Miracle-dz/UniFAR-FTUs huggingface dataset:
Rb localization and phosphorylation kinetics correlate with the cellular phenotype of cultured breast adenocarcinoma cells

SummaryRetinoblastoma protein (Rb) expression has been correlated with state of differentiation, proliferation rate, and metastatic potential in breast adenocarcinomas and established cell lines. These observations, based on immunoreactivity of total Rb rather than hypophosphorylated protein, do not address the relationship between functional Rb and indicators of an aggressive transformed cellular phenotype. We hypothesized that the distribution of functional Rb and the kinetics of Rb phosphorylation would differ between cell lines representing immortalized mammary epithelium (MCF10A), differentiated nommetastatic mammary adenocarcinoma (MCF-7), and poorly differentiated, highly metastatic mammary adenocarcinoma (MDA-MB-231) and that these differences would be informative of the cellular phenotype. Direct immunofluorescence microscopy was used to compare qualitatively the subcellular localization of total and hypophosphorylated Rb protein in synchronized and asynchronous cells. This technique was also used to quantitatively assess the amounts of hypophosphorylated Rb throughout the cell cycle in these representative cell lines. Total Rb stained more prominently than hypophosphorylated Rb in the nucleus of all asynchronous cells. Rb phosphorylation was more rapid in MCF-7 cells than in MCF10A cells, whereas Rb dephosphorylation appeared deregulated in MDA-MB-231 cells. We conclude that assessment of hypophosphorylated Rb may be more useful than assessment of total Rb for the evaluation of transformed breast adenocarcinoma phenotypes.
Psychophysical Assessment of Spatial Spread of Excitation in Electrical Hearing with Single and Dual Electrode Contact Maskers

Objective: To evaluate psychophysically the spatial spread of excitation in electrical hearing with a new dual contact masker and to investigate under which conditions it is possible to stimulate fibers in the immediate neighborhood of an electrode contact, which were not excited by neighboring electrode contacts. Design: In this study a psychophysical forward masking paradigm with a dual contact masker was used to avoid off-site listening, the electrical analogue of off-frequency listening. The masker stimulus (300 msec) is presented nonsimultaneously on two electrode contacts, one on the apical side and another on the basal side of the probe contact, followed by a probe stimulus of 20 msec. Unmasked probe thresholds were compared with masked ones at a number of masker-probe distances, whereas growth of masking curves were measured for a fixed masker contact pair. Standard selectivity measurements (single contact masking) and the recovery of forward masking with one masker contact were included for comparison with existing methods. All experiments were carried out with six participants who use the Clarion CII device with a HiFocus I electrode array. Results: For dual contact masking the amount of masking was significantly greater than for single contact masking and the width of the masking patterns was on average 1.1 mm broader than for single contact masking, resulting in a broad region of excitation, with masker-probe overlap for distances greater than 3 mm. Masking widths for dual and single contact masking were highly correlated. Growth of masking curves were highly nonlinear. They showed a strong elevation of the slope that starts for most subjects around the middle of the dynamic range or above. For 4 out of 6 subjects, no probe threshold was found above a masker amplitude of about 400–500 &mgr;A. The ratio of the maximum measurable masked probe thresholds and unmasked probe threshold ranged from 1.7 to 2.6 (S4 excluded). Recovery of masking functions follow an exponential decay. Time constants &tgr; for the recovery process ranged from 21.6 msec to 114.9 msec. Conclusions: With a dual contact masker (1) off-site listening can be avoided, leading to larger estimates of the width of excitation patterns than in single contact masking, (2) it can be estimated for which stimulation level there is complete overlap of excitation patterns of adjacent electrode contacts, (3) it can be shown that stimulation of nerve fibers in the immediate neighborhood of an electrode contact which were not excited by neighboring electrode contacts is only possible if the probe stimulation amplitude is sufficiently high in comparison with amplitudes on neighboring contacts.
Characterization of a glycine N‐methyltransferase gene knockout mouse model for hepatocellular carcinoma: Implications of the gender disparity in liver cancer susceptibility

