To What Extent is Collocation Knowledge Associated with Oral Proficiency? A Corpus-Based Approach to Word Association

This study examined the relationship between second language (L2) learners’ collocation knowledge and oral proficiency. A new approach to measuring collocation was adopted by eliciting responses through a word association task and using corpus-based measures (absolute frequency count, t-score, MI score) to analyze the degree to which stimulus words and responses were collocated. Oral proficiency was measured using human judgements and objective measures of fluency (articulation rate, silent pause ratio, filled pause ratio) and lexical richness (diversity, frequency, range). Forty Japanese university students completed a word association task and a spontaneous speaking task (picture narrative). Results indicated that speakers who used more low-frequency collocations in the word association task (i.e., lower collocation frequency scores) spoke faster with fewer silent pauses and were perceived to be more fluent. Speakers who provided more strongly associated collocations (as measured by MI) used more sophisticated lexical items and were perceived to be lexically proficient. Collocation knowledge remained as a unique predictor after the influence of learners’ vocabulary size (i.e., knowledge of single-word items) was considered. These findings support the key role that collocation plays in oral proficiency and provide important insights into understanding L2 speech development from the perspective of phraseological competence

Amnesia in Frontotemporal Dementia with Amyotrophic Lateral Sclerosis, Masquerading Alzheimer's Disease

A 68-year-old man with a clinical diagnosis of Alzheimer's disease (AD) later developed amyotrophic lateral sclerosis (ALS), which was confirmed at autopsy at age 72 years. Because neuronal loss and AD-type pathologies (Braak stage II for neurofibrillary tangles) were scant, TDP-43-positive intracytoplasmic inclusions in hippocampal dentate granular cells and in neurons in the subiculum and amygdala, even though small in amount, may represent the earliest lesions of ALS-related dementia and could be the cause of dementia in this patient. Although the persistent elevation of creatine kinase from the onset could be a pointer to the presence of motor involvement, more accurate characterization of dementia, which may differentiate ALS-related dementia and AD, is necessary

Silver diagnosis in neuropathology: principles, practice and revised interpretation

Silver-staining methods are helpful for histological identification of pathological deposits. In spite of some ambiguities regarding their mechanism and interpretation, they are widely used for histopathological diagnosis. In this review, four major silver-staining methods, modified Bielschowsky, Bodian, Gallyas (GAL) and Campbell–Switzer (CS) methods, are outlined with respect to their principles, basic protocols and interpretations, thereby providing neuropathologists, technicians and neuroscientists with a common basis for comparing findings and identifying the issues that still need to be clarified. Some consider “argyrophilia” to be a homogeneous phenomenon irrespective of the lesion and the method. Thus, they seek to explain the differences among the methods by pointing to their different sensitivities in detecting lesions (quantitative difference). Comparative studies, however, have demonstrated that argyrophilia is heterogeneous and dependent not only on the method but also on the lesion (qualitative difference). Each staining method has its own lesion-dependent specificity and, within this specificity, its own sensitivity. This “method- and lesion-dependent” nature of argyrophilia enables operational sorting of disease-specific lesions based on their silver-staining profiles, which may potentially represent some disease-specific aspects. Furthermore, comparisons between immunohistochemical and biochemical data have revealed an empirical correlation between GAL+/CS-deposits and 4-repeat (4R) tau (corticobasal degeneration, progressive supranuclear palsy and argyrophilic grains) and its complementary reversal between GAL-/CS+deposits and 3-repeat (3R) tau (Pick bodies). Deposits containing both 3R and 4R tau (neurofibrillary tangles of Alzheimer type) are GAL+/CS+. Although no molecular explanations, other than these empiric correlations, are currently available, these distinctive features, especially when combined with immunohistochemistry, are useful because silver-staining methods and immunoreactions are complementary to each other

