Global similarity with local differences in linkage disequilibrium between the Dutch and HapMap–CEU populations

The HapMap project has facilitated the selection of tagging single nucleotide polymorphisms (tagSNPs) for genome-wide association studies (GWAS) under the assumption that linkage disequilibrium (LD) in the HapMap populations is similar to the populations under investigation. Earlier reports support this assumption, although in most of these studies only a few loci were evaluated. We compared pair-wise LD and LD block structure across autosomes between the Dutch population and the CEU-HapMap reference panel. The impact of sampling distribution on the estimation of LD blocks was studied by bootstrapping. A high Pearson correlation (genome-wide; 0.93) between pair-wise

A microRNA profile of human CD8(+) regulatory T cells and characterization of the effects of microRNAs on Treg cell-associated genes.

Recently, regulatory T (Treg) cells have gained interest in the fields of immunopathology, transplantation and oncoimmunology. Here, we investigated the microRNA expression profile of human natural CD8(+)CD25(+) Treg cells and the impact of microRNAs on molecules associated with immune regulation. We purified human natural CD8(+) Treg cells and assessed the expression of FOXP3 and CTLA-4 by flow cytometry. We have also tested the ex vivo suppressive capacity of these cells in mixed leukocyte reactions. Using TaqMan low-density arrays and microRNA qPCR for validation, we could identify a microRNA 'signature' for CD8(+)CD25(+)FOXP3(+)CTLA-4(+) natural Treg cells. We used the 'TargetScan' and 'miRBase' bioinformatics programs to identify potential target sites for these microRNAs in the 3'-UTR of important Treg cell-associated genes. The human CD8(+)CD25(+) natural Treg cell microRNA signature includes 10 differentially expressed microRNAs. We demonstrated an impact of this signature on Treg cell biology by showing specific regulation of FOXP3, CTLA-4 and GARP gene expression by microRNA using site-directed mutagenesis and a dual-luciferase reporter assay. Furthermore, we used microRNA transduction experiments to demonstrate that these microRNAs impacted their target genes in human primary Treg cells ex vivo. We are examining the biological relevance of this 'signature' by studying its impact on other important Treg cell-associated genes. These efforts could result in a better understanding of the regulation of Treg cell function and might reveal new targets for immunotherapy in immune disorders and cancer

A new portable vibrator for plaster pouring: effect on the marginal fit at cylinder-abutment

OBJECTIVE: The aim of this study was to test a new portable vibrator for plaster pouring (developed for this purpose), comparing the effect of its use on the accuracy of working cast of implant-supported restorations to the conventional vibrator. MATERIAL AND METHODS: From a master cast with 2 implants, 30 transfer moldings were made randomly and divided into three groups: Group I (GI): pouring performed in an outsourced dental laboratory with conventional plaster vibrator (10 casts), Group II (GII): pouring performed in the laboratory of the Federal University of Santa Catarina (UFSC) with conventional plaster vibrator (10 casts) and Group III (GIII): pouring performed with the portable vibrator fabricated for this study (10 casts). The position of the analogue and marginal adaptation of the infrastructure were verified by testing the single screw on the master model and on the working model. The measurement of misfit was blindly performed with a precision microscope and analyzing unit, Quadra-Check 200. The data were statistically analyzed by analysis of variance (ANOVA) and the Holm-Sidak test (α=0.05). RESULTS: Means±standard deviations were as follows: GI: 19.19±4.73 µm; GII: 21.72±5.41 µm; GIII: 13.5±2.39 µm (P<0.05), with GIII significantly lower as compared to the other groups. CONCLUSION: Within the limitations of this study, it was concluded that a greater accuracy of working cast was achieved when a portable vibrator was used for casting molds

Efeito de sistemas de manejo do solo e velocidade de semeadura no desenvolvimento do sorgo forrageiro

