2,278 research outputs found

    Frequency doubling by active in vivo motility of mechanosensory neurons in the mosquito ear

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    Across vertebrate and invertebrate species, non-linear active mechanisms are employed to increase the sensitivity and acuity of hearing. In mosquitoes, the antennal hearing organs are known to use active force feedback to enhance auditory acuity to female generated sounds. This sophisticated form of signal processing involves active nonlinear events that are proposed to rely on the motile properties of mechanoreceptor neurons. The fundamental physical mechanism for active auditory mechanics is theorised to rely on a synchronization of motile neurons, with a characteristic frequency doubling of the force generated by an ensemble of motile mechanoreceptors. There is however no direct biomechanical evidence at the mechanoreceptor level, hindering further understanding of the fundamental mechanisms of sensitive hearing. Here, using in situ and in vivo atomic force microscopy, we measure and characterise the mechanical response of mechanosensory neuron units during forced oscillations of the hearing organ. Mechanoreceptor responses exhibit the hallmark of nonlinear feedback for force generation, with movements at twice the stimulus frequency, associated with auditory amplification. Simultaneous electrophysiological recordings exhibit similar response features, notably a frequency doubling of the firing rate. This evidence points to the nature of the mechanism, whereby active hearing in mosquitoes emerges from the double-frequency response of the auditory neurons. These results open up the opportunity to directly investigate active cellular mechanics in auditory systems, and they also reveal a pathway to study the nanoscale biomechanics and its dynamics of cells beyond the sense of hearing

    Synthetic Polymer Contamination in Bottled Water

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    Eleven globally sourced brands of bottled water, purchased in 19 locations in nine different countries, were tested for microplastic contamination using Nile Red tagging. Of the 259 total bottles processed, 93% showed some sign of microplastic contamination. After accounting for possible background (lab) contamination, an average of 10.4 microplastic particles >100 um in size per liter of bottled water processed were found. Fragments were the most common morphology (66%) followed by fibers. Half of these particles were confirmed to be polymeric in nature using FTIR spectroscopy with polypropylene being the most common polymer type (54%), which matches a common plastic used for the manufacture of bottle caps. A small fraction of particles (4%) showed the presence of industrial lubricants. While spectroscopic analysis of particles smaller than 100 um was not possible, the adsorption of the Nile Red dye indicates that these particles are most probably plastic. Including these smaller particles (6.5–100 um), an average of 325 microplastic particles per liter of bottled water was found. Microplastic contamination range of 0 to over 10,000 microplastic particles per liter with 95% of particles being between 6.5 and 100 um in size. Data suggests the contamination is at least partially coming from the packaging and/or the bottling process itself. Given the prevalence of the consumption of bottled water across the globe, the results of this study support the need for further studies on the impacts of micro- and nano- plastics on human health

    Synthesis and Biological Activity of Fused tetracyclic Pyrrolo[2,1-C][1,4]Benzodiazepines

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    Cancer remains the second major cause of death in the world. Thus, there is a pressing need to identify potential synthetic route for the development of novel anticancer agents which will serve as lead compounds to effectively combat this life-threatening epidemic. Pyrrolo[2,1-c][1,4]benzodiazepines (PBDs) have sparked a great interest as lead compounds because of their cancerostatic and anti-infective properties. The twisted molecular structure of PBD analogs provides both helical and chiral elements. In an effort to expand novel PBDs that interact with the key exocyclic amino group of the DNA-guanine base, we hypothesized that construction of a fused cyclic active system, would likely serve as an electrophilic site when compared to traditional electrophilic C11-N10 imine group. To examine our theory, we report herein the synthesis and cell viability/cytotoxicity of a series of PBD analogs using NCI-60 cell lines screening. Thus, compounds 1–13 were synthesized and fully characterized. The selected PBDs were found to have marginal inhibition of growth, up to 30%, for certain cell lines

    Barriers to and Facilitators of Help-Seeking Behavior Among Men Who Experience Sexual Violence

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    Research on sexual violence and related support services access has mainly focused on female victims; there is still a remarkable lack of research on men who experience sexual violence. Research demonstrates that people who both self-identify as men and are members of sexual-orientation minority populations are at higher risk of sexual violence. They are also less likely to either report or seek support services related to such experiences. The present study is an exploratory one aimed at filling the gap in the literature and better understanding how men, both straight and gay as well as cisgender and transgender, conceptualize, understand, and seek help related to sexual violence. A sample of 32 men was recruited on-line and participated in either a one-on-one in-depth interview (N = 19) or one of two focus group discussions (N = 13). All interviews and groups were audiotaped, professionally transcribed and coded using NVivo 9 qualitative software. The present analysis focused on barriers to and facilitators of support service access. Emergent and cross-cutting themes were identified and presented, with an emphasis on understanding what factors may prevent disclosure of a sexual violence experience and facilitate seeking support services and/or professional help. Through this analysis, the research team aims to add knowledge to inform the development of tools to increase service access and receipt, for use by both researchers and service professionals. Although this study contributes to the understanding of the issue of men’s experiences of sexual violence, more research with diverse populations is needed

    Nitrogen sources and net growth efficiency of zooplankton in three Amazon River plume food webs

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    The plasticity of nitrogen specific net growth efficiency (NGE) in marine mesozooplankton is currently unresolved, with discordant lines of evidence suggesting that NGE is constant, or that it varies with nitrogen source, food availability, and food quality in marine ecosystems. Specifically, the fate of nitrogen from nitrogen fixation is poorly known. We use 15N : 14N ratios in plankton in combination with hydrological data, nutrient profiles, and nitrogen fixation rate measurements to investigate the relationship between new nitrogen sources and the nitrogen specific NGE in three plankton communities along the outer Amazon River plume. The NGE of small (200–500 μm) mesozooplankton was estimated from the δ 15N differences between particulate nitrogen and zooplankton using an open system Rayleigh fractionation model. The transfer efficiency of nitrogen among larger (\u3e 500 μm) mesozooplankton was estimated from the change in δ 15N as a function of zooplankton size. The Amazon River was not a significant source of bioavailable nitrogen anywhere in our study region, and subsurface nitrate was the primary new nitrogen source for the outer shelf community, which was dominated by diatoms. N2 fixation was the principal new nitrogen source at sites of high diatom diazotroph association abundance and at oceanic sites dominated by Trichodesmium spp. and Synechococcus spp. Although we found clear spatial differences in food quantity, food quality, and diazotroph inputs into mesozooplankton, our data show no significant differences in mesozooplankton nitrogen transfer efficiency and NGE (for latter, mean ± SD: 59 ± 10%) among sites

    The VEGF receptor Flt-1 spatially modulates Flk-1 signaling and blood vessel branching

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    Blood vessel formation requires the integrated regulation of endothelial cell proliferation and branching morphogenesis, but how this coordinated regulation is achieved is not well understood. Flt-1 (vascular endothelial growth factor [VEGF] receptor 1) is a high affinity VEGF-A receptor whose loss leads to vessel overgrowth and dysmorphogenesis. We examined the ability of Flt-1 isoform transgenes to rescue the vascular development of embryonic stem cell–derived flt-1−/− mutant vessels. Endothelial proliferation was equivalently rescued by both soluble (sFlt-1) and membrane-tethered (mFlt-1) isoforms, but only sFlt-1 rescued vessel branching. Flk-1 Tyr-1173 phosphorylation was increased in flt-1−/− mutant vessels and partially rescued by the Flt-1 isoform transgenes. sFlt-1–rescued vessels exhibited more heterogeneous levels of pFlk than did mFlt-1–rescued vessels, and reporter gene expression from the flt-1 locus was also heterogeneous in developing vessels. Our data support a model whereby sFlt-1 protein is more efficient than mFlt-1 at amplifying initial expression differences, and these amplified differences set up local discontinuities in VEGF-A ligand availability that are important for proper vessel branching

    Adverse Childhood Experiences and Mental Health Conditions Among Multiracial Adolescents

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    The relationships between adverse childhood experiences (ACEs) and mental health conditions have received much attention in the literature. A particularly well-documented type of ACE is household dysfunction. However, compared to monoracial youth, little is known about the relationship between this type of ACE and mental health outcomes among multiracial adolescents. Objective The objective of this study was to verify the factor structure of the household dysfunction type of ACE using data from the National Survey of Children’s Health (NSCH), and then examine whether household dysfunction (measured as a latent construct) was associated with mental health conditions among multiracial adolescents. Design We used cross-sectional data collected in 2016 from caregivers who completed the NSCH and analyzed data from a subpopulation of adolescents (12–17) who reported more than one race (n = 1,231). Mplus 8.4 was used to conduct confirmatory factor analysis and probit models from a structural equation modeling framework. Results Results from this study indicated that the household dysfunction type of ACE, as a latent construct, had good model fit and was significantly associated with depression [standardized coefficient [B] = .50, 95% confidence interval [CI] .36, .65], anxiety [B = .61, 95% CI .48, .73], behavior problems [B = .58, 95% CI .44, .72], and ADHD [B = .54, 95% CI .38, .69] for multiracial adolescents. Conclusions Household dysfunction may result in adolescents being separated (physically or emotionally) from their caregivers, which may hinder adolescents’ ability to establish or maintain one of the most important relationships needed to promote racial/ethnic identity development and mental health. Implications for advancements in theory and NSCH are presented

    Ligand Trap of the Activin Receptor Type IIA Inhibits Osteoclast Stimulation of Bone Remodeling in Diabetic Mice with Chronic Kidney Disease

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    Dysregulation of skeletal remodeling is a component of renal osteodystrophy. Previously, we showed that activin receptor signaling is differentially affected in various tissues in chronic kidney disease (CKD). We tested whether a ligand trap for the activin receptor type 2A (RAP-011) is an effective treatment of the osteodystrophy of the CKD-mineral bone disorder. With a 70% reduction in the glomerular filtration rate, CKD was induced at 14 weeks of age in the ldlr−/− high fat-fed mouse model of atherosclerotic vascular calcification and diabetes. Twenty mice with CKD, hyperphosphatemia, hyperparathyroidism, and elevated activin A were treated with RAP-011, wherease 19 mice were given vehicle twice weekly from week 22 until the mice were killed at 28 weeks of age. The animals were then evaluated by skeletal histomorphometry, micro-computed tomography, mechanical strength testing, and ex vivo bone cell culture. Results in the CKD groups were compared with those of the 16 sham-operated ldlr−/− high fat-fed mice. Sham-operated mice had low-turnover osteodystrophy and skeletal frailty. CKD stimulated bone remodeling with significant increases in osteoclast and osteoblast numbers and bone resorption. Compared with mice with CKD and sham-operated mice, RAP-011 treatment eliminated the CKD-induced increase in these histomorphometric parameters and increased trabecular bone fraction. RAP-011 significantly increased cortical bone area and thickness. Activin A-enhanced osteoclastogenesis was mediated through p-Smad2 association with c-fos and activation of nuclear factor of activated T cells c1 (NFATc1). Thus, an ActRIIA ligand trap reversed CKD-stimulated bone remodeling, likely through inhibition of activin-A induced osteoclastogenesis

    'To live and die [for] Dixie': Irish civilians and the Confederate States of America

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    Around 20,000 Irishmen served in the Confederate army in the Civil War. As a result, they left behind, in various Southern towns and cities, large numbers of friends, family, and community leaders. As with native-born Confederates, Irish civilian support was crucial to Irish participation in the Confederate military effort. Also, Irish civilians served in various supporting roles: in factories and hospitals, on railroads and diplomatic missions, and as boosters for the cause. They also, however, suffered in bombardments, sieges, and the blockade. Usually poorer than their native neighbours, they could not afford to become 'refugees' and move away from the centres of conflict. This essay, based on research from manuscript collections, contemporary newspapers, British Consular records, and Federal military records, will examine the role of Irish civilians in the Confederacy, and assess the role this activity had on their integration into Southern communities. It will also look at Irish civilians in the defeat of the Confederacy, particularly when they came under Union occupation. Initial research shows that Irish civilians were not as upset as other whites in the South about Union victory. They welcomed a return to normalcy, and often 'collaborated' with Union authorities. Also, Irish desertion rates in the Confederate army were particularly high, and I will attempt to gauge whether Irish civilians played a role in this. All of the research in this paper will thus be put in the context of the Drew Gilpin Faust/Gary Gallagher debate on the influence of the Confederate homefront on military performance. By studying the Irish civilian experience one can assess how strong the Confederate national experiment was. Was it a nation without a nationalism
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