Spatial relationships between polymers in Sitka spruce: proton spin-diffusion studies

The spatial arrangement of polymers in Sitka spruce (Picea sitchensis) was investigated by NMR proton spin-diffusion studies, supplemented by deuterium-exchange experiments monitored by FTIR spectroscopy. The FTIR spectra of earlywood sections after vapour-phase exchange with deuterium oxide showed that 43% of the hydroxyl groups were accessible to deuteration. This value is lower than predicted in the absence of aggregation of cellulose microfibrils into larger units, but greater than the predicted level of deuteration if 3.5-nm microfibrils surrounded by hemicellulose sheaths were aggregated into 4×4 arrays without space for deuterium oxide to penetrate between the microfibrils. The rate of proton spin diffusion between lignin and cellulose was consistent with the presence of microfibril arrays with approximately these dimensions and with lignin located outside them, in both earlywood and latewood. Proton spin-diffusion data for hemicelluloses were complicated by difficulties in assigning signals to glucomannans and xylans, but there was evidence for the spatial association of one group of hemicelluloses, including acetylated glucomannans, with cellulose surfaces, while another group of hemicelluloses was in spatial proximity to lignin. These data are consistent with a number of nanoscale models for the Sitka spruce cell wall, including a model in which glucomannans are associated with microfibril surfaces within the aggregate and water can penetrate partially between these surfaces, and one in which all non-cellulosic polymers and water are excluded from the interior of each microfibril aggregate

Malignant lymphoma presenting as bilateral sensorineural hearing loss-A case report

Bilateral Sensorineural Hearing Loss is a rare disease that is often associated with other complex medical conditions. Primary central nervous system lymphoma is an uncommon and aggressive variant of non-Hodgkin lymphoma that can mimic many other neurological diseases. Herein, we present a rare case of lymphoma of the CNS as the etiology for progressive SSNHL. We describe a 58-year-old male with previous IgG4-disease presentation who was diagnosed with progressive sensorineural hearing loss. The condition evolved rapidly despite proper, conventional therapy. The patient acquired vestibular symptoms and other cranial nerve deficiencies and he was diagnosed with intracranial lymphoma, mainly in the cerebellar region. This case demonstrates that rare intracranial lymphoma can present initially as sensorineural hearing loss. A higher suspicion for malignancy should be held in mind for patients with a history of IgG4-related diseases and for patients presenting with progressing bilateral SSNHL that is not responding to therapy.Peer reviewe

Effects of social distancing on the incidence of Bell's palsy and sudden sensorineural hearing loss

Background The aetiology of idiopathic facial nerve palsy (Bell's palsy, BP) and sudden sensorineural hearing loss (SSNHL) are not known. It has been proposed that common respiratory tract viruses play a part in the pathophysiology of these diseases. Objectives The incidence of many infectious diseases decreased during the lockdown of the society that took place during the COVID-19 pandemic. We investigated a possible change in the incidence of BP and SSNHL during the lock-down. Material and Methods We searched the patient records for all BP and SSNHL cases between 1 Jan 2017 - 31 Aug 2020 at the hospital district of Helsinki and Uusimaa that covers a population of about 1.2 million. Results The mean monthly incidence on BP decreased during the COVID-19 pandemic lock-down. No change in the SSNHL incidence was discovered. Conclusions and Significance There is reason to speculate that one aetiologic reason for BP are transmittable respiratory tract pathogens.Peer reviewe

Patient-Reported Control of Asthma, Nasal Polyposis, and Middle-Ear Symptoms in NSAID-Exacerbated Respiratory Disease

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Intracellular coordination of potyviral RNA functions in infection

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Dynamics of Protein Accumulation from the 3 ' End of Viral RNA Are Different from Those in the Rest of the Genome in Potato Virus A Infection

One large open reading frame (ORF) encodes 10 potyviral proteins. We compared the accumulation of cylindrical inclusion (CI) protein from the middle, coat protein (CP) from the 3'end, and Renilla luciferase (RLUC) from two distinct locations in potato virus A (PVA) RNA. 5' RLUC was expressed from an rluc gene inserted between the P1 and helper component proteinase (HCPro) cistrons, and 3' RLUC was expressed from the gene inserted between the RNA polymerase and CP cistrons. Viral protein and RNA accumulation were quantitated (i) when expressed from PVA RNA in the presence of ectopically expressed genome-linked viral protein (VPg) and auxiliary proteins and (ii) at different time points during natural infection. The rate and timing of 3' RLUC and CP accumulation were found to be different from those of 5' RLUC and Cl. Ectopic expression of VPg boosted PVA RNA, 3' RLUC, and, together with HCPro, CP accumulation, whereas 5' RLUC and CI accumulation remained unaffected regardless of the increased viral RNA amount. In natural infection, the rate of the noteworthy minute early accumulation of 3' RLUC accelerated toward the end of infection. 5' RLUC accumulation, which was already pronounced at 2 days postinfection, increased moderately and stabilized to a constant level by day 5, whereas PVA RNA and CP levels continued to increase throughout the infection. We propose that these observations connect with the mechanisms by which potyvirus infection limits CP accumulation during early infection and specifically supports its accumulation late in infection, but follow-up studies are required to understand the mechanism of how this occurs. IMPORTANCE The results of this study suggest that the dynamics of potyviral protein accumulation are regulated differentially from the 3' end of viral RNA than from the rest of the genome, the significance of which would be to satisfy the needs of replication early and particle assembly late in infection.Peer reviewe

