Noble gas composition in rainwater and associated weather patterns

This work represents the first comprehensive noble gas study in rainwater. It was carried out in southeast Michigan. Results show that all rainwater samples are in disequilibrium with surface conditions. Two noble gas patterns are identified. The first one, associated with low‐pressure systems, presence of fog and light rainfall, displays a relative Ar enrichment together with Ne, Kr, and Xe depletion. The second one, associated with the passage of frontal systems, displays a mass‐dependent depletion pattern. Precipitation is characterized by thunderstorms, heavy rainfall, and high cloud ceiling heights. A diffusion mass‐transfer model suggests that noble gas patterns originate from ice. Complete re‐equilibration with surface conditions should occur within hours. For the first time, this study establishes a direct correlation between the noble gas composition in rainwater and weather patterns and highlights their potential to identify timing and location of recharge in shallow aquifer systems where infiltration is rapid. Key Points Noble gases in rainwater are in disequilibrium with surface conditions Rainwater noble gas patterns are associated with weather conditions Ice is the starting point of rainwater formation in southeast MichiganPeer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/99103/1/FigureS12.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/99103/2/FigureS5.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/99103/3/Supplementary_Text_3_revised2_Trackchanges.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/99103/4/FigureS1.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/99103/5/FigureS8.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/99103/6/TableS2.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/99103/7/Supplementary_all.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/99103/8/SuppText_2.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/99103/9/FigureS4.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/99103/10/FigureS9.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/99103/11/TableS3.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/99103/12/FigureS7.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/99103/13/TableS4.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/99103/14/SuppText_1.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/99103/15/FigureS10.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/99103/16/Supplementary_Text_3_revised2_NOhighlight.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/99103/17/FigureS3.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/99103/18/grl50610.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/99103/19/FigureS6.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/99103/20/FigureS11.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/99103/21/TableS1.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/99103/22/SuppText_4.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/99103/23/FigureS2.pd

Tunable Oscillations in the Purkinje Neuron

In this paper, we study the dynamics of slow oscillations in Purkinje neurons in vitro, and derive a strong association with a forced parametric oscillator model. We demonstrate the precise rhythmicity of the oscillations in Purkinje neurons, as well as a dynamic tunability of this oscillation using a photo-switchable compound. We show that this slow oscillation can be induced in every Purkinje neuron, having periods ranging between 10-25 seconds. Starting from a Hodgkin-Huxley model, we also demonstrate that this oscillation can be externally modulated, and that the neurons will return to their intrinsic firing frequency after the forced oscillation is concluded. These results signify an additional functional role of tunable oscillations within the cerebellum, as well as a dynamic control of a time scale in the brain in the range of seconds.Comment: 12 pages, 5 figure

Comparative Proteomic Analyses of the Parietal Lobe from Rhesus Monkeys Fed a High-Fat/Sugar Diet With and Without Resveratrol Supplementation, Relative to a Healthy Diet: Insights Into the Roles of Unhealthy Diets and Resveratrol on Function

A diet consisting of a high intake of saturated fat and refined sugars is characteristic of a Western-diet and has been shown to have a substantial negative effect on human health. Expression proteomics were used to investigate changes to the parietal lobe proteome of rhesus monkeys consuming either a high fat and sugar (HFS) diet, a HFS diet supplemented with resveratrol (HFS+RSV), or a healthy control diet for 2 years. Here we discuss the modifications in the levels of 12 specific proteins involved in various cellular systems including metabolism, neurotransmission, structural integrity, and general cellular signaling following a nutritional intervention. Our results contribute to a better understanding of the mechanisms by which resveratrol functions through the up- or down-regulation of proteins in different cellular sub-systems to affect the overall health of the brain

Neurodegeneration and Epilepsy in a Zebrafish Model of CLN3 Disease (Batten Disease)

