Insight into highly conserved H1 subtype-specific epitopes in influenza virus hemagglutinin

Influenza viruses continuously undergo antigenic changes with gradual accumulation of mutations in hemagglutinin (HA) that is a major determinant in subtype specificity. The identification of conserved epitopes within specific HA subtypes gives an important clue for developing new vaccines and diagnostics. We produced and characterized nine monoclonal antibodies that showed significant neutralizing activities against H1 subtype influenza viruses, and determined the complex structure of HA derived from a 2009 pandemic virus A/Korea/01/2009 (KR01) and the Fab fragment from H1-specific monoclonal antibody GC0587. The overall structure of the complex was essentially identical to the previously determined KR01 HA-Fab0757 complex structure. Both Fab0587 and Fab0757 recognize readily accessible head regions of HA, revealing broadly shared and conserved antigenic determinants among H1 subtypes. The beta-strands constituted by Ser110-Glu115 and Lys169-Lys170 form H1 epitopes with distinct conformations from those of H1 and H3 HA sites. In particular, Glu112, Glu115, Lys169, and Lys171 that are highly conserved among H1 subtype HAs have close contacts with HCDR3 and LCDR3. The differences between Fab0587 and Fab0757 complexes reside mainly in HCDR3 and LCDR3, providing distinct antigenic determinants specific for 1918 pdm influenza strain. Our results demonstrate a potential key neutralizing epitope important for H1 subtype specificity in influenza virus

A Narrow Internal Auditory Canal with Duplication in a Patient with Congenital Sensorineural Hearing Loss

A narrow internal auditory canal (IAC) with duplication is a rare anomaly of the temporal bone. It is associated with congenital sensorineural hearing loss. Aplasia or hypoplasia of the vestibulocochlear nerve may cause the hearing loss. We present an unusual case of an isolated narrow IAC with duplication that was detected by a CT scan. In this case, the IAC was divided by a bony septum into an empty stenotic inferoposterior portion and a large anterosuperior portion containing the facial nerve that was clearly delineated on MRI

Toward growth of wafer-scale single-crystal hexagonal boron nitride sheets

Hexagonal boron nitride (hBN) has a two-dimensional planar structure without dangling bonds and is considered an insulator material that can overcome the limitations of SiO2 and HfO2, which typically exhibit large densities of dangling bonds and charged impurities at the interface. However, most of the reported hBN films prepared by chemical vapor deposition (CVD) are polycrystalline with grain boundaries. The grain boundaries of a polycrystalline hBN cause current leakage and gas permeability. A recent notable study reports the growth of wafer-scale single-crystal hBN monolayer, which could mitigate the aforementioned problems caused by polycrystalline hBN films. In this perspective, we discuss the recent progress in the research on single-crystal hBN and the direction to be taken for single-crystal hBN in future. The progress is closely related to the development of a single-crystal substrate and large area of monolayer single-crystal was grown on Cu (111). In terms of the hBN growth, the next step would be to grow multilayer single-crystal hBN, which is expected to expand the scope of applications

The Fate of Tau Aggregates Between Clearance and Transmission

Neuronal accumulation of mis-folded tau is the pathological hallmark of multiple neurodegenerative disorders, including Alzheimer’s disease. Distinct from amyloid plaques, which appear simultaneously throughout the brain, tau pathology develops first in a specific brain region and then propagates to neuroanatomically connected brain regions, exacerbating the disease. Due to the implication in disease progression, prevention of tau transmission is recognized as an important therapeutic strategy that can halt disease progression in the brain. Recently, accumulating studies have demonstrated diverse cellular mechanisms associated with cell-to-cell transmission of tau. Once transmitted, mis-folded tau species act as a prion-like seed for native tau aggregation in the recipient neuron. In this review, we summarize the diverse cellular mechanisms associated with the secretion and uptake of tau, and highlight tau-trafficking receptors, which mediate tau clearance or cell-to-cell tau transmission

