Characterization of beta-lactamase from Mycobacterium butyricum ATCC 19979

beta-lactamase has been purified to a homogeneous state from Mycobacterium butyricum ATCC 19979. The molecular weight (Mr = 29,000) and the isoelectric point (4,0) of the enzyme have been determined. The enzyme showed both penicillinase and cephalosporinase activity, but had relatively more of the former. With respect to substrate-profile the enzyme resembled the plasmid specified TEM-type beta-lactamases commonly encountered in Gram-negative bacteria. The enzyme was insensitive to p-chloromercuribenzoate, sodium chloride, or iodine inhibition.     

A neural network model for kindling of focal epilepsy: basic mechanism

A simple neural network model is proposed for kindling — the phenomenon of generating epilepsy by means of repeated electrical stimulation. The model satisfies Dale's hypothesis, incorporates a Hebb-like learning rule and has low periodic activity in absence of shocks. Many of the experimental observations are reproduced and some new experiments are suggested. It is proposed that the main reason for kindling is the formation of a large number of excitatory synaptic connections due to learning.     

Exploration of highly selective fluorogenic ‘on–off' chemosensor for H2PO4− ions: ICT‐based sensing and ATPase activity profiling

Abstract In this study, the recognition contour of Chemosensor 1 was investigated using semiaqueous methanol (X_H, mole fraction = 0.31) for a range of anions and bioactive species. Host–receptor signalling based on the internal charge transfer mechanism for Chemosensor 1 was explored and reported. Structure of Chemosensor 1 and its plausible anion coordination based on hydrogen bonding is complemented with density functional theory. Consequently, we investigated the applicability of the synthesized probe in blood plasma, urine, tap water samples, and for monitoring of ATP in lysosomes by apyrase enzyme.     

Novel insights into the dynamics behavior of glucagon-like peptide-1 receptor with its small molecule agonists

Abstract

The glucagon-like peptide-1 receptor (GLP-1R) is a well-known target of therapeutics industries for the treatment of various metabolic diseases like type 2 diabetes and obesity. The structural–functional relationships of small molecule agonists and GLP-1R are yet to be understood. Therefore, an attempt was made on structurally known GLP-1R agonists (Compound 1, Compound 2, Compound A, Compound B, and (S)-8) to study their interaction with the extracellular domain of GLP-1R. In this study, we explored the dynamics, intrinsic stability, and binding mechanisms of these molecules through computational modeling, docking, molecular dynamics (MD) simulations and molecular mechanics Poisson–Boltzmann surface area (MM/PBSA) binding free energy estimation. Molecular docking study depicted that hydrophobic interaction (pi–pi stacking) plays a crucial role in maintaining the stability of the complex, which was also supported by intermolecular analysis from MD simulation study. Principal component analysis suggested that the terminal ends along with the turns/loops connecting adjacent helix and strands exhibit a comparatively higher movement of main chain atoms in most of the complexes. MM/PBSA binding free energy study revealed that non-polar solvation (van der Waals and electrostatic) energy subsidizes significantly to the total binding energy, and the polar solvation energy opposes the binding agonists to GLP-1R. Overall, we provide structural features information about GLP-1R complexes that would be conducive for the discovery of new GLP-1R agonists in the future for the treatment of various metabolic diseases.

Communicated by Ramaswamy H. Sarma     

Refinement of Imaging Predictors of Recurrent Events following Transient Ischemic Attack and Minor Stroke

Background

TIA and minor stroke have a high risk of recurrent stroke. Abnormalities on CT/CTA and MRI predict recurrent events in TIA and minor stroke. However there are many other imaging abnormalities that could potentially predict outcome that have not been assessed in this population. Also the definition of recurrent events used includes deterioration due to stroke progression or recurrent stroke and whether imaging is either of these is not known.

Aims

To improve upon the clinical, CT/CTA and MRI parameters that predict recurrent events after TIA and minor stroke by assessing further imaging parameters. Secondary aim was to explore predictors of stroke progression versus recurrent stroke.

Methods

510 consecutive TIA and minor stroke patients had CT/CTA and most had MRI. Primary outcome was recurrent events (stroke progression or recurrent stroke) within 90 days. Further imaging parameters were assessed for prediction of recurrent events (combined outcome of stroke progression and recurrent stroke). We also explored predictors of symptom progression versus recurrence individually.

Results

36 recurrent events (36/510, 7.1% (95% CI: 5.0–9.6)) including 19 progression and 17 recurrent strokes. On CT/CTA: white matter disease, prior stroke, aortic arch focal plaque≥4 mm, or intraluminal thrombus did not predict recurrent events (progression or recurrent stroke). On MRI: white matter disease, prior stroke, and microbleeds did not predict recurrent events. Parameters predicting the individual outcome of symptom progression included: ongoing symptoms at initial assessment, symptom fluctuation, intracranial occlusion, intracranial occlusion or stenosis, and the CT/CTA metric. No parameter was strongly predictive of a distinct recurrent stroke.

