Production of Oncolytic Measles Virus in Vero Cells: Impact of Culture Medium and Multiplicity of Infection.

Oncolytic measles virus (MeV) is a promising anti-cancer treatment. However, the production of high titers of infectious MeV (typically 10-10 TCID per dose) is challenging because the virus is unstable under typical production conditions. The objective of this study was to investigate how the multiplicity of infection (MOI) and different media-a serum-containing medium (SCM), a serum-free medium (SFM) and two chemically defined media (CDM)-affect MeV production.

KRAS Loss of Heterozygosity Promotes MAPK-Dependent Pancreatic Ductal Adenocarcinoma Initiation and Induces Therapeutic Sensitivity to MEK Inhibition.

Pancreatic cancer is characterized by the prevalence of oncogenic mutations in KRAS. Previous studies have reported that altered KRAS gene dosage drives progression and metastasis in pancreatic cancer. Whereas the role of oncogenic KRAS mutations is well characterized, the relevance of the partnering wild-type (WT) KRAS allele in pancreatic cancer is less well understood and controversial.

Dark force rising: Reawakening and targeting of fetal-like stem cells in colorectal cancer.

Stem cells play pivotal roles in maintaining intestinal homeostasis, orchestrating regeneration, and in key steps of colorectal cancer (CRC) initiation and progression. Intriguingly, adult stem cells are reduced during many of these processes. On the contrary, primitive fetal programs, commonly detected in development, emerge during tissue repair, CRC metastasis, and therapy resistance.

Predator mass mortality events restructure food webs through trophic decoupling.

Predators have a key role in structuring ecosystems. However, predator loss is accelerating globally, and predator mass-mortality events (MMEs)-rapid large-scale die-offs-are now emblematic of the Anthropocene epoch. Owing to their rare and unpredictable nature, we lack an understanding of how MMEs immediately impact ecosystems.

Interactive effects of temperature and bisphenol A on phytoplankton growth and community structure.

Environmental contamination of bisphenol A (BPA) is a widespread and multifaceted issue with vast ecological, social and economic consequences. Thus, understanding how local environmental conditions, such as temperature, interact with BPA to affect populations and community dynamics remain important areas of research. Here, we conduct laboratory experiments aimed at understanding how environmental gradients of both temperature and BPA concentration influence freshwater phytoplankton population growth and community structure.

Late-season corn stalk nitrate measurements across the US Midwest from 2006 to 2018.

The late-season Corn Stalk Nitrate Test (CSNT) is a well-known tool to help evaluate the after-the-fact performance of nitrogen management. The CSNT has the unique ability to distinguish between optimal and excessive corn nitrogen status, which makes it helpful for identifying the over-application of N so that farmers can adjust their future nitrogen decisions. This paper presents a multi-year and multi-location dataset of late-season corn stalk nitrate test measurements across the US Midwest from 2006 to 2018.

Effects of thermal fluctuations on biological processes: a meta-analysis of experiments manipulating thermal variability.

Thermal variability is a key driver of ecological processes, affecting organisms and populations across multiple temporal scales. Despite the ubiquity of variation, biologists lack a quantitative synthesis of the observed ecological consequences of thermal variability across a wide range of taxa, phenotypic traits and experimental designs. Here, we conduct a meta-analysis to investigate how properties of organisms, their experienced thermal regime and whether thermal variability is experienced in either the past (prior to an assay) or present (during the assay) affect performance relative to the performance of organisms experiencing constant thermal environments.

The long and the short of it: Mechanisms of synchronous and compensatory dynamics across temporal scales.

Synchronous dynamics (fluctuations that occur in unison) are universal phenomena with widespread implications for ecological stability. Synchronous dynamics can amplify the destabilizing effect of environmental variability on ecosystem functions such as productivity, whereas the inverse, compensatory dynamics, can stabilize function. Here we combine simulation and empirical analyses to elucidate mechanisms that underlie patterns of synchronous versus compensatory dynamics.

A Double-Edged Sword: Thioxanthenes Act on Both the Mind and the Microbiome.

The rising tide of antibacterial drug resistance has given rise to the virtual elimination of numerous erstwhile antibiotics, intensifying the urgent demand for novel agents. A number of drugs have been found to possess potent antimicrobial action during the past several years and have the potential to supplement or even replace the antibiotics. Many of these 'non-antibiotics', as they are referred to, belong to the widely used class of neuroleptics, the phenothiazines.

The spatial synchrony of species richness and its relationship to ecosystem stability.

Synchrony is broadly important to population and community dynamics due to its ubiquity and implications for extinction dynamics, system stability, and species diversity. Investigations of synchrony in community ecology have tended to focus on covariance in the abundances of multiple species in a single location. Yet, the importance of regional environmental variation and spatial processes in community dynamics suggests that community properties, such as species richness, could fluctuate synchronously across patches in a metacommunity, in an analog of population spatial synchrony.

Oncogenic BRAF, unrestrained by TGFβ-receptor signalling, drives right-sided colonic tumorigenesis.

Right-sided (proximal) colorectal cancer (CRC) has a poor prognosis and a distinct mutational profile, characterized by oncogenic BRAF mutations and aberrations in mismatch repair and TGFβ signalling. Here, we describe a mouse model of right-sided colon cancer driven by oncogenic BRAF and loss of epithelial TGFβ-receptor signalling. The proximal colonic tumours that develop in this model exhibit a foetal-like progenitor phenotype (Ly6a/Sca1) and, importantly, lack expression of Lgr5 and its associated intestinal stem cell signature.

