Antihistaminic effect of Bauhinia racemosa leaves

Bauhinia racemosa Lam. (Caesalpiniaceae) leaves have been used in the treatment of asthma traditionally and we therefore undertook this study to scientifically validate its benefit in asthma using suitable animal models. Antihistaminic principles are known to be useful in the treatment of asthma; hence, in the present work, the antihistaminic activity of an ethanol extract of B. racemosa (at a dose of 50 mg/kg, i.p.) was assessed using clonidine-induced catalepsy and haloperidol-induced catalepsy in Swiss albino mice. The results showed that the ethanol extract inhibits clonidine-induced catalepsy but there is no effect on haloperidol-induced catalepsy. This suggests that the inhibition is through an antihistaminic action and that there is no role of dopamine. Hence, we concluded that the ethanol extract has significant antihistaminic activity. The polar constituents in the ethanol extract of leaves of B. racemosa may be responsible for the antihistaminic activity and B. racemosa may therefore have a role in the treatment of asthma

Hydrodynamical analysis of symmetric nucleus-nucleus collisions at CERN/SPS energies

We present a coherent theoretical study of ultrarelativistic heavy-ion data obtained at the CERN/SPS by the NA35/NA49 Collaborations using 3+1-dimensional relativistic hydrodynamics. We find excellent agreement with the rapidity spectra of negative hadrons and protons and with the correlation measurements in two experiments: $S+S$ at 200 $AGeV$ and $Pb+Pb$ at 160 $AGeV$ (preliminary results). Within our model this implies that for $Pb+Pb$ ($S+S$) a quark-gluon-plasma of initial volume 174 $fm^3$ (24 $fm^3$) with a lifetime 3.4 $fm/c$ (1.5 $fm/c$) was formed. It is found that the Bose-Einstein correlation measurements do not determine the maximal effective radii of the hadron sources because of the large contributions from resonance decay at small momenta. Also within this study we present an NA49 acceptance corrected two-pion Bose-Einstein correlation function in the invariant variable, $Q_{inv}$.Comment: 21 pages, 11 Postscript figures (1 File, 775654 Bytes, has to be requested for submission via e.mail from [email protected]

Failing boys and moral panics: perspectives on the underachievement debate

The paper re-examines the underachievement debate from the perspective of the ‘discourse of derision’ that surrounds much writing in this area. It considers the contradictions and inconsistencies which underpin much of the discourse – from a reinterpretation of examination scores, to the conflation of the concepts of ‘under’ and ‘low’ achievement and finally to the lack of consensus on a means of defining and measuring the term underachievement. In doing so, this paper suggests a more innovative approach for understanding, re-evaluating and perhaps rejecting the notion of underachievement

Discovery, Optimization, and Characterization of ML417: A Novel and Highly Selective D3 Dopamine Receptor Agonist

To identify novel D3 dopamine receptor (D3R) agonists, we conducted a high-throughput screen using a β-arrestin recruitment assay. Counterscreening of the hit compounds provided an assessment of their selectivity, efficacy, and potency. The most promising scaffold was optimized through medicinal chemistry resulting in enhanced potency and selectivity. The optimized compound, ML417 (20), potently promotes D3R-mediated β-arrestin translocation, G protein activation, and ERK1/2 phosphorylation (pERK) while lacking activity at other dopamine receptors. Screening of ML417 against multiple G protein-coupled receptors revealed exceptional global selectivity. Molecular modeling suggests that ML417 interacts with the D3R in a unique manner, possibly explaining its remarkable selectivity. ML417 was also found to protect against neurodegeneration of dopaminergic neurons derived from iPSCs. Together with promising pharmacokinetics and toxicology profiles, these results suggest that ML417 is a novel and uniquely selective D3R agonist that may serve as both a research tool and a therapeutic lead for the treatment of neuropsychiatric disorders

Rotational Surfaces in L3\mathbb{L}^3 and Solutions in the Nonlinear Sigma Model

The Gauss map of non-degenerate surfaces in the three-dimensional Minkowski space are viewed as dynamical fields of the two-dimensional O(2,1) Nonlinear Sigma Model. In this setting, the moduli space of solutions with rotational symmetry is completely determined. Essentially, the solutions are warped products of orbits of the 1-dimensional groups of isometries and elastic curves in either a de Sitter plane, a hyperbolic plane or an anti de Sitter plane. The main tools are the equivalence of the two-dimensional O(2,1) Nonlinear Sigma Model and the Willmore problem, and the description of the surfaces with rotational symmetry. A complete classification of such surfaces is obtained in this paper. Indeed, a huge new family of Lorentzian rotational surfaces with a space-like axis is presented. The description of this new class of surfaces is based on a technique of surgery and a gluing process, which is illustrated by an algorithm.Comment: PACS: 11.10.Lm; 11.10.Ef; 11.15.-q; 11.30.-j; 02.30.-f; 02.40.-k. 45 pages, 11 figure