Conclusions

There was no imaging parameter that could improve upon our original CT/CTA or MRI metrics to predict the combined outcome of stroke progression or a recurrent stroke after TIA and minor stroke. We are better at using imaging to predict stroke progression rather than recurrent stroke.     

Alterations in Cortical Sensorimotor Connectivity following Complete Cervical Spinal Cord Injury: A Prospective Resting-State fMRI Study

Functional magnetic resonance imaging (fMRI) studies have demonstrated alterations during task-induced brain activation in spinal cord injury (SCI) patients. The interruption to structural integrity of the spinal cord and the resultant disrupted flow of bidirectional communication between the brain and the spinal cord might contribute to the observed dynamic reorganization (neural plasticity). However, the effect of SCI on brain resting-state connectivity patterns remains unclear. We undertook a prospective resting-state fMRI (rs-fMRI) study to explore changes to cortical activation patterns following SCI. With institutional review board approval, rs-fMRI data was obtained in eleven patients with complete cervical SCI (>2 years post injury) and nine age-matched controls. The data was processed using the Analysis of Functional Neuroimages software. Region of interest (ROI) based analysis was performed to study changes in the sensorimotor network using pre- and post-central gyri as seed regions. Two-sampled t-test was carried out to check for significant differences between the two groups. SCI patients showed decreased functional connectivity in motor and sensory cortical regions when compared to controls. The decrease was noted in ipsilateral, contralateral, and interhemispheric regions for left and right precentral ROIs. Additionally, the left postcentral ROI demonstrated increased connectivity with the thalamus bilaterally in SCI patients. Our results suggest that cortical activation patterns in the sensorimotor network undergo dynamic reorganization following SCI. The presence of these changes in chronic spinal cord injury patients is suggestive of the inherent neural plasticity within the central nervous system.     

Stability of grassland production is robust to changes in the consumer food web

Theory predicts that consumers may stabilise or destabilise plant production depending on model assumptions, and tests in aquatic food webs suggest that trophic interactions are stabilising. We quantified the effects of trophic interactions on temporal variability (standard deviation) and temporal stability (mean/standard deviation) of grassland biomass production and the plant diversity–stability relationship by experimentally removing heterotrophs (large vertebrates, arthropods, foliar and soil fungi) from naturally and experimentally assembled grasslands of varying diversity. In both grassland types, trophic interactions proportionately decreased plant community biomass mean and variability over the course of 6 years, leading to no net change in temporal stability or the plant diversity–stability relationship. Heterotrophs also mediated plant coexistence; their removal reduced diversity in naturally assembled grasslands. Thus, herbivores and fungi reduce biomass production, concurrently reducing the temporal variability of energy and material fluxes. Because of this coupling, grassland stability is robust to large food web perturbations.     

Regular mosaic pattern development: A study of the interplay between lateral inhibition, apoptosis and differential adhesion

Background

A significant body of literature is devoted to modeling developmental mechanisms that create patterns within groups of initially equivalent embryonic cells. Although it is clear that these mechanisms do not function in isolation, the timing of and interactions between these mechanisms during embryogenesis is not well known. In this work, a computational approach was taken to understand how lateral inhibition, differential adhesion and programmed cell death can interact to create a mosaic pattern of biologically realistic primary and secondary cells, such as that formed by sensory (primary) and supporting (secondary) cells of the developing chick inner ear epithelium.

Results

Four different models that interlaced cellular patterning mechanisms in a variety of ways were examined and their output compared to the mosaic of sensory and supporting cells that develops in the chick inner ear sensory epithelium. The results show that: 1) no single patterning mechanism can create a 2-dimensional mosaic pattern of the regularity seen in the chick inner ear; 2) cell death was essential to generate the most regular mosaics, even through extensive cell death has not been reported for the developing basilar papilla; 3) a model that includes an iterative loop of lateral inhibition, programmed cell death and cell rearrangements driven by differential adhesion created mosaics of primary and secondary cells that are more regular than the basilar papilla; 4) this same model was much more robust to changes in homo- and heterotypic cell-cell adhesive differences than models that considered either fewer patterning mechanisms or single rather than iterative use of each mechanism.

Conclusion

Patterning the embryo requires collaboration between multiple mechanisms that operate iteratively. Interlacing these mechanisms into feedback loops not only refines the output patterns, but also increases the robustness of patterning to varying initial cell states.