Production of bioactive, post-translationally modified, heterotrimeric, human recombinant type-I collagen in transgenic tobacco.

Collagen's biocompatibility, biodegradability and low immunogenicity render it advantageous for extensive application in pharmaceutical or biotechnological disciplines. However, typical collagen extraction from animal or cadaver sources harbors risks including allergenicity and potential sample contamination with pathogens. In this work, two human genes encoding recombinant heterotrimeric collagen type I (rhCOL1) were successfully coexpressed in tobacco plants with the human prolyl-4-hydroxylase (P4H) and lysyl hydroxylase 3 (LH3) enzymes, responsible for key posttranslational modifications of collagen. Plants coexpressing all five vacuole-targeted proteins generated intact procollagen yields of approximately 2% of the extracted total soluble proteins. Plant-extracted rhCOL1 formed thermally stable triple helical structures and demonstrated biofunctionality similar to human tissue-derived collagen supporting binding and proliferation of adult peripheral blood-derived endothelial progenitor-like cells. Through a simple, safe and scalable method of rhCOL1 production and purification from tobacco plants, this work broadens the potential applications of human recombinant collagen in regenerative medicine.

Rivastigmine augmentation in the management of chronic schizophrenia with comorbid dementia: an open-label study investigating effects on cognition, behaviour and activities of daily living.

Comorbid schizophrenia and dementia is becoming an increasingly common phenomenon. Because rivastigmine, a reversible acetylcholinesterase inhibitor, appears to delay the progression of Alzheimer's disease, it may also improve or delay the cognitive and behavioural disturbances evident in elderly chronic schizophrenia patients with comorbid cognitive decline. The aim of this study was to investigate augmentative rivastigmine administration in this population and to determine any effect on cognition, behaviour and 'activity of daily living' (ADLs) capabilities. Thirteen subjects with comorbid schizophrenia and dementia were administered open-label oral rivastigmine (9 mg/day) for a period of 12 weeks. The results indicated improvement in Mini-Mental State Examination scores (P<0.01), Alzheimer's Disease Assessment Scale-cognitive subscale scores (P<0.001), ADL scores (P<0.01) and Positive and Negative Syndrome Scale scores (P<0.01). Study observations indicate beneficial effects of rivastigmine administration in this subpopulation of schizophrenia patients. Following on from other studies of cholinesterase inhibitor agents, clinical improvement in this patient subpopulation may extend to the class of cholinesterase inhibitor agents in general and not necessarily be a specific effect of any of the medications. The effects noted may be specific to the subpopulation of comorbid schizophrenia and dementia rather than schizophrenia in general. Although speculative, these effects may be related to cholinergic dysfunction, which has been hypothesized to be present in some patients with schizophrenia.

Urethral masturbation and sexual disinhibition in dementia: a case report.

Urethral masturbation and sexual disinhibition as manifestations of behavioral and psychological symptoms of dementia (BPSD) are described in a 90-year-old patient who repeatedly self-inserted foreign bodies into his urethra. A diagnosis was made of late onset sexual disinhibition and hypersexuality in a patient with Dementia of the Alzheimer Type. Significant reduction of his sexual behavior was achieved with low doses of haloperidol. Similar symptoms are noted in Pick's disease, other fronto-temporal lesions, mania and following a seizure or treatment of Parkinson's disease, and have been described as Kluver-Busy-type. Clinicians should consider this diagnosis when investigating dysuria, cystitis, haematuria and urinary tract infections even in the very old.

A plasmodesmata-associated beta-1,3-glucanase in Arabidopsis.

Plasmodesmal conductivity is regulated in part by callose turnover, which is hypothesized to be determined by beta-1,3-glucan synthase versus glucanase activities. A proteomic analysis of an Arabidopsis thaliana plasmodesmata (Pd)-rich fraction identified a beta-1,3-glucanase as present in this fraction. The protein encoded by the putative plasmodesmal associated protein (ppap) gene, termed AtBG_ppap, had previously been found to be a post-translationally modified glycosylphosphatidylinositol (GPI) lipid-anchored protein. When fused to green fluorescent protein (GFP) and expressed in tobacco (Nicotiana tabacum) or Nicotiana benthamiana epidermal cells, this protein displays fluorescence patterns in the endoplasmic reticulum (ER) membrane system, along the cell periphery and in a punctate pattern that co-localizes with aniline blue-stained callose present around the Pd. Plasma membrane localization was verified by co-localization of AtBG_ppap:GFP together with a plasma membrane marker N-[3-triethylammoniumpropyl]-4-[p-diethylaminophenylhexatrienyl] pyridinium dibromide (FM4-64) in plasmolysed cells. In Arabidopsis T-DNA insertion mutants that do not transcribe AtBG_ppap, functional studies showed that GFP cell-to-cell movement between epidermal cells is reduced, and the conductivity coefficient of Pd is lower. Measurements of callose levels around Pd after wounding revealed that callose accumulation in the mutant plants was higher. Taken together, we suggest that AtBG_ppap is a Pd-associated membrane protein involved in plasmodesmal callose degradation, and functions in the gating of Pd.