A multi-modal data resource for investigating topographic heterogeneity in patient-derived xenograft tumors.

Patient-derived xenografts (PDXs) are an essential pre-clinical resource for investigating tumor biology. However, cellular heterogeneity within and across PDX tumors can strongly impact the interpretation of PDX studies. Here, we generated a multi-modal, large-scale dataset to investigate PDX heterogeneity in metastatic colorectal cancer (CRC) across tumor models, spatial scales and genomic, transcriptomic, proteomic and imaging assay modalities. To showcase this dataset, we present analysis to assess sources of PDX variation, including anatomical orientation within the implanted tumor, mouse contribution, and differences between replicate PDX tumors. A unique aspect of our dataset is deep characterization of intra-tumor heterogeneity via immunofluorescence imaging, which enables investigation of variation across multiple spatial scales, from subcellular to whole tumor levels. Our study provides a benchmark data resource to investigate PDX models of metastatic CRC and serves as a template for future, quantitative investigations of spatial heterogeneity within and across PDX tumor models

Penerapan Hukum Pidana Terhadap Tindak Pidana Makar Oleh Organisasi Papua Merdeka (Opm) Di Kabupaten Jayawijaya (Studiputusannomor 38/pid.b/2011/pn.wmn)

A mutiny criminal act is related to a state security. A munity threats legal interest and the safety of Unitary State of the Republic if Indonesia as stipulated in Chapter I book II of Penal Code which consist of three form, namely the mutiny which attacks the legal interests for the safety of Head of State or his/her Vice (Article 104 Penal Code), the unity of State regions (Article 106 Penal code), and the enforcement of State Government (Article 107 Penal Code. The formulations of problem in the research are whether the act done by the Liberating Papua Organization (LPO) is classified as mutiny, how the legal responsibilities towards the mutiny criminal act done by the LPO in the District Of Jayawijaya are, how the implementation of penal code on the mutiny criminal act done by the LPO in District of Jayawijaya based on the verdict No.38/Pid.B/2011/PN.Wmn is. The research result showed the act done by the LPO was a mutiny stipulated in the article 106 Penal code an hasfullfilled the elements whose goal was to conquer the region of state fully or partly under the foreign government with the intetion to separate some parts of the state region. The existence of conscious cooperation. Consequently, all defendants subjected tho the same crimes. Implementation of penal code towards the mutiny criminal act done the LPO in the verdict No.38/Pid.B/2011.PN.Wmn that the judge has implemented the Article 106 Penal Code Jo Article 55 clause (1) in the 1st , namely by sentencing 8 years in prison to every member of LPO

Caracterização da matéria orgânica e mineralógica dos solos das bacias dos rios Acre e Iaco, estado do Acre.

Na região Amazônica, o uso da terra tem levado, no decorrer dos anos, a um mosaico de agroecossistemas que caracterizam e registram a resposta do ambiente às suas alterações. Os conhecimentos pedoambientais e a ação antrópica nestes ambientes são de importância fundamental para o melhor uso dos ecossistemas. O objetivo do presente trabalho foi estudar duas bacias contíguas com componentes pedológicos distintos utilizando como base de estratificação a matéria orgânica e a mineralogia de forma a subsidiar o manejo dos solos nesta região. Nos perfis descritos e coletados nas duas bacias de estudo, bacia do rio Acre e Iaco, foram realizados: extração e fracionamento de substâncias húmicas, fracionamento físico da matéria orgânica para obtenção da fração leve e análises de difratometria por raios X, para análises mineralógicas. Os resultados revelaram o domínio de frações húmicas em superfície, sempre reduzindo em profundidade e diferenças mineralógicas nas bacias estudadas, onde a bacia do rio Acre apresentou minerais mais evoluídos como caulinita e gibbsita e na bacia do rio Iaco, mineralogia do tipo 2:1 como vermiculita e esmectita, que revela o caráter jovens de seus solos e uma maior vulnerabilidade a ação antrópica

