Accounting for differences in the bioactivity and bioavailability of vitamers

Essentially all vitamins exist with multiple nutritionally active chemical species often called vitamers. Our quantitative understanding of the bioactivity and bioavailability of the various members of each vitamin family has increased markedly, but many issues remain to be resolved concerning the reporting and use of analytical data. Modern methods of vitamin analysis rely heavily on chromatographic techniques that generally allow the measurement of the individual chemical forms of vitamins. Typical applications of food analysis include the evaluation of shelf life and storage stability, monitoring of nutrient retention during food processing, developing food composition databases and data needed for food labeling, assessing dietary adequacy and evaluating epidemiological relationships between diet and disease. Although the usage of analytical data varies depending on the situation, important issues regarding how best to present and interpret the data in light of the presence of multiple vitamers are common to all aspects of food analysis. In this review, we will evaluate the existence of vitamers that exhibit differences in bioactivity or bioavailability, consider when there is a need to address differences in bioactivity or bioavailability of vitamers, and then consider alternative approaches and possible ways to improve the reporting of data. Major examples are taken from literature and experience with vitamin B6 and folate

Shearing Interferometer for Quantifying the Coherence of Hard X-Ray Beams

We report a quantitative measurement of the full transverse coherence function of the 14.4 keV x-ray radiation produced by an undulator at the Swiss Light Source. An x-ray grating interferometer consisting of a beam splitter phase grating and an analyzer amplitude grating has been used to measure the degree of coherence as a function of the beam separation out to 30 m. Importantly, the technique provides a model-free and spatially resolved measurement of the complex coherence function and is not restricted to high resolution detectors and small fields of view. The spatial characterization of the wave front has important applications in discovering localized defects in beam line optics

The extinct, giant giraffid Sivatherium giganteum: skeletal reconstruction and body mass estimation

Sivatherium giganteum is an extinct giraffid from the Plio–Pleistocene boundary of the Himalayan foothills. To date, there has been no rigorous skeletal reconstruction of this unusual mammal. Historical and contemporary accounts anecdotally state that Sivatherium rivalled the African elephant in terms of its body mass, but this statement has never been tested. Here, we present a three-dimensional composite skeletal reconstruction and calculate a representative body mass estimate for this species using a volumetric method. We find that the estimated adult body mass of 1246 kg (857—1812 kg range) does not approach that of an African elephant, but confirms that Sivatherium was certainly a large giraffid, and may have been the largest ruminant mammal that has ever existed. We contrast this volumetric estimate with a bivariate scaling estimate derived from Sivatherium's humeral circumference and find that there is a discrepancy between the two. The difference implies that the humeral circumference of Sivatherium is greater than expected for an animal of this size, and we speculate this may be linked to a cranial shift in centre of mass

Mucosal immune responses following intestinal nematode infection.

In most natural environments, the large majority of mammals harbour parasitic helminths that often live as adults within the intestine for prolonged periods (1-2 years). Although these organisms have been eradicated to a large extent within westernized human populations, those living within rural areas of developing countries continue to suffer from high infection rates. Indeed, recent estimates indicate that approximately 2.5 billion people worldwide, mainly children, currently suffer from infection with intestinal helminths (also known as geohelminths and soil-transmitted helminths) . Paradoxically, the eradication of helminths is thought to contribute to the increased incidence of autoimmune diseases and allergy observed in developed countries. In this review, we will summarize our current understanding of host-helminth interactions at the mucosal surface that result in parasite expulsion or permit the establishment of chronic infections with luminal dwelling adult worms. We will also provide insight into the adaptive immune mechanisms that provide immune protection against re-infection with helminth larvae, a process that is likely to be key to the future development of successful vaccination strategies. Lastly, the contribution of helminths to immune modulation and particularly to the treatment of allergy and inflammatory bowel disease will be discussed

Iridum-catalysed C–H Borylation of β-aryl-aminopropionic acids

Iridium-catalysed catalytic, regioselective C–H borylation of β-aryl-aminopropionic acid derivatives gives access to 3,5-functionalised protected β-aryl-aminopropionic acid boronates. The synthetic versatility of these new boronates is demonstrated through telescoped functionalisation reaction to give diverse building blocks for medicinal chemistry. The C-H borylation is also effective for dipeptide substrates. We have exemplified this methodology in the synthesis of a pan av integrin antagonist

Differential expression analysis for sequence count data

*Motivation:* High-throughput nucleotide sequencing provides quantitative readouts in assays for RNA expression (RNA-Seq), protein-DNA binding (ChIP-Seq) or cell counting (barcode sequencing). Statistical inference of differential signal in such data requires estimation of their variability throughout the dynamic range. When the number of replicates is small, error modelling is needed to achieve statistical power.

*Results:* We propose an error model that uses the negative binomial distribution, with variance and mean linked by local regression, to model the null distribution of the count data. The method controls type-I error and provides good detection power. 