Use of Cryopreserved Osteogenic Matrix Cell Sheets for Bone Reconstruction

Abstract Skeletal diseases, such as nonunion and osteonecrosis, are now treatable with tissue engineering techniques. Single cell sheets called osteogenic matrix cell sheets (OMCSs) grown from cultured bone marrow-derived mesenchymal stem cells show high osteogenic potential; however, long preparation times currently limit their clinical application. Here, we report a cryopreservation OMCS transplantation method that shortens OMCS preparation time. Cryopreserved rat OMCSs were prepared using slow-and rapid-freezing methods, thawed, and subsequently injected scaffold-free into subcutaneous sites. Rapid-and slow-frozen OMCSs were also transplanted directly to the femur bone at sites of injury. Slow-freezing resulted in higher cell viability than rapid freezing, yet all two cryopreservation methods yielded OMCSs that survived and formed bone tissue. In the rapid-and slow-freezing groups, cortical gaps were repaired and bone continuity was observed within 6 weeks of OMCS transplantation. Moreover, while no significant difference was found in osteocalcin expression between the three experimental groups, the biomechanical strength of femurs treated with slow-frozen OMCSs was significantly greater than those of non-transplant at 6 weeks post-injury. Collectively, these data suggest that slow-frozen OMCSs have superior osteogenic potential and are better suited to produce a mineralized matrix and repair sites of bone injury

Implant failure in bilateral metal-on-metal hip resurfacing arthroplasties: a clinical and pathological study

Metal-on-metal hip resurfacing arthroplasties (MoMHRAs) have a high failure rate due to pseudotumour formation. It is not certain whether pseudotumours in bilateral MoMHRAs form on the basis of an adverse reaction to metal debris (ARMD) that is entirely due to a local innate and adaptive immune response to Cobalt-Chrome (Co-Cr) wear particles. To determine if there is a systemic component to ARMD in bilateral MoMHRAs, we examined the histology of ARMD in unilateral and bilateral MoMHRAs revised for pseudotumour and determined whether implant survival differed between these two groups. Periprosthetic tissue specimens from 119 hips revised for pseudotumour were examined. These were derived from 109 patients including 10 patients with bilateral MoMHRAs and 99 with sunilateral MoMHRAs including a cohort of 20 patients with bilateral MoMHRAs that had undergone only one MoMHRA revision for pseudotumour. The mean time to revision for pseudotumour of unilateral and bilateral MoMHRAs was determined. The histology of periprosthetic tissue was examined for evidence of the innate and adaptive immune response and scored semi-quantitatively. There was no significant difference in histological features of the innate / adaptive response between Group 1 bilateral pseudotumours and Group 2 and Group 3 unilateral pseudotumours. Histological features, including ALVAL scores, were similar in the periprosthetic tissues of right and left hips in Group 1 bilateral MoMHRAs. The mean time to first revision for pseudotumour of bilateral MoMHRAs (6.59 years) was not decreased compared with unilateral MoMHRAs (5.66 years) or bilateral MoMHRAs that had only one revision (7.05 years). Right and left hip pseudotumours in bilateral MoMHRAs exhibit similar histological features of the innate and adaptive immune response. Mean implant survival is not decreased in bilateral compared with unilateral MoMHRA cases. The findings suggest that pseudotumour formation is due more to a local than a systemic innate /adaptive immune response to components of metal wear

Adipose Tissue Dysfunction Signals Progression of Hepatic Steatosis Towards Nonalcoholic Steatohepatitis in C57Bl/6 Mice

OBJECTIVE - Nonalcoholic fatty liver disease (NAFLD) is linked to obesity and diabetes, suggesting an important role of adipose tissue in the pathogenesis of NAFLD. Here, we aimed to investigate the interaction between adipose tissue and liver in NAFLD and identify potential early plasma markers that predict nonalcoholic steatohepatitis (NASH). RESEARCH DESIGN AND METHODS - C57Bl/6 mice were chronically fed a high-fat diet to induce NAFLD and compared with mice fed a low-fat diet. Extensive histological and phenotypical analyses coupled with a time course study of plasma proteins using multiplex assay were performed. RESULTS - Mice exhibited pronounced heterogeneity in liver histological scoring, leading to classification into four subgroups: low-fat low (LFL) responders displaying normal liver morphology, low-fat high (LFH) responders showing benign hepatic steatosis, high-fat low (HFL) responders displaying pre-NASH with macrovesicular lipid droplets, and high fat high (HFH) responders exhibiting overt NASH characterized by ballooning of hepatocytes, presence of Mallory bodies, and activated inflammatory cells. Compared with HFL responders, HFH mice gained weight more rapidly and exhibited adipose tissue dysfunction characterized by decreased final fat mass, enhanced macrophage infiltration and inflammation, and adipose tissue remodeling. Plasma haptoglobin, IL-1β, TIMP-1, adiponectin, and leptin were significantly changed in HFH mice. Multivariate analysis indicated that in addition to leptin, plasma CRP, haptoglobin, eotaxin, and MIP-1α early in the intervention were positively associated with liver triglycerides. Intermediate prognostic markers of liver triglycerides included IL-18, IL-1β, MIP-1γ, and MIP-2, whereas insulin, TIMP-1, granulocyte chemotactic protein 2, and myeloperoxidase emerged as late markers. CONCLUSIONS - Our data support the existence of a tight relationship between adipose tissue dysfunction and NASH pathogenesis and point to several novel potential predictive biomarkers for NASH