Cancer-Associated Fibroblasts in Pancreatic Ductal Adenocarcinoma Determine Response to SLC7A11 Inhibition.

Cancer-associated fibroblasts (CAF) are major contributors to pancreatic ductal adenocarcinoma (PDAC) progression through protumor signaling and the generation of fibrosis, the latter of which creates a physical barrier to drugs. CAF inhibition is thus an ideal component of any therapeutic approach for PDAC. SLC7A11 is a cystine transporter that has been identified as a potential therapeutic target in PDAC cells.

Genome-wide DNA methylation analysis pre- and post-lenalidomide treatment in patients with myelodysplastic syndrome with isolated deletion (5q).

Myelodysplastic syndrome (MDS) with isolated deletion of chromosome 5q (MDS del5q) is a distinct subtype of MDS with quite favorable prognosis and excellent response to treatment with lenalidomide. Still, a relevant percentage of patients do not respond to lenalidomide and even experience progression to acute myeloid leukemia (AML). In this study, we aimed to investigate whether global DNA methylation patterns could predict response to lenalidomide.

Clinostat 3D Cell Culture: Protocols for the Preparation and Functional Analysis of Highly Reproducible, Large, Uniform Spheroids and Organoids.

Growing cells as 3D structures need not be difficult. Often, it is not necessary to change cell type, additives or growth media used. All that needs to be changed is the geometry: cells (whether primary, induced pluripotent, transformed or immortal) simply have to be grown in conditions that promote cell-cell adhesion while allowing gas, nutrient, signal, and metabolite exchange.

Observational, Retrospective Evaluation of a New Nurse-Initiated Emergency Department Pain Management Protocol.

Background: Triage nurses are important in pain management and in early relief of pain among patients admitted to the emergency department (ED).

Aims: To assess a new nurse-initiated pain management protocol, without the requirement for medical prescription, wich was implemented in October 2016 for patients with moderate or severe pain in the ED. It allows the administration of oral acetaminophen and oral oxycodone chlorydrate during the first evaluation of the patient by a nurse and eliminates the use of codeine or tramadol.

A RAC-GEF network critical for early intestinal tumourigenesis.

RAC1 activity is critical for intestinal homeostasis, and is required for hyperproliferation driven by loss of the tumour suppressor gene Apc in the murine intestine. To avoid the impact of direct targeting upon homeostasis, we reasoned that indirect targeting of RAC1 via RAC-GEFs might be effective. Transcriptional profiling of Apc deficient intestinal tissue identified Vav3 and Tiam1 as key targets.

Course-based undergraduate research experiences in a remote setting: Two case studies documenting implementation and student perceptions.

Inquiry-based components of ecology curricula can be valuable, exposing students to what it means to science, from conceiving of a meaningful question to effectively disseminating results to an audience. Here, we describe two approaches for implementing independent, remote research for undergraduates enacted in the spring semester of 2020 at Reed College in Portland, OR, reporting case studies from an intermediate-level ecology course and an interdisciplinary environmental science course. We report on both the challenges as well as the novel opportunities for independent research projects in such a setting, the details of how projects were implemented, the tools and resources that may help facilitate such endeavors, as well as perceptions on the effectiveness of this endeavor by students.

Response to and recovery from treatment in human liver-mimetic clinostat spheroids: a model for assessing repeated-dose drug toxicity.

Medicines are usually prescribed for repeated use over shorter or longer times. Unfortunately, repeated-dose animal toxicity studies do not correlate well with observations in man. As emphasized by the '3Rs' and the desire to phase-out animal research, models are needed.

Characterization of an Alginate Encapsulated LS180 Spheroid Model for Anti-colorectal Cancer Compound Screening.

Colorectal cancer is one of the leading causes of cancer-related deaths. A main problem for its treatment is resistance to chemotherapy, requiring the development of new drugs. The success rate of new candidate cancer drugs in clinical trials remains dismal.

Position paper of a German interdisciplinary round table on future designs of trials on adjunctive treatment with antiseizure drugs.

Purpose: Current trials on adjunctive treatment with antiseizure drugs often do not reveal results which are relevant for clinical practice.

Method: Therefore, an interdisciplinary group of German experts discussed a new framework for future antiseizure drug (ASD) trials in adults. This group included members of the executive board of the German Society of Epileptology, of the German institutes for health technology assessment (HTA), of patient organizations and of drug manufacturers.

Intranasal sufentanil versus intravenous morphine for acute severe trauma pain: A double-blind randomized non-inferiority study.

Background: Intravenous morphine (IVM) is the most common strong analgesic used in trauma, but is associated with a clear time limitation related to the need to obtain an access route. The intranasal (IN) route provides easy administration with a fast peak action time due to high vascularization and the absence of first-pass metabolism. We aimed to determine whether IN sufentanil (INS) for patients presenting to an emergency department with acute severe traumatic pain results in a reduction in pain intensity non-inferior to IVM.

Opportunities for behavioral rescue under rapid environmental change.

Laboratory measurements of physiological and demographic tolerances are important in understanding the impact of climate change on species diversity; however, it has been recognized that forecasts based solely on these laboratory estimates overestimate risk by omitting the capacity for species to utilize microclimatic variation via behavioral adjustments in activity patterns or habitat choice. The complex, and often context-dependent nature, of microclimate utilization has been an impediment to the advancement of general predictive models. Here, we overcome this impediment and estimate the potential impact of warming on the fitness of ectotherms using a benefit/cost trade-off derived from the simple and broadly documented thermal performance curve and a generalized cost function.