Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 20 de 240
Filter
1.
bioRxiv ; 2024 Apr 22.
Article in English | MEDLINE | ID: mdl-38712193

ABSTRACT

A remarkable demonstration of the flexibility of mammalian motor systems is primates' ability to learn to control brain-computer interfaces (BCIs). This constitutes a completely novel motor behavior, yet primates are capable of learning to control BCIs under a wide range of conditions. BCIs with carefully calibrated decoders, for example, can be learned with only minutes to hours of practice. With a few weeks of practice, even BCIs with randomly constructed decoders can be learned. What are the biological substrates of this learning process? Here, we develop a theory based on a re-aiming strategy, whereby learning operates within a low-dimensional subspace of task-relevant inputs driving the local population of recorded neurons. Through comprehensive numerical and formal analysis, we demonstrate that this theory can provide a unifying explanation for disparate phenomena previously reported in three different BCI learning tasks, and we derive a novel experimental prediction that we verify with previously published data. By explicitly modeling the underlying neural circuitry, the theory reveals an interpretation of these phenomena in terms of biological constraints on neural activity.

2.
Horm Behav ; 124: 104811, 2020 08.
Article in English | MEDLINE | ID: mdl-32592725

ABSTRACT

BACKGROUND: While there is evidence for increased food intake and craving during the luteal phase, underlying mechanisms are incompletely understood. The present study investigated electrophysiological responses to food pictures as a function of menstrual cycle phase. In addition, the moderating effects of progesterone, eating behaviors (restraint, emotional, orthorexic), negative affect, and premenstrual complaints were explored. METHODS: Using a within-subject design, 35 free-cycling women watched and rated pictures of food (high and low caloric) and control items during the follicular, the ovulatory, and the luteal phase (counterbalanced), while EEG was recorded to examine the late positive potentials (LPP). Salivary gonadal hormones and affect were examined at each occasion. Eating behaviors and premenstrual complaints were assessed once. RESULTS: For parietal regions, average LPPs were comparable between cycle phases but slightly larger LPP amplitudes were elicited by high caloric food pictures as compared to the neutral category. Descriptively, both food categories elicited larger parietal LPPs than neutral pictures during the luteal phase. Analyses of LPPs for central-parietal regions showed no effect of picture category or cycle phase, except higher amplitudes in the right area during the luteal phase. During the luteal phase, progesterone and functional interference from premenstrual symptoms (but not age, BMI, picture ratings, affect, estradiol, or eating behaviors) significantly predicted larger parietal LPPs towards high caloric (but not low caloric) pictures. CONCLUSION: Our findings suggest a heightened food cue reactivity during the luteal phase, which may relate to higher ovarian hormone secretion and more functional impact of premenstrual symptoms. This research contributes to a better understanding of menstrual health and the identification of preventive strategies for premenopausal women.


Subject(s)
Affect/physiology , Brain/physiology , Feeding Behavior/psychology , Food , Menstrual Cycle/psychology , Premenstrual Syndrome , Adolescent , Adult , Brain/diagnostic imaging , Cues , Electroencephalography , Emotions/physiology , Estradiol/analysis , Estradiol/metabolism , Evoked Potentials/physiology , Female , Humans , Luteal Phase/physiology , Menstrual Cycle/physiology , Premenstrual Syndrome/metabolism , Premenstrual Syndrome/physiopathology , Premenstrual Syndrome/psychology , Progesterone/analysis , Progesterone/metabolism , Saliva/chemistry , Saliva/metabolism , Young Adult
3.
Plant Cell Rep ; 38(1): 85-99, 2019 Jan.
Article in English | MEDLINE | ID: mdl-30406280

