The Role of Solar Wind Hydrogen in Space Weathering: Insights from Laboratory-Irradiated Northwest Africa 12008

Micrometeoroid impacts, solar wind plasma interactions, and regolith gardening drive the complicated and nuanced mechanism of space weathering (or optical maturation); a process by which a materials optical properties are changed as a result of chemical and physical alterations at the surface of grains on airless bodies. Reddened slopes, attenuated absorption bands, and an overall reduction in albedo in the visible and near-IR wavelength ranges are primarily the result of native iron nanoparticle (npFe0) production within glassy rims that form from sputtering and vaporization. The sizes and abundance of these particles provide information about the relative surface exposure age of a particular grain. In addition, many studies have indicated that composition greatly affects the rate at which optical maturation occurs. Despite our understanding of how npFe0 affects optical signatures, the relative roles of micrometeoroid bombardment and solar wind interactions remains undetermined. To simulate the early effects of weathering by the solar wind and to determine thresholds for optical change with respect to a given mineral phase, we irradiated a fine-grained lunar basalt with 1 keV H+ to a fluence of 6.4 x 1016 H+ per sq.cm. Surface alterations within four phases have been evaluated using transmission electron microscopy (TEM). We found that for a given fluence of H+, the extent of damage acquired by each grain was dependent on its composition. No npFe(0) was produced in any of the phases evaluated in this study. These results are consistent with many previous studies conducted using ions of similar energy, but they also provide valuable information about the onset of space weathering and the role of the solar wind during the early stages of optical maturation

Breast cancer-derived Dickkopf1 inhibits osteoblast differentiation and osteoprotegerin expression: Implication for breast cancer osteolytic bone metastases

Most breast cancer metastases in bone form osteolytic lesions, but the mechanisms of tumor-induced bone resorption and destruction are not fully understood. Although it is well recognized that Wnt/Β-catenin signaling is important for breast cancer tumorigenesis, the role of this pathway in breast cancer bone metastasis is unclear. Dickkopf1 (Dkk1) is a secreted Wnt/Β-catenin antagonist. In the present study, we demonstrated that activation of Wnt/Β-catenin signaling enhanced Dkk1 expression in breast cancer cells and that Dkk1 overexpression is a frequent event in breast cancer. We also found that human breast cancer cell lines that preferentially form osteolytic bone metastases exhibited increased levels of Wnt/Β-catenin signaling and Dkk1 expression. Moreover, we showed that breast cancer cell-produced Dkk1 blocked Wnt3A-induced osteoblastic differentiation and osteoprotegerin (OPG) expression of osteoblast precursor C2C12 cells and that these effects could be neutralized by a specific anti-Dkk1 antibody. In addition, we found that breast cancer cell conditioned media were able to block Wnt3A-induced NF-kappaB ligand reduction in C2C12 cells. Finally, we demonstrated that conditioned media from breast cancer cells in which Dkk1 expression had been silenced via RNAi were unable to block Wnt3A-induced C2C12 osteoblastic differentiation and OPG expression. Taken together, these results suggest that breast cancer-produced Dkk1 may be an important mechanistic link between primary breast tumors and secondary osteolytic bone metastases. © 2008 Wiley-Liss, Inc.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/60217/1/23625_ftp.pd

Housing environment and mental health of Europeans during the COVID-19 pandemic: a cross-country comparison

Many studies have investigated the impact of the COVID-19 pandemic on mental health. Throughout the pandemic, time spent at home increased to a great extent due to restrictive measures. Here we set out to investigate the relationship between housing conditions and the mental health of populations across European countries. We analyzed survey data collected during spring 2020 from 69,136 individuals from four cohorts from Denmark, France, and the UK. The investigated housing conditions included household density, composition, and crowding, access to outdoor facilities, dwelling type, and urbanicity. The outcomes were loneliness, anxiety, and life satisfaction. Logistic regression models were used, and results were pooled using random-effects meta-analysis. In the meta-analysis, living alone was associated with higher levels of loneliness (OR = 3.08, 95% CI 1.87–5.07), and lower life satisfaction (OR = 1.27, 95% CI 1.05–0.55), compared to living with others. Not having access to an outdoor space and household crowding were suggestively associated with worse outcomes. Living in crowded households, living alone, or lacking access to outdoor facilities may be particularly important in contributing to poor mental health during a lockdown. Addressing the observed fundamental issues related to housing conditions within society will likely have positive effects in reducing social inequalities, as well as improving preparedness for future pandemics

A direct role for SNX9 in the biogenesis of filopodia.

