Frontiers of molecular biology of cancer

Cancer is rooted in genetic background, with the expression of oncogenesis playing a pivotal role in the early stages of tumor formation. Acquired mutations in somatic cells primarily contribute to the development of most common cancers, while specific germline mutations are responsible for rare hereditary cancer syndromes. Within the realm of cancer-associated genes, oncogenes undergo activation, exhibiting phenotypic dominance, whereas tumor suppressor genes experience inactivation, displaying phenotypic recessiveness. The ongoing effort to improve our knowledge about molecular mechanisms involves defining pathways influencing cancer therapy. Technological advancements have made it possible to identify genes integral to cancer development and have significantly contributed to the growing success of precision medicine in oncology, with targeted therapies directed against tumors and components of the tumor microenvironment. This Special Issue, titled “Molecular Biology of Cancer—Implications for Diagnosis and Treatment”, comprises a total of eight contributions. These include five original articles and three reviews, offering fresh insights into cancer biology, molecular genetics, and innovative therapeutic approaches

An investigation into the perspectives of providers and learners on MOOC accessibility

An effective open eLearning environment should consider the target learner’s abilities, learning goals, where learning takes place, and which specific device(s) the learner uses. MOOC platforms struggle to take these factors into account and typically are not accessible, inhibiting access to environments that are intended to be open to all. A series of research initiatives are described that are intended to benefit MOOC providers in achieving greater accessibility and disabled learners to improve their lifelong learning and re-skilling. In this paper, we first outline the rationale, the research questions, and the methodology. The research approach includes interviews, online surveys and a MOOC accessibility audit; we also include factors such the risk management of the research programme and ethical considerations when conducting research with vulnerable learners. Preliminary results are presented from interviews with providers and experts and from analysis of surveys of learners. Finally, we outline the future research opportunities. This paper is framed within the context of the Doctoral Consortium organised at the TEEM'17 conference

The Colombian conflict: a description of a mental health program in the Department of Tolima.

Colombia has been seriously affected by an internal armed conflict for more than 40 years affecting mainly the civilian population, who is forced to displace, suffers kidnapping, extortion, threats and assassinations. Between 2005 and 2008, Médecins Sans Frontières-France provided psychological care and treatment in the region of Tolima, a strategic place in the armed conflict. The mental health program was based on a short-term multi-faceted treatment developed according to the psychological and psychosomatic needs of the population. Here we describe the population attending during 2005-2008, in both urban and rural settings, as well as the psychological treatment provided during this period and its outcomes.We observed differences between the urban and rural settings in the traumatic events reported, the clinical expression of the disorders, the disorders diagnosed, and their severity. Although the duration of the treatment was limited due to security reasons and access difficulties, patient condition at last visit improved in most of the patients. These descriptive results suggest that further studies should be conducted to examine the role of short-term psychotherapy, adapted specifically to the context, can be a useful tool to provide psychological care to population affected by an armed conflict

Targeting colorectal cancer via its microenvironment by inhibiting IGF-1 receptor-insulin receptor substrate and STAT3 signaling.

The tumor microenvironment (TME) exerts critical pro-tumorigenic effects through cytokines and growth factors that support cancer cell proliferation, survival, motility and invasion. Insulin-like growth factor-1 (IGF-1) and signal transducer and activator of transcription 3 (STAT3) stimulate colorectal cancer development and progression via cell autonomous and microenvironmental effects. Using a unique inhibitor, NT157, which targets both IGF-1 receptor (IGF-1R) and STAT3, we show that these pathways regulate many TME functions associated with sporadic colonic tumorigenesis in CPC-APC mice, in which cancer development is driven by loss of the Apc tumor suppressor gene. NT157 causes a substantial reduction in tumor burden by affecting cancer cells, cancer-associated fibroblasts (CAF) and myeloid cells. Decreased cancer cell proliferation and increased apoptosis were accompanied by inhibition of CAF activation and decreased inflammation. Furthermore, NT157 inhibited expression of pro-tumorigenic cytokines, chemokines and growth factors, including IL-6, IL-11 and IL-23 as well as CCL2, CCL5, CXCL7, CXCL5, ICAM1 and TGFβ; decreased cancer cell migratory activity and reduced their proliferation in the liver. NT157 represents a new class of anti-cancer drugs that affect both the malignant cell and its supportive microenvironment

Fuzzy Inference System for VOLT/VAR control in distribution substations in isolated power systems

This paper presents a fuzzy inference system for voltage/reactive power control in distribution substations. The purpose is go forward to automation distribution and its implementation in isolated power systems where control capabilities are limited and it is common using the same applications as in continental power systems. This means that lot of functionalities do not apply and computational burden generates high response times. A fuzzy controller, with logic guidelines embedded based upon heuristic rules resulting from operators at dispatch control center past experience, has been designed. Working as an on-line tool, it has been tested under real conditions and it has managed the operation during a whole day in a distribution substation. Within the limits of control capabilities of the system, the controller maintained successfully an acceptable voltage profile, power factor values over 0,98 and it has ostensibly improved the performance given by an optimal power flow based automation system

Double non-equivalent chain structure on vicinal Si(557)-Au surface

We study electronic and topographic properties of the vicinal Si(557)-Au surface using scanning tunneling microscopy and reflection of high energy electron diffraction technique. STM data reveal double wire structures along terraces. Moreover behavior of the voltage dependent STM tip - surface distance is different in different chains. While the one chain shows oscillations of the distance which are sensitive to the sign of the voltage bias, the oscillations in the other chain remain unchanged with respect to the positive/negative biases. This suggests that one wire has metallic character while the other one - semiconducting. The experimental results are supplemented by theoretical calculations within tight binding model suggesting that the observed chains are made of different materials, one is gold and the other one is silicon chain.Comment: 9 pages, 12 figures, accepted for publication in Phys. Rev.

Early assembly proteins of the large ribosomal subunit of the thermophilic archaebacterium Sulfolobus. Identification and binding to heterologous rRNA species.

Studies of ribosome structure in thermophilic archaebacteria may provide valuable information on (i) the mechanisms involved in the stabilization of nucleic acid-protein complexes at high temperatures and (ii) the degree of evolutionary conservation of the ribosomal components in the primary kingdoms of cell descent. In this work we investigate certain aspects of RNA/protein interaction within the large ribosomal subunits of the extremely thermophilic archaebacterium Sulfolobus solfataricus. The ribosomal proteins involved in the early reactions leading to in vitro particle assembly have been identified; it is shown that they can interact with the RNA in a temperature-independent fashion, forming a thermally stable "core" particle that can subsequently be converted into complete 50 S ribosomes. Among the protein components of the core particle, those capable of independently binding to 23 and 5 S RNA species have also been identified. Finally, we show that the early assembly proteins of Sulfolobus large ribosomal subunits are able to interact cooperatively with 23 S RNAs from other archaebacteria or from eubacteria, thereby suggesting that RNA/protein recognition sites are largely conserved within prokaryotic ribosomes. By contrast, no specific binding of the archaebacterial proteins to eukaryotic RNA could be demonstrated