instruction:
In this task, you're given a paragraph from the research paper and your task is to generate a suitable title for the research paper based on the given paper. Under 100 words is a good title length.
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Ramsay Hunt syndrome (RHS) is characterized by varicella zoster virus (VZV) infection in the geniculate ganglion of the facial nerve. It typically presents with ipsilateral facial palsy and vesicles in the external auditory canal [1] . Recognizing atypical clinical manifestations of RHS, though not frequently reported, is of clinical importance for clinicians. For instance, RHS without vesicles, condition known as zoster sine herpete [2] , is difficult to distinguish itself from Bell's palsy. Although the vestibulocochlear nerve is frequently co-involved during the course of RHS, multiple lower cranial nerve involvement has rarely been described in the literature [5] [6] [7] [8] [9] [10] [11] [12] . Additionally, laryngitis due to VZV associated with RHS is not a well-recognized clinical entity. We herein report a case of Ramsay Hunt syndrome with zoster pharyngitis involving multiple lower cranial nerves. A 66-year-old woman with a history of hypertension was hospitalized because of progressive dizziness, right-side facial weakness and dysphagia. The patient was in her usual state of health until 6 days before admission, when sore throat and odynophagia developed, associated with subjective fevers and anorexia. Two days before admission, the patient reported dizziness, right-side facial weakness associated with pain radiating to the right ear, and dysphagia. The patient denied headache, photophobia, neck stiffness, nausea or vomiting. On the morning of admission, the patient developed right-side tinnitus, unsteady gait and inability to close the right eye. On physical examination, the patient appeared to be in mild distress. The temperature was 101.8 8F, blood pressure 176/93 mm Hg, pulse 102 beats per minute, respirations 20 breaths per minute and oxygen saturation 97% on room air. Her heart sounds were regular without murmurs and her lungs were clear to auscultation. On otologic examination, a few vesicles were observed in the external auditory canal of the right ear with a normal tympanic membrane. Neurological examination revealed peripheral facial nerve palsy (VII), with involvement of the left vestibulocochlear nerve (VIII), glossopharyngeal nerve (IX) and vagus nerve (X) ( Table 1) . Spinal accessory nerve (XI) and hypoglossal nerve (XII) were intact. Flexible laryngoscopic examination revealed erythema and erosive lesions on the right side of the epiglottis and arytenoid. There was an asymmetry of the soft palate. A biopsy of the erosive lesions was not performed. A non-contrast computed tomography of the head and temporal bone revealed no abnormalities. Ramsay Hunt syndrome with laryngitis due to varicella zoster virus was suspected and the patient was started on acyclovir and steroid therapy. After the completion of a 7-day course of the combination therapy, the patient's neurological symptoms improved except for the facial nerve palsy. Healed erosions on the IDCases 2 (2015) 47-48 A B S T R A C T Ramsay Hunt syndrome is characterized by varicella zoster virus infection affecting the geniculate ganglion of the facial nerve. It typically presents with vesicles in the external auditory canal associated with auricular pain and peripheral facial nerve paralysis. Although vestibulocochlear nerve is frequently co-involved during the course of Ramsay Hunt syndrome, multiple lower cranial nerve involvement has rarely been described in the literature. In addition, laryngitis due to varicella zoster virus is a diagnostic challenge due to its unfamiliarity among clinicians. We report a case of Ramsay Hunt syndrome with laryngitis involving multiple lower cranial nerves.
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Ramsay Hunt syndrome and zoster laryngitis with multiple cranial nerve involvement-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/)


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Background: Nonadditivity in fitness effects from two or more mutations, termed epistasis, can result in compensation of deleterious mutations or negation of beneficial mutations. Recent evidence shows the importance of epistasis in individual evolutionary pathways. However, an unresolved question in molecular evolution is how often and how significantly fitness effects change in alternative genetic backgrounds. Results: To answer this question, we quantified the effects of all single mutations and double mutations between all positions in the IgG-binding domain of protein G (GB1). By observing the first two steps of all possible evolutionary pathways using this fitness profile, we were able to characterize the extent and magnitude of pairwise epistasis throughout an entire protein molecule. Furthermore, we developed a novel approach to quantitatively determine the effects of single mutations on structural stability (DDG U ). This enabled determination of the importance of stability effects in functional epistasis. Conclusions: Our results illustrate common biophysical mechanisms for occurrences of positive and negative epistasis. Our results show pervasive positive epistasis within a conformationally dynamic network of residues. The stability analysis shows that significant negative epistasis, which is more common than positive epistasis, mostly occurs between combinations of destabilizing mutations. Furthermore, we show that although significant positive epistasis is rare, many deleterious mutations are beneficial in at least one alternative mutational background. The distribution of conditionally beneficial mutations throughout the domain demonstrates that the functional portion of sequence space can be significantly expanded by epistasis.
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Article A Comprehensive Biophysical Description of Pairwise Epistasis throughout an Entire Protein Domain


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Gene 1 of the human coronavirus HCV 229E encompasses approximately 20.7 kb and contains two overlapping open reading frames, ORF 1a and ORF 1b. The downstream ORF 1b is expressed by a mechanism involving (01) ribosomal frameshifting. Translation of mRNA 1, which is thought to be equivalent to the viral genomic RNA, results in the synthesis of two large polyproteins, pp1a and pp1ab. These polyproteins contain motifs characteristic of papain-like and 3C-like proteinases, RNA-dependent RNA polymerases, helicases, and metal-binding proteins. In this study, we have produced pp1ab-specific monoclonal antibodies and have used them to detect an intracellular, 105-kDa viral polypeptide that contains the putative RNA polymerase domain. Furthermore, using trans cleavage assays with bacterially expressed HCV 229E 3Clike proteinase, we have demonstrated that the 105-kDa polypeptide is released from pp1ab by cleavage at the dipeptide bonds Gln-4068/Ser-4069 and Gln-4995/Ala-4996. These data contribute to the characterization of coronavirus 3C-like proteinase-mediated processing of pp1ab and provide the first identification of an HCV 229E ORF 1ab-encoded polypeptide in virus-infected cells. ᭧
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Characterization of a 105-kDa Polypeptide Encoded in Gene 1 of the Human Coronavirus HCV 229E