Queer Scrapscape: Hudinilson Jr.’s Cadernos de referências

Este ensaio lança luz sobre os Cadernos de referências (c. 1981-2013) do artista brasileiro Hudinilson Jr., uma série de álbuns de recortes densos e cheios de camadas. Através de uma análise de layouts e mídias, a investigação destaca as extensas implicações culturais e de design desencadeadas pela obra. O foco recai principalmente sobre as recorrências formais e estratégias narrativas identificadas em páginas duplas, revelando como elas condensam a poética queer do artista. Os Cadernos surgem como uma prática cotidiana de exploração do corpo humano, um espaço de auto-design e resistência cultural, e uma ferramenta de questionamento da relação entre o corpo exposto, a autoimagem e os meios de comunicação de massa.This essay sheds light on Brazilian artist Hudinilson Jr.’s Cadernos de referências (c. 1981-2013), a series of dense and layered scrapbooks. Through an analysis of layouts and media, the investigation highlights the extensive design and cultural implications that the practice triggers. The focus lies primarily on formal recurrences and narrative strategies identified on double page spreads, revealing how they condense the artist’s queer poetics. The Cadernos emerge as an everyday practice of exploration of the human body, a space for self-design and cultural resistance, and a tool for questioning the relationship between the exposed body, self-image, and mass media.Este ensayo echa luz sobre los Cadernos de referências (c. 1981-2013) del artista brasileño Hudinilson Jr., una serie de álbumes de recortes densos y llenos de capas. A través de un análisis de layouts y medios, la investigación resalta las extensas implicaciones culturales y de design desencadenadas por la obra. El enfoque recae principalmente en las recurrencias formales y estrategias narrativas identificadas en páginas dobles, revelando cómo condensan la poética queer del artista. Los Cadernos surgen como una práctica diaria de exploración del cuerpo humano, un espacio de auto-design y resistencia cultural, y una herramienta de cuestionamiento de la relación entre el cuerpo expuesto, la autoimagen y los medios de comunicación de masas

Queer Scrapscape : Hudinilson Jr.’s Cadernos de referências

This essay sheds light on Brazilian artist Hudinilson Jr.’s Cadernos de referências (c. 1981-2013), a series of dense and layered scrapbooks. Through an analysis of layouts and media, the investigation highlights the extensive design and cultural implications that the practice triggers. The focus lies primarily on formal recurrences and narrative strategies identified on double page spreads, revealing how they condense the artist’s queer poetics. The Cadernos emerge as an everyday practice of exploration of the human body, a space for self-design and cultural resistance, and a tool for questioning the relationship between the exposed body, self-image, and mass media

An RbAp48-like gene regulates adult stem cells in planarians.

Retinoblastoma-associated proteins 46 and 48 (RbAp46 and RbAp48) are factors that are components of different chromatin-modelling complexes, such as polycomb repressive complex 2, the activity of which is related to epigenetic gene regulation in stem cells. To date, no direct findings are available on the in vivo role of RbAp48 in stem-cell biology. We recently identified DjRbAp48 — a planarian ( Dugesia japonica ) homologue of human RBAP48 — expression of which is restricted to the neoblasts, the adult stem cells of planarians. In vivo silencing of DjRbAp48 induces lethality and inability to regenerate, even though neoblasts proliferate and accumulate after wounding. Despite a partial reduction in neoblast number, we were always able to detect a significant number of these cells in DjRbAp48 RNAi animals. Parallel to the decrease in neoblasts, a reduction in the number of differentiated cells and the presence of apoptotic-like neoblasts were detectable in RNAi animals. These findings suggest that DjRbAp48 is not involved in neoblast maintenance, but rather in the regulation of differentiation of stem-cell progeny. We discuss our data, taking into account the possibility that DjRbAp48 might control the expression of genes necessary for cell differentiation by influencing chromatin architecture

Deciphering the molecular machinery of stem cells: a look at the neoblast gene expression profile

Comparison of the gene-expression profiles of planarians in which all adult pluripotent stem cells (neoblasts) were eliminated and wild-type worms identified a putative neoblast-restricted gene set. This included many genes involved in chromatin modeling and RNA metabolism, suggesting that epigenetic modifications and post-transcriptional regulation are important for neoblast regulation

Comprehensive methylome map of lineage commitment from haematopoietic progenitors.

