (hydr)oxides is strongly affected by factors such as the Fe oxidation state, surface area, isomorphic substitution of Fe by other cations, pH and temperature.

STOP: Space-Time Occupancy Patterns for 3D Action Recognition from Depth Map Sequences

Abstract: This paper presents Space-Time Occupancy Patterns (STOP), a new visual representation for 3D action recognition from sequences of depth maps. In this new representation, space and time axes are divided into multiple segments to define a 4D grid for each depth map sequence. The advantage of STOP is that it preserves spatial and temporal contextual information between space-time cells while being flexible enough to accommodate intra-action variations. Our visual representation is validated with experiments on a public 3D human action dataset. For the challenging cross-subject test, we significantly improved the recognition accuracy from the previously reported 74.7% to 84.8%. Furthermore, we present an automatic segmentation and time alignment method for online recognition of depth sequences.

A research agenda for helminth diseases of humans: the problem of helminthiases.

Abstract: A disproportionate burden of helminthiases in human populations occurs in marginalised, low-income, and resource-constrained regions of the world, with over 1 billion people in developing areas of sub-Saharan Africa, Asia, and the Americas infected with one or more helminth species. The morbidity caused by such infections imposes a substantial burden of disease, contributing to a vicious circle of infection, poverty, decreased productivity, and inadequate socioeconomic development. Furthermore, helminth infection accentuates the morbidity of malaria and HIV/AIDS, and impairs vaccine efficacy. Polyparasitism is the norm in these populations, and infections tend to be persistent. Hence, there is a great need to reduce morbidity caused by helminth infections. However, major deficiencies exist in diagnostics and interventions, including vector control, drugs, and vaccines. Overcoming these deficiencies is hampered by major gaps in knowledge of helminth biology and transmission dynamics, platforms from which to help develop such tools. The Disease Reference Group on Helminths Infections (DRG4), established in 2009 by the Special Programme for Research and Training in Tropical Diseases (TDR), was given the mandate to review helminthiases research and identify research priorities and gaps. In this review, we provide an overview of the forces driving the persistence of helminthiases as a public health problem despite the many control initiatives that have been put in place; identify the main obstacles that impede progress towards their control and elimination; and discuss recent advances, opportunities, and challenges for the understanding of the biology, epidemiology, and control of these infections. The helminth infections that will be discussed include: onchocerciasis, lymphatic filariasis, soil-transmitted helminthiases, schistosomiasis, food-borne trematodiases, and taeniasis/cysticercosis.

Phosphate homeostasis and its role in bone health

Abstract: Phosphate is one of the most abundant minerals in the body, and its serum levels are regulated by a complex set of processes occurring in the intestine, skeleton, and kidneys. The currently known main regulators of phosphate homeostasis include parathyroid hormone (PTH), calcitriol, and a number of peptides collectively known as the “phosphatonins” of which fibroblast growth factor-23 (FGF-23) has been best defined. Maintenance of extracellular and intracellular phosphate levels within a narrow range is important for many biological processes, including energy metabolism, cell signaling, regulation of protein synthesis, skeletal development, and bone integrity. The presence of adequate amounts of phosphate is critical for the process of apoptosis of mature chondrocytes in the growth plate. Without the presence of this mineral in high enough quantities, chondrocytes will not go into apoptosis, and the normal physiological chain of events that includes invasion of blood vessels and the generation of new bone will be blocked, resulting in rickets and delayed growth. In the rest of the skeleton, hypophosphatemia will result in osteomalacia due to an insufficient formation of hydroxyapatite. This review will address phosphate metabolism and its role in bone health.