Filopodia are finger-like actin-rich protrusions that extend from the cell surface and are important for cell-cell communication and pathogen internalization. The small size and transient nature of filopodia combined with shared usage of actin regulators within cells confounds attempts to identify filopodial proteins. Here, we used phage display phenotypic screening to isolate antibodies that alter the actin morphology of filopodia-like structures (FLS) in vitro. We found that all of the antibodies that cause shorter FLS interact with SNX9, an actin regulator that binds phosphoinositides during endocytosis and at invadopodia. In cells, we discover SNX9 at specialized filopodia in Xenopus development and that SNX9 is an endogenous component of filopodia that are hijacked by Chlamydia entry. We show the use of antibody technology to identify proteins used in filopodia-like structures, and a role for SNX9 in filopodia

Physics and Applications of Laser Diode Chaos

An overview of chaos in laser diodes is provided which surveys experimental achievements in the area and explains the theory behind the phenomenon. The fundamental physics underpinning this behaviour and also the opportunities for harnessing laser diode chaos for potential applications are discussed. The availability and ease of operation of laser diodes, in a wide range of configurations, make them a convenient test-bed for exploring basic aspects of nonlinear and chaotic dynamics. It also makes them attractive for practical tasks, such as chaos-based secure communications and random number generation. Avenues for future research and development of chaotic laser diodes are also identified.Comment: Published in Nature Photonic

An international reproducibility study validating quantitative determination of ERBB2, ESR1, PGR, and MKI67 mRNA in breast cancer using MammaTyper (R)

Background: Accurate determination of the predictive markers human epidermal growth factor receptor 2 (HER2/ERBB2), estrogen receptor (ER/ESR1), progesterone receptor (PgR/PGR), and marker of proliferation Ki67 (MKI67) is indispensable for therapeutic decision making in early breast cancer. In this multicenter prospective study, we addressed the issue of inter- and intrasite reproducibility using the recently developed reverse transcription-quantitative real-time polymerase chain reaction-based MammaTyper (R) test. Methods: Ten international pathology institutions participated in this study and determined messenger RNA expression levels of ERBB2, ESR1, PGR, and MKI67 in both centrally and locally extracted RNA from formalin-fixed, paraffin-embedded breast cancer specimens with the MammaTyper (R) test. Samples were measured repeatedly on different days within the local laboratories, and reproducibility was assessed by means of variance component analysis, Fleiss' kappa statistics, and interclass correlation coefficients (ICCs). Results: Total variations in measurements of centrally and locally prepared RNA extracts were comparable; therefore, statistical analyses were performed on the complete dataset. Intersite reproducibility showed total SDs between 0.21 and 0.44 for the quantitative single-marker assessments, resulting in ICC values of 0.980-0.998, demonstrating excellent agreement of quantitative measurements. Also, the reproducibility of binary single-marker results (positive/negative), as well as the molecular subtype agreement, was almost perfect with kappa values ranging from 0.90 to 1.00. Conclusions: On the basis of these data, the MammaTyper (R) has the potential to substantially improve the current standards of breast cancer diagnostics by providing a highly precise and reproducible quantitative assessment of the established breast cancer biomarkers and molecular subtypes in a decentralized workup.Peer reviewe

IL-6 Mediated Degeneration of Forebrain GABAergic Interneurons and Cognitive Impairment in Aged Mice through Activation of Neuronal NADPH Oxidase

