A Strategy Utilizing Protein-Protein Interaction Hubs for the Treatment of Cancer Diseases.

We describe a strategy for the development of a rational approach of neoplastic disease therapy based on the demonstration that scale-free networks are susceptible to specific attacks directed against its connective hubs. This strategy involves the (i) selection of up-regulated hubs of connectivity in the tumors interactome, (ii) drug repurposing of these hubs, (iii) RNA silencing of non-druggable hubs, (iv) in vitro hub validation, (v) tumor-on-a-chip, (vi) in vivo validation, and (vii) clinical trial. Hubs are protein targets that are assessed as targets for rational therapy of cancer in the context of personalized oncology. We confirmed the existence of a negative correlation between malignant cell aggressivity and the target number needed for specific drugs or RNA interference (RNAi) to maximize the benefit to the patient's overall survival. Interestingly, we found that some additional proteins not generally targeted by drug treatments might justify the addition of inhibitors designed against them in order to improve therapeutic outcomes. However, many proteins are not druggable, or the available pharmacopeia for these targets is limited, which justifies a therapy based on encapsulated RNAi.

Shaping the root system: the interplay between miRNA regulatory hubs and phytohormones.

The root system commonly lies underground, where it provides anchorage for the aerial organs, as well as nutrients and water. Both endogenous and environmental cues contribute to the establishment of the root system. Among the endogenous cues, microRNAs (miRNAs), transcription factors, and phytohormones modulate root architecture. miRNAs belong to a subset of endogenous hairpin-derived small RNAs that post-transcriptionally control target gene expression, mostly transcription factors, comprising the miRNA regulatory hubs. Phytohormones are signaling molecules involved in most developmental processes. Some miRNAs and targets participate in more than one hormonal pathway, thereby providing new bridges in plant hormonal crosstalk. Unraveling the intricate network of molecular mechanisms underlying the establishment of root systems is a central aspect in the development of novel strategies for plant breeding to increase yield and optimize agricultural land use. In this review, we summarize recent findings describing the molecular mechanisms associated with the interplay between miRNA regulatory hubs and phytohormones to ensure the establishment of a proper root system. We focus on post-embryonic growth and development of primary, lateral, and adventitious roots. In addition, we discuss novel insights for future research on the interaction between miRNAs and phytohormones in root architecture.

Traffic impact studies committed to sustainability: The case of Rio de Janeiro.

This article investigates whether the traditional approaches to Traffic Impact Studies (TISs) have evolved to meet the current needs of a society increasingly concerned with sustainability, especially in Brazil. For this purpose, we conducted a comprehensive literature review to identify the main sustainability aspects that should be covered by these studies, including the most suitable analytic techniques for this purpose, in particular for traffic simulation. We then prepared a proposal for classifying traffic impact studies and applied it in a specific case, in the city of Rio de Janeiro, the study of the Porto Maravilha port district revitalization project. This enabled understanding the current state of the practice of these studies in the country, indicating they are in general very poor, justifying the need for improvements.

Effects of acute aerobic exercise on leukocyte inflammatory gene expression in systemic lupus erythematosus.

UNLABELLED: Systemic lupus erythematosus (SLE) is an autoimmune disease with a persistent systemic inflammation. Exercise induced inflammatory response in SLE remains to be fully elucidated. The aim of this study was to assess the effects of acuteexercise on leukocyte gene expression in active (SLEACTIVE) and inactive SLE (SLEINACTIVE) patients and healthy controls(HC). METHODS: All subjects (n = 4 per group) performed a 30-min single bout of acute aerobic exercise (~70% of VO2peak) on a treadmill, and blood samples were collected for RNA extraction from circulating leukocyte at baseline, at the end of exercise, and after three hours of recovery. The expression of a panel of immune-related genes was evaluated by a quantitative PCR array assay. Moreover, network-based analyses were performed to interpret transcriptional changes occurring after the exercise challenge. RESULTS: In all groups, a single bout of acute exercise led to the down-regulation of the gene expression of innate and adaptive immunity at the end of exercise (e.g., TLR3, IFNG, GATA3, FOXP3, STAT4) with a subsequent up-regulation occurring upon recovery. Exercise regulated the expression of inflammatory genes in the blood leukocytes of the SLE patients and HC, although the SLE groups exhibited fewer modulated genes and less densely connected networks (number of nodes: 29, 40 and 58; number of edges: 29, 60 and 195; network density: 0.07, 0.08 and 0.12, for SLEACTIVE, SLEINACTIVE and HC, respectively). CONCLUSION: The leukocytes from the SLE patients, irrespective of disease activity, showed a down-regulated inflammatory geneexpression immediately after acute aerobic exercise, followed by an up-regulation at recovery. Furthermore, less organized gene networks were observed in the SLE patients, suggesting that they may be deficient in triggering a normal exercised-induced immune transcriptional response.

Specimen Referral Network to Rapidly Scale-Up CD4 Testing: The Hub and Spoke Model for Haiti.

OBJECTIVES: Regular and quality CD4 testing is essential to monitor disease progression in people living with HIV. In Haiti, most laboratories have limited infrastructure and financial resources and have relied on manual laboratory techniques. We report the successful implementation of a national specimen referral network to rapidly increase patient coverage with quality CD4 testing while at the same time building infrastructure for referral of additional sample types over time. METHOD: Following a thorough baseline analysis of facilities, expected workload, patient volumes, cost of technology and infrastructure constraints at health institutions providing care to HIV patients, the Haitian National Public Health Laboratory designed and implemented a national specimen referral network. The specimen referral network was scaled up in a step-wise manner from July 2011 to July 2014. RESULTS: Fourteen hubs serving a total of 67 healthcare facilities have been launched; in addition, 10 healthcare facilities operate FACSCount machines, 21 laboratories operate PIMA machines, and 11 healthcare facilities are still using manual CD4 tests. The number of health institutions able to access automated CD4 testing has increased from 27 to 113 (315%). Testing volume increased 76% on average. The number of patients enrolled on ART at the first healthcare facilities to join the network increased 182% within 6 months following linkage to the network. Performance on external quality assessment was acceptable at all 14 hubs. CONCLUSION: A specimen referral network has enabled rapid uptake of quality CD4 testing, and served as a backbone to allow for other future tests to be scaled-up in a similar way.