The neuroimmune guidance cue netrin-1 promotes atherosclerosis by inhibiting the emigration of macrophages from plaques

Abstract: Atherosclerotic plaque formation is fueled by the persistence of lipid-laden macrophages in the artery wall. The mechanisms by which these cells become trapped, thereby establishing chronic inflammation, remain unknown. Here we found that netrin-1, a neuroimmune guidance cue, was secreted by macrophages in human and mouse atheroma, where it inactivated the migration of macrophages toward chemokines linked to their egress from plaques. Acting via its receptor, UNC5b, netrin-1 inhibited the migration of macrophages directed by the chemokines CCL2 and CCL19, activation of the actin-remodeling GTPase Rac1 and actin polymerization. Targeted deletion of netrin-1 in macrophages resulted in much less atherosclerosis in mice deficient in the receptor for low-density lipoprotein and promoted the emigration of macrophages from plaques. Thus, netrin-1 promoted atherosclerosis by retaining macrophages in the artery wall. Our results establish a causative role for negative regulators of leukocyte migration in chronic inflammation.

A brief survey of automatic methods for author name disambiguation

Abstract: Name ambiguity in the context of bibliographic citation records is a hard problem that affects the quality of services and content in digital libraries and similar systems. The challenges of dealing with author name ambiguity have led to a myriad of disambiguation methods. Generally speaking, the proposed methods usually attempt to group citation records of a same author by finding some similarity among them or try to directly assign them to their respective authors. Both approaches may either exploit supervised or unsupervised techniques. In this article, we propose a taxonomy for characterizing the current author name disambiguation methods described in the literature, present a brief survey of the most representative ones and discuss several open challenges.

Diagnosis and management of Chagas disease and cardiomyopathy.

Abstract: Chagas cardiomyopathy is the most severe and life-threatening manifestation of human Chagas disease--a 'neglected' tropical disease caused by the protozoan parasite Trypanosoma cruzi. The disease is endemic in all continental Latin American countries, but has become a worldwide problem because of migration of infected individuals to developed countries, mainly in Europe and North America. Chagas cardiomyopathy results from the combined effects of persistent parasitism, parasite-driven tissue inflammation, microvascular and neurogenic dysfunction, and autoimmune responses triggered by the infection. Clinical presentation varies widely according to the extent of myocardial damage, and manifests mainly as three basic syndromes that can coexist in an individual patient: heart failure, cardiac arrhythmia, and thromboembolism. NYHA functional class, left ventricular systolic function, and nonsustained ventricular tachycardia are important prognostic markers of the risk of death. Management of Chagas cardiomyopathy focuses on the treatment of the three main syndromes. The use of β-blockers in patients with Chagas disease and heart failure is safe, well tolerated, and should be encouraged. Most specialists and international institutions now recommend specific antitrypanosomal treatment of patients with chronic Chagas disease, even in the absence of evidence obtained from randomized clinical trials. Further research on the management of patients with Chagas cardiomyopathy is necessary.

Oxidants, antioxidants, and the beneficial roles of exercise-induced production of reactive species.

Abstract: This review offers an overview of the influence of reactive species produced during exercise and their effect on exercise adaptation. Reactive species and free radicals are unstable molecules that oxidize other molecules in order to become stable. Although they play important roles in our body, they can also lead to oxidative stress impairing diverse cellular functions. During exercise, reactive species can be produced mainly, but not exclusively, by the following mechanisms: electron leak at the mitochondrial electron transport chain, ischemia/reperfusion and activation of endothelial xanthine oxidase, inflammatory response, and autooxidation of catecholamines. Chronic exercise also leads to the upregulation of the body's antioxidant defence mechanism, which helps minimize the oxidative stress that may occur after an acute bout of exercise. Recent studies show a beneficial role of the reactive species, produced during a bout of exercise, that lead to important training adaptations: angiogenesis, mitochondria biogenesis, and muscle hypertrophy. The adaptations occur depending on the mechanic, and consequently biochemical, stimulus within the muscle. This is a new area of study that promises important findings in the sphere of molecular and cellular mechanisms involved in the relationship between oxidative stress and exercise.