Forage sorghum is a grass grown in dry and hot environments, where the productivity of other forages may be not economically viable. The aim of this study was to evaluate the effect of different management systems and sowing speeds on the development of forage sorghum cv. BRS 610. The soil of the experimental area was a Paleudult. The experiment was installed in field conditions, in FCA/UNESP, Botucatu Campus, using a randomized block split-plot design, with twelve treatments (four management systems and four sowing speeds). The management systems used were: no-tillage, disk harrowing + seeding; disk harrowing + two light disking + seeding; minimum tillage + seeding. The sowing speeds used were: 3, 5, 6 and 9 km h-1. The following variables were analyzed: plant population, plant height, stem diameter, mass of thousand grains, green mass yield and dry mass yield. The no-tilllalge system provided the highest plant population, stem diameter, green mass yield and dry mass yield. There was a reduction in the plant population and increase in stem diameter with the increase in the sowing speed. The speed of 5 km h-1 provided the highest green and dry mass yields (kg ha-1), followed by the speed of 3 km h-1.O sorgo forrageiro é uma gramínea indicada para cultivo em ambientes secos e quentes, nos quais a produtividade de outras forrageiras pode ser antieconômica. Objetivou-se, com este trabalho, estudar diferentes sistemas de manejo e diferentes velocidades de semeadura, no desenvolvimento do sorgo forrageiro cv. BRS 610. O solo da área experimental foi um Nitossolo Vermelho distroférrico. O experimento foi instalado em condições de campo, na FCA/UNESP, Campus de Botucatu-SP, utilizando-se o delineamento em blocos ao acaso, em esquema de parcela subdividida, com dezesseis tratamentos (quatro sistemas de manejo e quatro velocidades de semeadura). Os sistemas de manejo utilizados foram: semeadura direta; gradagem pesada; gradagem pesada + duas gradagens leves e escarificação. As velocidades na operação de semeadura utilizadas foram: 3, 5, 6 e 9 km h-1. Foram analisadas as seguintes variáveis: população de plantas, altura de plantas, diâmetro do colmo, massa de mil grãos e produtividades de massa verde e de massa seca. O sistema de semeadura direta foi o que proporcionou maior população de plantas, maior diâmetro do colmo e maior produção de massas verde e seca. Com o aumento da velocidade na operação de semeadura, houve redução da população de plantas e aumento do diâmetro do colmo. A velocidade de 5 km h-1 foi a que proporcionou maior produção de massas verde e seca (kg ha-1), seguida da velocidade de 3 km h-1.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Universidade Estadual do Sudoeste da Bahia Departamento de Engenharia Agrícola e SolosAssociação Educacional do Vale do Jurumirim Departamento de AgronomiaInstituto Federal de Educação, Ciência e Tecnologia Baiano Departamento de AgronomiaUniversidade Estadual Paulista Departamento de Engenharia RuralUniversidade Estadual Paulista Departamento de Produção VegetalUniversidade Estadual Paulista Departamento de Engenharia RuralUniversidade Estadual Paulista Departamento de Produção Vegeta

DNA Barcode Detects High Genetic Structure within Neotropical Bird Species

BACKGROUND: Towards lower latitudes the number of recognized species is not only higher, but also phylogeographic subdivision within species is more pronounced. Moreover, new genetically isolated populations are often described in recent phylogenies of Neotropical birds suggesting that the number of species in the region is underestimated. Previous COI barcoding of Argentinean bird species showed more complex patterns of regional divergence in the Neotropical than in the North American avifauna. METHODS AND FINDINGS: Here we analyzed 1,431 samples from 561 different species to extend the Neotropical bird barcode survey to lower latitudes, and detected even higher geographic structure within species than reported previously. About 93% (520) of the species were identified correctly from their DNA barcodes. The remaining 41 species were not monophyletic in their COI sequences because they shared barcode sequences with closely related species (N = 21) or contained very divergent clusters suggestive of putative new species embedded within the gene tree (N = 20). Deep intraspecific divergences overlapping with among-species differences were detected in 48 species, often with samples from large geographic areas and several including multiple subspecies. This strong population genetic structure often coincided with breaks between different ecoregions or areas of endemism. CONCLUSIONS: The taxonomic uncertainty associated with the high incidence of non-monophyletic species and discovery of putative species obscures studies of historical patterns of species diversification in the Neotropical region. We showed that COI barcodes are a valuable tool to indicate which taxa would benefit from more extensive taxonomic revisions with multilocus approaches. Moreover, our results support hypotheses that the megadiversity of birds in the region is associated with multiple geographic processes starting well before the Quaternary and extending to more recent geological periods

