Viability of Strongly-Coupled Scenarios with a Light Higgs-like Boson

We present a one-loop calculation of the oblique S and T parameters within strongly coupled models of electroweak symmetry breaking with a light Higgs-like boson. We use a general effective Lagrangian, implementing the chiral symmetry breaking SU(2)(L) circle times SU(2)(R) -> SU(2)(L+R) with Goldstone bosons, gauge bosons, the Higgs-like scalar, and one multiplet of vector and axial-vector massive resonance states. Using a dispersive representation and imposing a proper ultraviolet behavior, we obtain S and T at the next-to-leading order in terms of a few resonance parameters. The experimentally allowed range forces the vector and axial-vector states to be heavy, with masses above the TeV scale, and suggests that the Higgs-like scalar should have a WW coupling close to the standard model one. Our conclusions are generic and apply to more specific scenarios such as the minimal SO(5)/SO(4) composite Higgs model

Editorial: The CB2 cannabinoid system: A new strategy in neurodegenerative disorder and neuroinflammation

Editorial for Frontiers journal without abstrac

Tecnologia educacional: apoio à representação do professor de Ciência e Tecnologia e instrumento de estudo para o aluno

O artigo discute a necessidade de desenvolver, junto aos professores de Ciência e Tecnologia, a capacidade de representação dos conteúdos que ministram, em múltiplaslinguagens, apoiadas em diferentes meios de comunicação, ou tecnologias educacionais, sejam elas interativas ou convencionais, como forma de agregar valor ao seu próprio trabalho, qualificando o produto de sua pesquisa. Mesmo que a transmissão de conhecimento não seja considerada como a atividade preponderante do contexto da relação professor-aluno, educadores não devem descuidar do planejamento de elementos destinados a enriquecer a exposição de conteúdos, nos momentos em que isto se fizer necessário, seja em atividades presenciais ou à distância. Necessitam, para tanto, desenvolver habilidades específicas para conhecer e exploraras linguagens e os recursos tecnológicos oferecidos pelos ambientes de produção e disponibilização de multimídia, bem como de mídias convencionais, como as apresentaçõesorais, os livros ou mesmo o quadro (negro, verde ou branco). Além da reflexão sobre a importância de diferentes tecnologias educacionais na atividade docente, bem como no suportedo estudo dos alunos, serão relatadas experiências de produção de três CDs didáticos e de uma série de vídeos destinados, as quais descrevem objetivos, dificuldades e potencialidades desse tipo de mídia

Roles of Tumor-Educated Platelets (TEPs) in the biology of Non-Small Cell Lung Cancer (NSCLC): A systematic review. “Re-discovering the neglected biosources of the liquid biopsy family”

Due to their interactions with the neoplasm, platelets undergo various proteomic and transcriptomic modifications, resulting in the development of what is known as the “Tumor-Educated Platelets (TEPs) phenotype”. Consequently, in addition to their suitability for Liquid Biopsy (LB) applications, they play a pivotal role in the malignancy by communicating with Circulating Tumor Cells (CTCs), Tumor Microenvironment (TME), and the tumor itself through multiple mechanisms and at multiple levels, ultimately promoting the metastasis of cancer. Therefore, this Systematic Review of MEDLINE and the Cochrane Library present in-depth insights into these phenomena, with the aim of enhancing the understanding of the complex interplay between TEPs and Non-Small Cell Lung Cancer (NSCLC). This endeavor serves to provide context and drive medical research efforts, which are increasingly focused on developing novel diagnostic and therapeutic technologies that leverage the specific binding of these platelets to the disease

Polθ: emerging synthetic lethal partner in homologous recombination-deficient tumors

The most remarkable finding in synthetic lethality (SL) is the hypersensitivity to PARP inhibitors (PARPis) of the tumors harboring defects in genes involved in homologous repair (HR) such as BRCA1/2. Despite initial responsiveness to PARPi, the penetrance of the synthetic lethal interactions between BRCA1/2 genes and PARPi is incomplete. Thus, a significant proportion of HR-defective tumors experience intrinsic or acquired resistance, representing a key challenge of clinical research. An expanded concept of SL is opening new ways and includes novel forms of genetic interactions, investigating not only traditional SL of pairs genes but also SL between biological pathways that regulate the same essential survival cell function. In this context, recent research showed that HR and theta-mediated end-joining (TMEJ) pathways exhibit SL. DNA polymerase theta (Pol theta) is encoded by the POLQ gene and is a key component of the TMEJ, an essential backup pathway, intrinsically mutagenic, to repair resected double-strand breaks (DSBs) when the non-homologous end joining (NHEJ) and HR are impaired. Pol theta is broadly expressed in normal tissues, overexpressed in several cancers, and typically associated with poor outcomes and shorter relapse-free survival. Notably, HR-deficient tumor cells present the characteristic mutational signatures of the error-prone TMEJ pathway. According to this observation, the loss of HR proteins, such as BRCA1 or BRCA2, contributes to increasing the TMEJ-specific genomic profile, suggesting synthetic lethal interactions between loss of the POLQ and HR genes, and resulting in the emerging interest for Pol theta as a potential therapeutic target in BRCA1/2-associated tumors.This review summarizes the converging roles of the POLQ and HR genes in DNA DSB repair, the early-stage clinical trials using Pol theta inhibitor to treat HR-defective tumors and to overcome BRCA-reversion mutations responsible for therapeutic resistance, and the novel pleiotropic effects of Pol theta, paving the way for the development of unexplored synthetic lethality strategies