ABSTRACT

KEY MESSAGE: Two lines of Taxus × media hairy roots harbouring or not the TXS transgene demonstrated diverse gene expression and taxane yield during cultivation in PFD-supported two liquid-phase culture system. Two lines of Taxus × media hairy roots were subjected to single or twice-repeated supplementation with methyl jasmonate, sodium nitroprusside, L-phenylalanine, and sucrose feeding. One line harboured transgene of taxadiene synthase (ATMA), while the second (KT) did not. Both hairy root lines were cultured in two-phase culture systems containing perfluorodecalin (PFD) in aerated or degassed form. The relationship between TXS (taxadiene synthase), BAPT (baccatin III: 3-amino, 3-phenylpropanoyltransferase), and DBTNBT (3'-N-debenzoyl-2-deoxytaxol-N-benzoyltransferase) genes and taxane production was analysed. The ATMA and KT lines differed in their potential for taxane accumulation, secretion, and taxane profile. In ATMA biomass, both paclitaxel and baccatin III were detected, while in KT roots only paclitaxel. The most suitable conditions for taxane production for ATMA roots were found in single-elicited supported with PFD-degassed cultures (2 473.29 ± 263.85 µg/g DW), whereas in KT roots in single-elicited cultures with PFD-aerated (470.08 ± 25.15 µg/g DW). The extracellular levels of paclitaxel never exceeded 10% for ATMA roots, while for KT increased up to 76%. The gene expression profile was determined in single-elicited cultures supported with PFD-degassed, where in ATMA roots, the highest taxane yield was obtained, while in KT the lowest one. The gene expression pattern in both investigated root lines differed substantially what resulted in taxane yield characterized particular lines. The highest co-expression of TXS, BAPT and DBTNBT genes noted for ATMA roots harvested 48 h after elicitation corresponded with their higher ability for taxane production in comparison with the effects observed for KT roots.


Subject(s)
Fluorocarbons/metabolism , Isomerases/metabolism , Plant Roots/metabolism , Taxus/metabolism , Gene Expression Regulation, Plant , Isomerases/genetics , Plant Roots/genetics , Taxus/genetics
4.
Magn Reson Imaging ; 52: 24-32, 2018 10.
Article in English | MEDLINE | ID: mdl-29857037

ABSTRACT

MR in microscopy can non-invasively image the morphology of living tissue, which is of particular interest in studying the mammalian brain. Many studies use live animals for basic research on brain functions, disease pathogenesis, and drug development. However, in vitro systems are on the rise, due to advantages such as the absence of a blood-brain barrier, predictable pharmacokinetics, and reduced ethical restrictions. Hence, they present an inexpensive and adequate technique to answer scientific questions and to perform drug screenings. Some publications report the use of acute brain slices for MR microscopy studies, but these only permit single measurements over several hours. Repetitive MR measurements in longitudinal studies demand an MR-compatible setup which allows cultivation for several days or weeks, and hence properly functioning in vitro systems. Organotypic hippocampal slice cultures (OHSC) are a well-established and robust in vitro system which still exhibits most histological hallmarks of the hippocampal network in vivo. An MR compatible incubation platform is introduced in which OHSC are cultivated according to the interface method following Stoppini et al. In this cultivation method a tissue slice is placed onto a membrane with nutrition medium underneath and a gas atmosphere above, where the air-tissue interface perpendicular to the B0 field induces strong artefacts. We introduce a handling protocol that suppresses these artefacts and increases signal quality significantly to acquire high resolution images of tissue slices. An additional challenge is the lack of available of MR microscopy equipment suitable for small animal scanners. A Lenz lens with an attached capacitor can dramatically increase the SNR in these cases, and wirelessly bring the detection system in close proximity to the sample without compromising the OHSC system through the introduction of wired detectors. The resultant signal gain is demonstrated by imaging a PFA-fixed brain slice with a 72 mm diameter volume coil without a Lenz lens, and with a broadband and a self-resonant Lenz lens. In our setting, the self-resonant Lenz lens increases the SNR 10-fold over using the volume coil only.


Subject(s)
Brain/diagnostic imaging , Magnetic Resonance Imaging/instrumentation , Magnetic Resonance Imaging/methods , Animals , Artifacts , In Vitro Techniques , Mice , Microscopy , Models, Animal
5.
Nat Commun ; 8: 14535, 2017 03 06.
Article in English | MEDLINE | ID: mdl-28262691

ABSTRACT

Hyperpolarized (HP) tracers dramatically increase the sensitivity of magnetic resonance imaging (MRI) to monitor metabolism non-invasively and in vivo. Their production, however, requires an extra polarizing device (polarizer) whose complexity, operation and cost can exceed that of an MRI system itself. Furthermore, the lifetime of HP tracers is short and some of the enhancement is lost during transfer to the application site. Here, we present the production of HP tracers in water without an external polarizer: by Synthesis Amid the Magnet Bore, A Dramatically Enhanced Nuclear Alignment (SAMBADENA) is achieved within seconds, corresponding to a hyperpolarization of ∼20%. As transfer of the tracer is no longer required, SAMBADENA may permit a higher polarization at the time of detection at a fraction of the cost and complexity of external polarizers. This development is particularly promising in light of the recently extended portfolio of biomedically relevant para-hydrogen-tracers and may lead to new diagnostic applications.


