Time-of-Day Dictates Transcriptional Inflammatory Responses to Cytotoxic Chemotherapy

Many cytotoxic chemotherapeutics elicit a proinflammatory response which is often associated with chemotherapy-induced behavioral alterations. The immune system is under circadian influence; time-of-day may alter inflammatory responses to chemotherapeutics. We tested this hypothesis by administering cyclophosphamide and doxorubicin (Cyclo/Dox), a common treatment for breast cancer, to female BALB/c mice near the beginning of the light or dark phase. Mice were injected intravenously with Cyclo/Dox or the vehicle two hours after lights on (zeitgeber time (ZT2), or two hours after lights off (ZT14). Tissue was collected 1, 3, 9, and 24 hours later. Mice injected with Cyclo/Dox at ZT2 lost more body mass than mice injected at ZT14. Cyclo/Dox injected at ZT2 increased the expression of several pro-inflammatory genes within the spleen; this was not evident among mice treated at ZT14. Transcription of enzymes within the liver responsible for converting Cyclo/Dox into their toxic metabolites increased among mice injected at ZT2; furthermore, transcription of these enzymes correlated with splenic pro-inflammatory gene expression when treatment occurred at ZT2 but not ZT14. The pattern was reversed in the brain; pro-inflammatory gene expression increased among mice injected at ZT14. These data suggest that inflammatory responses to chemotherapy depend on time-of-day and are tissue specific

Computability, G\"odel's Incompleteness Theorem, and an inherent limit on the predictability of evolution

The process of evolutionary diversification unfolds in a vast genotypic space of potential outcomes. During the past century there have been remarkable advances in the development of theory for this diversification, and the theory's success rests, in part, on the scope of its applicability. A great deal of this theory focuses on a relatively small subset of the space of potential genotypes, chosen largely based on historical or contemporary patterns, and then predicts the evolutionary dynamics within this pre-defined set. To what extent can such an approach be pushed to a broader perspective that accounts for the potential open-endedness of evolutionary diversification? There have been a number of significant theoretical developments along these lines but the question of how far such theory can be pushed has not been addressed. Here a theorem is proven demonstrating that, because of the digital nature of inheritance, there are inherent limits on the kinds of questions that can be answered using such an approach. In particular, even in extremely simple evolutionary systems a complete theory accounting for the potential open-endedness of evolution is unattainable unless evolution is progressive. The theorem is closely related to G\"odel's Incompleteness Theorem and to the Halting Problem from computability theory.Comment: Journal of the Royal Society, Interface 201

Mammary Tumors Induce Central Pro-inflammatory Cytokine Expression, but Not Behavioral Deficits in Balb/C Mice

Breast cancer survivors are more likely to develop mood disorders and cognitive deficits than women in the general population. Previous studies suggest that peripheral tumors elicit central pro-inflammatory cytokine production, in turn leading to depression and cognitive deficits. In the current study, two cohorts of female Balb/C mice received bilateral orthotopic injections of syngeneic 67NR, 4T07, or 4T1cells (1 x 10(5) cells per injection) to induce mammary tumors. Approximately three weeks later, learned fear (via fear conditioning) or depressive-like behavior (via tail suspension and forced swim test) was assessed. Proinflammatory cytokine levels were increased in the serum (IL-1beta, TNFalpha, IFNgamma) and livers (IL-1beta, IL-6, TNFalpha) of mice with 4T07 or 4T1 tumors compared to 67NR tumors and the vehicle control. IL-1beta was increased in both the hippocampus and cortex of mice injected with 4T07 or 4T1 cell lines relative to the other treatment groups. However, mammary tumors had no effect on hippocampal doublecortin + and did not alter depressive-like behavior or learned fear. These data demonstrate that similarly sized tumors can produce differential immune responses and that tumor-induced central pro-inflammatory cytokine production can exist in the absence of depressive-like behavior or cognitive deficits

