Polarity-Specific Cortical Effects of Transcranial Direct Current Stimulation in Primary Somatosensory Cortex of Healthy Humans

Transcranial direct current stimulation (tDCS) is a noninvasive stimulation method that has been shown to modulate the excitability of the motor and visual cortices in human subjects in a polarity dependent manner in previous studies. The aim of our study was to investigate whether anodal and cathodal tDCS can also be used to modulate the excitability of the human primary somatosensory cortex (S1). We measured paired-pulse suppression (PPS) of somatosensory evoked potentials in 36 right-handed volunteers before and after anodal, cathodal or sham stimulation over the right non-dominant S1. Paired-pulse stimulation of the median nerve was performed at the dominant and non-dominant hand. After anodal tDCS, PPS was reduced in the ipsilateral S1 compared to sham stimulation, indicating an excitatory effect of anodal tDCS. In contrast, PPS in the stimulated left hemisphere was increased after cathodal tDCS, indicating an inhibitory effect of cathodal tDCS. Sham stimulation induced no pre-post differences. Thus, tDCS can be used to modulate the excitability of S1 in polarity-dependent manner, which can be assessed by paired-pulse suppression. An interesting topic for further studies could be the investigation of direct correlations between sensory changes and excitability changes induced by tDCS

Seasonal characteristics of bottom boundary layer detachment at the shelfbreak front in the Middle Atlantic Bight

Author Posting. © American Geophysical Union, 2004. This article is posted here by permission of American Geophysical Union for personal use, not for redistribution. The definitive version was published in Journal of Geophysical Research 109 (2004): C03049, doi:10.1029/2003JC002032.The seasonality of various characteristics of the detached bottom boundary layer of the Middle Atlantic Bight shelfbreak front is examined using a collection of high-resolution transects across the front. The analysis follows previous methodology in which accumulated temperature change along isopycnals within the front is used to infer the location of the detached layer. The seasonal mean isopycnal at which detachment occurs (approximately 26.0 kg m−3) is fairly constant throughout the year. However, the vertical scale of the detached layer varies significantly with season, extending 60−80 m above the bottom in winter and spring, but only 20−40 m above the bottom in summer. The vertical scale is controlled by the strength and depth of the seasonal pycnocline. The observations suggest that the detached layer is capable of extending into the euphotic zone during winter and spring.This work was funded by the Office of Naval Research under contracts N00014-01-1-0931 (C. L. and G. G.) and N00014-01-1-0772 (C. L. and G. G.) and by the National Science Foundation under grant OCE-0095261 (R. P.

Ligand-binding domain subregions contributing to bimodal agonism in cyclic nucleotide–gated channels

Cyclic nucleotide–gated (CNG) channels bind cGMP or cAMP in a cytoplasmic ligand–binding domain (BD), and this binding typically increases channel open probability (Po) without inducing desensitization. However, the catfish CNGA2 (fCNGA2) subtype exhibits bimodal agonism, whereby steady-state Po increases with initial cGMP-binding events (“pro” action) up to a maximum of 0.4, but decreases with subsequent cGMP-binding events (“con” action) occurring at concentrations >3 mM. We sought to clarify if low pro-action efficacy was either necessary or sufficient for con action to operate. To find BD residues responsible for con action or low pro-action efficacy or both, we constructed chimeric CNG channels: subregions of the fCNGA2 BD were substituted with corresponding sequence from the rat CNGA4 BD, which does not support con action. Constructs were expressed in frog oocytes and tested by patch clamp of cell-free membranes. For nearly all BD elements, we found at least one construct where replacing that element preserved robust con action, with a ratio of steady-state conductances, g(10 mM cGMP)/g(3 mM cGMP) < 0.75. When all of the BD sequence C terminal of strand β6 was replaced, g(10 mM cGMP)/g(3 mM cGMP) was increased to 0.95 ± 0.05 (n = 7). However, this apparent attenuation of con action could be explained by an increase in the efficacy of pro action for all agonists, controlled by a conserved “phosphate-binding cassette” motif that contacts ligand; this produces high Po values that are less sensitive to shifts in gating equilibrium. In contrast, substituting a single valine in the N-terminal helix αA abolished con action (g(30 mM cGMP)/g(3 mM cGMP) increased to 1.26 ± 0.24; n = 7) without large increases in pro-action efficacy. Our work dissociates the two functional features of low pro-action efficacy and con action, and moreover identifies a separate structural determinant for each