Epigenetic modifications must underlie lineage-specific differentiation as terminally differentiated cells express tissue-specific genes, but their DNA sequence is unchanged. Haematopoiesis provides a well-defined model to study epigenetic modifications during cell-fate decisions, as multipotent progenitors (MPPs) differentiate into progressively restricted myeloid or lymphoid progenitors. Although DNA methylation is critical for myeloid versus lymphoid differentiation, as demonstrated by the myeloerythroid bias in Dnmt1 hypomorphs, a comprehensive DNA methylation map of haematopoietic progenitors, or of any multipotent/oligopotent lineage, does not exist. Here we examined 4.6 million CpG sites throughout the genome for MPPs, common lymphoid progenitors (CLPs), common myeloid progenitors (CMPs), granulocyte/macrophage progenitors (GMPs), and thymocyte progenitors (DN1, DN2, DN3). Marked epigenetic plasticity accompanied both lymphoid and myeloid restriction. Myeloid commitment involved less global DNA methylation than lymphoid commitment, supported functionally by myeloid skewing of progenitors following treatment with a DNA methyltransferase inhibitor. Differential DNA methylation correlated with gene expression more strongly at CpG island shores than CpG islands. Many examples of genes and pathways not previously known to be involved in choice between lymphoid/myeloid differentiation have been identified, such as Arl4c and Jdp2. Several transcription factors, including Meis1, were methylated and silenced during differentiation, indicating a role in maintaining an undifferentiated state. Additionally, epigenetic modification of modifiers of the epigenome seems to be important in haematopoietic differentiation. Our results directly demonstrate that modulation of DNA methylation occurs during lineage-specific differentiation and defines a comprehensive map of the methylation and transcriptional changes that accompany myeloid versus lymphoid fate decisions

Drugs targeting the mitochondrial pore act as citotoxic and cytostatic agents in temozolomide-resistant glioma cells

<p>Abstract</p> <p>Background</p> <p>High grade gliomas are one of the most difficult cancers to treat and despite surgery, radiotherapy and temozolomide-based chemotherapy, the prognosis of glioma patients is poor. Resistance to temozolomide is the major barrier to effective therapy. Alternative therapeutic approaches have been shown to be ineffective for the treatment of genetically unselected glioma patients. Thus, novel therapies are needed. Mitochondria-directed chemotherapy is an emerging tool to combat cancer, and inner mitochondrial permeability transition (MPT) represents a target for the development of cytotoxic drugs. A number of agents are able to induce MPT and some of them target MPT-pore (MPTP) components that are selectively up-regulated in cancer, making these agents putative cancer cell-specific drugs.</p> <p>Objective</p> <p>The aim of this paper is to report a comprehensive analysis of the effects produced by selected MPT-inducing drugs (Betulinic Acid, Lonidamine, CD437) in a temozolomide-resistant glioblastoma cell line (ADF cells).</p> <p>Methods</p> <p>EGFRvIII expression has been assayed by RT-PCR. EGFR amplification and PTEN deletion have been assayed by differential-PCR. Drugs effect on cell viability has been tested by crystal violet assay. MPT has been tested by JC1 staining. Drug cytostatic effect has been tested by mitotic index analysis. Drug cytotoxic effect has been tested by calcein AM staining. Apoptosis has been assayed by Hoechst incorporation and Annexine V binding assay. Authophagy has been tested by acridine orange staining.</p> <p>Results</p> <p>We performed a molecular and genetic characterization of ADF cells and demonstrated that this line does not express the EGFRvIII and does not show EGFR amplification. ADF cells do not show PTEN mutation but differential PCR data indicate a hemizygous deletion of PTEN gene. We analyzed the response of ADF cells to Betulinic Acid, Lonidamine, and CD437. Our data demonstrate that MPT-inducing agents produce concentration-dependent cytostatic and cytotoxic effects in parallel with MPT induction triggered through MPTP. CD437, Lonidamine and Betulinic acid trigger apoptosis as principal death modality.</p> <p>Conclusion</p> <p>The obtained data suggest that these pharmacological agents could be selected as adjuvant drugs for the treatment of high grade astrocytomas that resist conventional therapies or that do not show any peculiar genetic alteration that can be targeted by specific drugs.</p

Plexin-B1 plays a redundant role during mouse development and in tumour angiogenesis

<p>Abstract</p> <p>Background</p> <p>Plexins are a large family of transmembrane receptors for the Semaphorins, known for their role in the assembly of neural circuitry. More recently, Plexins have been implicated in diverse biological functions, including vascular growth, epithelial tissue morphogenesis and tumour development. In particular, PlexinB1, the receptor for Sema4D, has been suggested to play a role in neural development and in tumour angiogenesis, based on in vitro studies. However, the tissue distribution of PlexinB1 has not been extensively studied and the functional relevance of this receptor in vivo still awaits experimental testing. In order to shed light on PlexinB1 function in vivo, we therefore undertook the genomic targeting of the mouse gene to obtain loss of function mutants.</p> <p>Results</p> <p>This study shows that PlexinB1 receptor and its putative ligand, Sema4D, have a selective distribution in nervous and epithelial tissues during development and in the adult. PlexinB1 and Sema4D show largely complementary cell distribution in tissues, consistent with the idea that PlexinB1 acts as the receptor for Sema4D in vivo. Interestingly, PlexinB1 is also expressed in certain tissues in the absence of Sema4D, suggesting Sema4D independent activities. High expression of PlexinB1 was found in lung, kidney, liver and cerebellum.</p> <p>Mutant mice lacking expression of semaphorin receptor PlexinB1 are viable and fertile. Although the axon collapsing activity of Sema4D is impaired in PlexinB1 deficient neurons, we could not detect major defects in development, or in adult histology and basic functional parameters of tissues expressing PlexinB1. Moreover, in the absence of PlexinB1 the angiogenic response induced by orthotopically implanted tumours was not affected, suggesting that the expression of this semaphorin receptor in endothelial cells is redundant.</p> <p>Conclusion</p> <p>Our expression analysis suggests a multifaceted role of PlexinB1 during mouse development and tissue homeostasis in the adult. Nonetheless, the genetic deletion of PlexinB1 does not result in major developmental defects or clear functional abnormalities. We infer that PlexinB1 plays a redundant role in mouse development and it is not strictly required for tumour induced angiogenesis.</p

