Critical values of facet joint angulation and tropism in the development of lumbar degenerative spondylolisthesis: an international, large-scale multicenter study by the AOSpine Asia Pacific Research Collaboration Consortium

published_or_final_versio

Is lumbar facet joint tropism developmental or secondary to degeneration? An international, large-scale multicenter study by the AOSpine Asia Pacific Research Collaboration Consortium

published_or_final_versio

TIG3 Tumor Suppressor-Dependent Organelle Redistribution and Apoptosis in Skin Cancer Cells

TIG3 is a tumor suppressor protein that limits keratinocyte survival during normal differentiation. It is also important in cancer, as TIG3 level is reduced in tumors and in skin cancer cell lines, suggesting that loss of expression may be required for cancer cell survival. An important goal is identifying how TIG3 limits cell survival. In the present study we show that TIG3 expression in epidermal squamous cell carcinoma SCC-13 cells reduces cell proliferation and promotes morphological and biochemical apoptosis. To identify the mechanism that drives these changes, we demonstrate that TIG3 localizes near the centrosome and that pericentrosomal accumulation of TIG3 alters microtubule and microfilament organization and organelle distribution. Organelle accumulation at the centrosome is a hallmark of apoptosis and we demonstrate that TIG3 promotes pericentrosomal organelle accumulation. These changes are associated with reduced cyclin D1, cyclin E and cyclin A, and increased p21 level. In addition, Bax level is increased and Bcl-XL level is reduced, and cleavage of procaspase 3, procaspase 9 and PARP is enhanced. We propose that pericentrosomal localization of TIG3 is a key event that results in microtubule and microfilament redistribution and pericentrosomal organelle clustering and that leads to cancer cell apoptosis

Viral Mimicry of Cdc2/Cyclin-Dependent Kinase 1 Mediates Disruption of Nuclear Lamina during Human Cytomegalovirus Nuclear Egress

The nuclear lamina is a major obstacle encountered by herpesvirus nucleocapsids in their passage from the nucleus to the cytoplasm (nuclear egress). We found that the human cytomegalovirus (HCMV)-encoded protein kinase UL97, which is required for efficient nuclear egress, phosphorylates the nuclear lamina component lamin A/C in vitro on sites targeted by Cdc2/cyclin-dependent kinase 1, the enzyme that is responsible for breaking down the nuclear lamina during mitosis. Quantitative mass spectrometry analyses, comparing lamin A/C isolated from cells infected with viruses either expressing or lacking UL97 activity, revealed UL97-dependent phosphorylation of lamin A/C on the serine at residue 22 (Ser22). Transient treatment of HCMV-infected cells with maribavir, an inhibitor of UL97 kinase activity, reduced lamin A/C phosphorylation by approximately 50%, consistent with UL97 directly phosphorylating lamin A/C during HCMV replication. Phosphorylation of lamin A/C during viral replication was accompanied by changes in the shape of the nucleus, as well as thinning, invaginations, and discrete breaks in the nuclear lamina, all of which required UL97 activity. As Ser22 is a phosphorylation site of particularly strong relevance for lamin A/C disassembly, our data support a model wherein viral mimicry of a mitotic host cell kinase activity promotes nuclear egress while accommodating viral arrest of the cell cycle

Structural Analysis of Papain-Like NlpC/P60 Superfamily Enzymes with a Circularly Permuted Topology Reveals Potential Lipid Binding Sites

NlpC/P60 superfamily papain-like enzymes play important roles in all kingdoms of life. Two members of this superfamily, LRAT-like and YaeF/YiiX-like families, were predicted to contain a catalytic domain that is circularly permuted such that the catalytic cysteine is located near the C-terminus, instead of at the N-terminus. These permuted enzymes are widespread in virus, pathogenic bacteria, and eukaryotes. We determined the crystal structure of a member of the YaeF/YiiX-like family from Bacillus cereus in complex with lysine. The structure, which adopts a ligand-induced, “closed” conformation, confirms the circular permutation of catalytic residues. A comparative analysis of other related protein structures within the NlpC/P60 superfamily is presented. Permutated NlpC/P60 enzymes contain a similar conserved core and arrangement of catalytic residues, including a Cys/His-containing triad and an additional conserved tyrosine. More surprisingly, permuted enzymes have a hydrophobic S1 binding pocket that is distinct from previously characterized enzymes in the family, indicative of novel substrate specificity. Further analysis of a structural homolog, YiiX (PDB 2if6) identified a fatty acid in the conserved hydrophobic pocket, thus providing additional insights into possible function of these novel enzymes

