Chitosan coated alginate beads containing poly(N-isopropylacrylamide) for dual-stimuli-responsive drug release

Chitosan coated alginate beads containing poly(N-isopropylacrylamide) (PNIPAAM), were prepared to be used as a controlled pH/temperature sensitive drug delivery system with improved encapsulation efficiency and delayed release rate. The studied beads were characterized by differential scanning calorimetry, scanning electron microscopy, and Fourier transform infrared spectroscopy. Water uptake and release studies using indomethacin as a model drug were also performed. The drug loading efficiency of the beads with the polyelectrolyte complex coating is significantly higher (84%) than that of the uncoated ones (74%). The equilibrium swelling of the developed materials was found to be pH- and thermoresponsive. For all the conditions it was found that the release profile was slower for the coated beads, indicating that the polyelectrolyte complex coating could slow down the release rate effectively. These results suggest that the studied smart system has potential to be used as an effective pH/temperature sustainable delivery system for biomedical applications

Into the virtual worlds:Conceptualizing the consumer-avatar journey in virtual environments

As digital representations of human controllers, consumer-avatars play a pivotal role in enabling immersive consumer experiences in virtual environments. Despite their significance in digital marketing research, the literature on consumer-avatars is highly fragmented and lacks comprehensive analysis across studies. To address this gap, we conducted a systematic literature review and developed a comprehensive conceptual framework of the consumer-avatar journey, encompassing three unique phases: Self Representation, Avatar Embodiment, and Avatar-Mediated Interactions. By integrating empirical evidence with multiple theoretical perspectives, including motivation, self-concept, identification, and presence theories, we explored consumer motivations for self representation, how avatar identification occurs, and how avatar-mediated interactions are facilitated by the sense of presence. Additionally, we examined the moderating roles of technological, social, and individual factors in these processes. Our study provides significant theoretical contributions to the current literature by consolidating fragmented research and offers practical insights for marketers to design effective strategies around consumer-avatars. By elaborating on each phase of the consumer-avatar journey, we developed 11 propositions and 5 research questions to guide future research on consumer-avatars

Crumbs 3b promotes tight junctions in an ezrin-dependent manner in mammalian cells

AMT-L is supported by the School of Biology, University of St Andrews. AMT-L, PAR and FJGM were funded by the Anonymous Trust, University of St Andrews. PAR is supported by the Melville Trust for the Care and Cure of Cancer. The mass spectrometry work was supported by the Wellcome Trust [grant number 094476/Z/10/Z], which funded the purchase of the TripleTOF 5600 mass spectrometer at the BSRC Mass Spectrometry and Proteomics Facility, University of St Andrews. The clinical study was supported by the Department of Pathology, Albert Einstein College of Medicine/ Montefiore Medical Center.Crumbs3 (CRB3) is a component of epithelial junctions that has been implicated in apical-basal polarity, apical identity, apical stability, cell adhesion and cell growth. CRB3 undergoes alternative splicing to yield two variants: CRB3a and CRB3b. Here, we describe novel data demonstrating that as with previous studies on CRB3a, CRB3b also promotes the formation of tight junctions. However, significantly we demonstrate that the 4.1-ezrin-radixin-moesin (FERM) binding motif (FBM) of CRB3b is required for CRB3b functionality and that ezrin binds to the FBM of CRB3b. Furthermore, we show that ezrin contributes to CRB3b functionality and the correct distribution of tight junction proteins. We demonstrate that both CRB3 isoforms are required for the production of functionally mature tight junctions and also the localization of ezrin to the plasma membrane. Finally, we demonstrate that reduced CRB3b expression in head and neck squamous cell carcinoma (HNSCC) correlates with cytoplasmic ezrin, a biomarker for aggressive disease, and show evidence that whilst CRB3a expression has no effect, low CRB3b and high cytoplasmic ezrin expression combined may be prognostic for HNSCC.PostprintPeer reviewe