High-throughput gene discovery in the rat

The rat is an important animal model for human diseases and is widely used in physiology. In this article we present a new strategy for gene discovery based on the production of ESTs from serially subtracted and normalized cDNA libraries, and we describe its application for the development of a comprehensive nonredundant collection of rat ESTs. Our new strategy appears to yield substantially more EST clusters per ESTs sequenced than do previous approaches that did not use serial subtraction. However, multiple rounds of library subtraction resulted in high frequencies of otherwise rare internally primed cDNAs, defining the limits of this powerful approach. To date, we have generated >200,000 3′ ESTs from >100 cDNA libraries representing a wide range of tissues and developmental stages of the laboratory rat. Most importantly, we have contributed to ∼50,000 rat UniGene clusters. We have identified, arrayed, and derived 5′ ESTs from >30,000 unique rat cDNA clones. Complete information, including radiation hybrid mapping data, is also maintained locally at http://genome.uiowa.edu/clcg.html. All of the sequences described in this article have been submitted to the dbEST division of the NCBI

The effect of Cimicifuga racemosa BNO 1055-fractions on liver fat content, proliferation of colon-epithelium and selected blood lipid parameters

Die Nachfrage nach Alternativen für die Hormonersatztherapie durch Östrogene (HET) zur Linderung menopausaler Beschwerden hat aufgrund ihres Risikoprofils zugenommen. Die entstandene Lücke bei der Behandlung moderater Beschwerden oder der Behandlung über einen längeren Zeitraum wurde u.a. mit einigen Präparaten auf pflanzlicher Basis, sogenannten Phytotherapeutika, gefüllt. Eine in der Therapie menopausaler Beschwerden etablierte Pflanze ist die Traubensilberkerze (Cimicifuga racemosa = CR). Der CR BNO 1055-Extrakt konnte für diese Versuchsreihe in seine verschiedenen Wirkbestandteile aufgereinigt werden. Diese Subfraktionen des CR BNO 1055-Extraktes wurden an Sprague-Dawley-Ratten in Bezug auf ihren metabolischen Effekt, die Lebersicherheit und ihren Effekt auf die Kolonepithelproliferation im Vergleich zu Estradiolbenzoat und einer ovarektomierten (ovx) Kontrollgruppe hin untersucht. Dazu wurden bestimmte Blutlipidparameter (HDL, LDL, Trigylceride, Gesamtcholesterin, Leptin), der Leberfettgehalt und die PCNA-positiven Zellen in der Kolonschleimhaut nach 4-wöchiger Gabe der CR BNO 1055-Subfraktionen und Estradiolbenzoat bestimmt. Die Ergebnisse wurden mit einer Kontrollgruppe, die ausschließlich sojafreies Futter erhielt, verglichen. In der Untersuchung der Blutlipidparameter zeigte sich kein signifikanter Effekt der CR BNO 1055-Subfraktionen. Der in Vorstudien bereits beschriebene, lipidsenkenden Effekt der Estradioltherapie konnte bestätigt werden. In der Untersuchung der Kolonepithelproliferation zeigte sich ebenfalls kein signifikanter Effekt der CR BNO 1055-Subfraktionen. Der ebenfalls bereits bekannte Effekt einer Proliferationszunahme unter Estradioltherapie konnte bestätigt werden. Die Messungen des Leberfettgehaltes zeigten eine signifikante Erhöhung bei einer der CR BNO 1055-Subgruppen und keinen Effekt bei der mit Estradiolbenzoat therapierten Tiere. Im Sinne einer möglichen Auswirkung auf den Leberfettstoffwechsel durch einzelne CR BNO 1055-Subfraktionen besteht hier zukünftig weiterer Forschungsbedarf.2014-05-0

Diffusion tensor imaging of the human thigh : consideration of DTI-based fiber tracking stop criteria

