Locus specific reduction of L1 expression in the cortices of individuals with amyotrophic lateral sclerosis

The activation and dysregulation of retrotransposons has been identified in the CNS of individuals with the fatal neurodegenerative disorder Amyotrophic lateral sclerosis (ALS). This includes elements from multiple different families and subfamilies of retrotransposons, however there is limited knowledge of the specific loci from which this expression occurs in ALS. The long interspersed element-1 (L1) is the only autonomous retrotransposon in the human genome and members of this family of elements maintain the ability to mobilise. Despite L1s contributing to 17% of the human genome only 80–100 L1s encode the required proteins for mobilisation and are retrotransposition competent. Identifying the specific loci from which L1 expression occurs will inform on the potential functional consequences of their expression, such as the potential for somatic retrotransposition or DNA damage caused by the endonuclease activity of the ORF2 protein of the L1. Here we characterised L1 loci expression using the L1EM tool (https://github.com/FenyoLab/L1EM) in RNA sequencing data from 518 samples across four tissues (motor cortex, frontal cortex, cerebellum and cervical spinal cord) in the Target ALS cohort obtained from the New York Genome Center. There was a significant reduction in total intact L1 expression (those that encode functional proteins) in two brain regions of individuals with ALS compared to controls and clustering of the ALS brain regions occurred based on their intact L1 expression profile. Although overall the levels of L1 expression were reduced in ALS/ALS with other neurological disorder (ND) there were individuals in which L1s were expressed at much higher levels than the rest of the ALS/ALSND cohort. Expressed L1 loci were more frequently located in introns compared to those not expressed and the level of L1 expression positively correlated with the expression of the gene in which it was located. Significant differences were observed in the expression profiles of L1s in ALS and specific features of these elements, such as location in the genome and whether or not they are intact, were significantly associated with those that were expressed in the cohort

Characterisation of the Function of a SINE-VNTR-Alu Retrotransposon to Modulate Isoform Expression at the MAPT Locus

SINE-VNTR-Alu retrotransposons represent one class of transposable elements which contribute to the regulation and evolution of the primate genome and have the potential to be involved in genetic instability and disease progression. However, these polymorphic elements have not been extensively analysed when addressing the missing heritability of neurodegenerative diseases, including Parkinson’s disease (PD) and amyotrophic lateral sclerosis (ALS). SVA_67, a retrotransposon insertion polymorphism, is located in a 1.8 Mb region of high linkage disequilibrium, called the MAPT locus, which is known to contribute to increased risk of developing PD, frontotemporal dementia and other tauopathies. To investigate the role of SVA_67 in directing differential gene expression at this locus, we characterised the impact of SVA_67 allele dosage on isoform expression of several genes in the MAPT locus using the datasets from both the Parkinson’s Progression Markers Initiative and New York Genome Center Consortium Target ALS cohort. The Parkinson’s data was from gene expression in the blood and the ALS data from a variety of CNS regions and allowed us to demonstrate that SVA_67 presence or absence correlated with both isoform- and tissue-specific expression of multiple genes at this locus. This study highlights the importance of addressing SVA polymorphism in disease genetics to gain insight into a better understanding of the role of these regulatory domains to a variety of neurodegenerative diseases

40th field trip New England Field Geologists: Rhode Island area, October 18 and 19, 1947

Trips in bedrock and glacial and shoreline features

Current practice in the referral of individuals with suspected dementia for neuroimaging by General Practitioners in Ireland and Wales

OBJECTIVES: While early diagnosis of dementia is important, the question arises whether general practitioners (GPs) should engage in direct referrals. The current study investigated current referral practices for neuroimaging in dementia, access to imaging modalities and investigated related GP training in Ireland and North Wales. METHODS: A questionnaire was distributed to GPs in the programme regions which included approximately two thirds of all GPs in the Republic of Ireland and all general practitioners in North Wales. A total of 2,093 questionnaires were issued. RESULTS: 48.6% of Irish respondents and 24.3% of Welsh respondents directly referred patients with suspected dementia for neuroimaging. Irish GPs reported greater direct access to neuroimaging than their Welsh counterparts. A very small percentage of Irish and Welsh GPs (4.7% and 10% respectively) had received training in neuroimaging and the majority who referred patients for neuroimaging were not aware of any dementia-specific protocols for referrals (93.1% and 95% respectively). CONCLUSIONS: The benefits of direct GP access to neuroimaging investigations for dementia have yet to be established. Our findings suggest that current GP speciality training in Ireland and Wales is deficient in dementia-specific and neuroimaging training with the concern being that inadequate training will lead to inadequate referrals. Further training would complement guidelines and provide a greater understanding of the role and appropriateness of neuroimaging techniques in the diagnosis of dementia.This work was part-funded under the European Regional Development Fund INTERREG 4 A Ireland Wales Programme (Project number: 087; www.irelandwales.ie) with matching funding from Bangor University, University College Dublin and Trinity College Dublin. The funding bodies had no role in the study design, data collection, analysis, decision to publish or manuscript preparation

