Search

The current series of studies are the first to examine brain responses to social aggression signals as a function of male and female sexual orientation. For the first set of studies (1a, 1b), axillary sweat had been collected from 17 heterosexual men and 17 heterosexual women aggressively responding to frustrating opponents (aggression condition) and while playing a construction game (control condition). Sweat samples were pooled according to sex and condition, and presented via a constant flow olfactometer to 17 gay and 23 heterosexual men (Study 1a), and 19 lesbian and 25 heterosexual women (Study 1b). Ongoing EEG was recorded from 61 scalp locations, chemosensory event-related potentials (CSERPs; P2, P3-1, P3-2) were analyzed, and neuronal sources calculated (low resolution electromagnetic tomography). Within the second set of studies (2a, 2b), pictures of males' and females' weak angry and neutral facial expressions were presented to 21 gay and 23 heterosexual men (Study 2a), and 19 lesbian and 26 heterosexual women (Study 2b), and ERPs (N170, P3) were analyzed. Gay men showed larger P3-1 amplitudes than heterosexual men upon presentation of male aggression sweat, accompanied by activation of the right inferior frontal gyrus (IFG, BA 10). Gay men also displayed longer N170 latencies in response to men's compared to women's angry facial expressions, while heterosexual men did not. In women, sexual orientation did not affect the processing of aggression sweat or anger expressions. Gay men showed preferential processing of chemosensory aggression signals (P3-1 amplitudes), indicating fine-tuned socioemotional sensitivity, related to activation of brain areas involved in emotion regulation (IFG). They further process the relative relevance of visual aggression signals (N170 latency). These results were in line with theories proposing a common evolutionary pathway for same-sex attraction and traits easing social integration. [ABSTRACT FROM AUTHOR]

Abstract Activation of AMPK has been associated with pro‐atrophic signaling in muscle. However, AMPK also has anti‐inflammatory effects, suggesting that in cachexia, a syndrome of inflammatory‐driven muscle wasting, AMPK activation could be beneficial. Here we show that the AMPK agonist AICAR suppresses IFNγ/TNFα‐induced atrophy, while the mitochondrial inhibitor metformin does not. IFNγ/TNFα impair mitochondrial oxidative respiration in myotubes and promote a metabolic shift to aerobic glycolysis, similarly to metformin. In contrast, AICAR partially restored metabolic function. The effects of AICAR were prevented by the AMPK inhibitor Compound C and were reproduced with A‐769662, a specific AMPK activator. AICAR and A‐769662 co‐treatment was found to be synergistic, suggesting that the anti‐cachectic effects of these drugs are mediated through AMPK activation. AICAR spared muscle mass in mouse models of cancer and LPS induced atrophy. Together, our findings suggest a dual function for AMPK during inflammation‐driven atrophy, wherein it can play a protective role when activated exogenously early in disease progression, but may contribute to anabolic suppression and atrophy when activated later through mitochondrial dysfunction and subsequent metabolic stress.

Non-alcoholic fatty liver disease (NAFLD) is the most frequent liver disease worldwide and can progress to non-alcoholic steatohepatitis (NASH), which is characterized by triglyceride accumulation, inflammation, and fibrosis. No pharmacological agents are currently approved to treat these conditions, but it is clear now that modulation of lipid synthesis and autophagy are key biological mechanisms that could help reduce or prevent these liver diseases. The folliculin (FLCN) protein has been recently identified as a central regulatory node governing whole body energy homeostasis, and we hypothesized that FLCN regulates highly metabolic tissues like the liver. We thus generated a liver specific Flcn knockout mouse model to study its role in liver disease progression. Using the methionine- and choline-deficient diet to mimic liver fibrosis, we demonstrate that loss of Flcn reduced triglyceride accumulation, fibrosis, and inflammation in mice. In this aggressive liver disease setting, loss of Flcn led to activation of transcription factors TFEB and TFE3 to promote autophagy, promoting the degradation of intracellular lipid stores, ultimately resulting in reduced hepatocellular damage and inflammation. Hence, the activity of FLCN could be a promising target for small molecule drugs to treat liver fibrosis by specifically activating autophagy. Collectively, these results show an unexpected role for Flcn in fatty liver disease progression and highlight new potential treatment strategies. [ABSTRACT FROM AUTHOR]

Polymer coatings on cellulosic fibres are widely used to enhance the natural fibre properties by improving, for example, the hydrophobicity and wet strength. Here, we investigate the effects of a terpolymer P(S-co-MABP-co-PyMA) coating on cotton linters and eucalyptus fibres to improve the resistance of cellulose fibres against wetness. Coated and uncoated fibres were characterised by using scanning electron microscopy, contact angle measurements, Raman spectroscopy and atomic force microscopy with the objective of correlating macroscopic properties such as the hydrophobicity of the fleece with microscopic properties such as the coating distribution and local nanomechanics. The scanning electron and fluorescence microscopy results revealed the distribution of the coating on the paper fleeces and fibres. Contact angle measurements proved the hydrophobic character of the coated fleece, which was also confirmed by Raman spectroscopy measurements that investigated the water uptake in single fibres. The water uptake also induced a change in the local mechanical properties, as measured by atomic force microscopy. These results verify the basic functionality of the hydrophobic coating on fibres and paper fleeces but call into question the homogeneity of the coating. [ABSTRACT FROM AUTHOR]

Sex-typed play behavior shows large sex differences and seems to be affected by prenatal sex hormones. For example, a smaller, more male-typical ratio between the second and fourth digit length (2D:4D), a proposed marker for prenatal testosterone exposure, has been shown to be related to sex-typed play preference in childhood. Nevertheless, it is still being debated whether 2D:4D displays a stable sex difference throughout childhood, as there are few longitudinal studies. In the present study, children's 2D:4D was measured on both hands on four occasions from early infancy to early childhood (T1: 5 months, T2: 9 months, T3: 20 months, and T4: 40 months) providing the rare possibility to test the temporal stability of the sex difference. Parents completed the Preschool Activities Inventory at T4 and reported on the number of older brothers and sisters as a measure for socialization influences. Parents described boys as playing more masculine and less feminine than girls. Boys had smaller 2D:4D than girls at all measurements (T1–T4) and on both hands (right/left). Nevertheless, 2D:4D increased significantly from T3 to T4 in both sexes. Girls, but not boys, who were described as playing more masculine and less feminine had more masculine 2D:4D ratios at T1–T4 on both hands (except for right 2D:4D at T2 and T3) and had more older brothers and fewer older sisters. These data underline the stability of the sex difference in 2D:4D and show the importance of both biological and social influences on sex-typed play behavior. [ABSTRACT FROM AUTHOR]