Formylated Peptide Receptor-1 (FPR1) mediated gut inflammation as a therapeutic target in Inflammatory Bowel Disease

Background: Formylated peptide receptor (FPR)-1 is a G-coupled receptor that senses foreign bacterial and host-derived mitochondrial formylated peptides (FPs), leading to innate immune system activation. Aim: We sought to investigate the role of FPR1-mediated inflammation and its potential as a therapeutic target in inflammatory bowel disease (IBD). Methods: We characterized FPR1 gene and protein expression in 8 human IBD (~1000 patients) datasets with analysis on disease subtype, mucosal inflammation, and drug response. We performed in vivo dextran-sulfate sodium (DSS) colitis in C57/BL6 FPR1 knockout mice. In ex vivo studies, we studied the role of mitochondrial FPs and pharmacological blockade of FPR1 using cyclosporin H in human peripheral blood neutrophils. Finally, we assess mitochondrial FPs as a potential mechanistic biomarker in the blood and stools of patients with IBD. Results: Detailed in silico analysis in human intestinal biopsies showed that FPR1 is highly expressed in IBD (n = 207 IBD vs 67 non-IBD controls, P &lt; .001), and highly correlated with gut inflammation in ulcerative colitis (UC) and Crohn’s disease (CD) (both P &lt; .001). FPR1 receptor is predominantly expressed in leukocytes, and we showed significantly higher FPR1+ve neutrophils in inflamed gut tissue section in IBD (17 CD and 24 UC; both P &lt; .001). Further analysis in 6 independent IBD (data available under Gene Expression Omnibus accession numbers GSE59071, GSE206285, GSE73661, GSE16879, GSE92415, and GSE235970) showed an association with active gut inflammation and treatment resistance to infliximab, ustekinumab, and vedolizumab. FPR1 gene deletion is protective in murine DSS colitis with lower gut neutrophil inflammation. In the human ex vivo neutrophil system, mitochondrial FP, nicotinamide adenine dinucleotide dehydrogenase subunit-6 (ND6) is a potent activator of neutrophils resulting in higher CD62L shedding, CD63 expression, reactive oxygen species production, and chemotactic capacity; these effects are inhibited by cyclosporin H. We screened for mitochondrial ND6 in IBD (n = 54) using ELISA and detected ND6 in stools with median values of 2.2 gg/mL (interquartile range [IQR] 0.0–4.99; range 0–53.3) but not in blood. Stool ND6 levels, however, were not significantly correlated with paired stool calprotectin, C-reactive protein, and clinical IBD activity. Conclusions: Our data suggest that FPR1-mediated neutrophilic inflammation is a tractable target in IBD; however, further work is required to clarify the clinical utility of mitochondrial FPs as a potential mechanistic marker for future stratification.</p

Reply to: New Meta- and Mega-analyses of Magnetic Resonance Imaging Findings in Schizophrenia: Do They Really Increase Our Knowledge About the Nature of the Disease Process?

This work was supported by National Institute of Biomedical Imaging and Bioengineering Grant No. U54EB020403 (to the ENIGMA consortium)

Prediction and Optimal Scheduling of Advertisements in Linear Television

Advertising is a crucial component of marketing and an important way for companies to raise awareness of goods and services in the marketplace. Advertising campaigns are designed to convey a marketing image or message to an audience of potential consumers and television commercials can be an effective way of transmitting these messages to a large audience. In order to meet the requirements for a typical advertising order, television content providers must provide advertisers with a predetermined number of impressions in the target demographic. However, because the number of impressions for a given program is not known a priori and because there are a limited number of time slots available for commercials, scheduling advertisements efficiently can be a challenging computational problem. In this case study, we compare a variety of methods for estimating future viewership patterns in a target demographic from past data. We also present a method for using those predictions to generate an optimal advertising schedule that satisfies campaign requirements while maximizing advertising revenue