CV19015

This report provides the main results and findings of the fourteenth annual underwater television survey on the ‘Smalls grounds’ ICES assessment area; Functional Unit 22. The survey was multi-disciplinary in nature collecting UWTV, CTD and other ecosystem data. A total of 41 UWTV stations were surveyed successfully (high quality image data), carried out over an isometric grid at 4.5nmi or 8.3km intervals. The precision, with a CV of 9%, was well below the upper limit of 20% recommended by SGNEPS (ICES, 2012). The 2019 abundance estimate was 30% higher than in 2018 and at 1121 million is below the MSY Btrigger reference point (990 million). Using the 2019 estimate of abundance and updated stock data implies catch in 2020 that correspond to the F ranges in the EU multi annual plan for Western Waters are between 2247 and 2820 tonnes (assuming that discard rates and fishery selection patterns do not change from the average of 2016–2018). One species of sea pens were recorded as present at the stations surveyed: Virgularia mirabilis. Trawl marks were observed at 57% of the stations surveyed

Getting beta-alpha without penguins

Oscillation effects in B0 -> Ks D0 and related processes are considered to determine delta=beta-alpha+pi. We suggest that D0 decays to CP eigenstates used in concert with inclusive D0 decays provide a powerful method for determining delta cleanly i.e. without any complication from penguin processes. The CP asymmetry is expected to be <=40% for D0 decays to non-CP eigenstates and <=80% for decays to CP eigenstates. This method can lead to a fairly accurate determination of delta with O(10^8-10^9) B-mesons.Comment: 4 pages 1 figure; Version 2: minor changes; references added; Some changes in response to Referee Comment

The Uncertainty in Newton's Constant and Precision Predictions of the Primordial Helium Abundance

The current uncertainty in Newton's constant, G_N, is of the order of 0.15%. For values of the baryon to photon ratio consistent with both cosmic microwave background observations and the primordial deuterium abundance, this uncertainty in G_N corresponds to an uncertainty in the primordial 4He mass fraction, Y_P, of +-1.3 x 10^{-4}. This uncertainty in Y_P is comparable to the effect from the current uncertainty in the neutron lifetime, which is often treated as the dominant uncertainty in calculations of Y_P. Recent measurements of G_N seem to be converging within a smaller range; a reduction in the estimated error on G_N by a factor of 10 would essentially eliminate it as a source of uncertainty in the calculation of the primordial 4He abundance.Comment: 3 pages, no figures, fixed typos, to appear in Phys. Rev.

Energy, interaction, and photoluminescence of spin-reversed quasielectrons in fractional quantum Hall systems

The energy and photoluminescence spectra of a two-dimensional electron gas in the fractional quantum Hall regime are studied. The single-particle properties of reversed-spin quasielectrons (QE$_{\rm R}$'s) as well as the pseudopotentials of their interaction with one another and with Laughlin quasielectrons (QE's) and quasiholes (QH's) are calculated. Based on the short-range character of the QE$_{\rm R}$--QE$_{\rm R}$ and QE$_{\rm R}$--QE repulsion, the partially unpolarized incompressible states at the filling factors $\nu={4\over11}$ and ${5\over13}$ are postulated within Haldane's hierarchy scheme. To describe photoluminescence, the family of bound $h($QE$_{\rm R})_n$ states of a valence hole $h$ and $n$ QE$_{\rm R}$'s are predicted in analogy to the found earlier fractionally charged excitons $h$QE$_n$. The binding energy and optical selection rules for both families are compared. The $h$QE$_{\rm R}$ is found radiative in contrast to the dark $h$QE, and the $h($QE$_{\rm R})_2$ is found non-radiative in contrast to the bright $h$QE$_2$.Comment: 9 pages, 6 figure