Severe Heat Cramps in a High School Football Player: A Case Report

We present a case study of an adolescent football player who suffered from severe full body muscle cramping after supplementing with creatine for two months. A paucity of data exists regarding the safety of creatine supplementation and its side effects on dehydration, body fluid/electrolyte balance, and other heat illnesses

α-MSH inhibits induction of C/EBPβ-DNA binding activity and NOS2 gene transcription in macrophages

α-MSH inhibits induction of C/EBPβ-DNA binding activity and NOS2 gene transcription in macrophages.Backgroundα-Melanocyte–stimulating hormone (α-MSH) is an endogenous tridecapeptide that exerts anti-inflammatory actions and abrogates postischemic renal injury in rodents. α-MSH inhibits lipopolysaccharide (LPS)-induced gene expression of several cytokines, chemokines, and nitric oxide synthase-2 (NOS2), but the molecular mechanisms underlying these effects have not been clearly defined. To test the hypothesis that α-MSH inhibits the expression of inducible trans-activating factors involved in NOS2 regulation, we used RAW 264.7 macrophage cells to examine the effects of α-MSH on the activation of nuclear factor-кB (NF-кB) and CCAAT/enhancer binding protein-β (C/EBPβ), trans-acting factors known to be involved in LPS + interferon (IFN)-γ induction of the NOS2 gene.MethodsGel shift assays were performed to identify NF-кB and C/EBP DNA binding activities in LPS + IFN-γ–treated RAW 264.7 cells in the presence and absence of α-MSH. NOS2 promoter assays were conducted to identify the effects of α-MSH on LPS + IFN-γ–mediated induction of NOS2 transcription.ResultsGel shift assays demonstrated LPS + IFN-γ induction of NF-кB and C/EBP family protein-DNA complexes in nuclei harvested from the cells. Supershift assays revealed that the C/EBP complexes were comprised of C/EBPβ, but not C/EBPα, C/EBPα, or C/EBPϵ. α-MSH (100 nmol/L) inhibited the LPS + IFN-γ–mediated induction of nuclear DNA binding activity of C/EBPβ, but not that of NF-кB (in contrast to reports in other cell types), as well as the activity of a murine NOS2 promoter-luciferase construct. In contrast, α-MSH (100 nmol/L) had no effect on the induction of NOS2 promoter-luciferase genes harboring deletion or mutation of the C/EBP box.ConclusionsThese data indicate that α-MSH inhibits the induction of C/EBPβ DNA binding activity and that this effect is a major mechanism by which α-MSH inhibits the transcription of the NOS2 gene. The inability of α-MSH to inhibit LPS + IFN-γ induction of NF-кB in murine macrophage cells, which contrasts with inhibitory effects of the neuropeptide in other cell types, suggests that cell-type–specific mechanisms are involved

Low Sucrose, Omega-3 Enriched Diet Has Region-Specific Effects on Neuroinflammation and Synaptic Function Markers in a Mouse Model of Doxorubicin-Based Chemotherapy

Chemotherapeutic agents such as doxorubicin may negatively affect long-term brain functioning in cancer survivors; neuroinflammation may play a causal role. Dietary approaches that reduce inflammation, such as lowering sucrose and increasing eicosapentaenoic acid plus docosahexaenoic acid (EPA + DHA), may attenuate chemotherapy-induced neuroinflammation and synaptic damage, thereby improving quality of life. Ovariectomized, C57BL/6 mice were assigned to a chemotherapy (9 mg/kg doxorubicin + 90 mg/kg cyclophosphamide) or vehicle two-injection regimen, with injections two and four weeks after starting diets. In Study 1, mice received low sucrose diets with EPA + DHA or No EPA + DHA for four to six weeks; tissues were collected four, seven, or 14 days after the second injection. Compared to vehicle, chemotherapy increased pro-inflammatory cytokine IL-1β at day seven in the cortex and hippocampus, and reduced gene expression of synaptic marker Shank 3 at all timepoints in cortex, while EPA + DHA increased expression of Shank 3. In Study 2, high or low sucrose/EPA + DHA or No EPA + DHA diets were fed for five weeks; tissues were collected ten days after the second injection. Among chemotherapy-treated mice, brain DHA was higher with low sucrose feeding. Furthermore, low sucrose increased gene expression of Shank 1, while EPA + DHA increased expression of Shank 3 and reduced protein concentrations of pro-inflammatory markers IL-5, IL-6 and KC/GRO in the cortex, but not the hippocampus. Low sucrose, EPA + DHA diets may attenuate neuroinflammation and synaptic damage induced by doxorubicin-based chemotherapy in specific brain regions

