A note on the evaluation of a beta-casein variant in bovine breeds by allele-specific PCR and relevance to β-casomorphin

peer-reviewedThis work was supported by Enterprise Ireland and by a Teagasc Walsh fellowship to A.F. Keating.Two genetic variants of the bovine β-casein gene (A1 and B) encode a histidine residue at codon 67, resulting in potential liberation of a bioactive peptide, β-casomorphin, upon digestion. An allele-specific PCR (AS-PCR) was evaluated to distinguish between the β-casomorphin-releasing variants (A1 and B) and the non-releasing variants. AS-PCR successfully distinguished β-casein variants in 41 of 42 animals as confirmed by sequence analysis. Overall, while the incidence of the homozygous A1 and B animals (i.e., homozygous for the histidine residue; 21.4%) was lower than that for animals without the histidine residue (30.9% respectively), 69% of animals carried at least one allele for the histidine residue at codon 67.Teagasc Walsh Fellowship ProgrammeEnterprise Irelan

An assessment of the mantle and slab components in the magmas of an oceanic arc volcano: Raoul Volcano, Kermadec arc

Raoul Volcano occupies a simple oceanic subduction setting in the northern part of the Kermadec arc on the Pacific–Australian convergent plate boundary. The primary inputs to the magmatic system that feeds the volcano are a subduction component derived from the subducting old Pacific oceanic lithosphere and its veneer of pelagic sediment, and the overlying peridotitic mantle wedge. Conservative trace elements that are very incompatible during mantle melting are relatively depleted in Raoul lavas indicating a source that has been depleted during an earlier melting event. Major element co-variations indicate magma genesis by 25% near fractional melting of a mantle source that is weakly depleted (2% melt extraction) relative to a fertile MORB source. An important influence on the composition of the mantle component is progressive melt extraction coupled with minimal advection of fresh material into the sub-arc zone followed by melt extraction from a melting column beneath the spreading centre of an adjacent back arc basin. High field strength element and rare earth element systematics indicate involvement of a subduction-related component of constant composition. Two fluid components can be distinguished, one enriched in large ion lithophile elements inferred to be an aqueous fluid that is continuously added to the ascending melt column and the other a less mobile fluid that transfers Th. A homogeneous subduction-related component of constant composition and magnitude arises if the slab-derived flux migrates from the slab–mantle interface to the sub-arc melting column by repeated episodes of amphibole formation and decomposition its composition is then governed by the distribution coefficients of pyroxene and its magnitude by the degree of amphibole saturation of mantle peridotite. The results from Raoul Volcano are comparable to those from other oceanic subduction-related arcs such as South Sandwich and Marianas suggesting that this is a general model for oceanic arcs

Biodiversity of nematode assemblages from the region of the Clarion-Clipperton Fracture Zone, an area of commercial mining interest

BACKGROUND: The possibility for commercial mining of deep-sea manganese nodules is currently under exploration in the abyssal Clarion-Clipperton Fracture Zone. Nematodes have potential for biomonitoring of the impact of commercial activity but the natural biodiversity is unknown. We investigate the feasibility of nematodes as biomonitoring organisms and give information about their natural biodiversity. RESULTS: The taxonomic composition (at family to genus level) of the nematode fauna in the abyssal Pacific is similar, but not identical to, the North Atlantic. Given the immature state of marine nematode taxonomy, it is not possible to comment on the commonality or otherwise of species between oceans. The between basin differences do not appear to be directly linked to current ecological factors. The abyssal Pacific region (including the Fracture Zone) could be divided into two biodiversity subregions that conform to variations in the linked factors of flux to the benthos and of sedimentary characteristics. Richer biodiversity is associated with areas of known phytodetritus input and higher organic-carbon flux. Despite high reported sample diversity, estimated regional diversity is less than 400 species. CONCLUSION: The estimated regional diversity of the CCFZ is a tractable figure for biomonitoring of commercial activities in this region using marine nematodes, despite the immature taxonomy (i.e. most marine species have not been described) of the group. However, nematode ecology is in dire need of further study

Kinetic and thermodynamic analysis of leech-derived tryptase inhibitor interaction with bovine tryptase and bovine trypsin

The interaction of leech-derived tryptase inhibitor (LDTI) with bovine liver capsule tryptase (BLCT) and bovine trypsin has been studied using both thermodynamic and kinetic approaches. Several differences were detected: (i) the equilibrium affinity of LDTI for BLCT (K-a = 8.9 x 10(5) M-1) is about 600-fold lower than that for bovine trypsin (K-a = 5.1 x 10(8) M-1); (ii) LDTI behaves as a purely non-competitive inhibitor of BLCT, while it is a purely competitive inhibitor of bovine trypsin. These functional data are compared with those previously reported for the LDTI binding to human tryptase, where tight inhibition occurs at two of the four active sites of the tetramer (K-a = 7.1 x 10(8) M-1). Amino acid sequence alignment of BLCT, human beta II-tryptase and bovine trypsin allows us to infer some possible structural basis for the observed functional differences

Building the case for insulin-like growth factor receptor-I involvement in thyroid-associated ophthalmopathy