Cathode engineering with perylene-diimide interlayer enabling over 17% efficiency single-junction organic solar cells

In organic solar cells (OSCs), cathode interfacial materials are generally designed with highly polar groups to increase the capability of lowering the work function of cathode. However, the strong polar group could result in a high surface energy and poor physical contact at the active layer surface, posing a challenge for interlayer engineering to address the trade-off between device stability and efficiency. Herein, we report a hydrogen-bonding interfacial material, aliphatic amine-functionalized perylene-diimide (PDINN), which simultaneously down-shifts the work function of the air stable cathodes (silver and copper), and maintains good interfacial contact with the active layer. The OSCs based on PDINN engineered silver-cathode demonstrate a high power conversion efficiency of 17.23% (certified value 16.77% by NREL) and high stability. Our results indicate that PDINN is an effective cathode interfacial material and interlayer engineering via suitable intermolecular interactions is a feasible approach to improve device performance of OSCs

Inter-vender and test-retest reliabilities of resting-state functional magnetic resonance imaging: Implications for multi-center imaging studies

This prospective multi-center study aimed to evaluate the inter-vendor and test-retest reliabilities of resting-state functional magnetic resonance imaging (RS-fMRI) by assessing the temporal signal-to-noise ratio (tSNR) and functional connectivity. Study included 10 healthy subjects and each subject was scanned using three 3 T MR scanners (GE Signa HDxt, Siemens Skyra, and Philips Achieva) in two sessions. The tSNR was calculated from the time course data. Inter-vendor and test-retest reliabilities were assessed with intra-class correlation coefficients (ICCs) derived from variant component analysis. Independent component analysis was performed to identify the connectivity of the default-mode network (DMN). In result, the tSNR for the DMN was not significantly different among the GE, Philips, and Siemens scanners (P = 0.638). In terms of vendor differences, the inter-vendor reliability was good (ICC = 0.774). Regarding the test-retest reliability, the GE scanner showed excellent correlation (ICC = 0.961), while the Philips (ICC = 0.671) and Siemens (ICC = 0.726) scanners showed relatively good correlation. The DMN pattern of the subjects between the two sessions for each scanner and between three scanners showed the identical patterns of functional connectivity. The inter-vendor and test-retest reliabilities of RS-fMRI using different 3 T MR scanners are good. Thus, we suggest that RS-fMRI could be used in multicenter imaging studies as a reliable imaging marker. © 2017 Elsevier Inc. All rights reserved.1

Lumbar Facet Joint Orientation in Degenerative Spondylolisthesis: the Role of Ethnic Variation in Asia Pacific

General PosterINTRODUCTION: Lumbar facet joint orien‐ tation has been reported to be associated with the development of degenerative spondylolisthesis (dSpl). The role of ethnici‐ ty regarding facet joint orientation remains uncertain. As such, the following study was performed across a wide‐ranging popula‐ tion base to assess the role of ethnicity in facet joint orientation in patients with dSpl in the Asia Pacific region. METHODS: A multi‐national, multi‐ethnic cross‐sectional image‐based study was per‐ formed in 34 institutions in Asia Pacific, identifying 448 cases. Lateral standing x‐ rays and axial MRIs and/or CT scans were obtained for patients with lumbar dSpl. Magnitude of slip displacement, level of dSpl, and left/right facet joint angulation, width‐curvature ratio, and gap width were noted on image assessment. Facet joint measurements were performed at each level from L3‐S1. Gender, age, BMI, and ethnicity were also noted.    RESULTS: The study included 389 patients with known ethnic origin (mean age: 61.4 years; 36.7% males, 63.3% females). The mean BMI was 25.6 kg/m2. The level of dSpl was most prevalent at L4/L5 (72.4%). There were 28.8% Indian, 28.5% Japanese, 17.5% Chinese, 8.2% Korean, 6.2% Thai, 4.6% Cau‐ casian, 2.3% Filipino, 2.3% Malay, and 1.3 were of mixed Asian origin. Accounting for patient demographics and displacement, there was a statistically significant differ‐ ence between ethnicity to that of left/right facet joint angulations, width‐curvature ratios, and gap widths from L3‐S1 between specific ethnic groups (p<0.05).    DISCUSSION: This is the largest study to address the role of ethnicity upon lumbar facet joint orientation in dSpl. Ethnicity plays a role in facet joint orientation and may influence the occurrence and severity of dSpl or be a potential consequence. An understanding of ethnic variability may be one factor which assists in identifying those patients at risk of postsurgical development or progression of dSpl

