Clathrin-mediated entry and cellular localization of chlorotoxin in human glioma

<p>Abstract</p> <p>Background</p> <p>Chlorotoxin (TM601), a scorpion venom- derived 36-AA peptide, is an experimental drug against recurrent glioma with tumor specificity but unknown route of intracellular distribution. The aim of this study was to evaluate the route of entry and cellular localization of TM601 in glioma cells.</p> <p>Results</p> <p>We have found that in human gliomas, lung carcinoma and normal vascular endothelial cells, TM601 localizes near trans-Golgi while in normal human dermal fibroblasts (NHDF) and astrocytes it is dispersed in the cytoplasm. The uptake of TM601 by U373 glioma cells is rapid, concentration and time dependent, not affected by inhibitors such as filipin (caveolae-dependent endocytosis) and amiloride (non-selective macropinocytosis), but significantly affected by chlorpromazine (clathrin-dependent intracellular transport of coated pits) resulting in intracellular build-up of the drug and clathrin near the Golgi. In contrast, TM601 uptake by NHDF cells was significantly affected by amiloride indicating that macropinocytosis is the dominant uptake route of TM601 in these cells.</p> <p>Conclusions</p> <p>In conclusion, we found a distinct cellular localization pattern and uptake of TM601 by glioma cells differing from that found in normal cells. Further insight into the cellular processing of TM601 should assist in the development of effective anti-glioma therapeutic modalities.</p

Criminal Victimisation and Depression in the Czech Republic

Since the fall of communism in 1989, criminal victimization has become an issue in the Czech Republic, & research indicates that it is a stressful experience. The relationship between criminal victimization & depression was examined by adding fear of crime, protection against crime, avoidance of crime, mastery over one's life, social support, & trust in government (as well as sociodemographic controls) to successive regression equations. A total of 703 Czech households in the second of a three-wave (1994-1996) panel study were studied. For men, the total & direct effects of criminal victimization on depression were significant. However, the relation of men's fear of crime & depression was mediated by avoidance. For women, criminal victimization was not related to depression. The relation of women's fear of crime & depression was mediated by mastery. Interpretations of these results are grounded in the different relevance criminal victimization has for the well-being of men & women

Application of Radiometric Surveys to Delineate between Sedimentary Terrain and Basement Complex: A case study of Sagamu and Abeokuta, South Western Nigeria

NaI (TI) detector crystal coupled to a Canberra series 10 plus multichannel analyser (MCA) was used to analyse the soil samples collected from Sagamu (Sedimentary terrain) and Abeokuta (Basement complex) in South Western Nigeria. The use of the soil samples is to determine the activity concentrations due to radium, thorium and potassium so as to delineate between the two terrains using radiometric survey. From the result of the activity concentrations of these radionuclide, the mean value of the activity concentrations of 40k (72±48) in sedimentary terrain is higher than in 226Ra (35± 20) and 232Thorium (43 ±26) respectively. In the basement complex, the average value of the activity concentration of 40k (80 ±46) was also higher in 226Ra (44±18) and 232Thorium (53 ± 25) respectively. The relatively high value recorded 40k radionuclide may be attributed to the perceived variations in the environment resulting from past activities. The results shows that the activity concentration of the radionuclides is higher in basement complex than in sedimentary terrain thus, delineate between the two terrains since it is well know that in basement complex, granites contain high concentrations of uranium, thorium and potassium. Keywords: key words: Activity concentrations, Basement complex, Radiometric survey, Sedimentary terrain, Soil sample

Valuation of Closely-Held Stock for Federal Tax Purposes: Approach to an Objective Method

The present double-standard approach to the valuation problem discriminates against owners of closely-held stock, that is, corporate shares which have no public market. The disparity of treatment is traceable to the unfortunate fact that, whereas actual sales or bona fide bid and asked prices govern the valuation for federal tax purposes of listed stocks and of unlisted stocks which are dealt in through brokers or have a market, the criteria employed in valuing closely-held stock are predominantly subjective. This makes a paradise for experts but they seldom agree and few, if any, of their assumptions and conclusions are anything more than unverified, and not always wholly disinterested, hunches. As a consequence, disagreement between taxpayer and revenue agent is frequent and the process of resolving disagreement is long and costly and the event uncertain. In short, the whole merry-go-round of valuing closely-held stock is wasteful and unfair. This paper and the study it reports are addressed to the possibility of improving the situation by making a fresh approach to the valuation of closely-held stock