Polyglutamine Genes Interact to Modulate the Severity and Progression of Neurodegeneration in Drosophila

The expansion of polyglutamine tracts in a variety of proteins causes devastating, dominantly inherited neurodegenerative diseases, including six forms of spinal cerebellar ataxia (SCA). Although a polyglutamine expansion encoded in a single allele of each of the responsible genes is sufficient for the onset of each disease, clinical observations suggest that interactions between these genes may affect disease progression. In a screen for modifiers of neurodegeneration due to SCA3 in Drosophila, we isolated atx2, the fly ortholog of the human gene that causes a related ataxia, SCA2. We show that the normal activity of Ataxin-2 (Atx2) is critical for SCA3 degeneration and that Atx2 activity hastens the onset of nuclear inclusions associated with SCA3. These activities depend on a conserved protein interaction domain of Atx2, the PAM2 motif, which mediates binding of cytoplasmic poly(A)-binding protein (PABP). We show here that PABP also influences SCA3-associated neurodegeneration. These studies indicate that the toxicity of one polyglutamine disease protein can be dramatically modulated by the normal activity of another. We propose that functional links between these genes are critical to disease severity and progression, such that therapeutics for one disease may be applicable to others

Amyloid-b peptide on sialyl-LewisX-selectin-mediated membrane tether mechanics at the cerebral endothelial cell surface

Increased deposition of amyloid-b peptide (Ab) at the cerebral endothelial cell (CEC) surface has been implicated in enhancement of transmigration of monocytes across the brain blood barrier (BBB) in Alzheimer’s disease (AD). In this study, quantitative immunofluorescence microscopy (QIM) and atomic force microscopy (AFM) with cantilevers biofunctionalized by sialyl-Lewisx (sLex) were employed to investigate Ab-altered mechanics of membrane tethers formed by bonding between sLex and p-selectin at the CEC surface, the initial mechanical step governing the transmigration of monocytes. QIM results indicated the ability for Ab to increase p-selectin expression at the cell surface and promote actin polymerization in both bEND3 cells (immortalized mouse CECs) and human primary CECs. AFM data also showed the ability for Ab to increase cell stiffness and adhesion probability in bEND3 cells. On the contrary, Ab lowered the overall force of membrane tether formation (Fmtf), and produced a bimodal population of Fmtf, suggesting subcellular mechanical alterations in membrane tethering. The lower Fmtf population was similar to the results obtained from cells treated with an F-actin-disrupting drug, latrunculin A. Indeed, AFM results also showed that both Ab and latrunculin A decreased membrane stiffness, suggesting a lower membrane-cytoskeleton adhesion, a factor resulting in lower Fmtf. In addition, these cerebral endothelial alterations induced by Ab were abrogated by lovastatin, consistent with its anti-inflammatory effects. In sum, these results demonstrated the ability for Ab to enhance p-selectin expression at the CEC surface and induce cytoskeleton reorganization, which in turn, resulted in changes in membrane-cytoskeleton adhesion and membrane tethering, mechanical factors important in transmigration of monocytes through the BBB.This work was supported by Alzheimer Association Grant NIRG-06-24448; NIH Grant 1P01 AG18357, R21NS052385, 5R21AG032579 and in part by 1P01HL095486 and AHA 0835676N; ‘‘Bolashak’’ scholarship and Ministry of Education and Science of the Republic of Kazakhstan 1029/GF2. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript