Lower levels of damaged protein biomarkers in the plasma of overweight type 2 diabetic men following supplementation with a standardised bilberry extract

Peer reviewedPublisher PD

Anti-transglutaminase 6 antibodies in children and young adults with cerebral palsy.

Objectives. We have previously reported a high prevalence of gluten-related serological markers (GRSM) in children and young adults with cerebral palsy (CP). The majority had no enteropathy to suggest coeliac disease (CD). Antibodies against transglutaminase 6 (anti-TG6) represent a new marker associated with gluten-related neurological dysfunction. The aim of this study was to investigate the prevalence of anti-TG6 antibodies in this group of individuals with an early neurological injury resulting in CP. Materials and Methods. Sera from 96 patients with CP and 36 controls were analysed for IgA/IgG class anti-TG6 by ELISA. Results. Anti-TG6 antibodies were found in 12/96 (13%) of patients with CP compared to 2/36 (6%) in controls. The tetraplegic subgroup of CP had a significantly higher prevalence of anti-TG6 antibodies 6/17 (35%) compared to the other subgroups and controls. There was no correlation of anti-TG6 autoantibodies with seropositivity to food proteins including gliadin. Conclusions. An early brain insult and associated inflammation may predispose to future development of TG6 autoimmunity

Brain fog and non-coeliac gluten sensitivity: Proof of concept brain MRI pilot study

Aims Non-Coeliac Gluten Sensitivity (NCGS) is poorly understood, particularly in terms of its neurological outcomes. We initially conducted a prospective postal survey to investigate its neurological presentation and symptom course. Results from this then motivated a follow-up pilot study utilising brain MRI to characterise potential diagnostic biomarkers for future research. Methods Patients with NCGS were recruited from a specialist centre and completed a prospective postal questionnaire (N = 125). This summarised symptoms experienced, their severity and their course. Onset time was compared by Chi-squared analysis to data from the same centre concerning coeliac disease patients (N = 224). Five respondents on a strict gluten-free diet who self-reported brain fog then attended a pilot study, completing MR brain imaging/questionnaires before/after a gluten challenge. “Baseline” data were assessed for abnormalities, while symptom severity and cerebral blood flow (CBF) were compared before/after challenge. Results Survey participants were aged 47 (85% female). Prevalence of neurological symptoms were: headaches (51%), brain fog (48%), balance issues (31%), tingling (19%). Median symptom resolution time was 48 hours, while onset was 90 minutes; onset pattern was not significantly different compared to CD patients (p = 0.322). Extra-intestinal symptoms worsened by 37%(±28) during a typical reaction. Predominantly non-statistical observations from the brain imaging study are discussed. Conclusions Neurological symptoms in NCGS are common, and onset time is comparable to that in CD. Brain imaging may be a useful future means of investigating physiological injury and responses to gluten in further study

A neogene history of mantle convective support beneath Borneo

Most, but not all, geodynamic models predict 1–2 km of mantle convective draw-down of the Earth's surface in a region centered on Borneo within southeast Asia. Nevertheless, there is geomorphic, geologic and geophysical evidence which suggests that convective uplift might have played some role in sculpting Bornean physiography. For example, a long wavelength free-air gravity anomaly of +60 mGal centered on Borneo coincides with the distribution of Neogene basaltic magmatism and with the locus of sub-plate slow shear wave velocity anomalies. Global positioning system measurements, an estimate of elastic thickness, and crustal isostatic considerations suggest that regional shortening does not entirely account for kilometer-scale regional elevation. Here, we explore the possible evolution of the Bornean landscape by extracting and modeling an inventory of 90 longitudinal river profiles. Misfit between observed and calculated river profiles is minimized by smoothly varying uplift rate as a function of space and time. Erosional parameters are chosen by assuming that regional uplift post-dates Eocene deposition of marine carbonate rocks. The robustness of this calibration is tested against independent geologic observations such as thermochronometric measurements, offshore sedimentary flux calculations, and the history of volcanism. A calculated cumulative uplift history suggests that kilometer-scale Bornean topography grew rapidly during Neogene times. This suggestion is corroborated by an offshore Miocene transition from carbonate to clastic deposition. Co-location of regional uplift and slow shear wave velocity anomalies immediately beneath the lithospheric plate implies that regional uplift could have been at least partly generated and maintained by temperature anomalies within an asthenospheric channel

Global dynamic topography observations reveal limited influence of large-scale mantle flow

