Circulating micrornas correlate with multiple myeloma and skeletal osteolytic lesions

Multiple myeloma (MM) is the second most frequent hematological disease and can cause skeletal osteolytic lesions. This study aims to evaluate the expression of circulating microRNAs (miR-NAs) in MM patients and to correlate those levels with clinicopathological features, including bone lesions. A panel of miRNAs associated with MM onset and progression, or with bone remodeling, was analyzed in the plasma of 82 subjects (47 MM patients; 35 healthy controls). Results show that miR-16-5p, miR-20a-5p, and miR-21-5p are differently expressed between MM patients and healthy controls. Receiver operating characteristic analyses indicate that their combined expression has potential as a molecular marker (Area Under the Curve, AUC of 0.8249). Furthermore, significant correlations were found between the analyzed miRNAs and disease stage, treatment, ß2 microglobulin, serum albumin and creatinine levels, but not with calcium levels or genetic alterations. In this cohort, 65.96% of MM patients had bone lesions, the majority of which were in the vertebrae. Additionally, miR-29c-3p was decreased in patients with osteolytic lesions compared with patients without bone disease. Interestingly, circulating levels of miR-29b-3p correlated with cervical and thoracic vertebral lesions, while miR-195-5p correlated with thoracic lesions. Our findings suggest circulating miRNAs can be promising biomarkers for MM diagnosis and that their levels correlate with myeloma bone disease and osteolytic lesions.The project was supported by AO Spine-ESA Grant Award 2018 (AO Foundation); As-sociação Portuguesa Contra a Leucemia, Sociedade Portuguesa de Hematologia, AMGEN; and by Portuguese funds through FCT-Fundação para a Ciência e a Tecnologia (FCT)/Ministério da Ciência, Tecnologia e Ensino Superior in the framework of the project POCI-01-0145-FEDER-031402-R2Bone (FEDER-Fundo Europeu de Desenvolvimento Regional funds through the COMPETE 2020-Operacional Programme for Competitiveness and Internationalisation—POCI, Portugal 2020)

Custo de produção de mudas clonais de Café Arábica produzidas por embriogênese somática

A produção de mudas clonais de café pode ser feita de diferentes formas. Entretanto, a produção por embriogênese somática é a que tem despontado como a mais promissora. A embriogênese somática permite a produção de mudas em larga escala a partir de folhas usadas como explantes. Plantas obtidas por esse processo apresentam comportamento semelhante ao de plantas oriundas de sementes, não havendo limitação para a sua utilização comercial. A produção de mudas clonais de café é realizada em laboratórios de cultura de tecidos adaptados para a produção em escala industrial, denominados de biofábricas. Todavia, a produção de mudas clonais via embriogênese somática é uma técnica que ainda não foi explorada comercialmente no Brasil e não existe uma estimativa do custo de produção de mudas clonais de café arábica. Assim, o objetivo no presente trabalho foi calcular o custo de produção de mudas clonais de café em uma biofábrica de pequeno porte, tendo-se como base o protocolo desenvolvido pela Fundação Procafé/Embrapa Café, com a colaboração de pesquisadores da Embrapa Recursos Genéticos e Biotecnologia e do Centro de Cooperação Internacional em Pesquisa Agronômica para o Desenvolvimento, CIRAD, França. Este trabalho apresenta também uma relação dos equipamentos e materiais necessários para a produção de mudas de café in vitro. O custo de produção de uma muda foi de R$0,97 para uma produção anual de 400.000 mudas, utilizando-se o plantio de embriões pré-germinados diretamente em tubetes. Caso a etapa de produção de plântulas em potes in vitro seja utilizada, o custo de produção passa a ser de R$1,34

On Tackling the Limits of Resolution in SAT Solving

The practical success of Boolean Satisfiability (SAT) solvers stems from the CDCL (Conflict-Driven Clause Learning) approach to SAT solving. However, from a propositional proof complexity perspective, CDCL is no more powerful than the resolution proof system, for which many hard examples exist. This paper proposes a new problem transformation, which enables reducing the decision problem for formulas in conjunctive normal form (CNF) to the problem of solving maximum satisfiability over Horn formulas. Given the new transformation, the paper proves a polynomial bound on the number of MaxSAT resolution steps for pigeonhole formulas. This result is in clear contrast with earlier results on the length of proofs of MaxSAT resolution for pigeonhole formulas. The paper also establishes the same polynomial bound in the case of modern core-guided MaxSAT solvers. Experimental results, obtained on CNF formulas known to be hard for CDCL SAT solvers, show that these can be efficiently solved with modern MaxSAT solvers

The Role of Individual Variables, Organizational Variables and Moral Intensity Dimensions in Libyan Management Accountants’ Ethical Decision Making

This study investigates the association of a broad set of variables with the ethical decision making of management accountants in Libya. Adopting a cross-sectional methodology, a questionnaire including four different ethical scenarios was used to gather data from 229 participants. For each scenario, ethical decision making was examined in terms of the recognition, judgment and intention stages of Rest’s model. A significant relationship was found between ethical recognition and ethical judgment and also between ethical judgment and ethical intention, but ethical recognition did not significantly predict ethical intention—thus providing support for Rest’s model. Organizational variables, age and educational level yielded few significant results. The lack of significance for codes of ethics might reflect their relative lack of development in Libya, in which case Libyan companies should pay attention to their content and how they are supported, especially in the light of the under-development of the accounting profession in Libya. Few significant results were also found for gender, but where they were found, males showed more ethical characteristics than females. This unusual result reinforces the dangers of gender stereotyping in business. Personal moral philosophy and moral intensity dimensions were generally found to be significant predictors of the three stages of ethical decision making studied. One implication of this is to give more attention to ethics in accounting education, making the connections between accounting practice and (in Libya) Islam. Overall, this study not only adds to the available empirical evidence on factors affecting ethical decision making, notably examining three stages of Rest’s model, but also offers rare insights into the ethical views of practising management accountants and provides a benchmark for future studies of ethical decision making in Muslim majority countries and other parts of the developing world

Lipocalin 2 modulates the cellular response to amyloid beta

The production, accumulation and aggregation of amyloid beta (Aß) peptides in Alzheimer's disease (AD) are influenced by different modulators. Among these are iron and iron-related proteins, given their ability to modulate the expression of the amyloid precursor protein and to drive Aß aggregation. Herein, we describe that lipocalin 2 (LCN2), a mammalian acute-phase protein involved in iron homeostasis, is highly produced in response to Aß1-42 by choroid plexus epithelial cells and astrocytes, but not by microglia or neurons. Although Aß1-42 stimulation decreases the dehydrogenase activity and survival of wild-type astrocytes, astrocytes lacking the expression of Lcn2 are not affected. This protection results from a lower expression of the proapoptotic gene Bim and a decreased inflammatory response. Altogether, these findings show that Aß toxicity to astrocytes requires LCN2, which represents a novel mechanism to target when addressing AD.Cell Death and Differentiation advance online publication, 23 May 2014; doi:10.1038/cdd.2014.68.We thank Dr. Ioannis Sotiropoulos for reagents and comments. Sandro Da Mesquita and Ana Catarina Ferreira are recipients of PhD fellowships and Fernanda Marques is recipient of a postdoctoral fellowship by the Fundacao para a Ciencia e Tecnologia (FCT, Portugal)/FEDER. This work was supported by a grant from FCT/FEDER (EXPL/NEUOSD/2196/2013)

Therapeutic DNA Vaccine Encoding Peptide P10 against Experimental Paracoccidioidomycosis

Paracoccidioidomycosis (PCM), caused by Paracoccidioides brasiliensis, is the most prevalent invasive fungal disease in South America. Systemic mycoses are the 10th most common cause of death among infectious diseases in Brazil and PCM is responsible for more than 50% of deaths due to fungal infections. PCM is typically treated with sulfonamides, amphotericin B or azoles, although complete eradication of the fungus may not occur and relapsing disease is frequently reported. A 15-mer peptide from the major diagnostic antigen gp43, named P10, can induce a strong T-CD4+ helper-1 immune response in mice. The TEPITOPE algorithm and experimental data have confirmed that most HLA-DR molecules can present P10, which suggests that P10 is a candidate antigen for a PCM vaccine. In the current work, the therapeutic efficacy of plasmid immunization with P10 and/or IL-12 inserts was tested in murine models of PCM. When given prior to or after infection with P. brasiliensis virulent Pb 18 isolate, plasmid-vaccination with P10 and/or IL-12 inserts successfully reduced the fungal burden in lungs of infected mice. In fact, intramuscular administration of a combination of plasmids expressing P10 and IL-12 given weekly for one month, followed by single injections every month for 3 months restored normal lung architecture and eradicated the fungus in mice that were infected one month prior to treatment. The data indicate that immunization with these plasmids is a powerful procedure for prevention and treatment of experimental PCM, with the perspective of being also effective in human patients

Extensive Copy-Number Variation of Young Genes across Stickleback Populations

MM received funding from the Max Planck innovation funds for this project. PGDF was supported by a Marie Curie European Reintegration Grant (proposal nr 270891). CE was supported by German Science Foundation grants (DFG, EI 841/4-1 and EI 841/6-1). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript