Familial neuralgia of occipital and intermedius nerves in a Chinese family

Cranial nerve neuralgia usually occurs sporadically. Nonetheless, familial cases of trigeminal neuralgia are not uncommon with a reported incidence of 1–2%, suggestive of an autosomal dominant inheritance. In contrast, familial occipital neuralgia is rarely reported with only one report in the literature. We present a Chinese family with five cases of occipital and nervus intermedius neuralgia alone or in combination in three generations. All persons afflicted with occipital neuralgia have suffered from paroxysmal ‘electric wave’-like pain for years. In the first generation, the father (index patient) was affected, in the second generation all his three daughters (with two sons spared) and in the third generation a daughter’s male offspring is affected. This familial pattern suggests an X-linked dominant or an autosomal dominant inheritance mode

Wind braking of magnetars

(adapted)Considering recent observations challenging the traditional magnetar model, we explore the wind braking of magnetars. There is evidence for strong multipole magnetic fields in active magnetars, but the dipole field inferred from spin down measurements may be strongly biased by a particle wind. Recent challenging observations of magnetars may be explained naturally in the wind braking scenario: (1) The supernova energies of magnetars are of normal value; (2) The non-detection in Fermi observations of magnetars; (3) The problem posed by the low-magnetic field soft gamma-ray repeaters; (4) The relation between magnetars and high magnetic field pulsars; (5) A decreasing period derivative during magnetar outbursts. Transient magnetars may still be magnetic dipole braking. This may explain why low luminosity magnetars are more likely to have radio emissions. In the wind braking scenario, magnetars are neutron stars with strong multipole field. For some sources, a strong dipole field may be no longer needed. A magnetism-powered pulsar wind nebula and a braking index smaller than three are the two predictions of the wind braking model.Comment: 34 pages, 1 table, 6 figures, accepted by Ap

Evaluating the Physicochemical Properties–Activity Relationship and Discovering New 1,2-Dihydropyridine Derivatives as Promising Inhibitors for PIM1-Kinase: Evidence from Principal Component Analysis, Molecular Docking, and Molecular Dynamics Studies

In this study, we evaluated the physicochemical properties related to the previously reported anticancer activity of a dataset comprising thirty 1,2-dihydropyridine derivatives. We utilized Principal Component Analysis (PCA) to identify the most significant influencing factors. The PCA analysis showed that the first two principal components accounted for 59.91% of the total variance, indicating a strong correlation between the molecules and specific descriptors. Among the 239 descriptors analyzed, 18 were positively correlated with anticancer activity, clustering with the 12 most active compounds based on their IC50 values. Six of these variables—LogP, Csp3, b_1rotN, LogS, TPSA, and lip_don—are related to drug-likeness potential. Thus, we then ranked the 12 compounds according to these six variables and excluded those violating the drug-likeness criteria, resulting in a shortlist of nine compounds. Next, we investigated the binding affinity of these nine shortlisted compounds with the use of molecular docking towards the PIM-1 Kinase enzyme (PDB: 2OBJ), which is overexpressed in various cancer cells. Compound 6 exhibited the best docking score among the docked compounds, with a docking score of −11.77 kcal/mol, compared to −12.08 kcal/mol for the reference PIM-1 kinase inhibitor, 6-(5-bromo-2-hydroxyphenyl)-2-oxo-4-phenyl-1,2-dihydropyridine-3-carbonitrile. To discover new PIM-1 kinase inhibitors, we designed nine novel compounds featuring hybrid structures of compound 6 and the reference inhibitor. Among these, compound 31 displayed the best binding affinity, with a docking score of −13.11 kcal/mol. Additionally, we performed PubChem database mining using the structure of compound 6 and the similarity search tool, identifying 16 structurally related compounds with various reported biological properties. Among these, compound 52 exhibited the best binding affinity, with a docking score of −13.03 kcal/mol. Finally, molecular dynamics (MD) studies were conducted to confirm the stability of the protein–ligand complexes obtained from docking the studied compounds to PIM-1 kinase, validating the potential of these compounds as PIM-1 kinase inhibitors

IgG from patients with pulmonary arterial hypertension and/or systemic sclerosis binds to vascular smooth muscle cells and induces cell contraction.

International audienceOBJECTIVES: Pulmonary arterial hypertension (PAH) is characterised by remodelling of pulmonary arteries with enhanced vascular smooth muscle cell (VSMC) contraction, migration and proliferation. The authors investigated the presence of antibodies to human VSMCs in the serum of patients with systemic sclerosis with or without PAH and idiopathic PAH (iPAH). METHODS AND RESULTS: Antibodies to VSMCs were detected by immunofluorescence in sera from healthy controls and patients with scleroderma without PAH, scleroderma-associated PAH and iPAH. Serum IgG from these patients induced contraction of VSMCs in a collagen matrix in contrast with IgG from healthy controls. Several protein spots of interest and target antigens were identified by two-dimensional immunoblotting and MS, including stress-induced phosphoprotein 1 and α-enolase. Finally, antibodies to stress-induced phosphoprotein 1 were detected by ELISA in sera from 84%, 76% and 24% of patients with scleroderma without PAH, scleroderma-associated PAH and iPAH, respectively, compared with only 3% of healthy controls. CONCLUSION: The authors have identified IgG that binds to VSMCs in the serum of patients with scleroderma and iPAH. These antibodies may be pathogenic by modulating vascular contraction. The target antigens of these antibodies are stress-induced phosphoprotein 1 and α-enolase