Meeting Report: The Role of Environmental Lighting and Circadian Disruption in Cancer and Other Diseases

Light, including artificial light, has a range of effects on human physiology and behavior and can therefore alter human physiology when inappropriately timed. One example of potential light-induced disruption is the effect of light on circadian organization, including the production of several hormone rhythms. Changes in light–dark exposure (e.g., by nonday occupation or transmeridian travel) shift the timing of the circadian system such that internal rhythms can become desynchronized from both the external environment and internally with each other, impairing our ability to sleep and wake at the appropriate times and compromising physiologic and metabolic processes. Light can also have direct acute effects on neuroendocrine systems, for example, in suppressing melatonin synthesis or elevating cortisol production that may have untoward long-term consequences. For these reasons, the National Institute of Environmental Health Sciences convened a workshop of a diverse group of scientists to consider how best to conduct research on possible connections between lighting and health. According to the participants in the workshop, there are three broad areas of research effort that need to be addressed. First are the basic biophysical and molecular genetic mechanisms for phototransduction for circadian, neuroendocrine, and neurobehavioral regulation. Second are the possible physiologic consequences of disrupting these circadian regulatory processes such as on hormone production, particularly melatonin, and normal and neoplastic tissue growth dynamics. Third are effects of light-induced physiologic disruption on disease occurrence and prognosis, and how prevention and treatment could be improved by application of this knowledge

Analysis of the mutational landscape of classic Hodgkin lymphoma identifies disease heterogeneity and potential therapeutic targets

Defining the mutational landscape of classic Hodgkin lymphoma is still a major research goal. New targeted next-generation sequencing (NGS) techniques may identify pathogenic mechanisms and new therapeutic opportunities related to this disease. We describe the mutational profile of a series of 57 cHL cases, enriched in Hodgkin and Reed-Sternberg (HRS) cells. Overall, the results confirm the presence of strong genomic heterogeneity. However, several variants were consistently detected in genes related to relevant signaling pathways, such as GM-CSF/IL-3, CBP/EP300, JAK/STAT, NF-kappaB, and numerous variants of genes affecting the B-cell receptor (BCR) pathway, such as BTK, CARD11, BCL10, among others. This unexpectedly high prevalence of mutations affecting the BCR pathway suggests some requirement for active BCR signaling for cHL cell viability. Additionally, incubation of a panel of cHL cellular models with selective BTK inhibitors in vitro constrains cell proliferation and causes cell death. Our results indicate new pathogenic mechanisms and therapeutic opportunities in this disease

RET Fusion Testing in Patients With NSCLC: The RETING Study

Introduction: RET inhibitors with impressive overall response rates are now available for patients with NSCLC, yet the identi fication of RET fusions remains a dif ficult challenge. Most guidelines encourage the upfront use of next -generation sequencing (NGS), or alternatively, fluorescence in situ hybridization (FISH) or reverse transcriptase-polymerase chain reaction (RT-PCR) when NGS is not possible or available. Taken together, the suboptimal performance of single-analyte assays to detect RET fusions, although consistent with the notion of encouraging universal NGS, is currently widening some of the clinical practice gaps in the implementation of predictive biomarkers in patients with advanced NSCLC. Methods: This situation prompted us to evaluate several RET assays in a large multicenter cohort of RET fusion -positive NSCLC (n 1 / 4 38) to obtain real -world data. In addition to RNA -based NGS (the criterion standard method), all positive specimens underwent break -apart RET FISH with two different assays and were also tested by an RT-PCR assay. Results: The most common RET partners were KIF5B (78.9%), followed by CCDC6 (15.8%). The two RET NGSpositive but FISH -negative samples contained a KIF5B(15)RET(12) fusion. The three RET fusions not identi fied with RT-PCR were AKAP13(35)-RET(12) , KIF5B(24)-RET(9) and KIF5B(24)-RET(11) . All three false -negative RT-PCR cases were FISH -positive, exhibited a typical break -apart pattern, and contained a very high number of positive tumor cells with both FISH assays. Signet ring cells, psammoma bodies, and pleomorphic features were frequently observed (in 34.2%, 39.5%, and 39.5% of tumors, respectively). Conclusions: In-depth knowledge of the advantages and disadvantages of the different RET testing methodologies could help clinical and molecular tumor boards implement and maintain sensible algorithms for the rapid and effective detection of RET fusions in patients with NSCLC. The likelihood of RET false -negative results with both FISH and RT-PCR reinforces the need for upfront NGS in patients with NSCLC. (c) 2024 The Authors. Published by Elsevier Inc. on behalf of the International Association for the Study of Lung Cancer. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/)

Targeted Destruction of Photosensitive Retinal Ganglion Cells with a Saporin Conjugate Alters the Effects of Light on Mouse Circadian Rhythms