The quantitative architecture of centromeric chromatin

The centromere, responsible for chromosome segregation during mitosis, is epigenetically defined by CENP-A containing chromatin. The amount of centromeric CENP-A has direct implications for both the architecture and epigenetic inheritance of centromeres. Using complementary strategies, we determined that typical human centromeres contain ∼400 molecules of CENP-A, which is controlled by a mass-action mechanism. This number, despite representing only ∼4% of all centromeric nucleosomes, forms a ∼50-fold enrichment to the overall genome. In addition, although pre-assembled CENP-A is randomly segregated during cell division, this amount of CENP-A is sufficient to prevent stochastic loss of centromere function and identity. Finally, we produced a statistical map of CENP-A occupancy at a human neocentromere and identified nucleosome positions that feature CENP-A in a majority of cells. In summary, we present a quantitative view of the centromere that provides a mechanistic framework for both robust epigenetic inheritance of centromeres and the paucity of neocentromere formation. DOI: http://dx.doi.org/10.7554/eLife.02137.00

Obstructive Sleep Apnea Is Associated with Liver Damage and Atherosclerosis in Patients with Non-Alcoholic Fatty Liver Disease

We assessed whether obstructive sleep apnea (OSA) and nocturnal hypoxemia are associated with severity of liver fibrosis and carotid atherosclerosis in patients with biopsy-proven NAFLD and low prevalence of morbid obesity. Secondary aim was to explore the association of OSA and hypoxemia with NASH and severity of liver pathological changes

Dual Face of Vγ9Vδ2-T Cells in Tumor Immunology: Anti- versus Pro-Tumoral Activities

published_or_final_versio

Improving acute promyelocytic leukemia (APL) outcome in developing countries through networking, results of the International Consortium on APL

Thanks to modern treatment with all-trans retinoic acid and chemotherapy, acute promyelocytic leukemia (APL) is now the most curable type of leukemia. However, this progress has not yielded equivalent benefit in developing countries. the International Consortium on Acute Promyelocytic Leukemia (IC-APL) was established to create a network of institutions in developing countries that would exchange experience and data and receive support from well-established US and European cooperative groups. the IC-APL formulated expeditious diagnostic, treatment, and supportive guidelines that were adapted to local circumstances. APL was chosen as a model disease because of the potential impact on improved diagnosis and treatment. the project included 4 national coordinators and reference laboratories, common clinical record forms, 5 subcommittees, and laboratory and data management training programs. in addition, participating institutions held regular virtual and face-to-face meetings. Complete hematological remission was achieved in 153/180 (85%) patients and 27 (15%) died during induction. After a median follow-up of 28 months, the 2-year cumulative incidence of relapse, overall survival (OS), and disease-free survival (DFS) were 4.5%, 80%, and 91%, respectively. the establishment of the IC-APL network resulted in a decrease of almost 50% in early mortality and an improvement in OS of almost 30% compared with historical controls, resulting in OS and DFS similar to those reported in developed countries.American Society of HematologyFondazione Umberto VeronesiRoche Saudi ArabiaFundacao de Apoio a Pesquisa do Estado de São PauloFundacion Mexicana para la SaludSt. Jude Children's Research HospitalCephalon EuropeUniv São Paulo, Hematol Oncol Div, Dept Internal Med, Med Sch Ribeirao Preto, BR-14048900 Ribeirao Preto, BrazilUniv São Paulo, Ctr Cell Based Therapy, BR-14048900 Ribeirao Preto, BrazilDana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USAClin Ruiz Puebla, Puebla, MexicoHosp Salvador, Dept Hematol, Santiago, ChileAsociac Espanola Primera Socorros Mutuos, Montevideo, UruguayHosp Univ Dr Jose E Gonzalez, Div Hematol, Monterrey, MexicoFundacao HEMOPE, Recife, PE, BrazilUniv Fed Rio Grande do Sul, Div Hematol, Porto Alegre, RS, BrazilUniv Fed Parana, Div Hematol, BR-80060000 Curitiba, Parana, BrazilUniv Campinas UNICAMP, Hematol & Hemotherapy Ctr, Campinas, BrazilUniv Fed Minas Gerais, Div Hematol, Belo Horizonte, MG, BrazilUniversidade Federal de São Paulo, São Paulo, BrazilSanta Casa Med Sch, Div Hematol, São Paulo, BrazilCtr Med Nacl Siglo XXI, Mexico City, DF, MexicoNorthwestern Univ, Feinberg Sch Med, Hematol Oncol Div, Chicago, IL 60611 USAAlbert Einstein Canc Ctr, New York, NY USAUniv Med Ctr, Dept Pediat & Adolescent Med, Freiburg, GermanyStanford Univ, Dept Med, Stanford, CA 94305 USAMem Sloan Kettering Canc Ctr, Dept Med, Leukemia Serv, Weill Cornell Med Coll, New York, NY 10021 USAKings Coll London Sch Med, Dept Med & Mol Genet, London, EnglandHannover Med Sch, Dept Hematol Hemostasis Oncol & Stem Cell Transpl, Hannover, GermanyHarvard Univ, Brigham & Womens Hosp, Sch Med, Dept Med, Boston, MA 02115 USASt Jude Childrens Res Hosp, Dept Oncol, Memphis, TN 38105 USAUniv Roma Tor Vergata, Dept Biopathol, Rome, ItalySanta Lucia Fdn, Rome, ItalyErasmus MC, Dept Hematol, Rotterdam, NetherlandsValencia Univ Med Sch, Hosp Univ La Fe, Dept Hematol, Valencia, SpainUniversidade Federal de São Paulo, São Paulo, BrazilFundacao de Apoio a Pesquisa do Estado de São Paulo: 1998/14247-6Web of Scienc

