Polysaccharide-Degrading Complex Produced in Wood and in Liquid Media by the Brown-Rot Fungus Poria Placenta

The polysaccharide-degrading enzymes produced by Poria placenta in decayed wood and liquid media were compared qualitatively and quantitatively. A single carbohydrate-degrading complex was isolated and purified from wood and liquid cultures that was active on both polysaccharides and glycosides. Quantitative differences in enzyme activities from decayed wood versus liquid media were observed. However, the purified extracellular carbohydrate-degrading complex isolated from decayed wood and from liquid cultures must be structurally similar because of similar isoelectric points, electrophoretic properties, and molecular sieving properties

A phase II study of capecitabine and oxalplatin combination chemotherapy in patients with inoperable adenocarcinoma of the gall bladder or biliary tract

Background: Advanced biliary tract carcinomas are associated with a poor prognosis, and palliative chemotherapy has only modest benefit. This multi-centre phase II study was conducted to determine the efficacy of capecitabine in combination with oxaliplatin in patients with inoperable gall bladder or biliary tract cancer. Methods: This was a Phase II, non-randomised, two-stage Simon design, multi-centre study. Ethics approval was sought and obtained by the North West MREC, and then locally by the West Glasgow Hospitals Research Ethics Com mittee. Eligible patients with inoperable locally advanced or metastatic adenocarcinoma of the gall bladder or biliary tract and with adequate performance status, haematologic, renal, and hepatic function were treated with capecit abine (1000 mg/m2 po, twice daily, days 1–14) and oxaliplatin (130 mg/m2 i.v., day 1) every 3 weeks for up to six cycles. The primary objective of the study was to determine the objective tumour response rates (complete and partial). The secondary objectives included assessment of toxicity, progression-free survival, and overall survival. Results: Forty-three patients were recruited between July 2003 and December 2005. The regimen was well tolerated with no grade 3/4 neutropenia or thrombocytopenia. Grade 3/4 sensory neuropathy was observed in six patients. Two-thirds of patients received their chemotherapy without any dose delays. Overall response rate was 23.8 % (95 % CI 12.05–39.5 %). Stable disease was observed in a further 13 patients (31 %) and progressive disease observed in 12 (28.6 %) of patients. The median progression-free survival was 4.6 months (95 % CI 2.8–6.4 months; Fig. 1) and the median overall survival 7.9 months (95 % CI 5.3–10.4 months; Fig. 2). Conclusion: Capecitabine combined with oxaliplatin has a lower disease control and shorter overall survival than the combination of cisplatin with gemcitabine which has subsequently become the standard of care in this disease. How ever, capecitabine in combination with oxaliplatin does have modest activity in this disease, and can be considered as an alternative treatment option for patients in whom cisplatin and/or gemcitabine are contra-indicated

TDP43 proteinopathy is associated with aberrant DNA methylation in human amyotrophic lateral sclerosis

Background Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by motor neurone (MN) degeneration and death. ALS can be sporadic (sALS) or familial, with a number of associated gene mutations, including C9orf72 (C9ALS). DNA methylation is an epigenetic mechanism whereby a methyl group is attached to a cytosine (5mC), resulting in gene expression repression. 5mC can be further oxidized to 5‐hydroxymethylcytosine (5hmC). DNA methylation has been studied in other neurodegenerative diseases, but little work has been conducted in ALS. Aims To assess differences in DNA methylation in individuals with ALS and the relationship between DNA methylation and TDP43 pathology. Methods Post mortem tissue from controls, sALS cases and C9ALS cases were assessed by immunohistochemistry for 5mC and 5hmC in spinal cord, motor cortex and prefrontal cortex. LMNs were extracted from a subset of cases using laser capture microdissection. DNA from these underwent analysis using the MethylationEPIC array to determine which molecular processes were most affected. Results There were higher levels of 5mC and 5hmC in sALS and C9ALS in the residual lower motor neurones (LMNs) of the spinal cord. Importantly, in LMNs with TDP43 pathology there was less nuclear 5mC and 5hmC compared to the majority of residual LMNs that lacked TDP43 pathology. Enrichment analysis of the array data suggested RNA metabolism was particularly affected. Conclusions DNA methylation is a contributory factor in ALS LMN pathology. This is not so for glia or neocortical neurones