Gene silencing in HIV-1 latency by polycomb repressive group

<p>Abstract</p> <p>Background</p> <p>The persistence of latently Human immunodeficiency virus-1 (HIV-1) infected cellular reservoirs in resting CD4⁺T cells is a major obstacle to HIV-1 eradication. The detailed mechanism of HIV-1 latency remains unclear. We investigated histones and their post-translational modification associated with HIV-1 latency in novel HIV-1 latently infected cell lines established previously, NCHA cells.</p> <p>Methods</p> <p>To examine histones and their modification linked with HIV-1 latency, the expression profiles for core histone proteins and histone deacetylases (HDACs) in NCHA cells were characterized by RT-PCR, ELISA, and western blot. The levels of histone acetylation and methylation at histone H3 Lys⁹(H3K9) and Lys²⁷(H3K27) in HIV-1 latently infected cells were analyzed by western blot and chromatin immunoprecipitation-sequencing (ChIP-seq).</p> <p>Results</p> <p>The expression levels for four core histone proteins (H2A, H2B, H3 and H4) and HDACs (HDAC1-8) in NCHA cells were not significantly different from those in their parental cells. Histone H3K9 and H3K27 acetylations in NCHA cells showed no difference in parental and NCHA cells, whereas the levels of di- and tri-methylation were increased in NCHA cells. The expression of EED which is a component of polycomb repressive complex 2 (PRC2), and BMI1 and RING2 which are constituents of PRC1, were upregulated in NCHA cells. In addition, more ubiquitylation at histone H2A was detected in NCHA cells.</p> <p>Conclusions</p> <p>Our results suggest that tri-methylation of histone H3K27 and H2A ubiquitylation via polycomb group protein may play a crucial role in epigenetic silencing accounting for HIV-1 latency in NCHA cells.</p

Isolated Shoulder Weakness due to a Small Cortical Infarction

Small cortical infarctions can produce isolated motor paresis in the upper extremities. Several cases of isolated hand or finger paresis have been reported, but isolated shoulder weakness is extremely rare. We report here a patient who developed isolated shoulder weakness due to a small cortical infarction in the medial precentral gyrus

Concurrent Multilocular Cystic Renal Cell Carcinoma and Leiomyoma in the Same Kidney: Previously Unreported Association

We present an unusual case of concurrent occurrence of a multilocular cystic renal cell carcinoma and a leiomyoma in the same kidney of a patient with no evident clinical symptoms. A 38-year-old man was found incidentally to have a cystic right renal mass on computed tomography. Laparoscopic radical nephrectomy was performed under a preoperative diagnosis of cystic renal cell carcinoma. Histology revealed a multilocular cystic renal cell carcinoma and a leiomyoma. This is the first report of this kind of presentation

Lung cancer with superior vena cava syndrome diagnosed by intravascular biopsy using EBUS-TBNA

AbstractSince superior vena cava syndrome (SVCS) is a critical condition, immediate diagnostic approach and therapy are imperative to avoid potentially life-threatening complications. Here, we report a case of lung cancer with SVCS, which was diagnosed through intravascular tumor biopsy using endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA). EBUS-TBNA enabled us to obtain tissue sufficient for diagnosis, without significant complications. Prompt diagnosis was followed by appropriate anticancer treatment and improvement in the symptoms. For patients suspected of SVCS and requiring prompt pathologic diagnosis, we can consider EBUS-TBNA to diagnose intravascular or mediastinal tumors and provide an accurate diagnosis

Notch1 binds and induces degradation of Snail in hepatocellular carcinoma

<p>Abstract</p> <p>Background</p> <p>Hepatocellular carcinoma (HCC) is a common, highly invasive malignant tumor associated with a high mortality rate. We previously reported that the aberrant expression of Snail via activation of reactive oxygen species contributes to the invasive property of HCC, in part by downregulation of E-cadherin through both transcriptional repression and epigenetic modification of the E-cadherin promoter. Having demonstrated the ability of Snail to bind and recruit histone deacetylase 1 and DNA methyltransferase 1 in this context, we set out to look for other interactions that could affect its ability to promote oncogenic transformation and cancer cell invasion.</p> <p>Results</p> <p>Using cells that stably expressed Snail, we characterized Snail protein interactors by tandem affinity purification and mass spectrometry. Immunoprecipitation and subcellular colocalization studies were performed to confirm our identification of the Notch1 intracellular domain (NICD) as a novel Snail-binding partner. NICD interaction with Snail was found to induce ubiquitination and MDM2-dependent degradation of Snail. Interestingly, NICD inhibited Snail-dependent invasive properties in both HCC cells and mouse embryonic fibroblasts.</p> <p>Conclusions</p> <p>Our study demonstrates that NICD can oppose Snail-dependent HCC cell invasion by binding and inducing proteolytic degradation of Snail. Although Notch signaling and Snail are both widely considered tumor-promoting factors, our findings indicate that the individual oncogenic contribution of Notch1 and Snail in malignant systems should be interpreted carefully, particularly when they are conjointly expressed.</p