Defining the Molecular Basis of Tumor Metabolism: a Continuing Challenge Since Warburg's Discovery

Cancer cells are the product of genetic disorders that alter crucial intracellular signaling pathways associated with the regulation of cell survival, proliferation, differentiation and death mechanisms. the role of oncogene activation and tumor suppressor inhibition in the onset of cancer is well established. Traditional antitumor therapies target specific molecules, the action/expression of which is altered in cancer cells. However, since the physiology of normal cells involves the same signaling pathways that are disturbed in cancer cells, targeted therapies have to deal with side effects and multidrug resistance, the main causes of therapy failure. Since the pioneering work of Otto Warburg, over 80 years ago, the subversion of normal metabolism displayed by cancer cells has been highlighted by many studies. Recently, the study of tumor metabolism has received much attention because metabolic transformation is a crucial cancer hallmark and a direct consequence of disturbances in the activities of oncogenes and tumor suppressors. in this review we discuss tumor metabolism from the molecular perspective of oncogenes, tumor suppressors and protein signaling pathways relevant to metabolic transformation and tumorigenesis. We also identify the principal unanswered questions surrounding this issue and the attempts to relate these to their potential for future cancer treatment. As will be made clear, tumor metabolism is still only partly understood and the metabolic aspects of transformation constitute a major challenge for science. Nevertheless, cancer metabolism can be exploited to devise novel avenues for the rational treatment of this disease. Copyright (C) 2011 S. Karger AG, BaselFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Univ Fed ABC UFABC, CCNH, Santo Andre, BrazilUniversidade Federal de São Paulo UNIFESP, Dept Ciencias Biol, São Paulo, BrazilUniversidade Federal de São Paulo UNIFESP, Dept Bioquim, São Paulo, BrazilUniv Fed Sao Carlos UFSCar, DFQM, Sorocaba, BrazilUniversidade Federal de São Paulo UNIFESP, Dept Ciencias Biol, São Paulo, BrazilUniversidade Federal de São Paulo UNIFESP, Dept Bioquim, São Paulo, BrazilFAPESP: 10/16050-9FAPESP: 10/11475-1FAPESP: 08/51116-0Web of Scienc