Waardenburg syndrome Type II

Two rare cases of Waardenburg type II are reported. First case had three main features of WS-profound SN hearing loss, hetrochromia iris and white forelock of hair. Second case had moderate SNHL and depigmentation of hair. Key words: Hetrochromia iris, white forelock hair.     

Evidence that genetic deletion of the TNF receptor p60 or p80 inhibits Fas mediated apoptosis in macrophages

Almost 19 members of the tumor necrosis factor (TNF) superfamily have been identified that interact with 29 different receptors. Whether these receptors communicate with each other is not understood. Recently, we have shown that receptor activator of NF-kappaB ligand signaling is modulated by genetic deletion of the TNF receptor. In the current report, we investigated the possibility of a cross-talk between Fas and TNF-alpha signaling pathway in macrophage cell lines derived from wild-type (WT) mice and from mice with genetic deletion of the type 1 TNF receptor (p60(-/-)), the type 2 TNF receptor (p80(-/-)), or both receptors (p60(-/-)p80(-/-)). We found that the macrophages expressing TNF receptors were highly sensitive to apoptosis induced by anti-Fas. The genetic deletion of TNF receptors, however, made the cells resistance to anti-Fas-induced apoptosis. Anti-Fas induced activation of caspase-3 and PARP cleavage in WT cells but not in TNF receptor-deleted cells. This difference was found to be independent of the expression of Fas, Fas-associated protein with death domain (FADD) or TNF receptor-associated death domain (TRADD). We found that anti-Fas induced recruitment of TNFR1 into Fas-complex. We also found that TRADD, which mediates TNF signaling, was constitutively bound to Fas receptor in TNF receptor-deleted cells but not in wild-type cells. Transient transfection of TNFR1 in TNFR1-deleted cells sensitized them to anti-Fas-induced apoptosis. Overall our results demonstrate that Fas signaling is modulated by the TNF receptors and thus provide the evidence of cross-talk between the receptors of two cytokines.     

Complete and incomplete lower motor neuron facial palsy in post-COVID-19 mucormycosis

Purpose:To study facial nerve palsy (FNP) in post-COVID-19-mucormycosis patients and its ocular complications, report different presentations of FNP in such patients, and propose its etiopathogenesis based on presentation and clinico-radiologic localization.Methods:A prospective cohort study was carried out in patients of post-COVID-19-mucormycosis who presented at our tertiary center, over a period of 3 months. Motor and sensory examination of the facial nerve was done to diagnose FNP and localize the lesion clinically. Slit-lamp examination was done for grading corneal involvement. MRI brain, orbit, and paranasal sinuses (PNS) with contrast were studied to find involvement along the facial nerve. It was assessed whether this site of lesion corresponded with clinical localization. Data were analyzed using the percentage of total cases and Fisher’s test.Results:A total of 300 patients with post-COVID-19 mucormycosis were examined, of which 30 (10%) patients were found to have FNP. All were lower motor neuron (LMN) type and were associated with corneal complications. The most common site clinically was distal to the chorda tympani (66.66%) and radiologically was infratemporal (IT) fossa (63.4%). The clinical localization significantly correlated with the radiological findings (P = 0.012). Twenty percent of patients showed incomplete involvement of facial musclesConclusion:FNP was found to be of LMN type. The most common site of insult was IT fossa. There was a good clinico-radiological correspondence of lesions. Isolated lesions were also found along the peripheral nerve course, presenting as incomplete facial palsy. Recognition of FNP in post-COVID-19 mucormycosis, in all its variable forms, is important to manage corneal complications.     

Dipole tensor-based atomic-resolution structure determination of a nanocrystalline protein by solid-state NMR

Magic-angle spinning (MAS) solid-state NMR (SSNMR) techniques have emerged in recent years for solving complete structures of uniformly labeled proteins lacking macroscopic order. Strategies used thus far have relied primarily on semiquantitative distance restraints, analogous to the nuclear Overhauser effect (NOE) routinely used in solution NMR. Here, we present a complementary approach for using relative orientations of molecular fragments, determined from dipolar line shapes. Whereas SSNMR distance restraints typically have an uncertainty of approximately 1 A, the tensor-based experiments report on relative vector (pseudobond) angles with precision of a few degrees. By using 3D techniques of this type, vector angle (VEAN) restraints were determined for the majority of the 56-residue B1 immunoglobulin binding domain of protein G [protein GB1 (a total of 47 HN-HN, 49 HN-HC, and 12 HA-HB restraints)]. By using distance restraints alone in the structure calculations, the overall backbone root-mean-square deviation (bbRMSD) was 1.01 +/- 0.13 A (1.52 +/- 0.12 A for all heavy atoms), which improved to 0.49 +/- 0.05 A (1.19 +/- 0.07 A) on the addition of empirical chemical shift [torsion angle likelihood obtained from shift and sequence similarity (TALOS)] restraints. VEAN restraints further improved the ensemble to 0.31 +/- 0.06 A bbRMSD (1.06 +/- 0.07 A); relative to the structure with distances alone, most of the improvement remained (bbRMSD 0.64 +/- 0.09 A; 1.29 +/- 0.07 A) when TALOS restraints were removed before refinement. These results represent significant progress toward atomic-resolution protein structure determination by SSNMR, capabilities that can be applied to a large range of membrane proteins and fibrils, which are often not amenable to solution NMR or x-ray crystallography.