BACKGROUND:Multiple studies have shown that plasma levels of the pro-inflammatory cytokine interleukin-6 (IL-6) are elevated in patients with important and prevalent adverse health conditions, including atherosclerosis, diabetes, obesity, obstructive sleep apnea, hypertension, and frailty. Higher plasma levels of IL-6, in turn, increase the risk of many conditions associated with aging including age-related cognitive decline. However, the mechanisms underlying this association between IL-6 and cognitive vulnerability remain unclear. METHODS AND FINDINGS:We investigated the role of IL-6 in brain aging in young (4 mo) and aged (24 mo) wild-type C57BL6 and genetically-matched IL-6(-/-) mice, and determined that IL-6 was necessary and sufficient for increased neuronal expression of the superoxide-producing immune enzyme, NADPH-oxidase, and this was mediated by non-canonical NFkappaB signaling. Furthermore, superoxide production by NADPH-oxidase was directly responsible for age-related loss of parvalbumin (PV)-expressing GABAergic interneurons, neurons essential for normal information processing, encoding, and retrieval in hippocampus and cortex. Targeted deletion of IL-6 or elimination of superoxide by chronic treatment with a superoxide-dismutase mimetic prevented age-related loss of PV-interneurons and reversed age-related cognitive deficits on three standard tests of spatial learning and recall. CONCLUSIONS:Present results indicate that IL-6 mediates age-related loss of critical PV-expressing GABAergic interneurons through increased neuronal NADPH-oxidase-derived superoxide production, and that rescue of these interneurons preserves cognitive performance in aging mice, suggesting that elevated peripheral IL-6 levels may be directly and mechanistically linked to long-lasting cognitive deficits in even normal older individuals. Further, because PV-interneurons are also selectively affected by commonly used anesthetic agents and drugs, our findings imply that IL-6 levels may predict adverse CNS effects in older patients exposed to these compounds through specific derangements in inhibitory interneurons, and that therapies directed at lowering IL-6 may have cognitive benefits clinically

An alternative approach to risk rank chemicals on the threat they pose to the aquatic environment

This work presents a new and unbiased method of risk ranking chemicals based on the threat they pose to the aquatic environment. The study ranked 12 metals, 23 pesticides, 11 other persistent organic pollutants (POPs), 13 pharmaceuticals, 10 surfactants and similar compounds and 2 nanoparticles (total of 71) of concern against one another by comparing their median UK river water and median ecotoxicity effect concentrations. To complement this, by giving an assessment on potential wildlife impacts, risk ranking was also carried out by comparing the lowest 10th percentile of the effects data with the highest 90th percentile of the exposure data. In other words, risk was pared down to just toxicity versus exposure. Further modifications included incorporating bioconcentration factors, using only recent water measurements and excluding either lethal or sub-lethal effects. The top ten chemicals, based on the medians, which emerged as having the highest risk to organisms in UK surface waters using all the ecotoxicity data were copper, aluminium, zinc, ethinylestradiol (EE2), linear alkylbenzene sulfonate (LAS), triclosan, manganese, iron, methomyl and chlorpyrifos. By way of contrast, using current UK environmental quality standards as the comparator to median UK river water concentrations would have selected 6 different chemicals in the top ten. This approach revealed big differences in relative risk; for example, zinc presented a million times greater risk then metoprolol and LAS 550 times greater risk than nanosilver. With the exception of EE2, most pharmaceuticals were ranked as having a relatively low risk.Open Access funded by Natural Environment Research Council. We would like to thank the UK's Department for Environment, Food and Rural Affairs for funding this project (CB0462). The views expressed here are of the authors alone. We would also like to thank colleagues at Brunel University and CEH for their advice on the project

Brain Deletion of Insulin Receptor Substrate 2 Disrupts Hippocampal Synaptic Plasticity and Metaplasticity

Diabetes mellitus is associated with cognitive deficits and an increased risk of dementia, particularly in the elderly. These deficits and the corresponding neurophysiological structural and functional alterations are linked to both metabolic and vascular changes, related to chronic hyperglycaemia, but probably also defects in insulin action in the brain. To elucidate the specific role of brain insulin signalling in neuronal functions that are relevant for cognitive processes we have investigated the behaviour of neurons and synaptic plasticity in the hippocampus of mice lacking the insulin receptor substrate protein 2 (IRS-2)