The neuronal ceroid lipofuscinoses are a group of lysosomal storage disorders that comprise the most common, genetically heterogeneous, fatal neurodegenerative disorders of children. They are characterised by childhood onset, visual failure, epileptic seizures, psychomotor retardation and dementia. CLN3 disease, also known as Batten disease, is caused by autosomal recessive mutations in the CLN3 gene, 80–85% of which are a ~1 kb deletion. Currently no treatments exist, and after much suffering, the disease inevitably results in premature death. The aim of this study was to generate a zebrafish model of CLN3 disease using antisense morpholino injection, and characterise the pathological and functional consequences of Cln3 deficiency, thereby providing a tool for future drug discovery. The model was shown to faithfully recapitulate the pathological signs of CLN3 disease, including reduced survival, neuronal loss, retinopathy, axonopathy, loss of motor function, lysosomal storage of subunit c of mitochondrial ATP synthase, and epileptic seizures, albeit with an earlier onset and faster progression than the human disease. Our study provides proof of principle that the advantages of the zebrafish over other model systems can be utilised to further our understanding of the pathogenesis of CLN3 disease and accelerate drug discovery

Cancer stem-like cells from head and neck cancers are chemosensitized by the Wnt antagonist, sFRP4, by inducing apoptosis, decreasing stemness, drug resistance and epithelial to mesenchymal transition

Cancer stem cells (CSCs) of head and neck squamous cell carcinoma (HNSCC) are defined by high self-renewal and drug refractory potential. Involvement of Wnt/ß-catenin signaling has been implicated in rapidly cycling cells such as CSCs, and inhibition of the Wnt/ß-catenin pathway is a novel approach to target CSCs from HNSCC. In this study, we found that an antagonist of FrzB/Wnt, the secreted frizzled-related protein 4 (sFRP4), inhibited the growth of CSCs from two HNSCC cell lines, Hep2 and KB. We enriched the CD44+ CSC population, and grew them in spheroid cultures. sFRP4 decreased the proliferation and increased the sensitivity of spheroids to a commonly used drug in HNSCC, namely cisplatin. Self-renewal in sphere formation assays decreased upon sFRP4 treatment, and the effect was reverted by the addition of Wnt3a. sFRP4 treatment of spheroids also decreased ß-catenin, confirming its action through the Wnt/ß-catenin signaling pathway. Quantitative PCR demonstrated a clear decrease of the stemness markers CD44 and ALDH, and an increase in CD24 and drug-resistance markers ABCG2 and ABCC4. Furthermore, we found that after sFRP4 treatment, there was a reversal in the expression of epithelial to mesenchymal (EMT) markers with the restoration of the epithelial marker E-cadherin, and depletion of EMT-specific markers twist, snail and N-cadherin. This is the first report demonstrating that the naturally occurring Wnt inhibitor, sFRP4, can be a potential drug to destroy CSC-enriched spheroids from HNSCCs. The repression of EMT and the decrease in stemness profile further strengthen the use of sFRP4 as a potent therapeutic against CSC

Multifunctional Properties of Chicken Embryonic Prenatal Mesenchymal Stem Cells- Pluripotency, Plasticity, and Tumor Suppression

The chick embryo represents an accessible and economical in vivo model, which has long been used in developmental biology, gene expression analysis, and loss/gain of function experiments. In the present study, we assessed and characterized bone marrow derived mesenchymal stem cells from prenatal day 13 chicken embryos (chBMMSCs) and determined some novel properties. After assessing the mesenchymal stem cell (MSC) properties of these cells by the presence of their signature markers (CD 44, CD 73, CD 90, CD 105, and vimentin), we ascertained a very broad spectrum of multipotentiality as these MSCs not only differentiated into the classic tri-lineages of MSCs but also into ectodermal, endodermal, and mesodermal lineages such as neuron, hepatocyte, islet cell, and cardiac. In addition to wide plasticity, we detected the presence of several pluripotent markers such as Oct4, Sox2, and Nanog. This is the first study characterizing prenatal chBMMSCs and their ability to not only differentiate into mesenchymal lineages but also into all the germ cell layer lineages. Furthermore, our studies indicate that prenatal chBMMSCs derived from the chick provide an excellent model for multi-lineage development studies because of their broad plasticity and faithful reproduction of MSC traits as seen in the human. Here, we also present evidence for the first time that media derived from prenatal chBMMSC cultures have an anti-tumorigenic, anti-migratory, and pro-apoptotic effect on human tumors cells acting through the Wnt-ß-catenin pathway. These data confirm that chBMMSCs are enriched with factors in their secretome that are able to destroy tumor cells. This suggests a commonality of properties of MSCs across species between human and chicken