*Availability:* A free open-source R software package, _DESeq_, is available from the Bioconductor project and from "http://www-huber.embl.de/users/anders/DESeq":http://www-huber.embl.de/users/anders/DESeq

Heterogeneous mantle source and magma differentiation of quaternary arc-like volcanic rocks from Tengchong, SE margin of the Tibetan Plateau

The Tengchong volcanic field north of the Burma arc comprises numerous Quaternary volcanoes in the southeastern margin of the Tibetan Plateau. The volcanic rocks are grouped into four units (1-4) from the oldest to youngest. Units 1, 3 and 4 are composed of olivine trachybasalt, basaltic trachyandesite and trachyandesite, and Unit 2 consists of hornblende dacite. The rocks of Units 1, 3, and 4 form a generally alkaline suite in which the rocks plot along generally linear trends on Harker diagrams with only slight offset from unit to unit. They contain olivine phenocrysts with Fo values ranging from 65 to 85 mol% and have Cr-spinel with Cr# ranging from 23 to 35. All the rocks have chondrite-normalized REE patterns enriched in LREE and primitive mantle-normalized trace element patterns depleted in Ti, Nb and Ta, but they are rich in Th, Ti and P relative to typical arc volcanics. Despite minor crustal contamination, 87Sr/ 86Sr ratios (0.706-0.709), εNd values (-3.2 to -8.7), and εHf values (+4.8 to -6.4) indicate a highly heterogeneous mantle source. The Pb isotopic ratios of the lavas ( 206Pb/ 204Pb = 18.02-18.30) clearly show an EMI-type mantle source. The underlying mantle source was previously modified by subduction of the Neo-Tethyan oceanic and Indian continental lithosphere. The present heterogeneous mantle source is interpreted to have formed by variable additions of fluids and sediments derived from the subducted Indian Oceanic lithosphere, probably the Ninety East Ridge. Magma generation and emplacement was facilitated by transtensional NS-trending strike-slip faulting. © 2011 The Author(s).published_or_final_versionSpringer Open Choice, 28 May 201

A Generalization of the Goldberg-Sachs Theorem and its Consequences

The Goldberg-Sachs theorem is generalized for all four-dimensional manifolds endowed with torsion-free connection compatible with the metric, the treatment includes all signatures as well as complex manifolds. It is shown that when the Weyl tensor is algebraically special severe geometric restrictions are imposed. In particular it is demonstrated that the simple self-dual eigenbivectors of the Weyl tensor generate integrable isotropic planes. Another result obtained here is that if the self-dual part of the Weyl tensor vanishes in a Ricci-flat manifold of (2,2) signature the manifold must be Calabi-Yau or symplectic and admits a solution for the source-free Einstein-Maxwell equations.Comment: 14 pages. This version matches the published on

Proteomics and phylogenetic analysis of the cathepsin L protease family of the helminth pathogen Fasciola hepatica: Expansion of a repertoire of virulence-associated factors

Cathepsin L proteases secreted by the helminth pathogen Fasciola hepatica have functions in parasite virulence including tissue invasion and suppression of host immune responses. Using proteomics methods alongside phylogenetic studies we characterized the profile of cathepsin L proteases secreted by adult F. hepatica and hence identified those involved in host-pathogen interaction. Phylogenetic analyses showed that the Fasciola cathepsin L gene family expanded by a series of gene duplications followed by divergence that gave rise to three clades associated with mature adult worms (Clades 1, 2, and 5) and two clades specific to infective juvenile stages (Clades 3 and 4). Consistent with these observations our proteomics studies identified representatives from Clades 1, 2, and 5 but not from Clades 3 and 4 in adult F. hepatica secretory products. Clades 1 and 2 account for 67.39 and 27.63% of total secreted cathepsin Ls, respectively, suggesting that their expansion was positively driven and that these proteases are most critical for parasite survival and adaptation. Sequence comparison studies revealed that the expansion of cathepsin Ls by gene duplication was followed by residue changes in the S2 pocket of the active site. Our biochemical studies showed that these changes result in alterations in substrate binding and suggested that the divergence of the cathepsin L family produced a repertoire of enzymes with overlapping and complementary substrate specificities that could cleave host macromolecules more efficiently. Although the cathepsin Ls are produced as zymogens containing a prosegment and mature domain, all secreted enzymes identified by MS were processed to mature active enzymes. The prosegment region was highly conserved between the clades except at the boundary of prosegment and mature enzyme. Despite the lack of conservation at this section, sites for exogenous cleavage by asparaginyl endopeptidases and a Leu-Ser ↓ His motif for autocatalytic cleavage by cathepsin Ls were preserved. © 2008 by The American Society for Biochemistry and Molecular Biology, Inc

Using coloured filters to reduce the symptoms of visual stress in children with reading delay

Background: Meares Irlen Syndrome (MIS), otherwise known as “visual stress”, is one condition that can cause difficulties with reading. Aim: This study aimed to compare the effect of two coloured-filter systems on the symptoms of visual stress in children with reading delay. Methods: The study design was a pre-test, post-test, randomized head-to-head comparison of two filter systems on the symptoms of visual stress in school children. A total of 68 UK mainstream schoolchildren with significant impairment in reading ability completed the study. Results: The filter systems appeared to have a large effect on the reported symptoms between pre and post three-month time points (d = 2.5, r = 0.78). Both filter types appeared to have large effects (Harris d = 1.79, r = 0.69 and DRT d = 3.22, r = 0.85). Importantly, 35% of participants’ reported that their symptoms had resolved completely; 72% of the 68 children appeared to gain improvements in three or more visual stress symptoms. Conclusion and significance: The reduction in symptoms, which appeared to be brought about by the use of coloured filters, eased the visual discomfort experienced by these children when reading. This type of intervention therefore has the potential to facilitate occupational engagement