Sensor-Carrying Platforms

Information and communication technology, autonomy, and miniaturization in terms of, for example, microelectromechanical systems are enabling technologies with significant impact on the development of sensors, sensor-carrying platforms, control systems, data gathering, storage, and analysis methods. Sensor-carrying platforms are grouped in stationary devices such as landers and moorings to dynamic platforms such as marine robotics, ships, aerial systems, and remote-sensing satellites from space. Lately, the development of low-cost small satellites with customized payload sensors and accessible mission control centers has opened for a democratization of the space for remote sensing as well. The mapping and monitoring strategy may be carried out by each type of sensor-carrying platform suitable for the mission. However, we see a quantum leap by operating heterogeneous sensor-carrying platforms for the most efficient mapping and monitoring in spatial and temporal scales. We are facing a paradigm shift in terms of resolution and coverage capabilities. There have been several research efforts to improve the technology and methodology for mapping and monitoring of the oceans. Today, we see that the mapping coverage may be 100–1000 times higher than the state-of-the-art technology 6 years ago. The entailed increase in data harvesting does also create new challenges in handling of big data sets. It is an increasing need to update the oceanographic and ecosystem numerical model capabilities, taking full benefit of the ongoing shift in technology. The Arctic can truly be characterized as a remote and harsh environment for scientific operations and even more demanding during the Polar Night due to the darkness. During winter operations, extreme coldness may also be a challenge dependent on the weather conditions. Enabling technology and proper operational procedures may be the only way to reveal and understand the processes taking place there. The spatial scale is enormous, and as several research campaigns have already taught us, the variability is huge not only during the seasons but also over the years. This clearly also tells us the importance of prolonged presence. In this chapter, we will briefly present the various sensor-carrying platforms and payload sensors. We will also describe the philosophy behind integrated operations using heterogenous platforms and why and how to bridge science and technology being successful in the development of autonomous systems for efficient and safe operations. Examples and experience from Arctic missions will also be presented.acceptedVersionThis is a post-peer-review, pre-copyedit version of an article. Locked until 9/4-2022 due to copyright restrictions. The final authenticated version is available online at: http://dx.doi.org/10.1007/978-3-030-33208-

Melanoma: A model for testing new agents in combination therapies

Treatment for both early and advanced melanoma has changed little since the introduction of interferon and IL-2 in the early 1990s. Recent data from trials testing targeted agents or immune modulators suggest the promise of new strategies to treat patients with advanced melanoma. These include a new generation of B-RAF inhibitors with greater selectivity for the mutant protein, c-Kit inhibitors, anti-angiogenesis agents, the immune modulators anti-CTLA4, anti-PD-1, and anti-CD40, and adoptive cellular therapies. The high success rate of mutant B-RAF and c-Kit inhibitors relies on the selection of patients with corresponding mutations. However, although response rates with small molecule inhibitors are high, most are not durable. Moreover, for a large subset of patients, reliable predictive biomarkers especially for immunologic modulators have not yet been identified. Progress may also depend on identifying additional molecular targets, which in turn depends upon a better understanding of the mechanisms leading to response or resistance. More challenging but equally important will be understanding how to optimize the treatment of individual patients using these active agents sequentially or in combination with each other, with other experimental treatment, or with traditional anticancer modalities such as chemotherapy, radiation, or surgery. Compared to the standard approach of developing new single agents for licensing in advanced disease, the identification and validation of patient specific and multi-modality treatments will require increased involvement by several stakeholders in designing trials aimed at identifying, even in early stages of drug development, the most effective way to use molecularly guided approaches to treat tumors as they evolve over time