Watch me playing, i am a professional: a first study on video game live streaming

Abstract: "Electronic-sport" (E-Sport) is now established as a new entertainment genre. More and more players enjoy streaming their games, which attract even more viewers. In fact, in a recent social study, casual players were found to prefer watching professional gamers rather than playing the game themselves. Within this context, advertising provides a significant source of revenue to the professional players, the casters (displaying other people's games) and the game streaming platforms. For this paper, we crawled, during more than 100 days, the most popular among such specialized platforms: Twitch.tv. Thanks to these gigabytes of data, we propose a first characterization of a new Web community, and we show, among other results, that the number of viewers of a streaming session evolves in a predictable way, that audience peaks of a game are explainable and that a Condorcet method can be used to sensibly rank the streamers by popularity. Last but not least, we hope that this paper will bring to light the study of E-Sport and its growing community. They indeed deserve the attention of industrial partners (for the large amount of money involved) and researchers (for interesting problems in social network dynamics, personalized recommendation, sentiment analysis, etc.).

Oral administration of sodium butyrate attenuates inflammation and mucosal lesion in experimental acute ulcerative colitis

Abstract: Butyrate is a four-carbon short-chain fatty acid that improves colonic trophism. Although several studies have shown the benefits of butyrate enemas in ulcerative colitis (UC), studies using the oral route are rare in the literature. In the present study, we evaluated the effect of butyrate intake in the immune response associated to UC. For that, mice were fed control or butyrate (0.5% sodium butyrate) diets for 14 days. Acute UC was induced by dextran sulphate sodium (DSS, 2.5%), replacing drinking water. The results showed that, in UC animals, oral butyrate significantly improved trophism and reduced leukocyte (eosinophil and neutrophil) infiltration in the colon mucosa and improved the inflammatory profile (activated macrophage, B and T lymphocytes) in cecal lymph nodes. In the small intestine, although mucosa histology was similar among groups, DSS treatment reduced duodenal transforming growth factor-β, increased interleukin-10 concentrations and increased memory T lymphocytes and dendritic cells in Peyer's patches. Butyrate supplementation was able to revert these alterations. When cecal butyrate concentration was analyzed in cecal content, it was still higher in the healthy animals receiving butyrate than in the UC+butyrate and control groups. In conclusion, our results show that oral administration of sodium butyrate improves mucosa lesion and attenuates the inflammatory profile of intestinal mucosa, local draining lymph nodes and Peyer's patches of DSS-induced UC. Our results also highlight the potential use of butyrate supplements as adjuvant in UC treatment.

Treatment of neuromyelitis optica: Review and recommendations

Abstract: Neuromyelitis optica (NMO) is an autoimmune demyelinating disease preferentially targeting the optic nerves and spinal cord. Once regarded as a variant of multiple sclerosis (MS), NMO is now recognized to be a different disease with unique pathology and immunopathogenesis that does not respond to traditional MS immunomodulators such as interferons. Preventive therapy in NMO has focused on a range of immunosuppressive medications, none of which have been validated in a rigorous randomized trial. However, multiple retrospective and a few recent prospective studies have provided evidence for the use of six medications for the prevention of NMO exacerbations: azathioprine, rituximab, mycophenolate mofetil, prednisone, methotrexate and mitoxantrone. This review provides a comprehensive analysis of each of these medications in NMO and concludes with a set of recommended consensus practices.

NLRP3 inflammasome-mediated neutrophil recruitment and hypernociception depend on leukotriene B(4) in a murine model of gout.