Theory Testing Using Quantitative Predictions of Effect Size

Traditional Null Hypothesis Testing procedures are poorly adapted to theory testing. The methodology can mislead researchers in several ways, including: (a) a lack of power can result in an erroneous rejection of the theory; (b) the focus on directionality (ordinal tests) rather than more precise quantitative predictions limits the information gained; and (c) the misuse of probability values to indicate effect size. An alternative approach is proposed which involves employing the theory to generate explicit effect size predictions that are compared to the effect size estimates and related confidence intervals to test the theoretical predictions. This procedure is illustrated employing the Transtheoretical Model. Data from a sample (N = 3,967) of smokers from a large New England HMO system were used to test the model. There were a total of 15 predictions evaluated, each involving the relation between Stage of Change and one of the other 15 Transtheoretical Model variables. For each variable, omega‐squared and the related confidence interval were calculated and compared to the predicted effect sizes. Eleven of the 15 predictions were confirmed, providing support for the theoretical model. Quantitative predictions represent a much more direct, informative, and strong test of a theory than the traditional test of significance

Precise Measures of Orbital Period, Before and After Nova Eruption for QZ Aurigae

For the ordinary classical nova QZ Aurigae (which erupted in 1964), we report 1317 magnitudes from 1912--2016, including four eclipses detected on archival photographic plates from long before the eruption. We have accurate and robust measures of the orbital period both pre-eruption and post-eruption, and we find that the orbital period decreased, with a fractional change of -290.71+-0.28 parts-per-million across the eruption, with the orbit necessarily getting smaller. Further, we find that the light curve outside of eclipses and eruption is flat at near B=17.14 from 1912--1981, whereupon the average light curve starts fading down to B=17.49 with large variability. QZ Aur is a robust counter-example against the Hibernation model for the evolution of cataclysmic variables, where the model requires that all novae have their period increase across eruptions. Large period decreases across eruptions can easily arise from mass imbalances in the ejecta, as are commonly seen in asymmetric nova shells.Comment: MNRAS in press, 24 pages, 5 tables, 6 figure

Eating Behaviors of Older Adults Participating in Government-Sponsored Programs with Different Demographic Backgrounds

The purpose of this study was to determine the food behaviors of nutritionally high-risk seniors as a function of their racial background, gender, marital status, and education level. A total of 69 seniors were identified to be at high nutritional risk using the Nutrition Screening Initiative (NSI) checklist. A supplemental questionnaire (SQ) was created to examine the risk factors in relation to the participant’s demographic background. Key results indicated that Asians practiced healthy food behaviors and women were more likely to eat alone (p≤0.05). Married participants (90.9%) were most likely to consume 2 meals or more each day. College educated individuals practiced healthier eating, eating 5 servings or more of fruits and vegetables (p≤0.01) and 2 or more servings of milk and milk products (p≤0.01). These preliminary findings indicate that more studies should be conducted to focus on the demographic characteristics and food behaviors among older populations

Valuation of Closely-Held Stock for Federal Tax Purposes: Approach to an Objective Method

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Subclinical infection of macaques and baboons with a baboon simarterivirus

Simarteriviruses (Arteriviridae: Simarterivirinae) are commonly found at high titers in the blood of African monkeys but do not cause overt disease in these hosts. In contrast, simarteriviruses cause severe disease in Asian macaques upon accidental or experimental transmission. Here, we sought to better understand the host-dependent drivers of simarterivirus pathogenesis by infecting olive baboons (n = 4) and rhesus monkeys (n = 4) with the simarterivirus Southwest baboon virus 1 (SWBV-1). Surprisingly, none of the animals in our study showed signs of disease following SWBV-1 inoculation. Three animals (two rhesus monkeys and one olive baboon) became infected and sustained high levels of SWBV-1 viremia for the duration of the study. The course of SWBV-1 infection was highly predictable: plasma viremia peaked between 1 × 107 and 1 × 108 vRNA copies/mL at 3–10 days post-inoculation, which was followed by a relative nadir and then establishment of a stable set-point between 1 × 106 and 1 × 107 vRNA copies/mL for the remainder of the study (56 days). We characterized cellular and antibody responses to SWBV-1 infection in these animals, demonstrating that macaques and baboons mount similar responses to SWBV-1 infection, yet these responses are ineffective at clearing SWBV-1 infection. SWBV-1 sequencing revealed the accumulation of non-synonymous mutations in a region of the genome that corresponds to an immunodominant epitope in the simarterivirus major envelope glycoprotein GP5, which likely contribute to viral persistence by enabling escape from host antibodies