Function and central projections of gustatory receptor neurons on the antenna of the noctuid moth Spodoptera littoralis

Chemosensory information is crucial for most insects to feed and reproduce. Olfactory signals are mainly used at a distance, whereas gustatory stimuli play an important role when insects directly contact chemical substrates. In noctuid moths, although the antennae are the main olfactory organ, they also bear taste sensilla. These taste sensilla detect sugars and hence are involved in appetitive learning but could also play an important role in food evaluation by detecting salts and bitter substances. To investigate this, we measured the responses of individual taste sensilla on the antennae of Spodoptera littoralis to sugars and salts using tip recordings. We also traced the projections of their neuronal axons into the brain. In each sensillum, we found one or two neurons responding to sugars: one NaCl-responsive and one water-sensitive neuron. Responses of these neurons were dose-dependent and similar across different locations on the antenna. Responses were dependent on the sex for sucrose and on both sex and location for glucose and fructose. We did not observe a spatial map for the projections from specific regions of the antennae to the deutocerebrum or the tritocerebrum/suboesophageal ganglion complex. In accordance with physiological recordings, back-fills from individual sensilla revealed up to four axons, in most cases targeting different projection zones

Thyroid function and deiodinase activities in rats with marginal iodine deficiency

The hypothesis tested was whether marginal iodine deficiency for a period of 6 wk affects iodothyronine deiodinase activities in liver and brain of rats. Male rats were fed purified diets either deficient or sufficient in iodine; the diets were fed on a restricted basis (60% of ad libitum intake). Body weight gain of the two groups was comparable. Iodine deficiency was evidenced by increased thyroid weight (26%), reduced urinary iodine excretion (80%), and reduced plasma T4 concentrations (22%). Activities of liver type I and brain type III deiodinase were unchanged, but the activity of type II deiodinase in brain was increased (28%) in the iodine-deficient rats. Food restriction per se significantly lowered T3 (30%) and T4 (22%) concentrations in plasma and decreased type III deiodinase activity in brain (30%). These results indicate that in marginal iodine deficiency the activities of hepatic type I deiodinase and brain type III deiodinase are unchanged, whereas that of brain type II deiodinase is increased

Aesthetics of self-scaling: parallaxed transregionalism and Kutluğ Ataman's art practice

This article examines relations of ethnography, contemporary art-practice, globalisation and scalar geopolitics with particular reference to Kutluğ Ataman’s artworks. Having been shortlisted for the Turner Prize at the Tate and awarded the prestigious international Carnegie Prize in 2004 with his forty-screen video installation Küba (2004), Ataman became an extremely well-known, globally acclaimed artist and filmmaker. Self-conscious of their global travel and critically attentive to the contemporary ethnographic turn in the visual arts scene, Ataman’s video-works perform a conscientious failure of representing cultural alterity as indigeneity. Concentrating on the artist’s engagement with ethnography, this article contains three main parts. Analyses of the selection of videos in each part will give an account of different scalar aspects of Ataman’s artworks. It will first revisit a previous study (Çakirlar 2011) on the artist’s earlier work of video-portraits including Never My Soul! (2002) and Women Who Wear Wigs (1999). A detailed discussion of Küba follows, which may be taken as the ‘hinge - work’ in Ataman’s oeuvre that marks a scalar transition in his critical focus - from body and identity to community and geopolitics. The discussion will then move to a brief analysis of the series Mesopotamian Dramaturgies, including the screen-based sculptures Dome (2009), Column (2009), Frame (2009), English as a Second Language (2009), and The Complete Works of William Shakespeare (2009). Rather than addressing scale as a differential concept, this article aims to demonstrate the ways in which Ataman’s art-practice produces self-scaling, self-regioning subjects that unsettle the hierarchical constructions of scale and facilitates a critique of the scalar normativity within the global art world’s regionalisms and internationalisms

Simple model to explain effects of plasma protein binding and tissue binding on calculated volumes of distribution, apparent elimination rate constants and clearances

A simple pharmacokinetic model, incorporating linear plasma protein binding, linear tissue binding, and first order elimination of free (unbound) drug, was studied. If Cl p is the plasma clearance, V f is the “true” volume of distribution of free drug, β is the apparent elimination rate constant, σ is the fraction of the drug which is free in plasma, f is the fraction of the drug which is free in the entire body, k f is the intrinsic elimination rate constant for free drug, and A TB o is the initial amount of drug which is bound to tissues, then the model indicates that the following relationships hold: (1) Cl p = V f σ k f ; (2) β = f k f ; and V dext = (σ/f) V f . Only σ, and not f, can be measured experimentally . Dividing Cl p by σ provides an estimate of the intrinsic clearance of free drug, V f k f . A plot of V dext versus σ has an intercept equal to V f , and the ratio of the slope/intercept is an estimate of A TB o /A f o , where A f o is the initial amount of free drug (equal to V f times initial concentration of free drug in plasma). Thus, an estimate of A TB o may be obtained. Dividing the intrinsic clearance by V f provides an estimate of k f . Thus, theoretically, estimates of V f , k f , A TB o and f may be obtained. The variables are not separated when β is plotted versus σ, and curvature of such plots is expected; no useful information is obtained from such plots.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/46634/1/228_2004_Article_BF00563079.pd

Sodium stibogluconate and CD47-SIRPa blockade overcome resistance of anti-CD20–opsonized B cells to neutrophil killing

Anti-CD20 antibodies such as rituximab are broadly used to treat B-cell malignancies. These antibodies can induce various effector functions, including immune cell-mediated antibody-dependent cellular cytotoxicity (ADCC). Neutrophils can induce ADCC toward solid cancer cells by trogoptosis, a cytotoxic mechanism known to be dependent on trogocytosis. However, neutrophils seem to be incapable of killing rituximab-opsonized B-cell lymphoma cells. Nevertheless, neutrophils do trogocytose rituximab-opsonized B-cell lymphoma cells, but this only reduces CD20 surface expression and is thought to render tumor cells therapeutically resistant to further rituximab-dependent destruction. Here, we demonstrate that resistance of B-cell lymphoma cells toward neutrophil killing can be overcome by a combination of CD47-SIRPa checkpoint blockade and sodium stibogluconate (SSG), an anti-leishmaniasis drug and documented inhibitor of the tyrosine phosphatase SHP-1. SSG enhanced neutrophil-mediated ADCC of solid tumor cells but enabled trogoptotic killing of B-cell lymphoma cells by turning trogocytosis from a mechanism that contributes to resistance into a cytotoxic anti-cancer mechanism. Tumor cell killing in the presence of SSG required both antibody opsonization of the target cells and disruption of CD47-SIRPa interactions. These results provide a more detailed understanding of the role of neutrophil trogocytosis in antibody-mediated destruction of B cells and clues on how to further optimize antibody therapy of B-cell malignancies

Refined histopathological predictors of BRCA1 and BRCA2 mutation status: A large-scale analysis of breast cancer characteristics from the BCAC, CIMBA, and ENIGMA consortia

Introduction: The distribution of histopathological features of invasive breast tumors in BRCA1 or BRCA2 germline mutation carriers differs from that of individuals with no known mutation. Histopathological features thus have utility for mutation prediction, including statistical modeling to assess pathogenicity of BRCA1 or BRCA2 variants of uncertain clinical significance. We analyzed large pathology datasets accrued by the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA) and the Breast Cancer Association Consortium (BCAC) to reassess histopathological predictors of BRCA1 and BRCA2 mutation status, and provide robust likelihood ratio (LR) estimates for statistical modeling. Methods: Selection criteria for study/center inclusion were estrogen receptor (ER) status or grade data available for invasive breast cancer diagnosed younger than 70 years. The dataset included 4,477 BRCA1 mutation carriers, 2,565 BRCA2 mutation carriers, and 47,565 BCAC breast cancer cases. Country-stratified estimates of the

The DZHK research platform: maximisation of scientific value by enabling access to health data and biological samples collected in cardiovascular clinical studies

The German Centre for Cardiovascular Research (DZHK) is one of the German Centres for Health Research and aims to conduct early and guideline-relevant studies to develop new therapies and diagnostics that impact the lives of people with cardiovascular disease. Therefore, DZHK members designed a collaboratively organised and integrated research platform connecting all sites and partners. The overarching objectives of the research platform are the standardisation of prospective data and biological sample collections among all studies and the development of a sustainable centrally standardised storage in compliance with general legal regulations and the FAIR principles. The main elements of the DZHK infrastructure are web-based and central units for data management, LIMS, IDMS, and transfer office, embedded in a framework consisting of the DZHK Use and Access Policy, and the Ethics and Data Protection Concept. This framework is characterised by a modular design allowing a high standardisation across all studies. For studies that require even tighter criteria additional quality levels are defined. In addition, the Public Open Data strategy is an important focus of DZHK. The DZHK operates as one legal entity holding all rights of data and biological sample usage, according to the DZHK Use and Access Policy. All DZHK studies collect a basic set of data and biosamples, accompanied by specific clinical and imaging data and biobanking. The DZHK infrastructure was constructed by scientists with the focus on the needs of scientists conducting clinical studies. Through this, the DZHK enables the interdisciplinary and multiple use of data and biological samples by scientists inside and outside the DZHK. So far, 27 DZHK studies recruited well over 11,200 participants suffering from major cardiovascular disorders such as myocardial infarction or heart failure. Currently, data and samples of five DZHK studies of the DZHK Heart Bank can be applied for

Associations of obesity and circulating insulin and glucose with breast cancer risk: a Mendelian randomization analysis.

BACKGROUND: In addition to the established association between general obesity and breast cancer risk, central obesity and circulating fasting insulin and glucose have been linked to the development of this common malignancy. Findings from previous studies, however, have been inconsistent, and the nature of the associations is unclear. METHODS: We conducted Mendelian randomization analyses to evaluate the association of breast cancer risk, using genetic instruments, with fasting insulin, fasting glucose, 2-h glucose, body mass index (BMI) and BMI-adjusted waist-hip-ratio (WHRadj BMI). We first confirmed the association of these instruments with type 2 diabetes risk in a large diabetes genome-wide association study consortium. We then investigated their associations with breast cancer risk using individual-level data obtained from 98 842 cases and 83 464 controls of European descent in the Breast Cancer Association Consortium. RESULTS: All sets of instruments were associated with risk of type 2 diabetes. Associations with breast cancer risk were found for genetically predicted fasting insulin [odds ratio (OR) = 1.71 per standard deviation (SD) increase, 95% confidence interval (CI) = 1.26-2.31, p  =  5.09  ×  10-4], 2-h glucose (OR = 1.80 per SD increase, 95% CI = 1.3 0-2.49, p  =  4.02  ×  10-4), BMI (OR = 0.70 per 5-unit increase, 95% CI = 0.65-0.76, p  =  5.05  ×  10-19) and WHRadj BMI (OR = 0.85, 95% CI = 0.79-0.91, p  =  9.22  ×  10-6). Stratified analyses showed that genetically predicted fasting insulin was more closely related to risk of estrogen-receptor [ER]-positive cancer, whereas the associations with instruments of 2-h glucose, BMI and WHRadj BMI were consistent regardless of age, menopausal status, estrogen receptor status and family history of breast cancer. CONCLUSIONS: We confirmed the previously reported inverse association of genetically predicted BMI with breast cancer risk, and showed a positive association of genetically predicted fasting insulin and 2-h glucose and an inverse association of WHRadj BMI with breast cancer risk. Our study suggests that genetically determined obesity and glucose/insulin-related traits have an important role in the aetiology of breast cancer