Cattle Toxicity from Woolly Locoweed (\u3cem\u3eAstragalus mollissimus\u3c/em\u3e): A Case Study in Central New Mexico

Livestock toxicity resulting from poisonous plants poses a significant challenge for ranchers, particularly concerning locoweeds (Astragalus spp. or Oxytropis spp.). This study investigated a case of cattle poisoning in central New Mexico, where clinical signs were consistent with locoweed toxicity. Rangeland conditions were hot and dry following earlier spring rains, promoting advantageous environmental conditions for a locoweed outbreak. Analysis of Woolly locoweed (Astragalus mollissimus) and animal samples from the ranch confirmed the presence of swainsonine, a key toxin in locoweeds. It can be concluded that the likely cause of cattle losses was locoweed toxicity, highlighting the need for proactive management strategies when environmental conditions are conducive to increases in locoweed populations

International Veterinary Epilepsy Task Force recommendations for a veterinary epilepsy-specific MRI protocol

Epilepsy is one of the most common chronic neurological diseases in veterinary practice. Magnetic resonance imaging (MRI) is regarded as an important diagnostic test to reach the diagnosis of idiopathic epilepsy. However, given that the diagnosis requires the exclusion of other differentials for seizures, the parameters for MRI examination should allow the detection of subtle lesions which may not be obvious with existing techniques. In addition, there are several differentials for idiopathic epilepsy in humans, for example some focal cortical dysplasias, which may only apparent with special sequences, imaging planes and/or particular techniques used in performing the MRI scan. As a result, there is a need to standardize MRI examination in veterinary patients with techniques that reliably diagnose subtle lesions, identify post-seizure changes, and which will allow for future identification of underlying causes of seizures not yet apparent in the veterinary literature. There is a need for a standardized veterinary epilepsy-specific MRI protocol which will facilitate more detailed examination of areas susceptible to generating and perpetuating seizures, is cost efficient, simple to perform and can be adapted for both low and high field scanners. Standardisation of imaging will improve clinical communication and uniformity of case definition between research studies. A 6–7 sequence epilepsy-specific MRI protocol for veterinary patients is proposed and further advanced MR and functional imaging is reviewed

CRISPR interference to evaluate modifiers of C9ORF72-mediated toxicity in FTD

Treatments for neurodegenerative disease, including Frontotemporal dementia (FTD) and Amyotrophic lateral sclerosis (ALS), remain rather limited, underscoring the need for greater mechanistic insight and disease-relevant models. Our ability to develop novel disease models of genetic risk factors, disease modifiers, and other FTD/ALS-relevant targets is impeded by the significant amount of time and capital required to develop conventional knockout and transgenic mice. To overcome these limitations, we have generated a novel CRISPRi interference (CRISPRi) knockin mouse. CRISPRi uses a catalytically dead form of Cas9, fused to a transcriptional repressor to knockdown protein expression, following the introduction of single guide RNA against the gene of interest. To validate the utility of this model we have selected the TAR DNA binding protein (TDP-43) splicing target, stathmin-2 (STMN2). STMN2 RNA is downregulated in FTD/ALS due to loss of TDP-43 activity and STMN2 loss is suggested to play a role in ALS pathogenesis. The involvement of STMN2 loss of function in FTD has yet to be determined. We find that STMN2 protein levels in familial FTD cases are significantly reduced compared to controls, supporting that STMN2 depletion may be involved in the pathogenesis of FTD. Here, we provide proof-of-concept that we can simultaneously knock down Stmn2 and express the expanded repeat in the Chromosome 9 open reading frame 72 (C9ORF72) gene, successfully replicating features of C9-associated pathology. Of interest, depletion of Stmn2 had no effect on expression or deposition of dipeptide repeat proteins (DPRs), but significantly decreased the number of phosphorylated Tdp-43 (pTdp-43) inclusions. We submit that our novel CRISPRi mouse provides a versatile and rapid method to silence gene expression in vivo and propose this model will be useful to understand gene function in isolation or in the context of other neurodegenerative disease models

A genome-wide scan for common alleles affecting risk for autism

Although autism spectrum disorders (ASDs) have a substantial genetic basis, most of the known genetic risk has been traced to rare variants, principally copy number variants (CNVs). To identify common risk variation, the Autism Genome Project (AGP) Consortium genotyped 1558 rigorously defined ASD families for 1 million single-nucleotide polymorphisms (SNPs) and analyzed these SNP genotypes for association with ASD. In one of four primary association analyses, the association signal for marker rs4141463, located within MACROD2, crossed the genome-wide association significance threshold of P < 5 × 10−8. When a smaller replication sample was analyzed, the risk allele at rs4141463 was again over-transmitted; yet, consistent with the winner's curse, its effect size in the replication sample was much smaller; and, for the combined samples, the association signal barely fell below the P < 5 × 10−8 threshold. Exploratory analyses of phenotypic subtypes yielded no significant associations after correction for multiple testing. They did, however, yield strong signals within several genes, KIAA0564, PLD5, POU6F2, ST8SIA2 and TAF1C

Chronic non-specific low back pain - sub-groups or a single mechanism?