Convective circulation of the Earth’s mantle maintains some fraction of surface topography that varies with space and time. Most predictive models show that this dynamic topography has peak amplitudes of about ±2km, dominated by wavelengths of 10⁴km. Here, we test these models against our comprehensive observational database of 2,120 spot measurements of dynamic topography that were determined by analysing oceanic seismic surveys. These accurate measurements have typical peak amplitudes of ±1km and wavelengths of approximately 10³km, and are combined with limited continental constraints to generate a global spherical harmonic model whose robustness has been carefully tested and benchmarked. Our power spectral analysis reveals significant discrepancies between observed and predicted dynamic topography. At longer wavelengths (such as 10⁴km), observed dynamic topography has peak amplitudes of about ±500m. At shorter wavelengths (such as 10³km), significant dynamic topography is still observed. We show that these discrepancies can be explained if short-wavelength dynamic topography is generated by temperature-driven density anomalies within a sub-plate asthenospheric channel. Stratigraphic observations from adjacent continental margins show that these dynamic topographic signals evolve quickly with time. More rapid temporal and spatial changes in vertical displacement of the Earth’s surface have direct consequences for fields as diverse as mantle flow, oceanic circulation and long-term climate change

Spatial and temporal patterns of Cenozoic dynamic topography around Australia

[1] Despite its importance, the spatial and temporal pattern of dynamic topography generated by mantle convective circulation is poorly known. We present accurate estimates of dynamic topography from oceanic basins and continental margins surrounding Australia. Our starting point is measurement of residual depth anomalies on the oldest oceanic floor adjacent to the continental shelf. These anomalies were determined from a combined dataset of ~200 seismic reflection and wide-angle images of well-sedimented oceanic crust. They have amplitudes of between −1 km and +0.5 km, and their spatial variation is broadly consistent with long-wavelength free-air gravity and shallow seismic tomographic anomalies. Along the Northwest Shelf, a regional depth anomaly of −300 to −700 m intersects the adjacent continental shelf. The temporal evolution of this anomaly was determined by analyzing the stratigraphic architecture of an extensive carbonate platform, which fringes the shelf and records a dramatic switch from progradation to aggradation during Neogene times. Three-dimensional seismic mapping calibrated by boreholes was used to calculate water-loaded subsidence histories at rollover points of clinoforms along the shelf. At 9 ± 3 Ma, the rate of subsidence increases from 5 to up 75 m Myr−1, generating a subsidence anomaly of −300 to −700 m. The amplitude of this anomaly varies along the shelf and cannot be generated by glacio-eustatic sea-level variation. Instead, we propose that a regional subsidence episode, which affects both the proximal shelf and the distal oceanic basin, was generated by convective drawdown. By combining our results with other published estimates of uplift and subsidence, a map of Australia, which shows the spatial and temporal pattern of dynamic topography is presented. Most, but not all, of Australia's epeirogeny can be attributed to rapid northward motion of the Australian plate over a pre-existing pattern of convective circulation

Continental residual topography extracted from global analysis of crustal structure

Continental topography is dominantly controlled by a combination of crustal thickness and density variations. Nevertheless, it is clear that some additional topographic component is supported by the buoyancy structure of the underlying lithospheric and convecting mantle. Isolating these secondary sources is not straightforward, but provides valuable information about mantle dynamics. Here, we estimate and correct for the component of topographic elevation that is crustally supported to obtain residual topographic anomalies for the major continents, excluding Antarctica. Crustal thickness variations are identified by assembling a global inventory of 26,725 continental crustal thickness estimates from local seismological data sets (e.g., wide-angle/refraction surveys, calibrated reflection profiles, receiver functions). In order to convert crustal seismic velocity into density, we develop a parametrization that is based upon a database of 1,136 laboratory measurements of seismic velocity as a function of density and pressure. In this way, 4,120 new measurements of continental residual topography are obtained. Observed residual topography mostly varies between ±1 and 2 km on wavelengths of 1,000–5,000 km. Our results are generally consistent with the pattern of residual depth anomalies observed throughout the oceanic realm, with long-wavelength free-air gravity anomalies, and with the distribution of upper mantle seismic velocity anomalies. They are also corroborated by spot measurements of emergent marine strata and by the global distribution of intraplate magmatism that is younger than 10 Ma. We infer that a significant component of residual topography is generated and maintained by a combination of lithospheric thickness variation and sub-plate mantle convection. Lithospheric composition could play an important secondary role, especially within cratonic regions

Novel POLG variants associated with late-onset de novo status epilepticus and progressive ataxia

Mitochondrial disease is phenotypically and genetically heterogeneous with an estimated prevalence of 1 in 4,300.1 Mutations in the POLG gene, encoding the catalytic subunit of DNA polymerase gamma, are an important cause of mitochondrial disease. The spectrum of clinical manifestations in POLG-related mitochondrial disease is variable,2 with disease onset ranging from adulthood-onset dominant or recessive progressive external ophthalmoplegia (chronic progressive external ophthalmoplegia), ataxia-neuropathy spectrum, myoclonic epilepsy, myopathy, and sensory ataxia to childhood-onset Alpers syndrome, which is characterized by intractable seizures, psychomotor regression, and hepatic impairment. Epilepsy is a poor prognostic factor in POLG mutations,3 and the onset of epilepsy often clusters in childhood (<5 years) and teenage.4 However, late-onset epileptic encephalopathy is uncommon.4,5 Herein, we describe a patient who died of de novo, late-onset refractory status epilepticus with the identification of 2 novel variants in the POLG gene