Comprehensive analysis of epigenetic clocks reveals associations between disproportionate biological ageing and hippocampal volume

The concept of age acceleration, the difference between biological age and chronological age, is of growing interest, particularly with respect to age-related disorders, such as Alzheimer’s Disease (AD). Whilst studies have reported associations with AD risk and related phenotypes, there remains a lack of consensus on these associations. Here we aimed to comprehensively investigate the relationship between five recognised measures of age acceleration, based on DNA methylation patterns (DNAm age), and cross-sectional and longitudinal cognition and AD-related neuroimaging phenotypes (volumetric MRI and Amyloid-β PET) in the Australian Imaging, Biomarkers and Lifestyle (AIBL) and the Alzheimer’s Disease Neuroimaging Initiative (ADNI). Significant associations were observed between age acceleration using the Hannum epigenetic clock and cross-sectional hippocampal volume in AIBL and replicated in ADNI. In AIBL, several other findings were observed cross-sectionally, including a significant association between hippocampal volume and the Hannum and Phenoage epigenetic clocks. Further, significant associations were also observed between hippocampal volume and the Zhang and Phenoage epigenetic clocks within Amyloid-β positive individuals. However, these were not validated within the ADNI cohort. No associations between age acceleration and other Alzheimer’s disease-related phenotypes, including measures of cognition or brain Amyloid-β burden, were observed, and there was no association with longitudinal change in any phenotype. This study presents a link between age acceleration, as determined using DNA methylation, and hippocampal volume that was statistically significant across two highly characterised cohorts. The results presented in this study contribute to a growing literature that supports the role of epigenetic modifications in ageing and AD-related phenotypes

Uncovering the heterogeneity and temporal complexity of neurodegenerative diseases with Subtype and Stage Inference

The heterogeneity of neurodegenerative diseases is a key confound to disease understanding and treatment development, as study cohorts typically include multiple phenotypes on distinct disease trajectories. Here we introduce a machine-learning technique\u2014Subtype and Stage Inference (SuStaIn)\u2014able to uncover data-driven disease phenotypes with distinct temporal progression patterns, from widely available cross-sectional patient studies. Results from imaging studies in two neurodegenerative diseases reveal subgroups and their distinct trajectories of regional neurodegeneration. In genetic frontotemporal dementia, SuStaIn identifies genotypes from imaging alone, validating its ability to identify subtypes; further the technique reveals within-genotype heterogeneity. In Alzheimer\u2019s disease, SuStaIn uncovers three subtypes, uniquely characterising their temporal complexity. SuStaIn provides fine-grained patient stratification, which substantially enhances the ability to predict conversion between diagnostic categories over standard models that ignore subtype (p = 7.18 7 10 124 ) or temporal stage (p = 3.96 7 10 125 ). SuStaIn offers new promise for enabling disease subtype discovery and precision medicine

Corrections for rooting volume and plant size reveal negative effects of neighbour presence on root allocation in peaplant

1. Plants are able to detect the presence of their neighbours below-ground. The associated root responses may affect plant performance, plant–plant interactions and community dynamics, but the extent and direction of these responses is heavily debated. 2. Some studies suggest that plants will over-proliferate roots in response to neighbours at the expense of reproduction, which was framed as a ‘tragedy of the commons’. Others propose an ‘ideal free distribution’ hypothesis stating that plants produce roots simply as a function of the amount of available nutrients. However, experimental evidence for either hypothesis that is unbiased by confounding effects of rooting volume and plant size in their experimental set-ups is still lacking. 3. We grew split-root pea plants in the presence or absence of a below-ground neighbour at a range of rooting volumes, while providing equal amounts of nutrients per plant. Path analyses were used to disentangle the direct effects of neighbour presence on allocation patterns from the confounding effects of rooting volume and plant size. 4. Within the chosen range of rooting volumes, the presence of a below-ground neighbour generally reduced plant root mass by 21% and total mass by 9%. A doubling of rooting volume generally increased plant root mass by 22% and total mass by 11%. Pod mass was only directly and positively correlated with vegetative mass. 5. The presence of a below-ground neighbour induced less root allocation but more pod allocation, whereas increased rooting volume caused a reduction in reproductive allocation. A large part of these effects, however, was indirectly mediated through the influence on plant total mass. 6. Synthesis. Not considering the effects of rooting volume and plant size may lead to misinterpretations of plant growth strategies in response to neighbours. Accounting for these factors, we found pea allocating less mass to roots in the presence of a below-ground neighbour. The obtained results can help to reconcile the various responses to below-ground neighbours as they are published in the literature