Self-reported empathy differs with gender and sexual orientation. The current study investigated whether mu-suppression, reflecting brain activity especially related to state empathy, also is modulated by gender and sexual orientation. Pictures of painful and non-painful actions were presented to 20 lesbians, 20 gay men, 20 heterosexual men and 20 heterosexual women, while EEG was recorded. Individual peak frequencies of mu-activity (electrodes C3, C4) were detected within the 6-11 Hz band for each participant, and mu-suppression indices were calculated. Further, verbal indicators of state empathy (pain ratings) and compassion were assessed. Only heterosexual individuals showed the typical pattern of enhanced mu-suppression in response to painful relative to non-painful pictures. Lesbian women and gay men did not show a differential mu-response. Moreover, they felt less compassion compared to heterosexual individuals. In line with this finding, the more compassion the participants reported, the stronger the mu-suppression in response to painful relative to non-painful pictures was. Pain ratings did not vary with sexual orientation. The lesser compassion reported by lesbian women and gay men is discussed as a mediator of their non-differential mu-suppression response. It is hypothesized that this pattern might relate to gay men and lesbian women tending to perceive the anonymous depicted actors as outgroup members, hence showing less compassion and reduced mu-suppression. As empathy is often related to negative feelings (empathic stress), a clear distinction between individuals to empathize with versus individuals not to emphasize with may well be an adaptive feature in same-sex oriented individuals. [ABSTRACT FROM AUTHOR]

Mosaic somatic mutations in the isocitrate dehydrogenase 1/2 (IDH1/2) genes have been identified in most enchondromas by targeted mutation analysis. Next-generation sequencing (NGS), that may detect even low-level mosaic mutation rates, has not previously been applied to enchondromas. Immunohistochemistry using the H09 clone is routinely used as a surrogate for the common R132H IDH1 mutation in gliomas. We compared immunohistochemistry and NGS results in a series of 13 enchondromas from 8 pediatric patients. NGS identified a heterozygous IDH mutation in all enchondromas, showing identical mutation status in patients with multiple tumors assessed, thereby confirming somatic mosaicism. A majority of the tumors harbored an IDH1 mutation (p.R132H in 3 tumors; p.R132C in 4 tumors from 2 patients; p.R132L and p.R132G in one tumor each). A p.R172S IDH2 mutation was identified in 4 enchondromas, but not in the ependymoma from one patient with Ollier disease, who further displayed a heterozygous STK11 missense mutation. IDH mutation rates varied between 14% (indicative of mutations in 28% of the cells and of intratumoral mosaicism) and 45% (tumor content was close to 100%). Cytoplasmic H09 reactivity was observed as expected in tumors with an IDH1 p.R132H mutation; cross-reactivity was seen with the p.R132L variant. This first NGS study of pediatric enchondromas confirms that IDH mutations may occur in a mosaic fashion. STK11 gene mutations may provide insights in the development of multiple cartilaginous tumors in enchondromatosis, this tumor suppressor gene having been shown in animal models to regulate both chondrocyte maturation and growth plate organization during development. [ABSTRACT FROM AUTHOR]

Copyright of Der Ophthalmologe is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

The small single-stranded DNA (ssDNA) bacteriophages of the subfamily Gokushovirinae were traditionally perceived as narrowly targeted, niche-specific viruses infecting obligate parasitic bacteria, such as Chlamydia. The advent of metagenomics revealed gokushoviruses to be widespread in global environmental samples. This study expands knowledge of gokushovirus diversity in the environment by developing a degenerate PCR assay to amplify a portion of the major capsid protein (MCP) gene of gokushoviruses. Over 500 amplicons were sequenced from 10 environmental samples (sediments, sewage, seawater and freshwater), revealing the ubiquity and high diversity of this understudied phage group. Residue-level conservation data generated from multiple alignments was combined with a predicted 3D structure, revealing a tendency for structurally internal residues to be more highly conserved than surface-presenting protein-protein or viral-host interaction domains. Aggregating this data set into a phylogenetic framework, many gokushovirus MCP clades contained samples from multiple environments, although distinct clades dominated the different samples. Antarctic sediment samples contained the most diverse gokushovirus communities, whereas freshwater springs from Florida were the least diverse. Whether the observed diversity is being driven by environmental factors or host-binding interactions remains an open question. The high environmental diversity of this previously overlooked ssDNA viral group necessitates further research elucidating their natural hosts and exploring their ecological roles. [ABSTRACT FROM AUTHOR]

The assessment and quantification of spatio-temporal soil characteristics and moisture patterns are important parameters in the monitoring and modeling of soil landscapes. Remote-sensing techniques can be applied to characterize and quantify soil moisture patterns, but only when dealing with bare soil. For soils with vegetation, it is only possible to quantify soil-moisture characteristics through indirect vegetation indicators, i.e. the 'vitality' of plants. The 'vitality' of vegetation is a sum of many indicators, whereby different stress factors can induce similar changes to the biochemical and physiological characteristics of plants. Analysis of the cause and effect of soil-moisture properties, patterns and stress factors can therefore only be carried out using an experimental approach that specifically separates the causes. The study describes an experimental approach and the results from using an imaging hyperspectral sensor AISA-EAGLE (400-970 nm) and a non-imaging spectral sensor ASD (400-2,500 nm) under controlled and comparable conditions in a laboratory to study the spectral response compared to biochemical and biophysical vegetation parameters ('vitality') as a function of soil moisture characteristics over the entire blooming period of Ash trees. At the same time that measurements were taken from the hyperspectral sensors, the following vegetation variables were also recorded: leaf area index (LAI), chlorophyll meter value - SPAD-205, vegetation height, C/N content and leaf water content as indicators of the 'vitality' and the state of the vegetation. The spectrum of each hyperspectral image was used to calculate a range of vegetation indices (VI's) with relationships for soil moisture characteristics and stress factors. The relationship between vegetation indices and plant 'vitality' indicators was analysed using a Generalized Additive Model (GAM). The results show that leaf water content is the most appropriate vegetation indicator for assessing the 'vitality' of vegetation. With the Water Index (WI) it was possible to differentiate between the moisture treatments of the control, moisture drought stress and the moisture flooding treatment over the entire growing season of the plants ( R = 0.94). There is a correlation between the 'vitality' vegetation parameters (LAI, C/N content and vegetation height) and the indicators NDVI, WI, PRI and Vog2. In our study with Ash trees the vegetation parameter chlorophyll was found not to be a suitable indicator for detecting the 'vitality' of plants using the spectral indicators. There is a possibility that the sensitivity of the indicators selected was too low compared to changes in the chlorophyll content of Ash trees. Adding the co-variable 'time' strengthens the correlation, whereas incorporating time and moisture treatment only improves the model very slightly. This shows that changes to the biochemical and biophysical characteristics caused by phenology, overlay a differentiation of the moisture treatments. [ABSTRACT FROM AUTHOR]

In numerous studies, spatial and spectral aggregations of pixel information using average values from imaging spectrometer data are suggested to derive spectral indices and the subsequent vegetation parameters that are derived from these. Currently, there are very few empirical studies that use hyperspectral data, to support the hypothesis for deriving land surface variables from different spectral and spatial scales. In the study at hand, for the first time ever, investigations were carried out on fundamental scaling issues using specific experimental test flights with a hyperspectral sensor to investigate how vegetation patterns change as an effect of (1) different spatial resolutions, (2) different spectral resolutions, (3) different spatial and spectral resolutions as well as (4) different spatial and spectral resolutions of originally recorded hyperspectral image data compared to spatial and spectral up- and downscaled image data. For these experiments, the hyperspectral sensor AISA-EAGLE/HAWK (DUAL) was mounted on an aircraft to collect spectral signatures over a very short time sequence of a particular day. In the first experiment, reflectance measurements were collected at three different spatial resolutions ranging from 1 to 3 m over a 2-h period in 1 day. In the second experiment, different spectral image data and different additional spatial data were collected over a 1-h period on a particular day from the same test area. The differently recorded hyperspectral data were then spatially and spectrally rescaled to synthesize different up- and down-rescaled images. The normalised difference vegetation index (NDVI) was determined from all image data. The NDVI heterogeneity of all images was compared based on methods of variography. The results showed that (a) the spatial NDVI patterns of up- and downscaled data do not correspond with the un-scaled image data, (b) only small differences were found between NDVI patterns determined from data recorded and resampled at different spectral resolutions and (c) the overall conclusion from the tests carried out is that the spatial resolution is more important in determining heterogeneity by means of NDVI than the depth of the spectral data. The implications behind these findings are that we need to exercise caution when interpreting and combining spatial structures and spectral indices derived from satellite images with differently recorded geometric resolutions. [ABSTRACT FROM AUTHOR]

The cellular function of folliculin (FLCN) is a mystery that still needs to be solved. It is known that mutation of FLCN can predispose Birt-Hogg-Dubé (BHD) patient's to renal cell carcinoma , renal and lung cysts, as well as skin fibrofolliculomas. FLCN has been classed as a tumour suppressor, but it is probable that cystic and the skin manifestations do not occur as a consequence of FLCN loss of heterozygosity. Discovery that FLCN is a direct substrate of AMP dependent protein kinase (AMPK) placed FLCN on the cell signalling map, downstream of AMPK. This breakthrough suggested that FLCN might be involved in cell energy homeostasis. Over these more recent years, BHD research has become much more complicated and interesting from a cell signalling perspective. Folliculin has been linked to numerous cell pathways that are known to cause cancer, involving cell growth, metabolism, cell adhesion, cell motility, cytokinesis, and cell survival. The collective evidence implies that FLCN may have a broader housekeeping role in the cell. Of particular importance, FLCN was recently been reported to have guanine exchange factor activity towards the small G protein Rab35 and implicates FLCN in vesicular trafficking and/or membrane sorting. This newer discovery will undoubtedly help in the continued challenge of solving the signalling puzzle that shrouds FLCN function. [ABSTRACT FROM AUTHOR]

Sustainable water quality management requires a profound understanding of water fluxes (precipitation, run-off, recharge, etc.) and solute turnover such as retention, reaction, transformation, etc. at the catchment or landscape scale. The Water and Earth System Science competence cluster (WESS, ) aims at a holistic analysis of the water cycle coupled to reactive solute transport, including soil-plant-atmosphere and groundwater-surface water interactions. To facilitate exploring the impact of land-use and climate changes on water cycling and water quality, special emphasis is placed on feedbacks between the atmosphere, the land surface, and the subsurface. A major challenge lies in bridging the scales in monitoring and modeling of surface/subsurface versus atmospheric processes. The field work follows the approach of contrasting catchments, i.e. neighboring watersheds with different land use or similar watersheds with different climate. This paper introduces the featured catchments and explains methodologies of WESS by selected examples. [ABSTRACT FROM AUTHOR]

Remote sensing is an important tool for studying patterns in surface processes on different spatiotemporal scales. However, differences in the spatiospectral and temporal resolution of remote sensing data as well as sensor-specific surveying characteristics very often hinder comparative analyses and effective up- and downscaling analyses. This paper presents a new methodical framework for combining hyperspectral remote sensing data on different spatial and temporal scales. We demonstrate the potential of using the 'One Sensor at Different Scales' (OSADIS) approach for the laboratory (plot), field (local), and landscape (regional) scales. By implementing the OSADIS approach, we are able (1) to develop suitable stress-controlled vegetation indices for selected variables such as the Leaf Area Index (LAI), chlorophyll, photosynthesis, water content, nutrient content, etc. over a whole vegetation period. Focused laboratory monitoring can help to document additive and counteractive factors and processes of the vegetation and to correctly interpret their spectral response; (2) to transfer the models obtained to the landscape level; (3) to record imaging hyperspectral information on different spatial scales, achieving a true comparison of the structure and process results; (4) to minimize existing errors from geometrical, spectral, and temporal effects due to sensor- and time-specific differences; and (5) to carry out a realistic top- and downscaling by determining scale-dependent correction factors and transfer functions. The first results of OSADIS experiments are provided by controlled whole vegetation experiments on barley under water stress on the plot scale to model LAI using the vegetation indices Normalized Difference Vegetation Index (NDVI) and green NDVI (GNDVI). The regression model ascertained from imaging hyperspectral AISA-EAGLE/HAWK (DUAL) data was used to model LAI. This was done by using the vegetation index GNDVI with an R of 0.83, which was transferred to airborne hyperspectral data on the local and regional scales. For this purpose, hyperspectral imagery was collected at three altitudes over a land cover gradient of 25 km within a timeframe of a few minutes, yielding a spatial resolution from 1 to 3 m. For all recorded spatial scales, both the LAI and the NDVI were determined. The spatial properties of LAI and NDVI of all recorded hyperspectral images were compared using semivariance metrics derived from the variogram. The first results show spatial differences in the heterogeneity of LAI and NDVI from 1 to 3 m with the recorded hyperspectral data. That means that differently recorded data on different scales might not sufficiently maintain the spatial properties of high spatial resolution hyperspectral images. [ABSTRACT FROM AUTHOR]

The role of busulfan (Bu) metabolites in the adverse events seen during hematopoietic stem cell transplantation and in drug interactions is not explored. Lack of availability of established analytical methods limits our understanding in this area. The present work describes a novel gas chromatography-tandem mass spectrometric assay for the analysis of sulfolane (Su) in plasma of patients receiving high-dose Bu. Su and Bu were extracted from a single 100 μL plasma sample by liquid-liquid extraction. Bu was separately derivatized with 2,3,5,6-tetrafluorothiophenolfluorinated agent. Mass spectrometric detection of the analytes was performed in the selected reaction monitoring mode on a triple quadrupole instrument after electronic impact ionization. Bu and Su were analyzed with separate chromatographic programs, lasting 5 min each. The assay for Su was found to be linear in the concentration range of 20-400 ng/mL. The method has satisfactory sensitivity (lower limit of quantification, 20 ng/mL) and precision (relative standard deviation less than 15 %) for all the concentrations tested with a good trueness (100 ± 5 %). This method was applied to measure Su from pediatric patients with samples collected 4 h after dose 1 ( n = 46), before dose 7 ( n = 56), and after dose 9 ( n = 54) infusions of Bu. Su (mean ± SD) was detectable in plasma of patients 4 h after dose 1, and higher levels were observed after dose 9 (249.9 ± 123.4 ng/mL). This method may be used in clinical studies investigating the role of Su on adverse events and drug interactions associated with Bu therapy. [Figure not available: see fulltext.] [ABSTRACT FROM AUTHOR]

Protein synthesis involves the translation of ribonucleic acid information into proteins, the building blocks of life. The initial step of protein synthesis is the binding of the eukaryotic translation initiation factor 4E (eIF4E) to the 7-methylguanosine (m7-GpppG) 5??cap of messenger RNAs. Low oxygen tension (hypoxia) represses cap-mediated translation by sequestering eIF4E through mammalian target of rapamycin (mTOR)-dependent mechanisms. Although the internal ribosome entry site is an alternative translation initiation mechanism, this pathway alone cannot account for the translational capacity of hypoxic cells. This raises a fundamental question in biology as to how proteins are synthesized in periods of oxygen scarcity and eIF4E inhibition. Here we describe an oxygen-regulated translation initiation complex that mediates selective cap-dependent protein synthesis. We show that hypoxia stimulates the formation of a complex that includes the oxygen-regulated hypoxia-inducible factor 2? (HIF-2?), the RNA-binding protein RBM4 and the cap-binding eIF4E2, an eIF4E homologue. Photoactivatable ribonucleoside-enhanced crosslinking and immunoprecipitation (PAR-CLIP) analysis identified an RNA hypoxia response element (rHRE) that recruits this complex to a wide array of mRNAs, including that encoding the epidermal growth factor receptor. Once assembled at the rHRE, the HIF-2?-RBM4-eIF4E2 complex captures the 5??cap and targets mRNAs to polysomes for active translation, thereby evading hypoxia-induced repression of protein synthesis. These findings demonstrate that cells have evolved a program by which oxygen tension switches the basic translation initiation machinery. [ABSTRACT FROM AUTHOR]

Brain development in mammals has been proposed to be promoted by successful adaptations to the social complexity as well as to the social and non-social chemical environment. Therefore, the communication via chemosensory signals might have been and might still be a phylogenetically ancient communication channel transmitting evolutionary significant information. In humans, the neuronal underpinnings of the processing of social chemosignals have been investigated in relation to kin recognition, mate choice, the reproductive state and emotional contagion. These studies reveal that human chemosignals are probably not processed within olfactory brain areas but through neuronal relays responsible for the processing of social information. It is concluded that the processing of human social chemosignals resembles the processing of social signals originating from other modalities, except that human social chemosignals are usually communicated without the allocation of attentional resources, that is below the threshold of consciousness. Deviances in the processing of human social chemosignals might be related to the development and maintenance of mental disorders. [ABSTRACT FROM AUTHOR]

The study aimed to investigate possible differences in lateralized olfactory processing in left- and right-handed subjects using a functional MRI paradigm. Twenty-four (14 female, 10 male) right-handers and 24 (14 female, 10 male) left-handers participated; their mean age was 24.0 years, all were in excellent health with no indication of any major nasal or other health problems. The rose-like odor phenyl ethyl alcohol and the smell of rotten eggs (HS) were used for relatively specific olfactory activation in a block design using a 1.5-T MR scanner. Results indicated no major differences in lateralized olfactory activation between left- and right-handers. This suggests that in simple olfactory tasks, handedness does not seem to play a substantial role in the processing of olfactory information. [ABSTRACT FROM AUTHOR]

Copyright of Der Nervenarzt is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

This study was to evaluate the treatment dosimetry, efficacy and toxicity of intensity modulated radiation therapy (IMRT) and fractionated stereotactic radiotherapy (FSRT) in the management of infratentorial ependymoma. Between 1999 and 2007, seven children (median age, 3.1 years) with infratentorial ependymoma were planned with either IMRT (3 patients) or SFRT (4 patients), the latter after conventional posterior fossa irradiation. Two children underwent gross total resection. Median prescribed dose was 59.4 Gy (range, 55.8-60). The median follow-up for surviving patients was 4.8 years (range, 1.3-8). IMRT (median dose, 59.4 Gy) and FSRT (median dose, 55.8 Gy) achieved similar optimal target coverage. Percentages of maximum doses delivered to the cochleae (59.5 vs 85.0% Gy; P = 0.05) were significantly inferior with IMRT, when compared to FSRT planning. Percentages of maximum doses administered to the pituitary gland (38.2 vs 20.1%; P = 0.05) and optic chiasm (38.1 vs 14.1%; P = 0.001) were, however, significantly higher with IMRT, when compared to FSRT planning. No recurrences were observed at the last follow-up. The estimated 3-year progression-free survival and overall survival were 87.5 and 100%, respectively. No grade >1 acute toxicity was observed. Two patients presented late adverse events (grade 2 hypoacousia) during follow-up, without cognitive impairment. IMRT or FSRT for infratentorial ependymomas is effective and associated with a tolerable toxicity level. Both treatment techniques were able to capitalize their intrinsic conformal ability to deliver high-dose radiation. Larger series of patients treated with these two modalities will be necessary to more fully evaluate these delivery techniques. [ABSTRACT FROM AUTHOR]

Under conditions of reduced tissue oxygenation, hypoxia-inducible factor (HIF) controls many processes, including angiogenesis and cellular metabolism, and also influences cell proliferation and survival decisions. HIF is centrally involved in tumour growth in inherited diseases that give rise to renal cell carcinoma (RCC), such as Von Hippel-Lindau syndrome and tuberous sclerosis complex. In this study, we examined whether HIF is involved in tumour formation of RCC in Birt-Hogg-Dubé syndrome. For this, we analysed a Birt-Hogg-Dubé patient-derived renal tumour cell line (UOK257) that is devoid of the Birt-Hogg-Dubé protein (BHD) and observed high levels of HIF activity. Knockdown of BHD expression also caused a threefold activation of HIF, which was not as a consequence of more HIF1α or HIF2α protein. Transcription of HIF target genes VEGF, BNIP3 and CCND1 was also increased. We found nuclear localization of HIF1α and increased expression of VEGF, BNIP3 and GLUT1 in a chromophobe carcinoma from a Birt-Hogg-Dubé patient. Our data also reveal that UOK257 cells have high lactate dehydrogenase, pyruvate kinase and 3-hydroxyacyl-CoA dehydrogenase activity. We observed increased expression of pyruvate dehydrogenase kinase 1 (a HIF gene target), which in turn leads to increased phosphorylation and inhibition of pyruvate dehydrogenase. Together with increased protein levels of GLUT1, our data reveal that UOK257 cells favour glycolytic rather than lipid metabolism (a cancer phenomenon termed the 'Warburg effect'). UOK257 cells also possessed a higher expression level of the L-lactate influx monocarboxylate transporter 1 and consequently utilized L-lactate as a metabolic fuel. As a result of their higher dependency on glycolysis, we were able to selectively inhibit the growth of these UOK257 cells by treatment with 2-deoxyglucose. This work suggests that targeting glycolytic metabolism may be used therapeutically to treat Birt-Hogg-Dubé-associated renal lesions. [ABSTRACT FROM AUTHOR]

Androstenone has often been discussed as a human social chemosignal, as it is one of the major contributing substances to the human body odor for which humans possess specific receptors. Here, we investigated whether male sexual orientation influences the perception of androstenone. Sensitivity to androstenone, subjective ratings of intensity, pleasantness, unpleasantness, and familiarity of the odor, as well as self-reported emotional responses (valence, arousal, dominance) to the odor were assessed in 13 homosexual and 14 heterosexual men. Isovaleric acid served as a control substance. Homosexual men displayed significantly higher olfactory sensitivity to the odor of androstenone than heterosexual men ( p < 0.05), but they did not differ from heterosexual men in their sensitivity to isovaleric acid ( p > 0.25). Moreover, both groups did not differ in their judgments of or in their emotional response to androstenone or isovaleric acid. The current results indicate that men's sexual orientation significantly impacts the perception of androstenone but that this effect does not necessarily extend to subjective judgments. [ABSTRACT FROM AUTHOR]

Copyright of Journal für Ästhetische Chirurgie is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Inactivation of the von Hippel–Lindau (VHL) tumor suppressor gene predisposes to vascular tumor formation in several organs. VHL regulates two evolutionary conserved pathways: the targeting of hydroxylated hypoxia-inducible factor-α (HIF-α) for proteasomal degradation and the remodeling of extracellular matrix (ECM). The biochemical mechanisms of the ECM assembly pathway remain poorly defined. Here, we provide evidence supporting a biochemical role for VHL in ECM assembly. We show that VHL directly binds to the collagen IV alpha 2 (COL4A2) chain and that this interaction is necessary for its assembly into the ECM. The VHL–COL4A2 interaction is dependent on endoplasmic reticulum (ER)-mediated COL4A2 hydroxylation and independent of cytosolic, hypoxia regulated HIF-α-modifying enzymes. We find that the N-terminal tail of COL4A2 protrudes from the ER lumen into the cytosol where it is bound by VHL. Failure of VHL to interact with COL4A2 correlates with loss of collagen IV network formation in vitro and collagen IV remodeling in vivo. Our data suggest a HIF-α-independent role for the VHL–COL4A2 interaction in suppression of angiogenic tumor formation through collagen IV network assembly.Oncogene (2008) 27, 1004–1012; doi:10.1038/sj.onc.1210709; published online 13 August 2007 [ABSTRACT FROM AUTHOR]

Inherited biallelic mutations of the ATM (ataxia-telangiectasia mutated) gene cause ataxia-telangiectasia, a rare autosomal recessive disorder associated with a high incidence of childhood leukaemias and lymphomas, suggesting that ATM gene alterations may be involved in lymphomagenesis. Loss of heterozygosity at 11q22-23 (location of the ATM gene) is a frequent event in sporadic lymphoid tumours, and several studies have reported a high prevalence of ATM gene alterations in diverse sporadic lymphoproliferative disorders, adding evidence to the postulated contribution of ATM in the pathogenesis of these tumours. This mini-review will summarize the recently published data concerning the ATM gene in sporadic lymphoid malignancies and will discuss the apparent paradox between the predominance of nonsense mutations observed in patient with ataxia-telangiectasia and the high proportion of missense alterations found in sporadic lymphoid tumours.Leukemia (2004) 18, 238-242. doi:10.1038/sj.leu.2403221 Published online 20 November 2003 [ABSTRACT FROM AUTHOR]

Continuous intrathecal administration of baclofen with implanted programmable pump systems is recommended in the treatment of severe spasticity of cerebral origin. Prior to pump implantation, a baclofen bolus test (BBT) is used to assess the effectiveness of intrathecal baclofen using clinical scales such as the Modified Ashworth Scale (MAS). In the literature, the time and period of maximum effect of a bolus dose of intrathecally administered baclofen in patients with cerebral spasticity is variously reported. The aim of the study was, therefore, to reveal the time course of the effect of a BBT on severe cerebral spasticity by the use of a recently described spasticity measurement method. Spasticity in knee joints of 13 patients with severe cerebral spasticity was repeatedly assessed using the MAS and also continuously recorded by the measurement of force under circular fibreglass casts. Force was recorded as nettorque by multiplying the force by the distance between sensor and joint axis, thus allowing inter-individual comparison. Half-hour time integrals (TI) of net-torque were determined 9 hours before and 22 hours after intrathecal baclofen administration. Post-BBT half-hour time integrals (TI +0, TI +0.5, to TI +22) were compared with the mean of 17 pre-BBT half-hour time integrals % MathType!Translator!2!1!AMS LaTeX.tdl!TeX -- AMS-LaTeX! % MathType!MTEF!2!1!+- % feaafeart1ev1aaatCvAUfeBSjuyZL2yd9gzLbvyNv2CaerbuLwBLn % hiov2DGi1BTfMBaeXafv3ySLgzGmvETj2BSbqefm0B1jxALjhiov2D % aebbnrfifHhDYfgasaacH8srps0lbbf9q8WrFfeuY-Hhbbf9v8qqaq % Fr0xc9pk0xbba9q8WqFfea0-yr0RYxir-Jbba9q8aq0-yq-He9q8qq % Q8frFve9Fve9Ff0dmeaabaqaciGacaGaaeqabaWaaeaaeaaakeaada % qadaqaamaanaaabaGaaeivaiaabMeaaaWaaSbaaSqaaiabgkHiTiaa % iMdacaaMe8UaaeiDaiaab+gacaaMe8UaeyOeI0IaaGymaaqabaaaki % aawIcacaGLPaaaaaa!4430! $$ {\left( {\overline{{{\text{TI}}}} _{{ - 9\;{\text{to}}\; - 1}} } \right)} $$ . Significantly lower post-BBT half-hour time integrals compared with % MathType!Translator!2!1!AMS LaTeX.tdl!TeX -- AMS-LaTeX! % MathType!MTEF!2!1!+- % feaafeart1ev1aaatCvAUfeBSjuyZL2yd9gzLbvyNv2CaerbuLwBLn % hiov2DGi1BTfMBaeXafv3ySLgzGmvETj2BSbqefm0B1jxALjhiov2D % aebbnrfifHhDYfgasaacH8srps0lbbf9q8WrFfeuY-Hhbbf9v8qqaq % Fr0xc9pk0xbba9q8WqFfea0-yr0RYxir-Jbba9q8aq0-yq-He9q8qq % Q8frFve9Fve9Ff0dmeaabaqaciGacaGaaeqabaWaaeaaeaaakeaada % qadaqaamaanaaabaGaaeivaiaabMeaaaWaaSbaaSqaaiabgkHiTiaa % iMdacaaMe8UaaeiDaiaab+gacaaMe8UaeyOeI0IaaGymaaqabaaaki % aawIcacaGLPaaaaaa!4430! $$ {\left( {\overline{{{\text{TI}}}} _{{ - 9\;{\text{to}}\; - 1}} } \right)} $$ were found between TI +2 and TI +8 (Dunnett adjusted p < 0.05). The median lowest TI after BBT of the 13 patients was TI +4. The lowest mean MAS scores were found 4 hours after BBT. The findings suggest that the greatest effect of BBT on cerebral spasticity occurs between 2 and 8.5 hours, with a maximal effect at 4 hours after intrathecal baclofen injection. Clinical scales used to determine the effect of BBT should thus be carried out during this period?ideally at 4 hours after baclofen injection. [ABSTRACT FROM AUTHOR]

Chronic infection with hepatitis C virus (HCV) is an emerging global epidemic. The development of effective HCV antiviral therapeutics continues to be a daunting challenge owing to the absence of adequate animal models and tissue-culture systems for analysis and propagation of the virus. Despite these obstacles, inhibitors of the replicative elements of HCV, immune modulators and non-specific hepatoprotective agents are being pursued and exciting progress has been made. Successful therapeutic intervention of HCV will probably require combination approaches and new approaches, including host drug discovery targets. [ABSTRACT FROM AUTHOR]

Continuous intrathecal administration of baclofen with implanted programmable pump systems is recommended in the treatment of severe spasticity of cerebral origin. Prior to pump implantation, a baclofen bolus test (BBT) is used to assess the effectiveness of intrathecal baclofen using the modified Ashworth Scale (MAS) and Penn Spasm Frequency Scales (SFS). The result of a BBT may be difficult to interpret in patients with reduced joint mobility caused by contractures. The aim of this study was to apply a new spasticity measurement which would quantify and visualise the effect of a BBT in 10 patients with severe cerebral spasticity and contractures. Spasticity was recorded continuously by the measurement of force under circular fibreglass casts in 10 knee joint contractures. Force was recorded as net-torque by multiplying the force and distance between sensor and joint axis, thus allowing inter-individual comparison. MAS, SFS, and two three-hour time integrals of net-torque were determined before and after intrathecally administered baclofen. No significant changes in MAS (p = 0.1) and SFS (p = 0.07) were observed; however, a significant reduction of time integrals of net-torque after baclofen administration (p = 0.005) was found. The present study shows that the antispastic effect of intrathecally administered BBT can be quantitatively assessed and visualised using the described method. It also suggests that this method can be helpful in the assessment of the effectiveness of the BBT in patients with severe spasticity of cerebral origin and contractures. [ABSTRACT FROM AUTHOR]

A new method will be presented which allows the perception of body odors in humans to be studied objectively. The analysis of body odor evoked potentials was used to investigate if and how the human brain is able to differentiate self from non self body odor for the first time. Six subjects (three females) participated in two experimental sessions. In each session, two body odors (axillary hair) were presented within an olfactory oddball paradigm. One of the odors was collected from the subject and the other from an odor donor of the same sex. In the first session the subjects' attention was distracted to a secondary task (passive paradigm), in the second session the subjects were asked to actively differentiate the odors (active paradigm). For the EEG recordings the odors were presented within a constantly flowing airstream. The results show that the subjects could hardly differentiate the body odors subjectively. However, it could be demonstrated that the central nervous processing of one's own odor was faster than the processing of the chemosensory non self signal. Moreover, in the active paradigm, the potentials appeared to be larger when the subjects perceived their own body odor. The conclusion is reached that the measurement of chemosensory event related potentials (CSERP) is the method of choice for the investigation of HLA associated body odors. [ABSTRACT FROM AUTHOR]

Discusses the insulin-dependent stimulation of protein synthesis. Cloning of cDNAs; Interaction of two related human complementary DNAs encoding polypeptides with the translation initiation factor elF-4E; Insulin and affinity of 4E-BP1 for alF-4E; Hyperphosphorylation and dissociation of cells from elF-4E.

Sigma-optokinetic nystagmus (σ-OKN) can be elicited in awake Java monkeys (Macaca fascicularis) when stationary periodic visual patterns (grid of black white stripes, row of equally spaced dots) are illuminated stroboscopically. Three methods were found to be useful in inducing the σ-OKN: postrotatory nystagmus, optokinetic afternystagmus (OKAN) following normal OKN and a gradual transition from ϕ-movement (ϕ-OKN) to σ-OKN. The properties found for σ-OKN in man are also present in monkeys with the one exception that monkeys have a long-lasting σ-OKAN in darkness which is not present in man. The average angular speed ¯V of σ-OKN slow phases was related to the flash frequency f and the spatial period P of the stripe pattern according to the following equation: {ie519-01} The constant k was 1 or close to 1. [ABSTRACT FROM AUTHOR]

Effects of Evans blue and four derivatives as well as of trypan blue and four derivatives, mostly smaller fragments but two compounds with an additional ethylene bridge in the center of the molecule, were studied on contractions of the rat vas deferens elicited by α,β-methylene ATP (α,β-McATP; mediated by P-purinoceptors), relaxations of the carbachol-precontracted guinea-pig taenia coli elicited by adenosine 5′-O-(2-thiodiphosphate) (ADPβS; mediated by P-purinoceptors), and the degradation of ATP by rat vas deferens tissue. All compounds shifted the concentration-response curve of α,β-MeATP in the rat vas deferens to the right, and most compounds increased the maximum of the curve. Each member of the Evans blue series was similar in potency to the corresponding member of the trypan blue series. Where three concentrations were tested, the Arunlakshana-Schild regression was linear, and the slope did not differ from 1. The apparent K values were between 0.8 and 385 μM. In the guinea-pig taenia coli, only the members of the trypan blue group were relatively potent, shifting the concentration-response curve of ADPβS to the right in a surmountable manner. In 2 of 3 cases where three concentrations were tested, the slope of the Arunlakshana-Schild regression was lower than 1. Apparent K values in the trypan blue group were between 5.2 and 324 μM. The removal of ATP from the medium by vas deferens tissue was decreased mainly by the members of the Evans blue group, with IC values between 13 and 158 (in 1 case >1000) μM. The results indicate that the position of the sulphonate residues at the terminal naphthalene rings of these compounds hardly influences P purinoceptor affinity but greatly influences P affinity and ecto-nucleotidase blockade. Among active compounds, apparent purinoceptor affinity and ecto-nucleotidase blockade increase with the size of the molecules up to Evans blue and trypan blue themselves; introduction of a central ethylene bridge does not result in a further gain in potency. NH01, the desmethyl derivative of Evans blue, seems to be interesting because it is the compound with the highest P- versus P-selectivity presently available. [ABSTRACT FROM AUTHOR]