Abstract: Objective Deposition of monosodium urate monohydrate (MSU) crystals in the joints promotes an intense inflammatory response and joint dysfunction. This study evaluated the role of the NLRP3 inflammasome and 5-lipoxygenase (5-LOX)–derived leukotriene B4 (LTB4) in driving tissue inflammation and hypernociception in a murine model of gout. Methods Gout was induced by injecting MSU crystals into the joints of mice. Wild-type mice and mice deficient in NLRP3, ASC, caspase 1, interleukin-1β (IL-1β), IL-1 receptor type I (IL-1RI), IL-18R, myeloid differentiation factor 88 (MyD88), or 5-LOX were used. Evaluations were performed to assess neutrophil influx, LTB4 activity, cytokine (IL-1β, CXCL1) production (by enzyme-linked immunosorbent assay), synovial microvasculature cell adhesion (by intravital microscopy), and hypernociception. Cleaved caspase 1 and production of reactive oxygen species (ROS) were analyzed in macrophages by Western blotting and fluorometric assay, respectively. Results Injection of MSU crystals into the knee joints of mice induced neutrophil influx and neutrophil-dependent hypernociception. MSU crystal–induced neutrophil influx was CXCR2-dependent and relied on the induction of CXCL1 in an NLRP3/ASC/caspase 1/IL-1β/MyD88–dependent manner. LTB4 was produced rapidly after injection of MSU crystals, and this was necessary for caspase 1–dependent IL-1β production and consequent release of CXCR2-acting chemokines in vivo. In vitro, macrophages produced LTB4 after MSU crystal injection, and LTB4 was relevant in the MSU crystal–induced maturation of IL-1β. Mechanistically, LTB4 drove MSU crystal–induced production of ROS and ROS-dependent activation of the NLRP3 inflammasome. Conclusion These results reveal the role of the NLRP3 inflammasome in mediating MSU crystal–induced inflammation and dysfunction of the joints, and highlight a previously unrecognized role of LTB4 in driving NLRP3 inflammasome activation in response to MSU crystals, both in vitro and in vivo.

A Systematic Review of Socioeconomic Indicators and Dental Caries in Adults

Abstract: Increasing evidence suggests that socioeconomic factors may be associated with an increased risk of dental caries. To provide better evidence of the association between dental caries in adults and socioeconomic indicators, we evaluated the relation between these two conditions in a thorough review of the literature. Seven databases were systematically searched: Pubmed, Cochrane, Web of Science, Bireme, Controlled Trials, Clinical Trials and the National Institute for Health and Clinical Excellence. No restrictions were placed on the language or year of publication. The search yielded 41 studies for systematic review. Two independent reviewers screened the studies for inclusion, extracted data and evaluated quality using the Newcastle-Ottawa scale. The following socioeconomic indicators were found: educational level, income, occupation, socio-economic status and the community index. These indicators were significantly associated with a greater occurrence of dental caries: the subject’s education, subject’s income, subject’s occupation and the Gini coefficient. A high degree of heterogeneity was found among the methods. Quality varied across studies. The criteria employed for socioeconomic indicators and dental caries should be standardized in future studies. The scientific evidence reveals that educational level, income, occupation and the Gini coefficient are associated with dental caries.

Hypercontractivity, sum-of-squares proofs, and their applications

Abstract: We study the computational complexity of approximating the 2-to-q norm of linear operators (defined as |A|2->q = maxv≠ 0|Av|q/|v|2) for q > 2, as well as connections between this question and issues arising in quantum information theory and the study of Khot's Unique Games Conjecture (UGC). We show the following: For any constant even integer q ≥ 4, a graph G is a small-set expander if and only if the projector into the span of the top eigenvectors of G's adjacency matrix has bounded 2->q norm. As a corollary, a good approximation to the 2->q norm will refute the Small-Set Expansion Conjecture --- a close variant of the UGC. We also show that such a good approximation can be obtained in exp(n2/q) time, thus obtaining a different proof of the known subexponential algorithm for Small-Set-Expansion. Constant rounds of the "Sum of Squares" semidefinite programing hierarchy certify an upper bound on the 2->4 norm of the projector to low degree polynomials over the Boolean cube, as well certify the unsatisfiability of the "noisy cube" and "short code" based instances of Unique-Games considered by prior works. This improves on the previous upper bound of exp(logO(1) n) rounds (for the "short code"), as well as separates the "Sum of Squares"/"Lasserre" hierarchy from weaker hierarchies that were known to require ω(1) rounds. We show reductions between computing the 2->4 norm and computing the injective tensor norm of a tensor, a problem with connections to quantum information theory. Three corollaries are: (i) the 2->4 norm is NP-hard to approximate to precision inverse-polynomial in the dimension, (ii) the 2->4 norm does not have a good approximation (in the sense above) unless 3-SAT can be solved in time exp(√n poly log(n)), and (iii) known algorithms for the quantum separability problem imply a non-trivial additive approximation for the 2->4 norm.