Neuropsychological and Behavioral Aspects of Noonan Syndrome

Abstract: The current paper introduces concise neuropsychological assessment as an essential tool for studying the contribution of cognition and behavior in the expression of genetic syndromes, like Noonan syndrome (NS). Cognitive and behavioral findings in NS show intelligence scores across a wide range, with a mildly lowered average level. Language and motor development are often delayed, but no longer dysfunctional in adulthood. Continuing mild problems in selective and sustained attention are noted, as well as suboptimal organization skills and compromised abilities to structure complex information. These problems seem to culminate in learning difficulties, requiring attention for special needs in education. It seems that a complex of psychosocial immaturity, alexithymia and amenable traits is typical of NS patients. Consequently, psychopathology or psychological problems in leading a self-serving life may often remain underreported. This is why the authors advocate the integration of the domain of social cognition and personality in NS assessment

Theory of low frequency magnetoelectric coupling in magnetostrictive-piezoelectric bilayers

A theoretical model is presented for low-frequency magnetoelectric (ME) effects in bilayers of magnetostrictive and piezoelectric phases. A novel approach, the introduction of an interface coupling parameter k, is proposed for the consideration of actual boundary conditions at the interface. An averaging method is used to estimate effective material parameters. Expressions for ME voltage coefficients are obtained by solving elastostatic and electrostatic equations. We consider both unclamped and rigidly clamped bilayers and three different field orientations of importance: (i) longitudinal fields in which the poling field, bias field and ac fields are all parallel to each other and perpendicular to the sample plane; (ii) transverse fields for magnetic fields parallel to each other and perpendicular to electric fields, and (iii) in-plane longitudinal fields for all the fields parallel to each other and to the sample plane. The theory predicts a giant ME coupling for bilayers with cobalt ferrite (CFO), nickel ferrite (NFO), or lanthanum strontium manganite (LSMO) for the magnetostrictive phase and barium titanate (BTO) or lead zirconate titanate (PZT) for the piezoelectric phase.Comment: To be published in Physical Review B, August 1, 200

Fragmentation processes of ionized 5-fluorouracil in the gas phase and within clusters

We have measured mass spectra for positive ions produced from neutral 5-fluorouracil by electron impact at energies from 0 to 100 eV. Fragment ion appearance energies of this (radio-)chemotherapy agent have been determined for the first time and we have identified several new fragment ions of low abundance. The main fragmentations are similar to uracil, involving HNCO loss and subsequent HCN loss, CO loss, or FCCO loss. The features adjacent to these prominent peaks in the mass spectra are attributed to tautomerization preceding the fragmentation and/or the loss of one or two additional hydrogen atoms. A few fragmentions are distinct for 5-fluorouracil compared to uracil, most notably the production of the reactive moiety CF+. Finally, multiphoton ionization mass spectra are compared for 5-fluorouracil from a laser thermal desorption source and from a supersonic expansion source. The detection of a new fragment ion at 114 u in the supersonic expansion experiments provides the first evidence for a clustering effect on the radiation response of 5-fluorouracil. By analogy with previous experiments and calculations on protonated uracil, this is assigned to NH3 loss from protonated 5-fluorouracil

A novel UBE3A sequence variant identified in eight related individuals with neurodevelopmental delay, results in a phenotype which does not match the clinical criteria of Angelman syndrome

Background: Loss of functional UBE3A, an E3 protein ubiquitin ligase, causes Angelman syndrome (AS), a neurodevelopmental disorder characterized by severe developmental delay, speech impairment, epilepsy, movement or balance disorder, and a characteristic behavioral pattern. We identified a novel UBE3A sequence variant in a large family with eight affected individuals, who did not meet the clinical AS criteria. Methods: Detailed clinical examination and genetic analysis was performed to establish the phenotypic diversity and the genetic cause. The function of the mutant UBE3A protein was assessed with respect to its subcellular localization, stability, and E3 ubiquitin ligase activity. Results: All eight affected individuals showed the presence of a novel maternally inherited UBE3A sequence variant (NM_130838.4(UBE3A):c.1018-1020del, p.(Asn340del), which is in line with a genetic AS diagnosis. Although they presented with moderate to severe intellectual disability, the phenotype did not match the clinical criteria for AS. In line with this, functional analysis of the UBE3A p.Asn340del mutant protein revealed no major deficits in UBE3A protein localization, stability, or E3 ubiquitin ligase activity. Conclusion: The p.(Asn340del) mutant protein behaves distinctly different from previously described AS-linked missense mutations in UBE3A, and causes a phenotype that is markedly different from AS. This study further extends the range of phenotypes that are associated with UBE3A loss, duplication, or mutation

Tackling bovine TB

On 18 December Defra revealed that during 2018, 32,601 badgers were killed, bringing the total number slaughtered under licence since 2013 to almost 67,000.1 ‘Effectiveness’ claims relate not to the impact on cattle TB, but rather to the ability of the contracted shooters to kill sufficient badgers to satisfy their licence requirements, which they can hardly fail to reach given that target numbers are ‘adjusted’ by Natural England part-way through the culls according to the contractors’ progress. Sixty per cent of the badgers have been killed by ‘controlled shooting’, a method rejected by both the government’s Independent Expert Panel2 and the BVA3 because of animal welfare concerns. During 2018 Natural England directly monitored just 89 (0.43 per cent) of controlled shooting events. It is deplorable that the chief veterinary officer (CVO) continues to support the roll-out of a policy that permits controlled shooting, when veterinary organisations have condemned the method on animal welfare grounds. It is particularly concerning that the CVO appears to have deflected responsibility for humaneness to Natural England’s chief scientist who, as far as we are aware, has no background in animal welfare science. It is also unacceptable for government to attribute reductions in herd bovine TB (bTB) incidents over the first four years of culling in the original ‘pilot’ cull zones to its badger culling policy.4 Independent analysis of this and more recent data from the Gloucestershire pilot cull zone5 indicate that new herd incidence is rising sharply, with 22 herd breakdowns in the 12 months to September 2017 (an increase of 29.4 per cent when compared to the 17 breakdowns reported by APHA for the previous 12 months). Analysis of the 2018 figures indicates that both incidence and prevalence are now rising even faster, with a further 24 herd breakdowns occurring between 1 January and 5 December 2018. To date, the government and its officials cite data that are two years out of date, but have declined to comment on this emerging evidence that, far from resulting in a substantial disease control benefit, badger culls may be leading to a sharp increase in bTB in cattle. Natural England’s chief scientist and the UK’s CVO continue to endorse a failing and inhumane policy, bringing their offices into serious disrepute. We urge them, and the BVA, to reconsider their support for further badger culling, and instead focus on the actual cause of bTB’s epidemic spread – a cattle skin test with a sensitivity of only 50 per cent,6,7 and the ongoing problems associated with cattle movements and on-farm biosecurity

