Footprint analysis of gait using a pressure sensor system.

The purpose of this study was to investigate if the detailed pressure data of the footprints of normal gait add essential information to the spatio-temporal variables of gait. The gait of 62 healthy adult subjects was investigated using GAITRite pressure sensor system. Each footprint was divided into 12 equal trapezoids and after that the hindfoot, midfoot and forefoot analysis was developed. A typical activation pattern of the sensors with two peaks of active area and peak pressure distribution during normal walking was obtained. The first peak reflected the heel strike, and the second peak reflected push-off at the end of the stance phase. The lowest pressure values were in the midfoot, where the lateral part of the foot activated sensors more than the medial part. The footprint patterns of right and left legs were symmetrical and corresponded with the symmetry found in the spatio-temporal variables of gait. The variability for the active area and the peak pressure were more pronounced for the lateral part of the midfoot and a smaller variation was seen in areas with concentrated observations (e.g. 1st, 2nd and 5th lateral trapezoids). Increasing active area in the forefoot was associated with decreasing pressure sensor activity in the midfoot. The footprint patterns identified the symmetry between the legs and at the same time revealed the velocity performance.     

YKL-40 in the brain and cerebrospinal fluid of neurodegenerative dementias

Background

YKL-40 (also known as Chitinase 3-like 1) is a glycoprotein produced by inflammatory, cancer and stem cells. Its physiological role is not completely understood but YKL-40 is elevated in the brain and cerebrospinal fluid (CSF) in several neurological and neurodegenerative diseases associated with inflammatory processes. Yet the precise characterization of YKL-40 in dementia cases is missing.

Methods

In the present study, we comparatively analysed YKL-40 levels in the brain and CSF samples from neurodegenerative dementias of different aetiologies characterized by the presence of cortical pathology and disease-specific neuroinflammatory signatures.

Results

YKL-40 was normally expressed in fibrillar astrocytes in the white matter. Additionally YKL-40 was highly and widely expressed in reactive protoplasmic cortical and perivascular astrocytes, and fibrillar astrocytes in sporadic Creutzfeldt-Jakob disease (sCJD). Elevated YKL-40 levels were also detected in Alzheimer’s disease (AD) but not in dementia with Lewy bodies (DLB). In AD, YKL-40-positive astrocytes were commonly found in clusters, often around β-amyloid plaques, and surrounding vessels with β-amyloid angiopathy; they were also distributed randomly in the cerebral cortex and white matter. YKL-40 overexpression appeared as a pre-clinical event as demonstrated in experimental models of prion diseases and AD pathology.CSF YKL-40 levels were measured in a cohort of 288 individuals, including neurological controls (NC) and patients diagnosed with different types of dementia. Compared to NC, increased YKL-40 levels were detected in sCJD (p < 0.001, AUC = 0.92) and AD (p < 0.001, AUC = 0.77) but not in vascular dementia (VaD) (p > 0.05, AUC = 0.71) or in DLB/Parkinson’s disease dementia (PDD) (p > 0.05, AUC = 0.70). Further, two independent patient cohorts were used to validate the increased CSF YKL-40 levels in sCJD. Additionally, increased YKL-40 levels were found in genetic prion diseases associated with the PRNP-D178N (Fatal Familial Insomnia) and PRNP-E200K mutations.

Conclusions

Our results unequivocally demonstrate that in neurodegenerative dementias, YKL-40 is a disease-specific marker of neuroinflammation showing its highest levels in prion diseases. Therefore, YKL-40 quantification might have a potential for application in the evaluation of therapeutic intervention in dementias with a neuroinflammatory component.

     

‘Rules that apply in times of crisis’: time,agency, and norm‐remaking during Nepal's People's War

This article explores how people in the former Maoist heartland of Nepal adopted previously transgressive norms and practices during the decade of the People's War (1996‐2006). By examining the rise in practices of beef‐eating and inter‐caste commensality, this article suggests that the temporal dimension of wartime ‘when different rules apply’ was crucial in making people accept new ideas and break established norms on a scale atypical for the ‘normal’ times of peace. Analysing the agency of Maoist activists, who self‐consciously tried to implement a project of radical social transformation, and those people who were caught in the midst of the Maoist transformative endeavour, this article argues that the contours of the ‘new society’ emerged not only due to revolutionaries’ intentional actions but also because of the ‘exceptional’ nature of wartime, which forced people to radically re‐create their daily lives. By transgressing social norms, ‘ordinary’ people did not deliberately undermine the normative order, but rather responded to the constraints of wartime, when people's agency and ethical choices were mostly driven by the need to secure the survival of their families and ensure the continuity of life itself.     

Quantitative proteomics combined with BAC TransgeneOmics reveals in vivo protein interactions

Protein interactions are involved in all cellular processes. Their efficient and reliable characterization is therefore essential for understanding biological mechanisms. In this study, we show that combining bacterial artificial chromosome (BAC) TransgeneOmics with quantitative interaction proteomics, which we call quantitative BAC–green fluorescent protein interactomics (QUBIC), allows specific and highly sensitive detection of interactions using rapid, generic, and quantitative procedures with minimal material. We applied this approach to identify known and novel components of well-studied complexes such as the anaphase-promoting complex. Furthermore, we demonstrate second generation interaction proteomics by incorporating directed mutational transgene modification and drug perturbation into QUBIC. These methods identified domain/isoform-specific interactors of pericentrin- and phosphorylation-specific interactors of TACC3, which are necessary for its recruitment to mitotic spindles. The scalability, simplicity, cost effectiveness, and sensitivity of this method provide a basis for its general use in small-scale experiments and in mapping the human protein interactome.     

Application of a Patient Derived Xenograft Model for Predicative Study of Uterine Fibroid Disease

Human uterine fibroids, benign tumors derived from the smooth muscle layers of the uterus, impose a major health burden to up to 50% of premenopausal women in their daily life. To improve our understanding of this disease, we developed and characterized a patient-derived xenograft model by subcutaneous transplantation of pieces of human uterine fibroid tissue into three different strains of severe combined immunodeficient mice. Engrafted uterine fibroid tissue preserved the classical morphology with interwoven bundles of smooth muscle cells and an abundant deposition of collagenous matrix, similar to uterine fibroids in situ. The grafts expressed both estrogen receptor 1 and progesterone receptor. Additionally, both receptors were up-regulated by estrogen treatment. Growth of the fibroid grafts was dependent on 17β-estradiol and progesterone supplementation at levels similar to women with the disease and was studied for up to 60 days at maximum. Co-treatment with the antiprogestin mifepristone reduced graft growth (four independent donors, p<0.0001 two-sided t-test), as did treatment with the mTOR inhibitor rapamycin (three independent donors, p<0.0001 two-sided t-test). This in vivo animal model preserves the main histological and functional characteristics of human uterine fibroids, is amenable to intervention by pharmacological treatment, and can thus serve as an adequate model for the development of novel therapies.     

Two perenniporiol derivatives,lanostane-type triterpenoids,from the cultured mycelia of Perenniporia ochroleuca

Two new perenniporiol derivatives, lanostane-type triterpenoids, were isolated from the benzene extract of cultured mycelia of Perenniporia ochroleuca. The structures of the two new compounds were elucidated by spectral data to be 3-O-acetyl-7,11-dihydroperenniporiol and 12β-acetoxyperenniporiol.