Hepatocellular carcinoma (HCC) is the fifth common cancer in the world and it mainly occurs in men. Glycine N‐methyltransferase (GNMT) participates in one‐carbon metabolism and affects DNA methylation by regulating the ratio of S‐adenosylmethionine to S‐adenosylhomocystine. Previously, we described that the expression of GNMT was diminished in human HCC. Here, we showed that 50% (3/6) male and 100% (7/7) female Gnmt−/− mice developed HCC, and their mean ages of HCC development were 17 and 16.5 months, respectively. In addition, 42.9% (3/7) of female Gnmt−/− mice had hemangioma. Wnt reporter assay demonstrated that Gnmt is a negative regulator for canonical Wnt signaling pathway. Beta‐catenin, cyclin D1 and c‐Myc, genes related to Wnt pathway, were upregulated in the liver tissues from both 11 weeks and HCC stage of Gnmt−/− mice. Furthermore, global DNA hypomethylation and aberrant expression of DNA methyltransferases 1 and 3b were found in the early and late stages of HCC development. Hierarchical cluster analysis of 6,023 transcripts from microarray data found that gene expression patterns of HCC tumors from male and female Gnmt−/− mice were distinctively different. Real‐time PCR confirmed that Gadd45a, Pak1, Mapk3 and Dsup3 genes of mitogen‐activated protein kinase (MAPK) pathway were activated in Gnmt−/− mice, especially in the female mice. Therefore, GNMT is a tumor suppressor gene for liver cancer, and it is associated with gender disparity in liver cancer susceptibility. © 2008 Wiley‐Liss, Inc.
Mice Expressing the Human CYP7A1 Gene in the Mouse CYP7A1 Knock-out Background Lack Induction of CYP7A1 Expression by Cholesterol Feeding and Have Increased Hypercholesterolemia When Fed a High Fat Diet*

Cholesterol 7α-hydroxylase (CYP7A1) catalyzes the rate-limiting step in the pathway responsible for the formation of the majority of bile acids. Transcription of the gene is regulated by the size of the bile acid pool and dietary and hormonal factors. The farnesoid X receptor and the liver X receptor (LXR) are responsible for regulation by bile acids and cholesterol, respectively. To study the effects of dietary cholesterol and fat upon expression of the human CYP7A1 gene, mice were generated by crossing transgenic mice carrying the humanCYP7A1 gene with mice that were homozygous knock-outs (CYP7A1−/−). The mice (mCYP7A1−/−/hCYP7A1) expressed the human gene at much higher levels than did the transgenics bred in the wild-type background. A diet containing 1% cholic acid reduced the expression of the human gene in mCYP7A1−/−/hCYP7A1 mice to undetectable levels. Cholestyramine (5%) increased the level of expression of the human gene and the mouse gene. Thus, farnesoid X receptor-mediated regulation was preserved. A diet containing 2% cholesterol increased expression of the mouse gene in wild-type mice, but it did not affect expression of the human gene in mCYP7A1−/−/hCYP7A1 mice. None of the diets altered the serum cholesterol or triglyceride levels in these mice; 1% cholic acid caused a redistribution of cholesterol from the high density lipoprotein to the low density lipoprotein density in the humanized mice but not in wild-type mice. A diet containing 30% saturated fat and 2% cholesterol caused a decrease in CYP7A1 levels in mCYP7A1−/−/hCYP7A1 mice. The serum cholesterol levels rose in all mice fed this diet. The increase was greater in the mCYP7A1−/−/hCYP7A1 mice. Together, these data suggest that the lack of an LXR element in the region from −56 to −49 of the human CYP7A1 promoter may account for some of the differences in response to diets between humans and rodents.
A novel cGMP‐regulated K+ channel in immortalized human kidney epithelial cells (IHKE‐1)