Copyright 2008 Wand and O'Connell; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.Background: Low back pain is a substantial health problem and has subsequently attracted a considerable amount of research. Clinical trials evaluating the efficacy of a variety of interventions for chronic non-specific low back pain indicate limited effectiveness for most commonly applied interventions and approaches. Discussion: Many clinicians challenge the results of clinical trials as they feel that this lack of effectiveness is at odds with their clinical experience of managing patients with back pain. A common explanation for this discrepancy is the perceived heterogeneity of patients with chronic non-specific low back pain. It is felt that the effects of treatment may be diluted by the application of a single intervention to a complex, heterogeneous group with diverse treatment needs. This argument presupposes that current treatment is effective when applied to the correct patient. An alternative perspective is that the clinical trials are correct and current treatments have limited efficacy. Preoccupation with sub-grouping may stifle engagement with this view and it is important that the sub-grouping paradigm is closely examined. This paper argues that there are numerous problems with the sub-grouping approach and that it may not be an important reason for the disappointing results of clinical trials. We propose instead that current treatment may be ineffective because it has been misdirected. Recent evidence that demonstrates changes within the brain in chronic low back pain sufferers raises the possibility that persistent back pain may be a problem of cortical reorganisation and degeneration. This perspective offers interesting insights into the chronic low back pain experience and suggests alternative models of intervention. Summary: The disappointing results of clinical research are commonly explained by the failure of researchers to adequately attend to sub-grouping of the chronic non-specific low back pain population. Alternatively, current approaches may be ineffective and clinicians and researchers may need to radically rethink the nature of the problem and how it should best be managed

Detector Description and Performance for the First Coincidence Observations between LIGO and GEO

For 17 days in August and September 2002, the LIGO and GEO interferometer gravitational wave detectors were operated in coincidence to produce their first data for scientific analysis. Although the detectors were still far from their design sensitivity levels, the data can be used to place better upper limits on the flux of gravitational waves incident on the earth than previous direct measurements. This paper describes the instruments and the data in some detail, as a companion to analysis papers based on the first data.Comment: 41 pages, 9 figures 17 Sept 03: author list amended, minor editorial change

All-sky search for periodic gravitational waves in LIGO S4 data

We report on an all-sky search with the LIGO detectors for periodic gravitational waves in the frequency range 50-1000 Hz and with the frequency's time derivative in the range -1.0E-8 Hz/s to zero. Data from the fourth LIGO science run (S4) have been used in this search. Three different semi-coherent methods of transforming and summing strain power from Short Fourier Transforms (SFTs) of the calibrated data have been used. The first, known as "StackSlide", averages normalized power from each SFT. A "weighted Hough" scheme is also developed and used, and which also allows for a multi-interferometer search. The third method, known as "PowerFlux", is a variant of the StackSlide method in which the power is weighted before summing. In both the weighted Hough and PowerFlux methods, the weights are chosen according to the noise and detector antenna-pattern to maximize the signal-to-noise ratio. The respective advantages and disadvantages of these methods are discussed. Observing no evidence of periodic gravitational radiation, we report upper limits; we interpret these as limits on this radiation from isolated rotating neutron stars. The best population-based upper limit with 95% confidence on the gravitational-wave strain amplitude, found for simulated sources distributed isotropically across the sky and with isotropically distributed spin-axes, is 4.28E-24 (near 140 Hz). Strict upper limits are also obtained for small patches on the sky for best-case and worst-case inclinations of the spin axes.Comment: 39 pages, 41 figures An error was found in the computation of the C parameter defined in equation 44 which led to its overestimate by 2^(1/4). The correct values for the multi-interferometer, H1 and L1 analyses are 9.2, 9.7, and 9.3, respectively. Figure 32 has been updated accordingly. None of the upper limits presented in the paper were affecte

Search for gravitational waves from binary inspirals in S3 and S4 LIGO data

We report on a search for gravitational waves from the coalescence of compact binaries during the third and fourth LIGO science runs. The search focused on gravitational waves generated during the inspiral phase of the binary evolution. In our analysis, we considered three categories of compact binary systems, ordered by mass: (i) primordial black hole binaries with masses in the range 0.35 M(sun) < m1, m2 < 1.0 M(sun), (ii) binary neutron stars with masses in the range 1.0 M(sun) < m1, m2 < 3.0 M(sun), and (iii) binary black holes with masses in the range 3.0 M(sun)< m1, m2 < m_(max) with the additional constraint m1+ m2 < m_(max), where m_(max) was set to 40.0 M(sun) and 80.0 M(sun) in the third and fourth science runs, respectively. Although the detectors could probe to distances as far as tens of Mpc, no gravitational-wave signals were identified in the 1364 hours of data we analyzed. Assuming a binary population with a Gaussian distribution around 0.75-0.75 M(sun), 1.4-1.4 M(sun), and 5.0-5.0 M(sun), we derived 90%-confidence upper limit rates of 4.9 yr^(-1) L10^(-1) for primordial black hole binaries, 1.2 yr^(-1) L10^(-1) for binary neutron stars, and 0.5 yr^(-1) L10^(-1) for stellar mass binary black holes, where L10 is 10^(10) times the blue light luminosity of the Sun.Comment: 12 pages, 11 figure

A Joint Search for Gravitational Wave Bursts with AURIGA and LIGO

The first simultaneous operation of the AURIGA detector and the LIGO observatory was an opportunity to explore real data, joint analysis methods between two very different types of gravitational wave detectors: resonant bars and interferometers. This paper describes a coincident gravitational wave burst search, where data from the LIGO interferometers are cross-correlated at the time of AURIGA candidate events to identify coherent transients. The analysis pipeline is tuned with two thresholds, on the signal-to-noise ratio of AURIGA candidate events and on the significance of the cross-correlation test in LIGO. The false alarm rate is estimated by introducing time shifts between data sets and the network detection efficiency is measured with simulated signals with power in the narrower AURIGA band. In the absence of a detection, we discuss how to set an upper limit on the rate of gravitational waves and to interpret it according to different source models. Due to the short amount of analyzed data and to the high rate of non-Gaussian transients in the detectors noise at the time, the relevance of this study is methodological: this was the first joint search for gravitational wave bursts among detectors with such different spectral sensitivity and the first opportunity for the resonant and interferometric communities to unify languages and techniques in the pursuit of their common goal.Comment: 18 pages, IOP, 12 EPS figure