ABSTRACT
The representability and transferability of effective pair potentials used in multiscale simulations of soft matter systems is ill understood. In this paper, we study liquid state systems composed of n-alkanes, the coarse-grained (CG) potential of which may be assumed pairwise additive and has been obtained using the conditional reversible work (CRW) method. The CRW method is a free-energy-based coarse-graining procedure, which, by means of performing the coarse graining at pair level, rigorously provides a pair potential that describes the interaction free energy between two mapped atom groups (beads) embedded in their respective chemical environments. The pairwise nature of the interactions combined with their dependence on the chemically bonded environment makes CRW potentials ideally suited in studies of chemical transferability. We report CRW potentials for hexane using a mapping scheme that merges two heavy atoms in one CG bead. It is shown that the model is chemically and thermodynamically transferable to alkanes of different chain lengths in the liquid phase at temperatures between the melting and the boiling point under atmospheric (1 atm) pressure conditions. It is further shown that CRW-CG potentials may be readily obtained from a single simulation of the liquid state using the free energy perturbation method, thereby providing a fast and versatile molecular coarse graining method for aliphatic molecules.
ABSTRACT
Based on gene expression data, we tested the P8A-CCL2 variant of the chemokine CCL2, able to interfere with the chemotactic properties of the parental molecule, in relapsing-remitting (RR)-EAE SJL. Only preventive treatment significantly delayed disease onset in a dose dependent manner. P8A-CCL2 administration, however, decreased demyelination, axonal loss and number of CNS infiltrating T cells and macrophages. Immunological analysis revealed that P8A-CCL2 does not act on Ag-specific T cell proliferation and does not interfere with the differentiation of IFNgamma-releasing effectors T cells. These results suggest that the therapeutic mechanism of P8A-CCL2 may rely on interference with immune cell recruitment.
Subject(s)
Chemokine CCL2/pharmacology , Chemotaxis, Leukocyte/drug effects , Encephalomyelitis, Autoimmune, Experimental/drug therapy , Encephalomyelitis, Autoimmune, Experimental/immunology , Myelin Sheath/drug effects , Adult , Animals , Cell Proliferation/drug effects , Chemokine CCL2/chemical synthesis , Chemokine CCL2/therapeutic use , Chemotaxis, Leukocyte/immunology , Disease Models, Animal , Dose-Response Relationship, Drug , Encephalomyelitis, Autoimmune, Experimental/physiopathology , Female , Humans , Immunologic Factors/pharmacology , Immunologic Factors/therapeutic use , Interferon-gamma/metabolism , Macrophages/drug effects , Macrophages/immunology , Male , Mice , Mice, Inbred C57BL , Middle Aged , Myelin Sheath/immunology , Myelin Sheath/pathology , Neuroprotective Agents/pharmacology , Neuroprotective Agents/therapeutic use , T-Lymphocytes/drug effects , T-Lymphocytes/immunology , Wallerian Degeneration/drug therapy , Wallerian Degeneration/immunology , Wallerian Degeneration/physiopathologySubject(s)
Contrast Media/pharmacology , Dog Diseases/diagnostic imaging , Kidney Diseases/veterinary , Kidney/diagnostic imaging , Polysaccharides/pharmacology , Animals , Blood Pressure/drug effects , Body Weight , Dog Diseases/physiopathology , Dogs , Female , Heart Rate/drug effects , Kidney Diseases/diagnostic imaging , Kidney Diseases/physiopathology , Kidney Function Tests/methods , Kidney Function Tests/veterinary , Male , Respiration/drug effects , Statistics, Nonparametric , Ultrasonography, Doppler, Color/methods , Ultrasonography, Doppler, Color/veterinaryABSTRACT
This case report describes the clinical and neuropathological findings in three young English bulldogs affected by cerebellar cortical degeneration. The dogs, born from the same parents, were presented with clinical signs indicating progressive cerebellar dysfunction: a wide-based stance, severe cerebellar ataxia characterised by marked hypermetria, spasticity, and intention tremors of the head and trunk with loss of balance. On histopathological examination, lesions were confined to the cerebellum and consisted of diffuse degenerative cortical lesions, and there was a loss of Purkinje and granule cells. The history, clinical signs and neuropathological findings confirmed the diagnosis of cerebellar cortical degeneration. To the authors' knowledge, this is the first report of cerebellar cortical degeneration in the English bulldog.
Subject(s)
Dog Diseases/diagnosis , Spinocerebellar Degenerations/veterinary , Animals , Cerebellar Ataxia/diagnosis , Cerebellar Ataxia/veterinary , Diagnosis, Differential , Dog Diseases/genetics , Dog Diseases/pathology , Dogs , Male , Neurologic Examination/veterinary , Pedigree , Spinocerebellar Degenerations/diagnosisABSTRACT
The present paper reports the clinical and neuropathological findings in two cats with a neuropathologically confirmed diagnosis of necrosis of the hippocampus and piriform lobe. The cats were presented because of acute onset of behavioural changes and complex partial seizures. The neurological examination suggested a forebrain lesion. The results of blood examination were within the normal range, and the cerebrospinal fluid (CSF) analysis and computed tomography (CT) scan in one cat did not show any abnormality. Despite therapy with diazepam (Valium; Roche) there was deterioration of the clinical signs and the cats were euthanased. The neuropathological examination revealed hippocampal necrosis that included the piriform lobe.