Effects of eight small aromatic isothiocyanatosulphonates, of the aliphatic 2-isothiocyanatoethene-1-sulphonate (IES), and of the parent amines were studied on contractions of the rat vas deferens elicited by α,β-methy-lene ATP (α,β-MeATP; mediated by P-purinoceptors), relaxations of the carbachol-precontracted guinea-pig taenia coli elicited by adenosine 5′-O-(2-thiodiphosphate) (ADPβS; mediated by P-purinoceptors), and the degradation of ATP by rat vas deferens tissue. The aromatic isothiocyanato-sulphonates all reduced contractions of the rat vas deferens elicited by α,β-methy-lene ATP. The antagonism was non-competitive, with depression of the maximum of the concentration-response curve of α,β-MeATP and incomplete reversibility. The IC values were between 11 and 54 μM. In the guineapig taenia coli, the aromatic compounds shifted the concentration-response curve of ADPβS to the right in a surmountable manner (one exception), and where three concentrations were tested, the Arunlakshana-Schild regression was linear and its slope did not differ from 1. The apparent K values were between 10 and 214 μM. The removal of ATP from the medium by vas deferens tissue was decreased by the aromatic isothiocyanates with IC values between 25 and 464 μM. IES and the parent amines were inactive or almost inactive (parent amines not tested on ATP breakdown). The results indicate that the isothiocyanato residue as well as the aromatic core are essential for P-purinoceptor blockade. At the P-purinoceptor, potency increases with the size of the molecules but is independent of the position of the isothiocyanato and sulphonate substituents. No simple structure-activity relationship for the P-purinoceptor and the ATP-degrading ecto-nucleotidases can be derived beyond the apparent lack of a major influence of the position of the substituents. 2-Isothiocyanatonaphthalene1-sulphonate (β-INS) seems to be interesting because of relatively high P-selectivity versus both the P-purinoceptor and ecto-nucleotidases. [ABSTRACT FROM AUTHOR]

Effects of suramin and five analogs or fragments of suramin were studied on contractions of the rat vas deferens elicited by α,β-methylene ATP (α,β-McATP; mediated by P-purinoceptors), relaxations of the carbachol-precontracted guinea-pig taenia coli elicited by adenosine 5′-O-(2-thiodiphosphate) (ADPβS; mediated by P-purinoceptors), and the degradation of ATP by rat vas deferens tissue. One compound, NF023, differed from suramin by removal of two p-methylbenzamido groups, whereas another, BSt101, differed from NF023 by additional removal of the three sulphonate residues from one of the terminal naphthalene rings. The compounds all shifted the concentration-response curve of α,β-MeATP in the rat vas deferens to the right and simultaneously increased the maximum of the curve. Where three concentrations were tested, the Arunlakshana-Schild regression was linear, and the slope did not differ from 1. The apparent K values were between 1 and 3672 μM. In the guinea-pig taenia coli, the compounds shifted the concentration-response curve of ADPβS to the right in a parallel manner, but in the one case where three concentrations were tested, the slope of the Arunlakshana-Schild regression was lower than 1. Apparent K values were between 10 and 786 μM. The removal of ATP from the medium by vas deferens tissue was decreased only by suramin, NF023 and BSt101, with IC values between 170 and 590 μM. The results indicate that P-purinoceptor affinity, P-purinoceptor affinity and the ecto-nucleotidase effect all increase with the size of the molecule. BSt101 resembled NF023 in potency at all three sites, indicating that the possession of a second naphthalene-trisulphonate group is not a prerequisite for relatively high affinity. NF023 is interesting because it is P- versus P-selective and, in addition, the compound with the highest P- versus ecto-nucleotidase-selectivity presently available. [ABSTRACT FROM AUTHOR]

Single fibre recordings were performed from the auditory nerve of the caiman, Caiman crocodilus. All neurones were spontaneously active (1-80 imp/s). Clicks evoked multiple peaks in the post stimulus time histogram spaced at 1/CF. At high intensities irregularities were observed. The latencies of the first peak observable were intensity-dependent and related to CF. The number of peaks was correlated with tuning properties of the fibre. Frequency threshold curves were asymmetrical, with low frequency slopes less steep than high frequency slopes. Q dB was between 1.5 and 7 with best tuning at high CF. CF ranged from 30 Hz to 2.8 kHz, lowest thresholds down to 5 dB SPL. Intensity functions were nonmonotonic. In isointensity contours the best frequency shifted downwards with increasing stimulus level. At highest levels a response dip was observed above CF. Phase locking, two tone suppression and excitability by combination tones were observed. In comparison to the mammalian cochlea similarities and differences were found. [ABSTRACT FROM AUTHOR]

Copyright of European Journal of Wood & Wood Products / Holz als Roh- und Werkstoff is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of European Journal of Wood & Wood Products / Holz als Roh- und Werkstoff is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of European Journal of Wood & Wood Products / Holz als Roh- und Werkstoff is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

The effect of stimulation of the crossed olivocochlear bundle on the compound action potential recorded at the round window can be blocked by injection of Flaxedil into the scale tympani. The block is reversible and the stimulation effect reappears when Flaxedil is washed out. Intravenously applied Flaxedil, however, is without effect. [ABSTRACT FROM AUTHOR]

The signalling output of many transmembrane receptors that mediate cell-cell communication is restricted by the endosomal sorting complex required for transport (ESCRT), but the impact of this machinery on Eph tyrosine kinase receptor function is unknown. We identified the ESCRT-associated adaptor protein HD-PTP as part of an EphB2 proximity-dependent biotin identification (BioID) interactome, and confirmed this association using co-immunoprecipitation. HD-PTP loss attenuates the ephrin-B2:EphB2 signalling-induced collapse of cultured cells and axonal growth cones, and results in aberrant guidance of chick spinal motor neuron axons in vivo. HD-PTP depletion abrogates ephrin-B2-induced EphB2 clustering, and EphB2 and Src family kinase activation. HD-PTP loss also accelerates ligand-induced EphB2 degradation, contrasting the effects of HD-PTP loss on the relay of signals from other cell surface receptors. Our results link Eph function to the ESCRT machinery and demonstrate a role for HD-PTP in the earliest steps of ephrin-B:EphB signalling, as well as in obstructing premature receptor depletion. [ABSTRACT FROM AUTHOR]

The article discusses the study on genetic variants of the ataxia telangiectasia-mutated (ATM) variants to childhood T-lineage acute lymphoblastic leukemia (T-ALL). Nucleotide substitution was reported to reached 60 percent in 16 selected ATM exons in 103 T-ALL. In the coding part of ATM, five alterations were also found which were 2.6 fold higher in T-ALL than the controls. Higher allelic frequency was also found in the intronic substitution of IVS62+8A/C.