One-Step Generation of Multifunctional Polyelectrolyte Microcapsules via Nanoscale Interfacial Complexation in Emulsion (NICE)

Polyelectrolyte microcapsules represent versatile stimuli-responsive structures that enable the encapsulation, protection, and release of active agents. Their conventional preparation methods, however, tend to be time-consuming, yield low encapsulation efficiency, and seldom allow for the dual incorporation of hydrophilic and hydrophobic materials, limiting their widespread utilization. In this work, we present a method to fabricate stimuli-responsive polyelectrolyte microcapsules in one step based on nanoscale interfacial complexation in emulsions (NICE) followed by spontaneous droplet hatching. NICE microcapsules can incorporate both hydrophilic and hydrophobic materials and also can be induced to trigger the release of encapsulated materials by changes in the solution pH or ionic strength. We also show that NICE microcapsules can be functionalized with nanomaterials to exhibit useful functionality, such as response to a magnetic field and disassembly in response to light. NICE represents a potentially transformative method to prepare multifunctional nanoengineered polyelectrolyte microcapsules for various applications such as drug delivery and cell mimicry.112823Ysciescopu

Axonal Preservation in Deep Subcortical White Matter Lesions in the Ageing Brain

Cerebral white matters lesions (WML) are seen in 94% of the population aged 64 and over and are associated with cognitive decline and depression. We used immunohistochemistry and stereological methods on post mortem brain samples derived from the Medical Research Council Cognitive Function and Ageing Study (MRC-CFAS) cohort to investigate the axonal density within deep subcortical lesions. There was no significant difference between the lesional and control white matter, therefore, we conclude that there is axonal preservation within these lesions that are characterized by demyelination

Evaluation of HeartMath training for improving personal resilience and psychophysiological coherence

Abstract The goal of this study was to evaluate the influence of a HeartMath training apparatus on personal resilience and physiological coherence. A within group, pre-test and post-test, outcome evaluative design was employed to assess changes in dependent variables. A small convenience sample of 6 participants, 4 women and 2 men, with a mean age of 49 years and an age range from 25 to 68 years, each completed 4 HeartMath training sessions which included 9 tools and techniques. Non-parametric statistical analysis for quantitative data indicated significant increases in physiological coherence and personal resilience perceptions. Thematic content analysis for qualitative data yielded unequivocally positive, experiential descriptions. Integrative findings are discussed in relation to previous and future research

Broad clinical phenotypes associated with TAR-DNA binding protein (TARDBP) mutations in amyotrophic lateral sclerosis

The finding of TDP-43 as a major component of ubiquitinated protein inclusions in amyotrophic lateral sclerosis (ALS) has led to the identification of 30 mutations in the transactive response-DNA binding protein (TARDBP) gene, encoding TDP-43. All but one are in exon 6, which encodes the glycine-rich domain. The aim of this study was to determine the frequency of TARDBP mutations in a large cohort of motor neurone disease patients from Northern England (42 non-superoxide dismutase 1 (SOD1) familial ALS (FALS), nine ALS-frontotemporal dementia, 474 sporadic ALS (SALS), 45 progressive muscular atrophy cases). We identified four mutations, two of which were novel, in two familial (FALS) and two sporadic (SALS) cases, giving a frequency of TARDBP mutations in non-SOD1 FALS of 5% and SALS of 0.4%. Analysis of clinical data identified that patients had typical ALS, with limb or bulbar onset, and showed considerable variation in age of onset and rapidity of disease course. However, all cases had an absence of clinically overt cognitive dysfunction