RF Driven Multicusp H- Ion Source

An rf driven multicusp source capable of generating 1-ms H{sup -} beam pulses with a repetition rate as high as 150 Hz has been developed. This source can be operated with a filament or other types of starter. There is almost no lifetime limitation and a clean plasma can be maintained for a long period of operation. It is demonstrated that rf power as high as 25 kW could be coupled inductively to the plasma via a glass-coated copper-coil antenna. The extracted H{sup -} current density achieved is about 200 mA/cm{sup 2}

Determination of Matter Surface Distribution of Neutron-rich Nuclei

We demonstrate that the matter density distribution in the surface region is determined well by the use of the relatively low-intensity beams that become available at the upcoming radioactive beam facilities. Following the method used in the analyses of electron scattering, we examine how well the density distribution is determined in a model-independent way by generating pseudo data and by carefully applying statistical and systematic error analyses. We also study how the determination becomes deteriorated in the central region of the density, as the quality of data decreases. Determination of the density distributions of neutron-rich nuclei is performed by fixing parameters in the basis functions to the neighboring stable nuclei. The procedure allows that the knowledge of the density distributions of stable nuclei assists to strengthen the determination of their unstable isotopes.Comment: 41 pages, latex, 27 figure

Continuous glucose monitoring metrics and pregnancy outcomes in insulin-treated diabetes : A post-hoc analysis of the GlucoMOMS trial

Funding Information: BWM is supported by a NHMRC investigatorgrant (GNT1176437) and BWM reports consultancy, travel support and research funding from Merck. All other authors declare no conflict of interest. The GlucoMOMS trial was funded by ZonMw, the Dutch Organisation for Health Research and Development, project number 80‐82310‐97‐11157. Continuous Glucose Monitors were purchased at a discount price at Medtronic®, Heerlen, The Netherlands. Neither ZonMw nor Medtronic had a role in study design, data collection, data analysis, data interpretation, or writing of the reports of either the original study or the current post hoc analysis. 10 Publisher Copyright: © 2023 The Authors. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.Peer reviewedPublisher PD

A "Starless" Core that Isn't: Detection of a Source in the L1014 Dense Core with the Spitzer Space Telescope

We present observations of L1014, a dense core in the Cygnus region previously thought to be starless, but data from the Spitzer Space Telescope shows the presence of an embedded source. We propose a model for this source that includes a cold core, heated by the interstellar radiation field, and a low-luminosity internal source. The low luminosity of the internal source suggests a substellar object. If L1014 is representative, other "starless" cores may turn out to harbor central sources.Comment: 7 pages, To appear in the ApJS Spitzer Special Editio

Antiproton annihilations in nuclei

Recent results from LEAR experiment PS187 are presented. Preliminary data for the inclusive production of ..pi../sup +/, K/sup +/, and p from the annihilation of 180 MeV antiprotpns in /sup 28/Si and /sup 238/U are compared with predictions of intranuclear cascade calculations. Proton and pion production data are well reproduced by the calculations, but kaon yields at low momenta appear to be strongly suppressed in the experimental data. 8 refs., 5 figs

Information transmission in genetic regulatory networks: a review

Genetic regulatory networks enable cells to respond to the changes in internal and external conditions by dynamically coordinating their gene expression profiles. Our ability to make quantitative measurements in these biochemical circuits has deepened our understanding of what kinds of computations genetic regulatory networks can perform and with what reliability. These advances have motivated researchers to look for connections between the architecture and function of genetic regulatory networks. Transmitting information between network's inputs and its outputs has been proposed as one such possible measure of function, relevant in certain biological contexts. Here we summarize recent developments in the application of information theory to gene regulatory networks. We first review basic concepts in information theory necessary to understand recent work. We then discuss the functional complexity of gene regulation which arrises from the molecular nature of the regulatory interactions. We end by reviewing some experiments supporting the view that genetic networks responsible for early development of multicellular organisms might be maximizing transmitted 'positional' information.Comment: Submitted to J Phys: Condens Matter, 31 page