Putative adverse outcome pathways relevant to neurotoxicity

Anna K. Bal-Price et al.© 2015 Informa Healthcare USA. The Adverse Outcome Pathway (AOP) framework provides a template that facilitates understanding of complex biological systems and the pathways of toxicity that result in adverse outcomes (AOs). The AOP starts with an molecular initiating event (MIE) in which a chemical interacts with a biological target(s), followed by a sequential series of KEs, which are cellular, anatomical, and/or functional changes in biological processes, that ultimately result in an AO manifest in individual organisms and populations. It has been developed as a tool for a knowledge-based safety assessment that relies on understanding mechanisms of toxicity, rather than simply observing its adverse outcome. A large number of cellular and molecular processes are known to be crucial to proper development and function of the central (CNS) and peripheral nervous systems (PNS). However, there are relatively few examples of well-documented pathways that include causally linked MIEs and KEs that result in adverse outcomes in the CNS or PNS. As a first step in applying the AOP framework to adverse health outcomes associated with exposure to exogenous neurotoxic substances, the EU Reference Laboratory for Alternatives to Animal Testing (EURL ECVAM) organized a workshop (March 2013, Ispra, Italy) to identify potential AOPs relevant to neurotoxic and developmental neurotoxic outcomes. Although the AOPs outlined during the workshop are not fully described, they could serve as a basis for further, more detailed AOP development and evaluation that could be useful to support human health risk assessment in a variety of ways.Peer Reviewe

In vitro synthesis of infectious dna of murine leukaemia virus.

DNA synthesised in vitro by purified virions of murine leukaemia virus is infectious. Neither RNA nor protein is required for infectivity. Transfection with reverse transcriptase product shows a single-hit dose response and results in the production of complete, infectious virus

Dengue Fever Surveillance in Mato Grosso do Sul: Insights from Genomic Analysis and Implications for Public Health Strategies

Since its discovery in early 1916, dengue fever, a common vector-borne illness in Brazil, has resulted in extensive urban outbreaks and poses a serious threat to the public’s health. Understanding the dynamics of Dengue Virus (DENV) serotypes circulating in different regions of Brazil is essential for implementing effective disease control and prevention measures. In response to this urgent need, we conducted an on-site training program in genomic surveillance in collaboration with the Central Laboratory of Health and the Secretary of Health of the Mato Grosso do Sul state. This initiative resulted in the generation of 177 DENV genome sequences collected between May 2021 and May 2022, a period during which over 11,391 dengue fever cases were reported in the state. Through this approach, we were able to identify the co-circulation of two different dengue serotypes (DENV1 and DENV2) as well as the existence of diverse viral lineages within each genotype, suggesting that multiple introduction events of different viral strains occurred in the region. By integrating epidemiological data, our findings unveiled temporal fluctuations in the relative abundance of different serotypes throughout various epidemic seasons, highlighting the complex and changing dynamics of DENV transmission throughout time. These findings demonstrate the value of ongoing surveillance activities in tracking viral transmission patterns, monitoring viral evolution, and informing public health actions

The nanomechanical signature of breast cancer

Cancer initiation and progression follow complex molecular and structural changes in the extracellular matrix and cellular architecture of living tissue. However, it remains poorly understood how the transformation from health to malignancy alters the mechanical properties of cells within the tumour microenvironment. Here, we show using an indentation-type atomic force microscope (IT-AFM) that unadulterated human breast biopsies display distinct stiffness profiles. Correlative stiffness maps obtained on normal and benign tissues show uniform stiffness profiles that are characterized by a single distinct peak. In contrast, malignant tissues have a broad distribution resulting from tissue heterogeneity, with a prominent low-stiffness peak representative of cancer cells. Similar findings are seen in specific stages of breast cancer in MMTV-PyMT transgenic mice. Further evidence obtained from the lungs of mice with late-stage tumours shows that migration and metastatic spreading is correlated to the low stiffness of hypoxia-associated cancer cells. Overall, nanomechanical profiling by IT-AFM provides quantitative indicators in the clinical diagnostics of breast cancer with translational significance