1 K+ channels from the apical membrane of immortalized human kidney epithelial (IHKE‐1) cells were investigated in the cell‐attached membrane configuration as well as in excised membranes using the patch clamp technique. 2 In cell‐attached membrane patches the open probability (Po) of the K+ channel was 0.42 ± 0.06 (mean ± s.e.m., n= 22) and its conductance was 94 ± 5 pS with 145 mM K+ in the pipette (n= 25). In excised membrane patches the Po of the channel was 0.55 ± 0.03 (n= 86) and its conductance was 65 ± 2 pS (n= 68) with 145 mM K+ on one side of the membrane and 3.6 mM K+ on the other. The I‐V curve of the K+ channel was not rectifying. 3 The channel was inhibited by several blockers of K+ channels such as 1 mM Ba2+ (cell‐attached membrane: 78 ± 8 %, n= 9; excised: 80 ± 4 %, n= 26), 10 mM TEA+ (excised inside‐out: 48 ± 5 %, n= 34; excised outside‐out: 100 ± 0 %, n= 26), 0.1 mM verapamil (excised: 73 ± 9 %, n= 12), and 10 nM charybdotoxin (excised outside‐out: 67 ± 9 %, n= 9). 4 The K+ channel was activated by depolarization and rising cytosolic Ca2+. Half‐maximal activity occurred at a cytosolic Ca2+ concentration of 200 nM. In the cell‐attached membrane configuration the K+ channel was inhibited in a concentration‐dependent manner by atrial natriuretic peptide (ANP). Powas blocked equally well by 10 nM ANP (52 ± 7 %, n= 10), brain natriuretic peptide (BNP; 37 ± 11 %, n= 6) and C‐type natriuretic peptide (CNP; 44 ± 13 %, n= 8). 8‐Bromoguanosine 3′,5′ cyclic monophosphate (8‐Br‐cGMP, 0.1 mM) also inhibited Poof this K+ channel, by 70 ± 10 % (n= 5). 5 In excised membrane patches cGMP inhibited Po of this K+ channel in a concentration‐dependent manner. The first significant effects were measured at a concentration of 1 μm (22 ± 7 %, n= 6), and greatest effects were obtained at 0.1 mM (34 ± 5 %, n= 15). cAMP (0.1 mM, n= 5) as well as GTP (0.1 mM, n= 5) had no significant effects on Po of this K+ channel. ATP (0.1 mM) had a weak inhibitory effect (17 ± 5 %, n= 14). Addition of Mg‐ATP to cGMP did not increase the inhibitory effect (30 ± 4 %, n= 14). KT5823 (1 μm), a specific inhibitor of cGMP‐dependent protein kinases, did not significantly alter the cGMP‐induced reduction in Po of the K+ channel in three excised membrane patches. 6 The results present the first electrophysiological characterization of a mammalian K+ channel that is directly regulated by cGMP.
Prognostic significance of acute renal injury in acute tumor lysis syndrome

Acute tumor lysis syndrome (ATLS) caused by the destruction of malignant cells leads to metabolic abnormalities, which may either remain isolated (biological ATLS) or subsequently lead to renal dysfunction (clinical ATLS). We compared hospital and 6-month survival in patients with ATLS with hematological malignancies with or without acute renal injury. Sixty-three patients (median age, 50 years; range, 32–64) were included with ATLS. Twenty-eight had no ARI (including 17 (61%) who subsequently required dialysis) whereas 35 had an ATLS-related ARI (including 31 (89%) who required dialysis). Acute leukemia (n = 28) and lymphoma (n = 30) were the main malignancies. All patients had high tumor burdens. Hospital and 6-month mortality rates were significantly lower in patients without ARI (7% and 21%, respectively) than in the ATLS-related renal injury group (51% and 66%). After adjustment for acute disease severity, presence of ARI at ICU admission was associated with higher hospital mortality (odds ratio, 10.41; 95% confidence interval, 2.01–19.170; p = 0.005) and 6-month mortality (odds ratio, 5.61; 95% confidence interval, 1.64–54.66; p = 0.006), compared to patients without renal injury. Our study suggests that in patients with ATLS, ICU management when acute renal injury is present is associated with higher short- and long-term mortality.
Identification and Mode of Inheritance of Quantitative Trait Loci for Secondary Metabolite Abundance in Tomato[OPEN]