Subject(s)
Carbon Isotopes/chemistry , Contrast Media/chemistry , Magnetic Resonance Imaging/methods , Propionates/chemistry , Animals , Contrast Media/pharmacokinetics , Humans , Hydrogen/chemistry , Hydrogenation , Magnetic Fields , Magnetic Resonance Imaging/instrumentation , Propionates/pharmacokinetics , Rats , Staining and Labeling/methods , Water/chemistry
6.
Perception ; 45(11): 1211-1221, 2016 Nov.
Article in English | MEDLINE | ID: mdl-27259566

ABSTRACT

The human motion processing area, hMT+, has been labeled the critical neural area for processing of real and illusory visual motion in radial 2D patterns. However, the activation in hMT+ during perception of illusory rotation in the looming double-circular Pinna Figure (PF) generated in 3D space has not been observed yet. To do so, an optic-flow like motion of rings (looming) in PF was generated on a computer screen. A psychophysically precise nulling procedure allowed quantifying the individual amount of the perceived illusory rotation in PF (PI) for each participant. The interpolation of the individual illusory motion parameters created a subjectively non-rotating PF and a physically rotating control stimulus of identical rotary strength as the PI. The physically rotating control was a double-circular figure which diverged from PF only in its arrangement of luminance gradients. In a 3-Tesla scanner, participants were presented with a random order of rotating and non-rotating figures (illusory, real, no rotation, and nulled PI). Both types, illusory and real rotation, when equal in perceptual strength for the observer, were found to be processed by hMT+.

7.
J Magn Reson ; 268: 58-67, 2016 07.
Article in English | MEDLINE | ID: mdl-27179228

ABSTRACT

The hyperpolarization of nuclear spins promises great advances in chemical analysis and medical diagnosis by substantially increasing the sensitivity of nuclear magnetic resonance (NMR). Current methods to produce a hyperpolarized sample, however, are arduous, time-consuming or costly and require elaborate equipment. Recently, a much simpler approach was introduced that holds the potential, if harnessed appropriately, to revolutionize the production of hyperpolarized spins. It was reported that high levels of hyperpolarization in nuclear spins can be created by irradiation with a laser beam carrying orbital angular momentum (twisted light). Aside from these initial reports however, no further experimental verification has been presented. In addition, this effect has so far evaded a critical theoretical examination. In this contribution, we present the first independent attempt to reproduce the effect. We exposed a sample of immersion oil or a fluorocarbon liquid that was placed within a low-field NMR spectrometer to Laguerre-Gaussian and Bessel laser beams at a wavelength of 514.5nm and various topological charges. We acquired (1)H and (19)F NMR free induction decay data, either during or alternating with the irradiation that was parallel to B0. We observed an irregular increase in NMR signal in experiments where the sample was exposed to beams with higher values of the topological charge. However, at no time did the effect reach statistical significance of 95%. Given the measured sensitivity of our setup, we estimate that a possible effect did not exceed a hyperpolarization (at 5mT) of 0.14-6%, depending on the assumed hyperpolarized volume. It should be noted though, that there were some differences between our setup and the previous implementation of the experiment, which may have inhibited the full incidence of this effect. To approach a theoretical description of this effect, we considered the interaction of an electron with a plane wave, which is known to be able to induce electronic (e.g. in rubidium) and subsequent nuclear hyperpolarization. Compared to the plane wave, the additional transitions caused by a twisted wave are of the order of 10(-3) less. This suggests that the twist of the laser is unlikely to be responsible for the hyperpolarization of nuclear spins, unless a new mechanism of momentum transfer is identified.


Subject(s)
Biopolymers/chemistry , Biopolymers/radiation effects , Lasers , Magnetic Resonance Spectroscopy/methods , Biopolymers/analysis , Radiation Dosage , Reproducibility of Results , Scattering, Radiation , Sensitivity and Specificity , Spin Labels
8.
Biomed Tech (Berl) ; 60 Suppl 1: s193-226, 2015 Sep.
Article in English | MEDLINE | ID: mdl-26360473
9.
Lett Appl Microbiol ; 61(1): 36-43, 2015 Jul.
Article in English | MEDLINE | ID: mdl-25800964

