Muhammad, S. | Search bioRxiv

bioRxiv2021

Meta-analysis on reporting practices as a source of heterogeneity in in vitro cancer research

BackgroundHeterogeneity of results of exact same research experiments oppose a significant socio-economic burden. In vitro research presents the early step of basic science and drug development projects. Insufficient methodological reporting is likely to be one of the contributors to results heterogeneity, however, little knowledge on reporting habits of in vitro cancer research and their effects on results reproducibility is available. Glioblastoma is a form of brain cancer with largely unmet clinical need. MethodsHere we use systematic review to describe reporting practices in in vitro glioblastoma research using the U87-MG cell line and perform multilevel random-effects meta-analysis followed by meta-regression to explore sources of heterogeneity within that literature, and any associations between reporting characteristics and reported findings. ResultsIn 137 identified articles, the overall methodological reporting is disappointing, e.g., the control type, mediums glucose level and cell density are reported in only 36.5, 21.2 and 16.8 percent of the articles, respectively. After adjustments for different drug concentrations and treatment durations, a three-level meta-analysis proves meaningful results heterogeneity across the studies (I2 = 70.1%). ConclusionsOur results further support the ongoing efforts of establishing consensus reporting practices to elevate durability of results. By doing so, we hope that this work will raise awareness of how stricter reporting may help to improve the frequency of successful translation of preclinical results into human application, not only in neuro-oncology. FundingWe received no specific funding for this project.

cancer biology↗

bioRxiv2020

Glucose transporter expression and regulation following a fast in the ruby-throated hummingbird, Archilochus colubris.

Hummingbirds subsist almost exclusively on nectar sugar and face extreme challenges blood sugar regulation. Transmembrane sugar transport is mediated by facilitative glucose transporters (GLUTs) and the capacity for sugar transport is dependent on both the activity of GLUTs and their localisation to the plasma membrane (PM). In this study, we determined the relative protein abundance in whole-tissue (WT) homogenates and PM fractions via immunoblot using custom antibodies for GLUT1, GLUT2, GLUT3, and GLUT5 in flight muscle, heart, and, liver of ruby-throated hummingbirds (Archilochus colubris). GLUTs examined were detected in nearly all tissues tested. Hepatic GLUT1 was minimally present in WT homogenates and absent in PM fractions. GLUT5 was expressed in hummingbird flight muscles at levels comparable to that of their liver, consistent with the hypothesised uniquely high fructose-uptake and oxidation capacity of this tissue. To assess GLUT regulation, we fed ruby-throated hummingbirds 1M sucrose ad libitum for 24 hours followed by either 1 hour of fasting or continued ad libitum feeding until sampling. We measured relative GLUT abundance and concentrations of circulating sugars. Blood fructose concentration in fasted hummingbirds declined from [~]5mM to [~]0.18mM, while fructose-transporting PM GLUT2 and PM GLUT5 did not change in abundance. Blood glucose concentrations remained elevated in both fed and fasted hummingbirds, at [~]30mM, while glucose-transporting PM GLUT1 and PM GLUT3 in the flight muscle and liver, respectively, declined in fasted birds. Our results suggest that glucose uptake capacity is dynamically reduced in response to fasting, allowing for maintenance of elevated blood glucose levels, while fructose uptake capacity remains constitutively elevated promoting depletion of blood total fructose within the first hour of a fast. Summary statementHummingbird ingest nectar rich in glucose and fructose. When fasted, tissue capacity for circulating glucose import declines while remaining elevated for fructose. This may underlie maintenance of high blood glucose and rapid depletion of blood fructose.

zoology↗