Chronic Exposure to the Herbicide, Atrazine, Causes Mitochondrial Dysfunction and Insulin Resistance

There is an apparent overlap between areas in the USA where the herbicide, atrazine (ATZ), is heavily used and obesity-prevalence maps of people with a BMI over 30. Given that herbicides act on photosystem II of the thylakoid membrane of chloroplasts, which have a functional structure similar to mitochondria, we investigated whether chronic exposure to low concentrations of ATZ might cause obesity or insulin resistance by damaging mitochondrial function. Sprague-Dawley rats (n = 48) were treated for 5 months with low concentrations (30 or 300 µg kg−1 day−1) of ATZ provided in drinking water. One group of animals was fed a regular diet for the entire period, and another group of animals was fed a high-fat diet (40% fat) for 2 months after 3 months of regular diet. Various parameters of insulin resistance were measured. Morphology and functional activities of mitochondria were evaluated in tissues of ATZ-exposed animals and in isolated mitochondria. Chronic administration of ATZ decreased basal metabolic rate, and increased body weight, intra-abdominal fat and insulin resistance without changing food intake or physical activity level. A high-fat diet further exacerbated insulin resistance and obesity. Mitochondria in skeletal muscle and liver of ATZ-treated rats were swollen with disrupted cristae. ATZ blocked the activities of oxidative phosphorylation complexes I and III, resulting in decreased oxygen consumption. It also suppressed the insulin-mediated phosphorylation of Akt. These results suggest that long-term exposure to the herbicide ATZ might contribute to the development of insulin resistance and obesity, particularly where a high-fat diet is prevalent

Apolipoprotein A-II Influences Apolipoprotein E-Linked Cardiovascular Disease Risk in Women with High Levels of HDL Cholesterol and C-Reactive Protein

Background: In a previous report by our group, high levels of apolipoprotein E (apoE) were demonstrated to be associated with risk of incident cardiovascular disease in women with high levels of C-reactive protein (CRP) in the setting of both low (designated as HR1 subjects) and high (designated as HR2 subjects) levels of high-density lipoprotein cholesterol (HDL-C). To assess whether apolipoprotein A-II (apoA-II) plays a role in apoE-associated risk in the two female groups. Methodology/Principal: Outcome event mapping, a graphical data exploratory tool; Cox proportional hazards multivariable regression; and curve-fitting modeling were used to examine apoA-II influence on apoE-associated risk focusing on HDL particles with apolipoprotein A-I (apoA-I) without apoA-II (LpA-I) and HDL particles with both apoA-I and apoA-II (LpA-I:A-II). Results of outcome mappings as a function of apoE levels and the ratio of apoA-II to apoA-I revealed within each of the two populations, a high-risk subgroup characterized in each situation by high levels of apoE and additionally: in HR1, by a low value of the apoA-II/apoA-I ratio; and in HR2, by a moderate value of the apoA-II/apoA-I ratio. Furthermore, derived estimates of LpA-I and LpA-I:A-II levels revealed for high-risk versus remaining subjects: in HR1, higher levels of LpA-I and lower levels of LpA-I:A-II; and in HR2 the reverse, lower levels of LpA-I and higher levels of LpA-I:A-II. Results of multivariable risk modeling as a function of LpA-I and LpA-I:A-II (dichotomized as highest quartile versus combined three lower quartiles) revealed association of risk only for high levels of LpA-I:A-II in the HR2 subgroup (hazard ratio 5.31, 95% CI 1.12-25.17, p = 0.036). Furthermore, high LpA-I: A-II levels interacted with high apoE levels in establishing subgroup risk. Conclusions/Significance: We conclude that apoA-II plays a significant role in apoE-associated risk of incident CVD in women with high levels of HDL-C and CRP