Docking and molecular dynamics studies of peripheral site ligand–oximes as reactivators of sarin-inhibited human acetylcholinesterase

In the present work, we performed docking and molecular dynamics simulations studies on two groups of long-tailored oximes designed as peripheral site binders of acetylcholinesterase (AChE) and potential penetrators on the blood brain barrier. Our studies permitted to determine how the tails anchor in the peripheral site of sarin-inhibited human AChE, and which aminoacids are important to their stabilization. Also the energy values obtained in the docking studies corroborated quite well with the experimental results obtained before for these oximes.     

RASPA: molecular simulation software for adsorption and diffusion in flexible nanoporous materials

A new software package, RASPA, for simulating adsorption and diffusion of molecules in flexible nanoporous materials is presented. The code implements the latest state-of-the-art algorithms for molecular dynamics and Monte Carlo (MC) in various ensembles including symplectic/measure-preserving integrators, Ewald summation, configurational-bias MC, continuous fractional component MC, reactive MC and Baker's minimisation. We show example applications of RASPA in computing coexistence properties, adsorption isotherms for single and multiple components, self- and collective diffusivities, reaction systems and visualisation. The software is released under the GNU General Public License.     

Morphological variation among the inner ears of extinct and extant baleen whales (Cetacea: Mysticeti)

Living mysticetes (baleen whales) and odontocetes (toothed whales) differ significantly in auditory function in that toothed whales are sensitive to high‐frequency and ultrasonic sound vibrations and mysticetes to low‐frequency and infrasonic noises. Our knowledge of the evolution and phylogeny of cetaceans, and mysticetes in particular, is at a point at which we can explore morphological and physiological changes within the baleen whale inner ear. Traditional comparative anatomy and landmark‐based 3D‐geometric morphometric analyses were performed to investigate the anatomical diversity of the inner ears of extinct and extant mysticetes in comparison with other cetaceans. Principal component analyses (PCAs) show that the cochlear morphospace of odontocetes is tangential to that of mysticetes, but odontocetes are completely separated from mysticetes when semicircular canal landmarks are combined with the cochlear data. The cochlea of the archaeocete Zygorhiza kochii and early diverging extinct mysticetes plot within the morphospace of crown mysticetes, suggesting that mysticetes possess ancestral cochlear morphology and physiology. The PCA results indicate variation among mysticete species, although no major patterns are recovered to suggest separate hearing or locomotor regimes. Phylogenetic signal was detected for several clades, including crown Cetacea and crown Mysticeti, with the most clades expressing phylogenetic signal in the semicircular canal dataset. Brownian motion could not be excluded as an explanation for the signal, except for analyses combining cochlea and semicircular canal datasets for Balaenopteridae. J. Morphol. 277:1599–1615, 2016. © 2016 Wiley Periodicals, Inc.     

Identifying the brain regions associated with acute spasticity in patients diagnosed with an ischemic stroke

Spasticity is a common impairment found in patients that have been diagnosed with a stroke. Little is known about the pathophysiology of spasticity at the level of the brain. This retrospective study was performed to identify an association between the area of the brain affected by an ischemic stroke and the presence of acute spasticity. Physical and occupational therapy assessments from all patients (n?=?441) that had suffered a stroke and were admitted into a local hospital over a 4-year period were screened for inclusion in this study. Subjects that fit the inclusion criteria were grouped according to the presence (n?=?42) or absence (n?=?129) of acute spasticity by the Modified Ashworth Scale score given during the hospital admission assessment. Magnetic resonance images from 20 subjects in the spasticity group and 52 from the control group were then compared using lesion density plots and voxel-based lesion–symptom mapping. An association of acute spasticity with the gray matter regions of the insula, basal ganglia, and thalamus was found in this study. White matter tracts including the pontine crossing tract, corticospinal tract, internal capsule, corona radiata, external capsule, and the superior fronto-occipital fasciculus were also found to be significantly associated with acute spasticity. This is the first study to describe an association between a region of the brain affected by an infarct and the presence of acute spasticity. Understanding the regions associated with acute spasticity will aid in understanding the pathophysiology of this musculoskeletal impairment at the level of the brain.     

Caspase 3 activation and PARP cleavage in lymphocytes from newborn babies of diabetic mothers with unbalanced glycaemic control

Several epidemiological studies showed that gestational diabetes mellitus is the most frequent metabolic disorder of pregnancy, the pathogenesis of which has yet to be completely clarified. The aim of this study was to investigate the presence and processing of caspase 3 (Casp3) and poly(ADP‐ribose) polymerase 1 (PARP1) in cord blood lymphocytes as markers of apoptosis in relation to glycaemic control during intrauterine life. Our results showed a specific positive correlation between the levels of active Casp3 (17–19 kDa) and the inactive form of PARP1 (89 kDa) in lymphocytes isolated from newborn babies of diabetic women with unbalanced glycaemic control, with a direct correlation between the activation of casp3 and the inactivation of PARP1, that makes lymphocytes unresponsive towards lipopolysaccharide stimulation, highlighting an altered functional response. Besides more studies are required to fully correlate the activation of the apoptotic process during the intrauterine life with the foetal health later in life, our study indicates that a cord blood lymphocyte, an easily accessible source, is informative about the activation of apoptotic stimuli in circulating cells of newborn babies in relation to the glycaemic control reached by the mother during pregnancy. Copyright © 2013 John Wiley & Sons, Ltd.     

Influence of Action-Effect Associations Acquired by Ideomotor Learning on Imitation

According to the ideomotor theory, actions are represented in terms of their perceptual effects, offering a solution for the correspondence problem of imitation (how to translate the observed action into a corresponding motor output). This effect-based coding of action is assumed to be acquired through action-effect learning. Accordingly, performing an action leads to the integration of the perceptual codes of the action effects with the motor commands that brought them about. While ideomotor theory is invoked to account for imitation, the influence of action-effect learning on imitative behavior remains unexplored. In two experiments, imitative performance was measured in a reaction time task following a phase of action-effect acquisition. During action-effect acquisition, participants freely executed a finger movement (index or little finger lifting), and then observed a similar (compatible learning) or a different (incompatible learning) movement. In Experiment 1, finger movements of left and right hands were presented as action-effects during acquisition. In Experiment 2, only right-hand finger movements were presented during action-effect acquisition and in the imitation task the observed hands were oriented orthogonally to participants’ hands in order to avoid spatial congruency effects. Experiments 1 and 2 showed that imitative performance was improved after compatible learning, compared to incompatible learning. In Experiment 2, although action-effect learning involved perception of finger movements of right hand only, imitative capabilities of right- and left-hand finger movements were equally affected. These results indicate that an observed movement stimulus processed as the effect of an action can later prime execution of that action, confirming the ideomotor approach to imitation. We further discuss these findings in relation to previous studies of action-effect learning and in the framework of current ideomotor approaches to imitation.