Objectives: To consider the tract-based analysis of DTI parameters in human muscle by assessing different fiber tracking stop criteria settings on diffusion parameters. Materials and methods: 30 healthy volunteers underwent a 3 T MRI. Diffusion-weighted images were acquired to perform DTI and fiber tracking analysis for six thigh muscles. Whole thigh muscles were evaluated by fiber tractography using different fiber tracking stop parameters [FA (0.01–0.15) to (0.4–0.99); angle 10°–30°, step size 0.75 mm, 1.5 mm, 3 mm]. Diffusion and tractography-derived parameters per stop criterion were compared using a repeated measure ANOVA including Bonferroni-corrected post hoc tests. Results: We found significant differences in all examined diffusion parameters between different stop criteria (main effect p < 0.001). We showed different influence of tracking parameters on diffusion parameters in examined muscles (main effect p ≤ 0.001). Conclusions: Statistically significant differences in fiber tracking results using different stop criteria were shown. Fiber tracking stop criteria do have an important influence on study results and should be considered in the development of study protocols and comparison of studies. We recommend a FA minimum of 0.10 and a step size lower than voxel size, e.g., a half with a constant ratio between step size and angle of 10°/mm

Diffusion tensor imaging of the human thigh : consideration of DTI-based fiber tracking stop criteria

Objectives: To consider the tract-based analysis of DTI parameters in human muscle by assessing different fiber tracking stop criteria settings on diffusion parameters. Materials and methods: 30 healthy volunteers underwent a 3 T MRI. Diffusion-weighted images were acquired to perform DTI and fiber tracking analysis for six thigh muscles. Whole thigh muscles were evaluated by fiber tractography using different fiber tracking stop parameters [FA (0.01–0.15) to (0.4–0.99); angle 10°–30°, step size 0.75 mm, 1.5 mm, 3 mm]. Diffusion and tractography-derived parameters per stop criterion were compared using a repeated measure ANOVA including Bonferroni-corrected post hoc tests. Results: We found significant differences in all examined diffusion parameters between different stop criteria (main effect p < 0.001). We showed different influence of tracking parameters on diffusion parameters in examined muscles (main effect p ≤ 0.001). Conclusions: Statistically significant differences in fiber tracking results using different stop criteria were shown. Fiber tracking stop criteria do have an important influence on study results and should be considered in the development of study protocols and comparison of studies. We recommend a FA minimum of 0.10 and a step size lower than voxel size, e.g., a half with a constant ratio between step size and angle of 10°/mm

Diffusion tensor imaging of the human calf : Variation of inter- and intramuscle-specific diffusion parameters

Purpose: To investigate to what extent inter- and intramuscular variations of diffusion parameters of human calf muscles can be explained by age, gender, muscle location, and body mass index (BMI) in a specific age group (20-35 years). Materials and Methods: Whole calf muscles of 18 healthy volunteers were evaluated. Magnetic resonance imaging (MRI) was performed using a 3T scanner and a 16-channel Torso XL coil. Diffusion-weighted images were acquired to perform fiber tractography and diffusion tensor imaging (DTI) analysis for each muscle of both legs. Fiber tractography was used to separate seven lower leg muscles. Associations between DTI parameters and confounds were evaluated. All muscles were additionally separated in seven identical segments along the z-axis to evaluate intramuscular differences in diffusion parameters. Results: Fractional anisotropy (FA) and mean diffusivity (MD) were obtained for each muscle with low standard deviations (SDs) (SDFA: 0.01-0.02; SDMD: 0.07-0.14(10-3)). We found significant differences in FA values of the tibialis anterior muscle (AT) and extensor digitorum longus (EDL) muscles between men and women for whole muscle FA (two-sample t-tests; AT: P=0.0014; EDL: P=0.0004). We showed significant intramuscular differences in diffusion parameters between adjacent segments in most calf muscles (P <0.001). Whereas muscle insertions showed higher (SD 0.03-0.06) than muscle bellies (SD 0.01-0.03), no relationships between FA or MD with age or BMI were found. Conclusion: Inter- and intramuscular variations in diffusion parameters of the calf were shown, which are not related to age or BMI in this age group. Differences between muscle belly and insertion should be considered when interpreting datasets not including whole muscles