Non-image related responses to light, such as the synchronization of circadian rhythms to the day/night cycle, are mediated by classical rod/cone photoreceptors and by a small subset of retinal ganglion cells that are intrinsically photosensitive, expressing the photopigment, melanopsin. This raises the possibility that the melanopsin cells may be serving as a conduit for photic information detected by the rods and/or cones. To test this idea, we developed a specific immunotoxin consisting of an anti-melanopsin antibody conjugated to the ribosome-inactivating protein, saporin. Intravitreal injection of this immunotoxin results in targeted destruction of melanopsin cells. We find that the specific loss of these cells in the adult mouse retina alters the effects of light on circadian rhythms. In particular, the photosensitivity of the circadian system is significantly attenuated. A subset of animals becomes non-responsive to the light/dark cycle, a characteristic previously observed in mice lacking rods, cones, and functional melanopsin cells. Mice lacking melanopsin cells are also unable to show light induced negative masking, a phenomenon known to be mediated by such cells, but both visual cliff and light/dark preference responses are normal. These data suggest that cells containing melanopsin do indeed function as a conduit for rod and/or cone information for certain non-image forming visual responses. Furthermore, we have developed a technique to specifically ablate melanopsin cells in the fully developed adult retina. This approach can be applied to any species subject to the existence of appropriate anti-melanopsin antibodies

Arrecifes de corales de aguas frías como posibles indicadores de emisiones de hidrocarburos en el banco de Galicia y determinación de su edad mediante racemizacion de aminoácidos

Este proyecto tiene como objetivo analizar la posible relación entre los corales de aguas frías encontrados en el Banco de Galicia con los procesos tectónicos y las estructuras relacionadas con la migración y la emisión de fluidos ricos en hidrocarburos (debido a su interés económico), así como la creación de un algoritmo que establezca una relación entre el grado de racemización sufrido por los aminoácidos de las muestras y la edad de estas. Para ello, se han recopilado datos y muestras en el área de estudio, gracias a los cuales se ha creado una base de datos que contiene una clasificación de las muestras recogidas junto a los datos más relevantes de que están relacionados con el objetivo de este trabajo. Estas muestras han sido proporcionadas por el IGME y fueron recogidas mayoritariamente en la campaña oceanográfica DIVA ARTABRIA II. Con estas muestras se han llevado a cabo análisis de laboratorio como el estudio de racemización de aminoácidos, el análisis de biomarcadores y la datación por uranio-torio de los esqueletos aragoníticos de los corales de aguas frías. Para finalizar, se han estudiado dichos datos con el objeto de comprobar la hipótesis de que los corales de aguas frías colonizan zonas con emisiones de hidrocarburos, conocer su edad y en última instancia crear un algoritmo capaz de datar dichos corales a partir del grado de racemización de sus aminoácidos. Palabras clave: corales de aguas frías, Banco de Galicia, campaña oceanográfica, DIVA ARTABRIA II, base de datos, racemización, aminoácidos, biomarcadores, datación uranio-torio, hidrocarburos, algoritmo. ABSTRACT This project studies the relationship between cold-water corals found in the Galicia Bank with tectonic processes and with the structures related to migration and hydrocarbon-rich fluids emissions. Firstly, data and samples in the study were collected, through to classify the collected samples with the most relevant characteristics to our research scope. Sampling and data collection provided by the IGME were collected in the DIVA ARTABRIA II oceanographic cruise. Secondly, the current work presents a systematic laboratory analysis that allowed the study of aminoacid racemization as well as the analysis of biomarkers and the uranium-thorium dating of aragonitic cold-water coral skeletons. Finally, this data was studied to test the hypothesis that cold-water corals colonize areas with emissions of hydrocarbons, know its age and ultimately create and algorithm capable of dating these corals from the degree of racemization in its amino acids. Keywords: cold-water corals, Galicia Bank, oceanographic cruise, DIVA ARTABRIA II, database, racemization, amino acids, biomarkers, uranium-thorium datation, hydrocarbons, algorithm

O Significado Actual do Karaté - Arte Marcial / Desporto de Combate?

Analisando sumariamente os suportes conceptuais dos significados dos conceitos de "arte" e "marcial", desconstruindo o significado do conceito de técnica na base da pedagogia do ensino nos desportos de combate e artes marciais com destaque para o Karaté, passa pelo significado do desporto humanizante. Conclui-se que não há razão para dicotomizar divergentemente o karaté em arte marcial ou desporto de combate, utilizando argumentações ideológicas ou desequilibradas pela ignorância cultural em um dos significantes, pelo que elogia a urgência permanente de comunicação entre partes

Postnatal Development and Functional Adaptations of the Melanopsin Photoreceptive System in the Albino Mouse Retina

This study demonstrates that the mammalian retinal melanopsin system is strongly dependent on ambient light conditions and suggests that day/night cycles might have a decisive influence on its postnatal development