Animal welfare impacts of badger culling operations

We are writing to express our extreme concern following recent media coverage1, 2 relating to the methodology being used by contractors to kill badgers under licence, as part of the government’s policy to control bovine TB in cattle. The coverage relates to the shooting of badgers that have been captured in live traps. Covert video footage (https://bit.ly/2Eud1iR ) from Cumbria shows a trapped badger being shot with a firearm at close range, following which it appears to take close to a minute to stop moving. The contractor clearly observes the animal during this time but makes no attempt to expedite the death of the badger and prevent further suffering, as required by the current Natural England best practice guide which states: ‘Immediately after shooting, the animal should be checked to ensure it is dead, and if there is any doubt, a second shot must be taken as soon as possible.’3 The conversation between the contractor and his companion also suggests they were considering moving the badger to another site before finally bagging the carcase, again breaching the best practice guide. While the footage only relates to the experience of a single badger, and while the degree to which the badger was conscious in the period immediately following the shot is unclear, we can by no means be certain that the badger did not suffer. It also raises serious questions about the training, competence and behaviour of contractors, in relation to both badger welfare, and biosecurity. This adds to existing concerns relating to the humaneness of ‘controlled shooting’ (targeting free-roaming badgers with rifles), which continues to be a permitted method under culling licences, in spite of the reservations expressed by both the government-commissioned Independent Expert Panel in its 2014 report,4 and the BVA, which concluded in 2015 that it ‘can no longer support the continued use of controlled shooting as part of the badger control policy’.5 (However, it has since continued to support the issuing of licences which permit the method). The BVA has consistently indicated its support for what it calls the ‘tried and tested’ method of trapping and shooting, but has thus far failed to provide comprehensive and robust evidence for the humaneness of this method. Figure1 Download figure Open in new tab Download powerpoint Natural England reported that its monitors observed 74 (just over 0.6 per cent) of controlled shooting events for accuracy and humaneness During 2017, almost 20,000 badgers were killed under licence across 19 cull zones, around 60 per cent of which were killed by controlled shooting, the remainder being trapped and shot.6 Natural England reported that its monitors observed 74 (just over 0.6 per cent) of controlled shooting events for accuracy and humaneness. No information has been provided on the extent to which trapping and shooting activities were monitored. This raises serious concerns about the extent of suffering that might be experienced by very large numbers of animals, for which contractors are not being held to account. If contractors reach their maximum culling targets set by Natural England for 2018, as many as 41,000 additional badgers could be killed.7 The extent to which these animals will suffer is once again being left in the hands of contractors, with woefully inadequate oversight, and in the face of anecdotal evidence of breaches of best practice guidance. This situation is clearly unacceptable from an animal welfare perspective and it is our view that by endorsing the policy, the BVA is contradicting the principles contained within its own animal welfare strategy.8 We therefore urge the BVA to withdraw its support for any further licensed badger culling, and the RCVS to make it clear that any veterinarian who provides support for culling activities that result in unnecessary and avoidable animal suffering could face disciplinary proceedings. The veterinary profession has no business supporting this licensed mass killing with all its inherent negative welfare and biosecurity implications, and for which the disease control benefits are, at best, extremely uncertain. We believe the continued support for the culls by veterinary bodies in the face of poor evidence for its efficacy damages the credibility of the profession, and that same support in the face of potential animal suffering on a large scale undermines its reputation. We stand ready to discuss these issues in more detail

Correspondence : In support of the IES method of evaluating light source colour rendition

Version of RecordPublishe

Magnetotransport in a pseudomorphic GaAs/GaInAs/GaAlAs heterostructure with a Si delta-doping layer

Magnetotransport properties of a pseudomorphic GaAs/Ga0.8In0.2As/Ga0.75Al0.25As heterostructure are investigated in pulsed magnetic fields up to 50 T and at temperatures of T=1.4 K and 4.2 K. The structure studied consists of a Si delta-layer parallel to a Ga0.8In0.2As quantum well (QW). The dark electron density of the structure is n_e=1.67x 10^16 m^-2. By illumination the density can be increased up to a factor of 4; this way the second subband in the Ga0.8In0.2As QW can become populated as well as the Si delta-layer. The presence of electrons in the delta-layer results in drastic changes in the transport data, especially at magnetic fields beyond 30 T. The phenomena observed are interpreted as: 1) magnetic freeze-out of carriers in the delta-layer when a low density of electrons is present in the delta-layer, and 2) quantization of the electron motion in the two dimensional electron gases in both the Ga0.8In0.2As QW and the Si delta-layer in the case of high densities. These conclusions are corroborated by the numerical results of our theoretical model. We obtain a satisfactory agreement between model and experiment.Comment: 23 pages, RevTex, 11 Postscript figures (accepted for Phys. Rev. B

Finished genome of the fungal wheat pathogen Mycosphaerella graminicola Reveals dispensome structure, chromosome plasticity, and stealth pathogenesis.

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