ABSTRACT

UNLABELLED: The Escherichia coli K-12 strain BL21/pETSD10 was used to produce recombinant endocellular 1,3-ß-glucanase. This enzyme is responsible for the hydrolysis of the glycosidic bond in specific polysaccharides with tracts of unsubstituted ß-1,3-linked glucosyl residues. Conditions for the overproduction were experimentally examined, and the optimal values of the process on a bioreactor scale were found by interpolation of the experimental data. Cell induction was preferred during log-phase with relatively high cell density at OD600 near 1·1 with 0·074 g l(-1) of Isopropyl ß-D-1-thiogalactopyranoside (IPTG). The higher concentration of IPTG favors high enzyme production but with an excess of ballast protein. 1,3-ß-glucanase production was favoured with moderate culture aeration (0·7-0·9 vvm) and moderate stirring (125-150 rev min(-1) ). The highest specific glucanase activity (252 U g(-1) ) was found during validated experiments carried out at aeration at 135 rev min(-1) and stirring at 0·8 vvm. Due to high-tonnage industrial applications (i.e. to hemicellulose hydrolysis), the enzymatic preparation did not need to be highly purified. After pretreatment (precipitation with ammonium sulphate and dialysis) of the crude preparation, the enzymatic protein was one of the three main proteins in the preparation. The reaction rate with respect to the substrate (CM-curdlan) was described by the first order reaction equation (k = 1·95 l h(-1 ) g(-1) ). Products formed in the reaction are composed of nine glucose units on average. In the reaction conditions, the preparation showed very good stability (t1/2 = 202 h). SIGNIFICANCE AND IMPACT OF THE STUDY: The results contribute to the knowledge of cultivation parameters of E. coli K-12 strain BL21/pETSD10 on a bioreactor scale to overproduce an enzyme degrading ß-1,3-glucans. The optimal values of protein concentration, specific activity and total glucanase activity as a function of aeration and stirring were evaluated by numerical analysis. The obtained values were validated as positive. The protein degrades some bonds in hemicellulose. Thus, the protein could be applied as one of the degrading components for hemicellulose.


Subject(s)
Bioreactors , Escherichia coli K12/enzymology , Glucan 1,3-beta-Glucosidase/biosynthesis , Recombinant Proteins/biosynthesis , beta-Glucans/metabolism , Endopeptidases/metabolism , Escherichia coli K12/genetics , Escherichia coli K12/metabolism , Glucan 1,3-beta-Glucosidase/genetics , Hydrolysis , Isopropyl Thiogalactoside/chemistry , Kinetics , Molecular Sequence Data , Recombinant Proteins/genetics
10.
Skin Res Technol ; 21(1): 61-8, 2015 Feb.
Article in English | MEDLINE | ID: mdl-25066249

ABSTRACT

PURPOSE: The aim of this study was to demonstrate the feasibility of a custom-made phased-array microcoil within a 400 MHz animal system for the morphological characterization of human skin tissue in correlation with histopathology. MATERIALS AND METHODS: A dedicated 7-channel microcoil-based MR detector arranged in a phased-array geometry was developed to combine the advantages of both a large field of view and a high signal-to-noise ratio. Standard gradient echo sequences were adapted for the characterization of skin morphology ex vivo. RESULTS: In this study, the feasibility of using this type of microdetector, combined with specially manufactured sample holders, to achieve high-resolution MR images of fresh and formalin-fixed, normal and hidradenitis suppurativa diseased skin was successfully demonstrated. The setup presented in this work allows reliable acquisitions of high-resolution images with in-plane resolution up to 25 × 25 µm², and 100 µm in the orthogonal direction, thereby allowing the differentiation of typical layers of the skin, sebaceous glands and hair follicle. CONCLUSION: This study demonstrates that MR microscopy on skin biopsies can be applied at low cost on a standard animal MR imaging system. The successful imaging of different skin structures ex vivo is a prerequisite for non-invasive, in vivo application of skin MR microscopy for accurate complementary disease diagnosis in dermatology.