Genome-wide association analysis reveals variants on chromosome 19 that contribute to childhood risk of chronic otitis media with effusion

To identify genetic risk factors of childhood otitis media (OM), a genome-wide association study was performed on Finnish subjects, 829 affected children, and 2118 randomly selected controls. The most significant and validated finding was an association with an 80 kb region on chromosome 19. It includes the variants rs16974263 (P = 1.77 x 10(-7), OR = 1.59), rs268662 (P = 1.564 x 10(-6), OR = 1.54), and rs4150992 (P = 3.37 x 10(-6), OR = 1.52), and harbors the genes PLD3, SERTAD1, SERTAD3, HIPK4, PRX, and BLVRB, all in strong linkage disequilibrium. In a sub-phenotype analysis of the 512 patients with chronic otitis media with effusion, one marker reached genome-wide significance (rs16974263, P = 2.92 x 10(-8)). The association to this locus was confirmed but with an association signal in the opposite direction, in a UK family cohort of 4860 subjects (rs16974263, P = 3.21 x 10(-4), OR = 0.72; rs4150992, P = 1.62 x 10(-4), OR = 0.71). Thus we hypothesize that this region is important for COME risk in both the Finnish and UK populations, although the precise risk variants or haplotype background remain unclear. Our study suggests that the identified region on chromosome 19 includes a novel and previously uncharacterized risk locus for OM.Peer reviewe

Formation of Potato virus A-induced RNA granules and viral translation are interrelated processes required for optimal virus accumulation

RNA granules are cellular structures, which play an important role in mRNA translation, storage, and degradation. Animal (+)RNA viruses often co-opt RNA granule proteins for viral reproduction. However, the role of RNA granules in plant viral infections is poorly understood. Here we use Potato virus A (PVA) as a model potyvirus and demonstrate that the helper component-proteinase (HCpro), the potyviral suppressor of RNA silencing, induces the formation of RNA granules. We used confocal microscopy to demonstrate the presence of host RNA binding proteins including acidic ribosomal protein P0, argonaute 1 (AGO1), oligouridylate-binding protein 1 (UBP1), varicose (VCS) and eukaryotic initiation factor iso4E (eIF(iso)4E) in these potyvirus-induced RNA granules. We show that the number of potyviral RNA granules is down-regulated by the genome-linked viral protein (VPg). We demonstrated previously that VPg is a virus-specific translational regulator that co-operates with potyviral RNA granule components P0 and eIF(iso)4E in PVA translation. In this study we show that HCpro and varicose, components of potyviral RNA granules, stimulate VPg-promoted translation of the PVA, whereas UBP1 inhibits this process. Hence, we propose that PVA translation operates via a pathway that is interrelated with potyviral RNA granules in PVA infection. The importance of these granules is evident from the strong reduction in viral RNA and coat protein amounts that follows knock down of potyviral RNA granule components. HCpro suppresses antiviral RNA silencing during infection, and our results allow us to propose that this is also the functional context of the potyviral RNA granules we describe in this studyPeer reviewe

Panel 3 : Genetics and Precision Medicine of Otitis Media

Objective. The objective is to perform a comprehensive review of the literature up to 2015 on the genetics and precision medicine relevant to otitis media. Data Sources. PubMed database of the National Library of Medicine. Review Methods. Two subpanels were formed comprising experts in the genetics and precision medicine of otitis media. Each of the panels reviewed the literature in their respective fields and wrote draft reviews. The reviews were shared with all panel members, and a merged draft was created. The entire panel met at the 18th International Symposium on Recent Advances in Otitis Media in June 2015 and discussed the review and refined the content. A final draft was made, circulated, and approved by the panel members. Conclusion. Many genes relevant to otitis media have been identified in the last 4 years in advancing our knowledge regarding the predisposition of the middle ear mucosa to commensals and pathogens. Advances include mutant animal models and clinical studies. Many signaling pathways are involved in the predisposition of otitis media. Implications for Practice. New knowledge on the genetic background relevant to otitis media forms a basis of novel potential interventions, including potential new ways to treat otitis media.Peer reviewe

A mouse-to-man candidate gene study identifies association of chronic otitis media with the loci TGIF1 and FBXO11

Chronic otitis media with effusion (COME) is the most common cause of hearing loss in children, and known to have high heritability. Mutant mouse models have identified Fbxo11, Evi1, Tgif1, and Nisch as potential risk loci. We recruited children aged 10 and under undergoing surgical treatment for COME from 35 hospitals in the UK, and their nuclear family. We performed association testing with the loci FBXO11, EVI1, TGIF1 and NISCH and sought to replicate significant results in a case-control cohort from Finland. We tested 1296 families (3828 individuals), and found strength of association with the T allele at rs881835 (p = 0.006, OR 1.39) and the G allele at rs1962914 (p = 0.007, OR 1.58) at TGIF1, and the A allele at rs10490302 (p = 0.016, OR 1.17) and the G allele at rs2537742 (p = 0.038, OR 1.16) at FBXO11. Results were not replicated. This study supports smaller studies that have also suggested association of otitis media with polymorphism at FBX011, but this is the first study to report association with the locus TGIF1. Both FBX011 and TGIF1 are involved in TGF-beta signalling, suggesting this pathway may be important in the transition from acute to chronic middle ear inflammation, and a potential molecular target.Peer reviewe