Low Sucrose, Omega-3 Enriched Diet Has Region-Specific Effects on Neuroinflammation and Synaptic Function Markers in a Mouse Model of Doxorubicin-Based Chemotherapy

Chemotherapeutic agents such as doxorubicin may negatively affect long-term brain functioning in cancer survivors; neuroinflammation may play a causal role. Dietary approaches that reduce inflammation, such as lowering sucrose and increasing eicosapentaenoic acid plus docosahexaenoic acid (EPA + DHA), may attenuate chemotherapy-induced neuroinflammation and synaptic damage, thereby improving quality of life. Ovariectomized, C57BL/6 mice were assigned to a chemotherapy (9 mg/kg doxorubicin + 90 mg/kg cyclophosphamide) or vehicle two-injection regimen, with injections two and four weeks after starting diets. In Study 1, mice received low sucrose diets with EPA + DHA or No EPA + DHA for four to six weeks; tissues were collected four, seven, or 14 days after the second injection. Compared to vehicle, chemotherapy increased pro-inflammatory cytokine IL-1β at day seven in the cortex and hippocampus, and reduced gene expression of synaptic marker Shank 3 at all timepoints in cortex, while EPA + DHA increased expression of Shank 3. In Study 2, high or low sucrose/EPA + DHA or No EPA + DHA diets were fed for five weeks; tissues were collected ten days after the second injection. Among chemotherapy-treated mice, brain DHA was higher with low sucrose feeding. Furthermore, low sucrose increased gene expression of Shank 1, while EPA + DHA increased expression of Shank 3 and reduced protein concentrations of pro-inflammatory markers IL-5, IL-6 and KC/GRO in the cortex, but not the hippocampus. Low sucrose, EPA + DHA diets may attenuate neuroinflammation and synaptic damage induced by doxorubicin-based chemotherapy in specific brain regions

Constraints on the Universal CIV Mass Density at z~6 from Early IR Spectra Obtained with the Magellan FIRE Spectrograph

We present a new determination of the intergalactic CIV mass density at 4.3 < z < 6.3. Our constraints are derived from high signal-to-noise spectra of seven quasars at z > 5.8 obtained with the newly commissioned FIRE spectrograph on the Magellan Baade telescope, coupled with six observations of northern objects taken from the literature. We confirm the presence of a downturn in the CIV abundance at =5.66 by a factor of 4.1 relative to its value at =4.96, as measured in the same sightlines. In the FIRE sample, a strong system previously reported in the literature as CIV at z=5.82 is re-identified as MgII at z=2.78, leading to a substantial downward revision in $\Omega_{CIV}$ for these prior studies. Additionally we confirm the presence of at least two systems with low-ionization CII, SiII, and OI absorption but relatively weak signal from CIV. The latter systems systems may be of interest if the downward trend in $\Omega_{CIV}$ at high redshift is driven in part by ionization effects.Comment: 14 pages, 6 figures, 2 tables. Submitted to Ap

Generation of three-dimensional multiple spheroid model of olfactory ensheathing cells using floating liquid marbles

We describe a novel protocol for three-dimensional culturing of olfactory ensheathing cells (OECs), which can be used to understand how OECs interact with other cells in three dimensions. Transplantation of OECs is being trialled for repair of the paralysed spinal cord, with promising but variable results and thus the therapy needs improving. To date, studies of OEC behaviour in a multicellular environment have been hampered by the lack of suitable three-dimensional cell culture models. Here, we exploit the floating liquid marble, a liquid droplet coated with hydrophobic powder and placed on a liquid bath. The presence of the liquid bath increases the humidity and minimises the effect of evaporation. Floating liquid marbles allow the OECs to freely associate and interact to produce OEC spheroids with uniform shapes and sizes. In contrast, a sessile liquid marble on a solid surface suffers from evaporation and the cells aggregate with irregular shapes. We used floating liquid marbles to co-culture OECs with Schwann cells and astrocytes which formed natural structures without the confines of gels or bounding layers. This protocol can be used to determine how OECs and other cell types associate and interact while forming complex cell structuresJSJ was funded by a grant from the Perry Cross Spinal Research Foundation; NTN was funded from Griffith University through a start-up grant and a grant from the Griffith University Research Infrastructure Program; JAK was funded by an Australian Research Council Discovery Grant DP150104495; JT was funded by an Eskitis Institute scholarship; CO was funded by a Griffith Sciences scholarship; RV was funded by a Griffith University International Postgraduate Research Scholarshi