Subject(s)
Hidradenitis Suppurativa/pathology , Magnetic Resonance Imaging/instrumentation , Magnetics/instrumentation , Microscopy/instrumentation , Skin/pathology , Specimen Handling/instrumentation , Dermoscopy/instrumentation , Equipment Design , Equipment Failure Analysis , Humans , Image Enhancement/instrumentation , In Vitro Techniques , Miniaturization , Reproducibility of Results , Sensitivity and Specificity
12.
Transl Psychiatry ; 4: e443, 2014 Sep 16.
Article in English | MEDLINE | ID: mdl-25226552

ABSTRACT

The serotonin transporter gene-linked polymorphic region (5-HTTLPR) has been implicated in moderating vulnerability to stress-related psychopathology upon exposure to environmental adversity. A recent meta-analysis suggests a potential biological pathway conveying genotype-dependent stress sensitivity by demonstrating a small, but significant association of 5-HTTLPR and cortisol stress reactivity. An arguably more potent approach to detect larger effects when investigating the 5-HTTLPR stress sensitivity hypothesis is to account for both genetic and epigenetic variation in the serotonin transporter gene (SLC6A4). Here, we applied this approach in an experimental setting. Two hundred healthy adults were exposed to a laboratory stressor (Trier Social Stress Test) and cortisol response patterns were assessed as a function of 5-HTTLPR and DNA methylation profiles in SLC6A4. Specifically, we analyzed 83 CpG sites within a 799-bp promoter-associated CpG island of SLC6A4 using a highly sensitive bisulfite pyrosequencing method. Our results suggest that SLC6A4 methylation levels significantly moderate the association of 5-HTTLPR and cortisol stress reactivity. For individuals displaying low levels of SLC6A4 methylation, the S allele relates to increased cortisol stress reactivity in a dose-dependent fashion accounting for 7-9% of the variance in the endocrine stress response. By contrast, no such effect occurred under conditions of high SLC6A4 methylation, indicating that epigenetic changes may compensate for genotype-dependent differences in stress sensitivity. Studying epigenetic markers may advance gene-environment interaction research on 5-HTTLPR as they possibly capture the net effects of environmental influences relevant for stress-related phenotypes under serotonergic control.


Subject(s)
DNA Methylation/genetics , Hydrocortisone/genetics , Serotonin Plasma Membrane Transport Proteins/genetics , Stress, Psychological/genetics , Adolescent , Adult , Analysis of Variance , Female , Humans , Hydrocortisone/metabolism , Male , Saliva/metabolism , Young Adult
13.
Mol Psychiatry ; 19(12): 1314-25, 2014 Dec.
Article in English | MEDLINE | ID: mdl-25048006

ABSTRACT

Over the last few years, awareness of autism spectrum disorder (ASD) in adults has increased. The precise etiology of ASD is still unresolved. Animal research, genetic and postmortem studies suggest that the glutamate (Glu) system has an important role, possibly related to a cybernetic imbalance between neuronal excitation and inhibition. To clarify the possible disruption of Glu metabolism in adults with high-functioning autism, we performed a magnetic resonance spectroscopy (MRS) study investigating the anterior cingulate cortex (ACC) and the cerebellum in adults with high-functioning ASD. Twenty-nine adult patients with high-functioning ASD and 29 carefully matched healthy volunteers underwent MRS scanning of the pregenual ACC and the left cerebellar hemisphere. Metabolic data were compared between groups and were correlated with psychometric measures of autistic features. We found a significant decrease in the cingulate N-acetyl-aspartate (NAA) and the combined Glu and glutamine (Glx) signals in adults with ASD, whereas we did not find other metabolic abnormalities in the ACC or the cerebellum. The Glx signal correlated significantly with psychometric measures of autism, particularly with communication deficits. Our data support the hypothesis that there is a link between disturbances of the cingulate NAA and Glx metabolism, and autism. The findings are discussed in the context of the hypothesis of excitatory/inhibitory imbalance in autism. Further research should clarify the specificity and dynamics of these findings regarding other neuropsychiatric disorders and other brain areas.


Subject(s)
Child Development Disorders, Pervasive/metabolism , Glutamic Acid/metabolism , Gyrus Cinguli/metabolism , Adult , Aspartic Acid/analogs & derivatives , Aspartic Acid/metabolism , Brain Mapping , Cerebellum/metabolism , Child Development Disorders, Pervasive/psychology , Female , Glutamine/metabolism , Humans , Magnetic Resonance Spectroscopy , Male , Psychometrics
14.
Transl Psychiatry ; 4: e402, 2014 Jun 17.
Article in English | MEDLINE | ID: mdl-24937096