The pathogenesis of orbital Graves' disease (GD), a process known as thyroid-associated ophthalmopathy (TAO), remains incompletely understood. The thyrotropin receptor (TSHR) represents the central autoantigen involved in GD and has been proposed as the thyroid antigen shared with the orbit that could explain the infiltration of immune cells into tissues surrounding the eye. Another cell surface protein, insulin-like growth factor-I receptor (IGF-IR), has recently been proposed as a second antigen that participates in TAO by virtue of its interactions with anti-IGF-IR antibodies generated in GD, its apparent physical and functional complex formation with TSHR, and its necessary involvement in TSHR post-receptor signaling. The proposal that IGF-IR is involved in TAO has provoked substantial debate. Furthermore, several studies from different laboratory groups, each using different experimental models, have yielded conflicting results. In this article, we attempt to summarize the biological characteristics of IGF-IR and TSHR. We also review the evidence supporting and refuting the postulate that IGF-IR is a self-antigen in GD and that it plays a potentially important role in TAO. The putative involvement of IGF-IR in disease pathogenesis carries substantial clinical implications. Specifically, blocking this receptor with monoclonal antibodies can dramatically attenuate the induction by TSH and pathogenic antibodies generated in GD of proinflammatory genes in cultured orbital fibroblasts and fibrocytes. These cell types appear critical to the development of TAO. These observations have led to the conduct of a now-completed multicenter therapeutic trial of a fully human monoclonal anti-IGF-IR blocking antibody in moderate to severe, active TAO

Independent evolution of pain insensitivity in African mole-rats: origins and mechanisms

The naked mole-rat (Heterocephalus glaber) is famous for its longevity and unusual physiology. This eusocial species that lives in highly ordered and hierarchical colonies with a single breeding queen, also discovered secrets enabling somewhat pain-free living around 20 million years ago. Unlike most mammals, naked mole-rats do not feel the burn of chili pepper's active ingredient, capsaicin, nor the sting of acid. Indeed, by accumulating mutations in genes encoding proteins that are only now being exploited as targets for new pain therapies (the nerve growth factor receptor TrkA and voltage-gated sodium channel, Na(V)1.7), this species mastered the art of analgesia before humans evolved. Recently, we have identified pain insensitivity as a trait shared by several closely related African mole-rat species. One of these African mole-rats, the Highveld mole-rat (Cryptomys hottentotus pretoriae), is uniquely completely impervious and pain free when confronted with electrophilic compounds that activate the TRPA1 ion channel. The Highveld mole-rat has evolved a biophysical mechanism to shut down the activation of sensory neurons that drive pain. In this review, we will show how mole-rats have evolved pain insensitivity as well as discussing what the proximate factors may have been that led to the evolution of pain-free traits

Where Technology and Field Information Meet: The Metal Detector Handbook

The Metal Detector Handbook for Humanitarian Demining explains what all operators need to know about modern metal detectors. If trying to test, select or simply use a detector to its optimal ability, this handbook will show the user exactly what is needed. The handbook is in pocket A5 format and is resistant to field use

Reply to: Critical revision of the ZEPLIN-I sensitivity to WIMP interactions

Recent objections (Phys.Lett. B 637, 156) to the published Zeplin I limit (Astropart. Phys 23, 444) are shown to arise from misunderstandings of the calibration data and procedure, and a misreading of the data in one of the referenced papers.Comment: 5 page

Temporal Changes in Astronauts Muscle and Cardiorespiratory Physiology Pre-, In-, and Post-Spaceflight

NASAs vision for future exploration missions depends on the ability to protect astronauts health and safety for performance of Extravehicular Activity (EVA), and to allow astronauts to safely egress from vehicles in a variety of landing scenarios (e.g. water landing upon return to Earth and undefined planetary/lunar landings). Prolonged exposure to spaceflight results in diminished tolerance to prolonged physical activity, decreased cardiac and sensorimotor function, and loss of bone mineral density, muscle mass, and muscle strength. For over 50 years exercise has been the primary countermeasure against these physiologic decrements during spaceflight, and while the resulting protection is adequate for ISS missions (i.e., Soyuz landing, microgravity EVAs), there is little information regarding time-course changes in muscle and aerobic performance. As spaceflight progresses towards longer exploration missions and vehicles with less robust exercise capabilities compared to ISS, countermeasures will need to be combined and optimized to protect crew health and performance across all organ systems over the course of exploration missions up to 3 years in duration. This will require a more detailed understanding of the dynamic effects of spaceflight on human performance. Thus, the focus of this study is quantifying decrements in physical performance over different mission durations, and to provide detailed information on the physiological rational for why and when observed changes in performance occur. The research proposed will temporally profile changes in astronauts cardiorespiratory fitness, muscle mass, strength, and endurance over spaceflight missions of 2 months, 6 months, and up to 1 year in duration. Additionally, an extrapolation model will provide predictions for changes associated with exploration missions 2-3 years in duration. To accomplish these objectives astronauts will be asked to participate in pre, in, post-flight measurement of muscle performance, muscle size, cardiorespiratory fitness and submaximal performance capabilities, as well as non-invasive assessment of cerebral and muscle oxygenation and perfusion (Table 1). Additionally, ambulatory and in-flight exercise, nutrition, and sleep will be monitored using a variety of commercial technologies and in-flight assessment tools. Significance: Our detailed testing protocol will provide valuable information for describing how and when spaceflight-induced muscle and aerobic based adaptations occur over the course of spaceflight missions up to and beyond 1 year. This information will be vital in the assessment as to whether humans can be physically ready for deep space exploration such as Mars missions with current technology, or if additional mitigation strategies are necessary