Grand Unification in RS1

We study unification in the Randall-Sundrum scenario for solving the hierarchy problem, with gauge fields and fermions in the bulk. We calculate the one-loop corrected low-energy effective gauge couplings in a unified theory, broken at the scale M_GUT in the bulk. We find that, although this scenario has an extra dimension, there is a robust (calculable in the effective field theory) logarithmic dependence on M_GUT, strongly suggestive of high-scale unification, very much as in the (4D) Standard Model. Moreover, bulk threshold effects are naturally small, but volume-enhanced, so that we can accommodate the measured gauge couplings. We show in detail how excessive proton decay is forbidden by an extra U(1) bulk gauge symmetry. This mechanism requires us to further break the unified group using boundary conditions. A 4D dual interpretation, in the sense of the AdS/CFT correspondence, is provided for all our results. Our results show that an attractive unification mechanism can combine with a non-supersymmetric solution to the hierarchy problem.Comment: Latex, 23 pages. In the revised version, Eq. (3.3) has been modified with no change in the central result of the paper and a reference has been adde

Myc Promoter-Binding Protein-1 (MBP-1) Is a Novel Potential Prognostic Marker in Invasive Ductal Breast Carcinoma

Background Alpha-enolase is a glycolytic enzyme that catalyses the formation of phosphoenolpyruvate in the cell cytoplasm. \u3b1-Enolase and the predominantly nuclear Myc promoter-binding protein-1 (MBP-1) originate from a single gene through the alternative use of translational starting sites. MBP-1 binds to the P2 c-myc promoter and competes with TATA-box binding protein (TBP) to suppress gene transcription. Although several studies have shown an antiproliferative effect of MBP-1 overexpression on several human cancer cells, to date detailed observations of \u3b1-enolase and MBP-1 relative expression in primary tumors versus normal tissues and their correlation with clinicopathological features have not been undertaken. Methodology and Findings We analyzed \u3b1-enolase and MBP-1 expression in normal breast epithelium and primary invasive ductal breast carcinoma (IDC) from 177 patients by Western blot and immunohistochemical analyses, using highly specific anti-\u3b1-enolase monoclonal antibodies. A significant increase in the expression of cytoplasmic \u3b1-enolase was observed in 98% of the tumors analysed, compared to normal tissues. Nuclear MBP-1 was found in almost all the normal tissues while its expression was retained in only 35% of the tumors. Statistically significant associations were observed among the nuclear expression of MBP-1 and ErbB2 status, Ki-67 expression, node status and tumor grade. Furthermore MBP-1 expression was associated with good survival of patients with IDC. Conclusions MBP-1 functions in repressing c-myc gene expression and the results presented indicate that the loss of nuclear MBP-1 expression in a large number of IDC may be a critical step in the development and progression of breast cancer and a predictor of adverse outcome. Nuclear MBP-1 appears to be a novel and valuable histochemical marker with potential prognostic value in breast cancer

The intersection of homologous recombination (HR) and mismatch repair (MMR) pathways in DNA repair-defective tumors

Homologous recombination (HR) and mismatch repair (MMR) defects are driver mutational imprints and actionable biomarkers in DNA repair-defective tumors. Although usually thought as mutually exclusive pathways, recent preclinical and clinical research provide preliminary evidence of a functional crosslink and crosstalk between HRR and MMR. Shared core proteins are identified as key players in both pathways, broadening the concept of DNA repair mechanism exclusivity in specific tumor types. These observations may result in unexplored forms of synthetic lethality or hypermutable tumor phenotypes, potentially impacting the cancer risk management, and considerably expanding in the future the therapeutic window for DNA repair-defective tumors

Induced expression of P-gp and BCRP transporters on brain endothelial cells using transferrin functionalized nanostructured lipid carriers:A first step of a potential strategy for the treatment of Alzheimer's disease

P-glycoprotein (P-gp) and Breast Cancer Resistance Protein (BCRP) are two transporters expressed in human neural stem/progenitor cells and at the Blood-Brain Barrier (BBB) level with decreased activity in the early stage of Alzheimer's disease (AD). Both proteins, have a protective role for the embryonic stem cells in the early developmental step, maintaining them in an undifferentiated state, and limit the access of exogenous and endogenous agents to the brain. Recently, MC111 selected from a P-gp/BCRP ligands library was investigated as multitarget strategy for AD treatment, considering its ability to induce the expression and activity of both proteins. However, MC111 clinical use could be limited for the ubiquitous physiological expression of efflux transporters and its moderate toxicity towards endothelial cells. Therefore, a selective MC111 delivery system based on nanostructured lipid carriers (NLC) functionalized with transferrin were developed. The results proved the formation of NLC with average size about 120 nm and high drug encapsulation efficiency (EE% greater than 50). In vitro studies on hCMEC/D3 cells revealed that the MC111 was selectively released by NLC at BBB level and then inducing the activity and expression of BCRP and P-gp, involved in the clearance of amyloid p peptide on brain endothelial cells