CellProfiler plugins -- an easy image analysis platform integration for containers and Python tools

CellProfiler is a widely used software for creating reproducible, reusable image analysis workflows without needing to code. In addition to the >90 modules that make up the main CellProfiler program, CellProfiler has a plugins system that allows for creation of new modules which integrate with other Python tools or tools that are packaged in software containers. The CellProfiler-plugins repository contains a number of these CellProfiler modules, especially modules that are experimental and/or dependency-heavy. Here, we present an upgraded CellProfiler-plugins repository with examples of accessing containerized tools, improved documentation, and added citation/reference tools to facilitate the use and contribution of the community.Comment: 17 pages, 2 figures, 1 tabl

hnRNPA2 Mediated Acetylation Reduces Telomere Length in Response to Mitochondrial Dysfunction

Telomeres protect against chromosomal damage. Accelerated telomere loss has been associated with premature aging syndromes such as Werner’s syndrome and Dyskeratosis Congenita, while, progressive telomere loss activates a DNA damage response leading to chromosomal instability, typically observed in cancer cells and senescent cells. Therefore, identifying mechanisms of telomere length maintenance is critical for understanding human pathologies. In this paper we demonstrate that mitochondrial dysfunction plays a causal role in telomere shortening. Furthermore, hnRNPA2, a mitochondrial stress responsive lysine acetyltransferase (KAT) acetylates telomere histone H4at lysine 8 of (H4K8) and this acetylation is associated with telomere attrition. Cells containing dysfunctional mitochondria have higher telomere H4K8 acetylation and shorter telomeres independent of cell proliferation rates. Ectopic expression of KAT mutant hnRNPA2 rescued telomere length possibly due to impaired H4K8 acetylation coupled with inability to activate telomerase expression. The phenotypic outcome of telomere shortening in immortalized cells included chromosomal instability (end-fusions) and telomerase activation, typical of an oncogenic transformation; while in non-telomerase expressing fibroblasts, mitochondrial dysfunction induced-telomere attrition resulted in senescence. Our findings provide a mechanistic association between dysfunctional mitochondria and telomere loss and therefore describe a novel epigenetic signal for telomere length maintenance

Integrated genomic analyses identify ARID1A and ARID1B alterations in the childhood cancer neuroblastoma

Neuroblastomas are tumors of peripheral sympathetic neurons and are the most common solid tumor in children. To determine the genetic basis for neuroblastoma we performed whole-genome sequencing (6 cases), exome sequencing (16 cases), genome-wide rearrangement analyses (32 cases), and targeted analyses of specific genomic loci (40 cases) using massively parallel sequencing. On average each tumor had 19 somatic alterations in coding genes (range, 3–70). Among genes not previously known to be involved in neuroblastoma, chromosomal deletions and sequence alterations of chromatin remodeling genes, ARID1A and ARID1B, were identified in 8 of 71 tumors (11%) and were associated with early treatment failure and decreased survival. Using tumor-specific structural alterations, we developed an approach to identify rearranged DNA fragments in sera, providing personalized biomarkers for minimal residual disease detection and monitoring. These results highlight dysregulation of chromatin remodeling in pediatric tumorigenesis and provide new approaches for the management of neuroblastoma patients

A biologist’s guide to planning and performing quantitative bioimaging experiments

Technological advancements in biology and microscopy have empowered a transition from bioimaging as an observational method to a quantitative one. However, as biologists are adopting quantitative bioimaging and these experiments become more complex, researchers need additional expertise to carry out this work in a rigorous and reproducible manner. This Essay provides a navigational guide for experimental biologists to aid understanding of quantitative bioimaging from sample preparation through to image acquisition, image analysis, and data interpretation. We discuss the interconnectedness of these steps, and for each, we provide general recommendations, key questions to consider, and links to high-quality open-access resources for further learning. This synthesis of information will empower biologists to plan and execute rigorous quantitative bioimaging experiments efficiently