Silicic acid (Si(OH)(4)) is a significant influence upon the atomic absorption signal of aluminium measured by graphite furnace atomic absorption spectrometry (GFAAS).

We have identified silicic acid (Si(OH)(4)) as an important modifier of the absorbance signal of aluminium measured by graphite furnace atomic absorption spectrometry (GFAAS). The presence of Si(OH)(4) enhanced the signal by as much as 50%. The extent of the enhancement was dependent upon both [Al] and [Si(OH)(4)] and was maximal when [Al]< or =4.44 micromol dm(-3) and [Si(OH)(4)]> or =0.50 mmol dm(-3). The enhancement of the Al absorbance signal was not linearly related to [Si(OH)(4)] and the effect was, generally, saturated, for all [Al] tested, at [Si(OH)(4)]> or =0.50 mmol dm(-3). Si(OH)(4) was significantly more effective in enhancing the Al absorbance signal than Mg(NO(3))(2). However, the co-occurrence of 10 mmol dm(-3) Mg(NO(3))(2) and 2 mmol dm(-3) Si(OH)(4) in samples abolished the enhancement due to Si(OH)(4). The presence of Si(OH)(4) in samples could result in an overestimation of the Al content of those samples by as much as 50%. Errors in the measurement of Al in samples containing Si(OH)(4) could be prevented using matrix-matched calibration standards. Our observation could have serious implications for the determination of Al in aqueous samples of both geochemical and biological interest. It may also point towards the application of Si(OH)(4) as a novel and effective matrix modifier in the determination of Al by GFAAS since the inclusion of Si(OH)(4) in standards and samples improved the limit of detection of Al from ca 8 nmol dm(-3) to 3 nmol dm(-3).     

Metal-mediated formation of fibrillar ABri amyloid

British amyloid (ABri) peptide is precipitated as amyloid fibrils in pathological lesions which are characteristic of familial British dementia. Unlike for other amyloidogenic peptides which have been implicated in neurodegenerative disease, for example, Abeta in Alzheimer's disease and alpha synuclein in Parkinson's disease, nothing is yet known as to whether metals mediate the formation of ABri amyloid fibrils. We show herein that a concentration of ABri, which had not previously been shown to spontaneously form amyloid, formed fibrils when incubated for 12 months at 37 degrees C. The additional presence of Al(III), in particular, or Fe(III) increased significantly both the number and the size of the fibrillar amyloid deposits which were very similar in appearance to amyloid described in hippocampal plaques in familial British dementia. Co-incubation of ABri with either Zn(II) or Cu(II) precipitated the peptide but did not result in the formation of amyloid fibrils.     

A specific method for the determination of millimicrogram amounts of urinary oestrone

1. A new combined radioactivity-fluorescence method is described for urinary oestrone, which involves acid hydrolysis, extraction and purification of the phenolic fraction, saponification, a Girard T separation and alumina chromatography of acetylated oestrone. 2. Sulphuric acid fluorescence is used for quantitation and specificity is achieved by the addition of tritiated oestrone to the urine hydrolysate. This radioactive tracer functions both as an internal corrector for purification losses and enables the demonstration of constant specific activity through the oestrone peaks to act as an index of specificity in each determination. 3. By using one-fifth of a 24hr. urine sample, 1mug. of urinary oestrone/24hr. can be determined with an accuracy of +/-4%. Fluorescence emission spectra from processed urine samples are identical with that of authentic oestrone acetate. 4. The advantages of the method are its high sensitivity and specificity, which is achieved with relative convenience.     

Human pro-islet amyloid polypeptide (ProIAPP1-48) forms amyloid fibrils and amyloid spherulites in vitro

Deposition of β sheets of islet amyloid polypeptide (IAPP) in pancreatic tissue is implicated in the aetiology of type 2 diabetes mellitus (T2DM). IAPP is cleaved from its precursor protein, pro-islet amyloid polypeptide (ProIAPP) and incomplete cleavage results in ProIAPP_1-48, which is found co-deposited with IAPP. Cu(II) prevents IAPP from forming amyloid and herein we investigated if it would also prevent ProIAPP_1-48 from forming β sheets. Excess Cu(II) prevented ProIAPP_1-48 from forming amyloid and additionally reversed the formation of β sheets in pre-formed fibrils of the peptide. The latter was also true for ProIAPP_1-48 fibrils formed in the presence of Al(III). An unexpected finding was the formation of spherulites of ProIAPP_1-48 which were only observed in preparations which included Al(III). The spherulites were 40-100 μm in diameter and stained positively for Al(III) suggesting a role for this metal in their formation.The abolition by Cu(II) of the propensity of ProIAPP_1-48 to form amyloid may have important implications for the treatment of T2DM. The immediate significance for diabetes of the equally novel observation of spherulites of ProIAPP_1-48 is unknown though, as with spherulites of Aβ₄₂ in Alzheimer's disease, there may be implications for the aetiology of the disease.     

Galectin‐3 binds Neisseria meningitidis and increases interaction with phagocytic cells

Galectin‐3 is expressed and secreted by immune cells and has been implicated in multiple aspects of the inflammatory response. It is a glycan binding protein which can exert its functions within cells or exogenously by binding cell surface ligands, acting as a molecular bridge or activating signalling pathways. In addition, this lectin has been shown to bind to microorganisms. In this study we investigated the interaction between galectin‐3 and Neisseria meningitidis, an important extracellular human pathogen, which is a leading cause of septicaemia and meningitis. Immunohistochemical analysis indicated that galectin‐3 is expressed during meningococcal disease and colocalizes with bacterial colonies in infected tissues from patients. We show that galectin‐3 binds to N. meningitidis and we demonstrate that this interaction requiresfull‐length, intact lipopolysaccharide molecules. We found that neither exogenous nor endogenous galectin‐3 contributes to phagocytosis of N. meningitidis; instead exogenous galectin‐3 increases adhesion to monocytes and macrophages but not epithelial cells. Finally we used galectin‐3 deficient (Gal‐3^?/?) mice to evaluate the contribution of galectin‐3 to meningococcal bacteraemia. We found that Gal‐3^?/? mice had significantly lower levels of bacteraemia compared with wild‐type mice after challenge with live bacteria, indicating that galectin‐3 confers an advantage to N. meningitidis during systemic infection.     

Dopamine-induced α-synuclein oligomers show self- and cross-propagation properties

Amyloid aggregates of α-synuclein (αS) protein are the predominant species present within the intracellular inclusions called Lewy bodies in Parkinson’s disease (PD) patients. Among various aggregates, the low-molecular weight ones broadly ranging between 2 and 30 mers are known to be the primary neurotoxic agents responsible for the impairment of neuronal function. Recent research has indicated that the neurotransmitter dopamine (DA) is one of the key physiological agents promoting and augmenting αS aggregation, which is thought to be a significant event in PD pathologenesis. Specifically, DA is known to induce the formation of soluble oligomers of αS, which in turn are responsible for inducing several important cellular changes leading to cellular toxicity. In this report, we present the generation, isolation, and biophysical characterization of five different dopamine-derived αS oligomers (DSOs) ranging between 3 and 15 mers, corroborating previously published reports. More importantly, we establish that these DSOs are also capable of replication by self-propagation, which leads to the replication of DSOs upon interaction with αS monomers, a process similar to that observed in mammilian prions. In addition, DSOs are also able to cross-propagate amyloid-β (Aβ) aggregates involved in Alzheimer’s disease (AD). Interestingly, while self-propagation of DSOs occur with no net gain in protein structure, cross-propagation proceeds with an overall gain in β-sheet conformation. These results implicate the involvement of DSOs in the progression of PD, and, in part, provide a molecular basis for the observed co-existence of AD-like pathology among PD patients.