An Actin-Based Wave Generator Organizes Cell Motility

Although many of the regulators of actin assembly are known, we do not understand how these components act together to organize cell shape and movement. To address this question, we analyzed the spatial dynamics of a key actin regulator—the Scar/WAVE complex—which plays an important role in regulating cell shape in both metazoans and plants. We have recently discovered that the Hem-1/Nap1 component of the Scar/WAVE complex localizes to propagating waves that appear to organize the leading edge of a motile immune cell, the human neutrophil. Actin is both an output and input to the Scar/WAVE complex: the complex stimulates actin assembly, and actin polymer is also required to remove the complex from the membrane. These reciprocal interactions appear to generate propagated waves of actin nucleation that exhibit many of the properties of morphogenesis in motile cells, such as the ability of cells to flow around barriers and the intricate spatial organization of protrusion at the leading edge. We propose that cell motility results from the collective behavior of multiple self-organizing waves

Systematic review of symptom clusters in cardiovascular disease

Background: Although individual symptoms and symptom trajectories for various cardiovascular conditions have been reported, there is limited research identifying the symptom clusters that may provide a better understanding of patients’ experiences with heart disease. Aims: To summarize the state of the science in symptom cluster research for patients with acute coronary syndrome, myocardial infarction, coronary artery bypass surgery, and heart failure through systematic review and to provide direction for the translation of symptom cluster research into the clinical setting. Methods: Databases were searched for articles from January 2000 through to May 2015 using MESH terms “symptoms, symptom clusters, acute coronary syndrome (ACS), myocardial infarction (MI), coronary heart disease (CHD), ischemic heart disease (IHD), heart failure (HF), coronary artery bypass surgery (CABS), cluster analyses, and latent classes.” The search was limited to human studies, English language articles, and original articles investigating symptom clusters in individuals with heart disease. Fifteen studies meeting the criteria were included. Results: For patients with ACS and MI, younger persons were more likely to experience clusters with the most symptoms. Older adults were more likely to experience clusters with the lowest number of symptoms and more diffuse and milder symptom clusters that are less reflective of classic ACS presentations. For HF patients, symptom clusters frequently included physical and emotional/cognitive components; edema clustered in only three studies. Symptom expression was congruent across geographical regions and cultures. Conclusions: The findings demonstrated similarities in symptom clusters during ACS, MI, and HF, despite multiple methods and analyses. These results may help clinicians to prepare at-risk patients for proper treatment-seeking and symptom self-management behaviors

Evidence for a correlation between the sizes of quiescent galaxies and local environment to z ~ 2

We present evidence for a strong relationship between galaxy size and environment for the quiescent population in the redshift range 1 < z < 2. Environments were measured using projected galaxy overdensities on a scale of 400 kpc, as determined from ~ 96,000 K-band selected galaxies from the UKIDSS Ultra Deep Survey (UDS). Sizes were determined from ground-based K-band imaging, calibrated using space-based CANDELS HST observations in the centre of the UDS field, with photometric redshifts and stellar masses derived from 11-band photometric fitting. From the resulting size-mass relation, we confirm that quiescent galaxies at a given stellar mass were typically ~ 50 % smaller at z ~ 1.4 compared to the present day. At a given epoch, however, we find that passive galaxies in denser environments are on average significantly larger at a given stellar mass. The most massive quiescent galaxies (M_stellar > 2 x 10^11 M_sun) at z > 1 are typically 50 % larger in the highest density environments compared to those in the lowest density environments. Using Monte Carlo simulations, we reject the null hypothesis that the size-mass relation is independent of environment at a significance > 4.8 sigma for the redshift range 1 < z < 2. In contrast, the evidence for a relationship between size and environment is much weaker for star-forming galaxies.Comment: Accepted for publication in MNRAS. 16 pages, 11 figures, 6 table

Efeitos da dinâmica de uso da terra sobre os estoques de carbono e nutrientes em um argissolo amarelo na Amazônia Ocidental.

Este trabalho teve por objetivo discutir acerca dos estoques de carbono e nutrientes contidos em um Argissolo Amarelo Distrófico textura média/argilosa relevo plano a suave ondulado submetido a diferentes usos pelos pequenos agricultores (agricultura familiar)

Ageing enhances cellular immunity to myeloperoxidase and experimental anti-myeloperoxidase glomerulonephritis

OBJECTIVES: Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis is an autoimmune disease characterised by small blood vessel inflammation, commonly affecting the kidneys and respiratory tract. It is unclear why the incidence of this condition increases with age. Previous studies in a passive antibody transfer system in aged mice have implicated innate effectors. To test the hypothesis that autoimmunity to myeloperoxidase, an autoantigen responsible for ANCA-associated vasculitis, increases with age, anti-myeloperoxidase autoimmunity was studied in murine models of active autoimmunity and disease induced by cellular immunity. METHODS: Young (8 weeks) and aged (either 15 or 22 month) mice were immunised with whole proteins or peptides from ovalbumin, as a model foreign antigen, or myeloperoxidase protein or peptides. Mice were subjected to a model of active anti-myeloperoxidase glomerulonephritis. Cellular and humoral immune responses and tissue inflammation were assessed. RESULTS: While cellular immunity to ovalbumin was diminished in aged mice, cellular autoimmunity to myeloperoxidase and its immunodominant CD4+ and CD8+ T cell epitopes was increased after immunization with either MPO peptides or whole MPO protein, assessed by peptide and antigen specific production of the pro-inflammatory cytokines interferon-γ and interleukin-17A. MPO-ANCA titres were not increased in aged mice compared with young mice. In experimental anti-MPO glomerulonephritis, cell mediated injury was increased, likely due to CD4+ and CD8+ T cells, innate immunity and the increased vulnerability of aged kidneys. CONCLUSION: Heightened cellular immunity to MPO develops with ageing in mice and may contribute to the increased incidence and severity of ANCA-associated vasculitis in older people

Arabidopsis \u3ci\u3eACTIN-DEPOLYMERIZING FACTOR3\u3c/i\u3e Is Required for Controlling Aphid Feeding from the Phloem

The actin cytoskeleton network has an important role in plant cell growth, division, and stress response. Actin-depolymerizing factors (ADFs) are a group of actin-binding proteins that contribute to reorganization of the actin network. Here, we show that the Arabidopsis (Arabidopsis thaliana) ADF3 is required in the phloem for controlling infestation by Myzus persicae Sülzer, commonly known as the green peach aphid (GPA), which is an important phloem sap-consuming pest of more than fifty plant families. In agreement with a role for the actin-depolymerizing function of ADF3 in defense against the GPA, we show that resistance in adf3 was restored by overexpression of the related ADF4 and the actin cytoskeleton destabilizers, cytochalasin D and latrunculin B. Electrical monitoring of the GPA feeding behavior indicates that the GPA stylets found sieve elements faster when feeding on the adf3 mutant compared to the wild-type plant. In addition, once they found the sieve elements, the GPA fed for a more prolonged period from sieve elements of adf3 compared to the wild-type plant. The longer feeding period correlated with an increase in fecundity and population size of the GPA and a parallel reduction in callose deposition in the adf3 mutant. The adf3-conferred susceptibility to GPA was overcome by expression of the ADF3 coding sequence from the phloem-specific SUC2 promoter, thus confirming the importance of ADF3 function in the phloem. We further demonstrate that the ADF3- dependent defense mechanism is linked to the transcriptional up-regulation of PHYTOALEXIN-DEFICIENT4, which is an important regulator of defenses against the GPA

Antiviral activity of silymarin against chikungunya virus

Citation: Lani, R., Hassandarvish, P., Chiam, C. W., Moghaddam, E., Chu, J. J. H., Rausalu, K., . . . Zandi, K. (2015). Antiviral activity of silymarin against chikungunya virus. Scientific Reports, 5, 10. doi:10.1038/srep11421The mosquito-borne chikungunya virus (CHIKV) causes chikungunya fever, with clinical presentations such as severe back and small joint pain, and debilitating arthritis associated with crippling pains that persist for weeks and even years. Although there are several studies to evaluate the efficacy of drugs against CHIKV, the treatment for chikungunya fever is mainly symptom-based and no effective licensed vaccine or antiviral are available. Here, we investigated the antiviral activity of three types of flavonoids against CHIKV in vitro replication. Three compounds: silymarin, quercetin and kaempferol were evaluated for their in vitro antiviral activities against CHIKV using a CHIKV replicon cell line and clinical isolate of CHIKV of Central/East African genotype. A cytopathic effect inhibition assay was used to determine their activities on CHIKV viral replication and quantitative reverse transcription PCR was used to calculate virus yield. Antiviral activity of effective compound was further investigated by evaluation of CHIKV protein expression using western blotting for CHIKV nsP1, nsP3, and E2E1 proteins. Briefly, silymarin exhibited significant antiviral activity against CHIKV, reducing both CHIKV replication efficiency and down-regulating production of viral proteins involved in replication. This study may have important consequence for broaden the chance of getting the effective antiviral for CHIKV infection