ABSTRACT

The serotonin transporter (SERT) gene-linked polymorphic region (5-HTTLPR) has been implicated in moderating the link between life stress and depression. However, respective molecular pathways of gene-environment (GxE) interaction are largely unknown. Sustained alterations in SERT gene expression profiles, possibly mediated by epigenetic modifications, are a frequent correlate of depression and may thus constitute a putative mediator of GxE interaction. Here, we aimed to investigate joint effects of 5-HTTLPR and self-reported environmental adversity throughout the lifespan (prenatal, early and recent stress/trauma) on in vivo SERT mRNA expression in peripheral blood cells. To further evaluate whether environmentally induced changes in SERT expression are mediated by epigenetic modifications, we analyzed 83 CpG sites within a 799-bp promoter-associated CpG island of the SERT gene using the highly sensitive method of bisulfite pyrosequencing. Participants were 133 healthy young adults. Our findings show that both the 5-HTTLPR S allele and maternal prenatal stress/child maltreatment are associated with reduced in vivo SERT mRNA expression in an additive manner. Remarkably, individuals carrying both the genetic and the environmental risk factors exhibited 32.8% (prenatal stress) and 56.3% (child maltreatment) lower SERT mRNA levels compared with those without any risk factor. Our data further indicated that changes in SERT mRNA levels were unlikely to be mediated by DNA methylation profiles within the SERT CpG island. It is thus conceivable that the persistent changes in SERT expression may in turn relate to altered serotonergic functioning and possibly convey differential disease vulnerability associated with 5-HTTLPR and early adversity.


Subject(s)
Child Abuse/psychology , Gene-Environment Interaction , Genetic Predisposition to Disease , Pregnancy Complications/physiopathology , Prenatal Exposure Delayed Effects/physiopathology , Serotonin Plasma Membrane Transport Proteins/genetics , Stress, Psychological/complications , Adult , Child , CpG Islands/genetics , DNA Methylation/genetics , Depression , Female , Humans , Male , Pregnancy , RNA, Messenger/metabolism , Risk Factors , Sequence Analysis, DNA/methods , Serotonin Plasma Membrane Transport Proteins/metabolism , Young Adult
15.
Cell Death Dis ; 5: e1199, 2014 Apr 24.
Article in English | MEDLINE | ID: mdl-24763056

ABSTRACT

Despite intensive multimodal therapies, the overall survival rate of patients with ductal adenocarcinoma of the pancreas is still poor. The chemo- and radioresistance mechanisms of this tumor entity remain to be determined in order to develop novel treatment strategies. In cancer, endocytosis and membrane trafficking proteins are known to be utilized and they also critically regulate essential cell functions like survival and proliferation. On the basis of these data, we evaluated the role of the endosomal proteins adaptor proteins containing pleckstrin homology domain, phosphotyrosine binding domain and a leucine zipper motif (APPL)1 and 2 for the radioresistance of pancreatic carcinoma cells. Here, we show that APPL2 expression in pancreatic cancer cells is upregulated after irradiation and that depletion of APPL proteins by small interfering RNA (siRNA) significantly reduced radiation survival in parallel to impairing DNA double strand break (DSB) repair. In addition, APPL knockdown diminished radiogenic hyperphosphorylation of ataxia telangiectasia mutated (ATM). Activated ATM and APPL1 were also shown to interact after irradiation, suggesting that APPL has a more direct role in the phosphorylation of ATM. Double targeting of APPL proteins and ATM caused similar radiosensitization and concomitant DSB repair perturbation to that observed after depletion of single proteins, indicating that ATM is the central modulator of APPL-mediated effects on radiosensitivity and DNA repair. These data strongly suggest that endosomal APPL proteins contribute to the DNA damage response. Whether targeting of APPL proteins is beneficial for the survival of patients with pancreatic adenocarcinoma remains to be elucidated.


Subject(s)
Adaptor Proteins, Signal Transducing/metabolism , Ataxia Telangiectasia Mutated Proteins/metabolism , Pancreatic Neoplasms/metabolism , Pancreatic Neoplasms/pathology , Radiation Tolerance , Cell Survival/radiation effects , DNA Breaks, Double-Stranded/radiation effects , DNA Repair/radiation effects , Endosomes/metabolism , Endosomes/radiation effects , Enzyme Activation/radiation effects , Gene Knockdown Techniques , Humans , Phosphorylation/radiation effects , Protein Binding/radiation effects , Radiation Tolerance/radiation effects , X-Rays , Pancreatic Neoplasms
16.
Eur Psychiatry ; 29(5): 304-6, 2014 Jun.
Article in English | MEDLINE | ID: mdl-24630741