Metabolite QTL for secondary metabolism in a Solanum pennelli introgression line population show different modes of inheritance and network properties linking the traits. A large-scale metabolic quantitative trait loci (mQTL) analysis was performed on the well-characterized Solanum pennellii introgression lines to investigate the genomic regions associated with secondary metabolism in tomato fruit pericarp. In total, 679 mQTLs were detected across the 76 introgression lines. Heritability analyses revealed that mQTLs of secondary metabolism were less affected by environment than mQTLs of primary metabolism. Network analysis allowed us to assess the interconnectivity of primary and secondary metabolism as well as to compare and contrast their respective associations with morphological traits. Additionally, we applied a recently established real-time quantitative PCR platform to gain insight into transcriptional control mechanisms of a subset of the mQTLs, including those for hydroxycinnamates, acyl-sugar, naringenin chalcone, and a range of glycoalkaloids. Intriguingly, many of these compounds displayed a dominant-negative mode of inheritance, which is contrary to the conventional wisdom that secondary metabolite contents decreased on domestication. We additionally performed an exemplary evaluation of two candidate genes for glycolalkaloid mQTLs via the use of virus-induced gene silencing. The combined data of this study were compared with previous results on primary metabolism obtained from the same material and to other studies of natural variance of secondary metabolism.
Effect of Educational Kinesiology upon Simple Response Times and Choice Response Times

The purpose of this study was to determine whether Educational Kinesiology® integration movements or repatterning in conjunction with the integration movements affect the response times of college students to a visual stimulus. Ten men and ten women were randomly assigned to each of the three conditions: control, Edu-K movement, or repatterned Edu-K movements. Each subject was pretested on simple and choice response-time tasks. Following the pretest, subjects in the control group sat quietly for 10 minutes. The movement group utilized seven Brain Gym® activities. Subjects in the repatterned group experienced Dennison's Laterality Repatterning prior to doing the same Brain Gym activities. All subjects were then retested to assess changes in performance using 30 trials of each task. Statistical analyses indicated significant differences in improvement between the groups on the 4-choice task, with the repatterned group showing greater change than the Edu-K movement-only group, who in turn showed greater improvement than the control group. The groups improved by 6%, 31/2%, and 1%, respectively. No group differences were significant on the simple task, although a similar trend was indicated. Men responded faster than women on both tasks; however, the amount of improvement was similar for both.
Protein dynamics-induced variation of excitation energy transfer pathways

Strong anticorrelation between the fluorescence emission of different emitters is observed by employing single-molecule fluorescence spectroscopy on photosystem I at cryogenic temperatures. This anticorrelation demonstrates a time-dependent interaction between pigments participating in the exciton transfer chain, implying that uniquely defined energy transfer pathways within the complex do not exist. Fluctuations of the chromophores themselves or their immediate protein surroundings induce changes in their site energy, and, as a consequence, these fluctuations change the coupling within the excitation transfer pathways. The time scales of the site energy fluctuations of the individual emitters do not meet the time scales of the observed correlated emission behavior. Therefore, the emitters must be fed individually by energetically higher lying states, causing the observed intensity variations. This phenomenon is shown for photosystem I pigment–protein complexes from 2 different cyanobacteria (Thermosynechococcus elongatus and Synechocystis sp. PCC 6803) with strongly different spectral properties underlining the general character of the findings. The variability of energy transfer pathways might play a key role in the extreme robustness of light-harvesting systems in general.
Optimal Configuration of Fractional Frequency Reuse System for LTE Cellular Networks

In interference-limited OFDMA systems, fractional frequency reuse (FFR) algorithms can be used to combine the superior performance offerings of a universal reuse plan near cell center and a higher reuse plan near cell edge. A proper configuration of FFR requires knowledge of throughput statistics at all locations in the cell coverage area. This paper introduces an analytical optimization technique to configure a FFR solution for the downlink of LTE cellular system based on a throughput model developed herein. The optimal configuration is based on maximizing the average sector throughput subject to a minimum cell-edge performance and other performance constraints related to the standard reuse plans.
Differential tissue growth and patterns of cell death in mouse limb autopod morphogenesis

Programmed cell death (PCD) is considered one of the most important cellular processes in the morphogenesis of organs and tissues during animal development. Although the embryonic limb has been established as a classic model for the study of PCD, detailed studies on this process' contribution to morphogenesis are still lacking. In the present work, using modern computer‐aided techniques, we estimated the contribution of PCD to mouse limb morphogenesis. For the detection of apoptotic cell death, we stained whole embryonic limbs with acridine orange or, in some instances, used the TUNEL technique, and visualized the tissues by confocal laser scanning microscopy. We found that cell death patterns are dynamic during limb development, and occur in gradients oriented with the main limb axes, anteroposterior, dorsoventral and distoproximal. Interdigital apoptosis in the autopod was initially detected at the most distal region, and then more proximally as development proceeded. Interestingly, we found that digit separation is more pronounced on the dorsal side, contrary to what is expected from the apoptotic cell distribution, which shows more abundant cell death in the ventral region. Using 2‐D and 3‐D models, we found that most digit individualization occurs rather by digit growth than by interdigital cell death. Therefore, digits do not mainly individualize by degeneration of preformed interdigital tissue, but probably by a dynamic balance between proliferation and cell death, reducing interdigital growth, which results in protrusion of digits. We determined the expression pattern of fgf‐8 during the period of digit individualization, as the product of this gene could participate in defining the limb growth pattern. Initially, fgf‐8 expression was coincident with the apical ectodermal ridge, but when cell death was first detected in the interdigits, fgf‐8 expression became restricted to the tip of the growing digits. Therefore, FGF‐8 could be one of the factors responsible for differential digit‐interdigit growth, and might also act as a survival factor on interdigital tissue. We also found that the expression patterns of rar‐β, bmp‐2, bmp‐4, bmp‐7, msx‐1, and msx‐2 genes, proposed to be involved in the activation of interdigital cell death, did not overlap with, or were not highly expressed in the major zones of cell death in the developing limb. © 2001 Wiley‐Liss, Inc.
“Action and Reaction” – the Impact of European Youth Mobility on the Economy and the Labour Market

Within the framework of the international MOVE project, we are carrying out quantitative data analysis for the countries of the European Union / EFTA to reveal the labour market and economic effects of youth mobility. Following the Introduction, the theoretical framework of youth mobility is described including the centre – periphery model in the analysis of youth mobility, the brain-drain effect involved in youth mobility and the theories dealing with the effect of youth mobility on both labour market and economic growth. Then, two models describing the effects of incoming youth mobility on youth unemployment and prosperity are elaborated upon, in which economic, social and state indicators are also taken into consideration. In the third section, panel OLS regression analysis is used for modelling. 30 European countries are covered with data for ten years (2004-2013). The analyses are carried out for three groups of countries separately: centre-receiving countries, periphery-sending countries and all the EU / EFTA countries included. In the analysis, other economic, social and state indicators that may influence youth unemployment rate and per capita GDP of the receiving countries (such as minimum wages, FDI outward, adult education level or urban population) are controlled for. Our hypotheses include that the increase of incoming youth mobility has a beneficial effect on the labour market and on economic growth, i.e. it decreases youth unemployment and increases per capita GDP in the receiving countries in all the three cases. The next section, “Results of the analysis” reveals that in all the examined country groups, incoming youth mobility decreases youth unemployment rate and promotes economic growth in the receiving countries. Therefore, both of our hypotheses have been failed to be rejected. The Summary section provides the main consequences and conclusions of the analysis. Our results can contribute to the elaboration of the Human Resource Strategy of the European Union. It has become obvious that the benefits in both the sending and receiving countries can be increased by promoting youth mobility. The former model including two actors (the migrant and the receiving country) has been extended with the sending country, the organizing institution and multinational and domestic companies. From all actors, flexibility is necessary in migration issues to ensure the free movement of potential labour force.
Effect of latent myofascial trigger points on strength measurements of the upper trapezius: a case-controlled trial.

PURPOSE The purpose of this article was to determine whether strength is altered in the upper trapezius in the presence of latent myofascial trigger points (MTrP). METHODS This study was case controlled and used convenience sampling. The sample recruited was homogeneous with respect to age, sex, height, and body mass. Participants were assessed for the presence of latent MTrP in the upper trapezius and placed into two groups: an experimental group that had latent MTrP in the upper trapezius and a control group that did not. Eighteen women (mean age 21.4 y, SD 1.89; mean height 156.9 cm, SD 4.03; and mean body mass 51.7 kg, SD 5.84) made up the experimental group, and 19 women (mean age 20.3 y, SD 1.86; mean height 158.6 cm, SD 3.14; and mean body mass 53.2 kg, SD 5.17) made up the control group. We obtained strength measurements of the non-dominant arm using a handheld dynamometer and compared them between the two groups. RESULTS The difference in the strength measurements between the two groups was not statistically significant (p=0.59). CONCLUSIONS The presence of latent MTrPs may not affect the strength of the upper trapezius.