Is lumbar facet joint tropism developmental or secondary to remodeling changes? An international, large-scale multicenter study by the AOSAP collaboration consortium

Session: Free Papers Spine: Degenerative 1: abstract no. 40328INTRODUCTION: Facet joint tropism is asymmetry in orientation of the bilateral facets. Some studies have shown that tropism may increase the risk of disc degeneration and herniations, as well as degenerative spondylolisthesis (DS). It remains controversial whether FJT is a pre-existing developmental phenomena or secondary to progressive joint remodeling. The following study addressed the occurrence of FJT of the lower lumbar spine (i.e. L3-S1) in a degenerative spondylolisthesis patient model. METHODS: This was an international, multi-center cross-sectional study of 267 patients with single level DS recruited from 33 spine institutes in Asia Pacific. FJT (≥8 degrees asymmetry) was assessed on MRI from L3-S1 and in relation to the level of DS. Patient demographic were noted and assessed in relation to FJT of each lumbar segment. RESULTS: 65% were females (mean age of 63 years; mean BMI: 26 kg/m2). FJT was present in 31.3% to 50.6% of DS levels. FJT involved 33.3% to 58.8% of the one or two non-DS levels adjacent to the DS level. Patient demographics were not found to be significantly related to FJT at any level (p>0.05). CONCLUSION: To the authors’ knowledge, this is one of the largest studies conducted, in particular in an Asian population, addressing the “origins concept” of FJT. Although levels with DS were noted to have FJT, adjacent levels with no DS also exhibited tropism and were not related to age and other patient demographics. This study suggested that FJT may have a pre-disposed orientation

Is lumbar facet joint tropism development or secondary to remodeling changes? An international, large-scale multi-centre study by the APSAP collaboration consortium

Session - Free Papers Spine Degenerative 1: abstract no. 40328INTRODUCTION: Facet joint tropism is asymmetry in orientation of the bilateral facets. Some studies have shown that tropism may increase the risk of disc degeneration and herniations, as well as degenerative spondylolisthesis (DS). It remains controversial whether FJT is a pre-existing developmental phenomena or secondary to progressive joint remodeling. The following study addressed the occurrence of FJT of the lower lumbar spine (i.e. L3-S1) in a degenerative spondylolisthesis patient model. METHODS: This was an international, multi-center cross-sectional study of 267 patients with single level DS recruited from 33 spine institutes in Asia Pacific. FJT (≥8 degrees asymmetry) was assessed on MRI from L3-S1 and in relation to the level of DS. Patient demographic were noted and assessed in relation to FJT of each lumbar segment. RESULTS: 65% were females (mean age of 63 years; mean BMI: 26 kg/m2). FJT was present in 31.3% to 50.6% of DS levels. FJT involved 33.3% to 58.8% of the one or two non-DS levels adjacent to the DS level. Patient demographics were not found to be significantly related to FJT at any level (p>0.05). CONCLUSION: To the authors’ knowledge, this is one of the largest studies conducted, in particular in an Asian population, addressing the “origins concept” of FJT. Although levels with DS were noted to have FJT, adjacent levels with no DS also exhibited tropism and were not related to age and other patient demographics. This study suggested that FJT may have a pre-disposed orientation