ABSTRACT

Psychosis-proneness or schizotypy is a personality organisation mirroring individual risk for schizophrenia-development. Believed to be a fully dimensional construct sharing considerable geno- and phenotypal variance with clinical schizophrenia, it has become an increasingly promising tool for basic psychosis-research. Although many studies show genetic commonalities between schizotypy and schizophrenia, changes in regulation of gene expression have never been examined in schizotypy before. We therefore extracted RNA from the blood, a valid surrogate for brain tissue, of a large sample of 67 healthy male volunteers and correlated the activities of all genes relevant for dopaminergic neurotransmission with the positive schizotypy-scale of the O-LIFE. We found significant negative correlations regarding the expression of the genes COMT, MAOB, DRD4, DRD5 and FOS, indicating that increased schizotypy coincides with higher levels of dopaminergic dysregulation on the mRNA-level. Considering the advantages of this method, we suggest that it be applied more often in fundamental psychosis-research.


Subject(s)
Catechol O-Methyltransferase/genetics , Monoamine Oxidase/genetics , Oncogene Proteins v-fos/genetics , Psychotic Disorders/genetics , Receptors, Dopamine D4/genetics , Receptors, Dopamine D5/genetics , Humans , Male
17.
J Exp Bot ; 65(4): 1095-109, 2014 Mar.
Article in English | MEDLINE | ID: mdl-24420577

ABSTRACT

The purpose of the study was to investigate the role of salicylic acid (SA) signalling in Ny-1-mediated hypersensitive resistance (HR) of potato (Solanum tuberosum L.) to Potato virus Y (PVY). The responses of the Ny-1 allele in the Rywal potato cultivar and transgenic NahG-Rywal potato plants that do not accumulate SA were characterized at the cytological, biochemical, transcriptome, and proteome levels. Analysis of noninoculated and inoculated leaves revealed that HR lesions started to develop from 3 d post inoculation and completely restricted the virus spread. At the cytological level, features of programmed cell death in combination with reactive oxygen species burst were observed. In response to PVY infection, SA was synthesized de novo. The lack of SA accumulation in the NahG plants led to the disease phenotype due to unrestricted viral spreading. Grafting experiments show that SA has a critical role in the inhibition of PVY spreading in parenchymal tissue, but not in vascular veins. The whole transcriptome analysis confirmed the central role of SA in orchestrating Ny-1-mediated responses and showed that the absence of SA leads to significant changes at the transcriptome level, including a delay in activation of expression of genes known to participate in defence responses. Moreover, perturbations in the expression of hormonal signalling genes were detected, shown as a switch from SA to jasmonic acid/ethylene signalling. Viral multiplication in the NahG plants was accompanied by downregulation of photosynthesis genes and activation of multiple energy-producing pathways.


Subject(s)
Plant Diseases/immunology , Plant Proteins/genetics , Potyvirus/physiology , Salicylic Acid/metabolism , Solanum tuberosum/genetics , Transcriptome , Apoptosis , Cyclopentanes/metabolism , Down-Regulation , Energy Metabolism , Ethylenes/metabolism , Gene Expression Regulation, Plant , Host-Pathogen Interactions , Oxylipins/metabolism , Photosynthesis , Plant Diseases/virology , Plant Growth Regulators/metabolism , Plant Immunity , Plant Leaves/genetics , Plant Leaves/immunology , Plant Leaves/virology , Plant Proteins/metabolism , Reactive Oxygen Species/metabolism , Signal Transduction , Solanum tuberosum/immunology , Solanum tuberosum/virology
18.
Magn Reson Med ; 70(5): 1220-8, 2013 Nov.
Article in English | MEDLINE | ID: mdl-23203228

ABSTRACT

With the recent proposal of using magnetic fields that are nonlinear by design for spatial encoding, new flexibility has been introduced to MR imaging. The new degrees of freedom in shaping the spatially encoding magnetic fields (SEMs) can be used to locally adapt the imaging resolution to features of the imaged object, e.g., anatomical structures, to reduce peripheral nerve stimulation during in vivo experiments or to increase the gradient switching speed by reducing the inductance of the coils producing the SEMs and thus accelerate the imaging process. In this work, the potential of nonlinear and nonbijective SEMs for spatial encoding during transmission in multidimensional spatially selective excitation is explored. Methods for multidimensional spatially selective excitation radiofrequency pulse design based on nonlinear encoding fields are introduced, and it is shown how encoding ambiguities can be resolved using parallel transmission. In simulations and phantom experiments, the feasibility of selective excitation using nonlinear, nonbijective SEMs is demonstrated, and it is shown that the spatial resolution with which the target distribution of the transverse magnetization can be realized varies locally. Thus, the resolution of the target pattern can be increased in some regions compared with conventional linear encoding. Furthermore, experimental proof of principle of accelerated two-dimensional spatially selective excitation using nonlinear SEMs is provided in this study.


Subject(s)
Algorithms , Data Compression/methods , Image Enhancement/instrumentation , Image Interpretation, Computer-Assisted/instrumentation , Magnetic Resonance Imaging/instrumentation , Signal Processing, Computer-Assisted/instrumentation , Image Enhancement/methods , Image Interpretation, Computer-Assisted/methods , Magnetic Fields , Magnetic Resonance Imaging/methods , Nonlinear Dynamics , Phantoms, Imaging , Reproducibility of Results , Sensitivity and Specificity
19.
Genes Brain Behav ; 11(6): 643-50, 2012 Aug.
Article in English | MEDLINE | ID: mdl-22420614

ABSTRACT

The S-allele of the 5-HTTLPR has been identified as a genetic vulnerability factor, being associated with an increased risk for affective disorders and/or maladaptive traits (e.g. neuroticism), especially after exposition to negative life-events (LEs). Alternatively, it has been hypothesized that this genetic risk factor might constitute a genetic plasticity factor. That is, S-allele carriers are not only vulnerable to the negative effects of a preponderance of stressful LEs but also disproportionally benefit from a preponderance of positive environmental influences. We tested this hypothesis in 357 subjects who were genotyped for the 5-HTTLPR and provided self-reports of neuroticism, life-satisfaction and LEs. Results showed a relatively increased number of positive LEss to be associated with reduced neuroticism (men: ß = -0.501, P < 0.05, women: ß = -0.369, P < 0.005) and increased life satisfaction (ß = 0.494, P < 0.001) within SS-homozygotes. Within SL-heterozygotes, similar tendencies were found. No associations were detected in LL-homozygotes. Extreme Group comparisons revealed a genotype × LE interaction (F(2,198) = 5.593, P < 0.005), with SS-homozygotes having experienced predominantly positive LEs exhibiting reduced neuroticism (women: F(1,34) = 4.764, P < 0.05; men: F(1,17) = 2.092, P = 0.17), and increased life satisfaction (F(1,53) = 4.057, P < 0.05), as compared to LL-homozygotes having experienced predominantly positive LEs. Our data support the idea that the S-allele of the 5-HTTLPR is associated with an overall increased reactivity to environmental influences, be they positive or negative in nature. These findings constitute a promising add-on to earlier data and support the plasticity hypothesis.


Subject(s)
Alleles , Life Change Events , Mood Disorders/genetics , Neuronal Plasticity/genetics , Personality/genetics , Serotonin Plasma Membrane Transport Proteins/genetics , Adult , Environment , Female , Genetic Predisposition to Disease/epidemiology , Genetic Predisposition to Disease/genetics , Humans , Male , Mood Disorders/epidemiology , Risk Factors , Young Adult
20.
Magn Reson Med ; 67(1): 258-68, 2012 Jan.
Article in English | MEDLINE | ID: mdl-21630351

ABSTRACT

The aim of this study was to evaluate the performance of a closed circuit MR compatible pneumatically driven pump system using a ventricular assist device as pulsatile flow pump for in vitro 3D flow simulation. Additionally, a pressure control unit was integrated into the flow circuit. The performance of the pump system and its test-retest reliability was evaluated using a stenosis phantom (60% lumen narrowing). Bland-Altman analysis revealed a good test-retest reliability (mean differences = -0.016 m/s, limits of agreement = ±0.047 m/s) for in vitro flow measurements. Furthermore, a rapid prototyping in vitro model of a normal thoracic aorta was integrated into the flow circuit for a direct comparison of flow characteristics with in vivo data in the same subject. The pneumatically driven ventricular assist device was attached to the ascending aorta of the in vitro model to simulate the beating left ventricle. In the descending part of the healthy aorta a flexible stenosis was integrated to model an aortic coarctation. In vivo and in vitro comparison showed significant (P = 0.002) correlations (r = 0.9) of mean velocities. The simulation of increasing coarctation grade led to expected changes in the flow patterns such as jet flow in the post-stenotic region and increased velocities.


Subject(s)
Blood Pressure Determination/instrumentation , Heart-Assist Devices , Magnetic Resonance Imaging/instrumentation , Equipment Design , Equipment Failure Analysis , Feedback
SELECTION OF CITATIONS
SEARCH DETAIL
...