Space-use patterns highlight behavioural differences linked to lameness, parity, and days in milk in barn-housed dairy cows

This is the author accepted manuscript. The final version is available from Public Library of Science (PLoS) via the DOI in this record.Lameness is a key health and welfare issue affecting commercial herds of dairy cattle, with potentially significant economic impacts due to the expense of treatment and lost milk production. Existing lameness detection methods can be time-intensive, and under-detection remains a significant problem leading to delayed or missed treatment. Hence, there is a need for automated monitoring systems that can quickly and accurately detect lameness in individual cows within commercial dairy herds. Recent advances in sensor tracking technology have made it possible to observe the movement, behaviour and space-use of a range of animal species over extended time-scales. However, little is known about how observed movement behaviour and space-use patterns in individual dairy cattle relate to lameness, or to other possible confounding factors such as parity or number of days in milk. In this cross-sectional study, ten lame and ten non-lame barn-housed dairy cows were classified through mobility scoring and subsequently 55 tracked using a wireless local positioning system. Nearly 900,000 spatial locations were recorded in total, allowing a range of movement and space-use measures to be determined for each individual cow. Using linear models, we highlight where lameness, parity, and the number of days in milk have a significant effect on the observed space-use patterns. Non-lame cows spent more time, and had higher site fidelity (on a day-to-day basis they were more likely to revisit areas they had visited previously), in the feeding area. Non-lame cows also had a larger full range size within the barn. In contrast, lame cows spent more time, and had a higher site-fidelity, in the cubicle (resting) areas of the barn than non-lame cows. Higher parity cows were found to spend more time in the right-hand-side area of the barn, closer to the passageway to the milking parlour. The number of days in milk was found to positively affect the core range size, but with a negative interaction effect with lameness. Using a simple predictive model, we demonstrate how it is possible to accurately determine the lameness status of all individual cows within the study using only two observed space-use measures, the proportion of time spent in the feeding area and the full range size. Our findings suggest that differences in individual movement and space-use behaviour could be used as indicators of health status for automated monitoring within a Precision Livestock Farming approach, potentially leading to faster diagnosis and treatment, and improved animal welfare for dairy cattle and other managed animal species

Statistical Analysis of Molecular Signal Recording

A molecular device that records time-varying signals would enable new approaches in neuroscience. We have recently proposed such a device, termed a “molecular ticker tape”, in which an engineered DNA polymerase (DNAP) writes time-varying signals into DNA in the form of nucleotide misincorporation patterns. Here, we define a theoretical framework quantifying the expected capabilities of molecular ticker tapes as a function of experimental parameters. We present a decoding algorithm for estimating time-dependent input signals, and DNAP kinetic parameters, directly from misincorporation rates as determined by sequencing. We explore the requirements for accurate signal decoding, particularly the constraints on (1) the polymerase biochemical parameters, and (2) the amplitude, temporal resolution, and duration of the time-varying input signals. Our results suggest that molecular recording devices with kinetic properties similar to natural polymerases could be used to perform experiments in which neural activity is compared across several experimental conditions, and that devices engineered by combining favorable biochemical properties from multiple known polymerases could potentially measure faster phenomena such as slow synchronization of neuronal oscillations. Sophisticated engineering of DNAPs is likely required to achieve molecular recording of neuronal activity with single-spike temporal resolution over experimentally relevant timescales.United States. Defense Advanced Research Projects Agency. Living Foundries ProgramGoogle (Firm)New York Stem Cell Foundation. Robertson Neuroscience Investigator AwardNational Institutes of Health (U.S.) (EUREKA Award 1R01NS075421)National Institutes of Health (U.S.) (Transformative R01 1R01GM104948)National Institutes of Health (U.S.) (Single Cell Grant 1 R01 EY023173)National Institutes of Health (U.S.) (Grant 1R01DA029639)National Institutes of Health (U.S.) (Grant 1R01NS067199)National Science Foundation (U.S.) (CAREER Award CBET 1053233)National Science Foundation (U.S.) (Grant EFRI0835878)National Science Foundation (U.S.) (Grant DMS1042134)Paul G. Allen Family Foundation (Distinguished Investigator in Neuroscience Award

Genetic evaluation of dementia with Lewy bodies implicates distinct disease subgroups

The APOE locus is strongly associated with risk for developing Alzheimer's disease and dementia with Lewy bodies. In particular, the role of the APOE ϵ4 allele as a putative driver of α-synuclein pathology is a topic of intense debate. Here, we performed a comprehensive evaluation in 2466 dementia with Lewy bodies cases versus 2928 neurologically healthy, aged controls. Using an APOE-stratified genome-wide association study approach, we found that GBA is associated with risk for dementia with Lewy bodies in patients without APOE ϵ4 (P = 6.58 × 10-9, OR = 3.41, 95% CI = 2.25-5.17), but not with dementia with Lewy bodies with APOE ϵ4 (P = 0.034, OR = 1.87, 95%, 95% CI = 1.05-3.37). We then divided 495 neuropathologically examined dementia with Lewy bodies cases into three groups based on the extent of concomitant Alzheimer's disease co-pathology: Pure dementia with Lewy bodies (n = 88), dementia with Lewy bodies with intermediate Alzheimer's disease co-pathology (n = 66) and dementia with Lewy bodies with high Alzheimer's disease co-pathology (n = 341). In each group, we tested the association of the APOE ϵ4 against the 2928 neurologically healthy controls. Our examination found that APOE ϵ4 was associated with dementia with Lewy bodies + Alzheimer's disease (P = 1.29 × 10-32, OR = 4.25, 95% CI = 3.35-5.39) and dementia with Lewy bodies + intermediate Alzheimer's disease (P = 0.0011, OR = 2.31, 95% CI = 1.40-3.83), but not with pure dementia with Lewy bodies (P = 0.31, OR = 0.75, 95% CI = 0.43-1.30). In conclusion, although deep clinical data were not available for these samples, our findings do not support the notion that APOE ϵ4 is an independent driver of α-synuclein pathology in pure dementia with Lewy bodies, but rather implicate GBA as the main risk gene for the pure dementia with Lewy bodies subgroup

Conceptual Frameworks and Methods for Advancing Invasion Ecology

Invasion ecology has much advanced since its early beginnings. Nevertheless, explanation, prediction, and management of biological invasions remain difficult. We argue that progress in invasion research can be accelerated by, first, pointing out difficulties this field is currently facing and, second, looking for measures to overcome them. We see basic and applied research in invasion ecology confronted with difficulties arising from (A) societal issues, e.g., disparate perceptions of invasive species; (B) the peculiarity of the invasion process, e.g., its complexity and context dependency; and (C) the scientific methodology, e.g., imprecise hypotheses. To overcome these difficulties, we propose three key measures: (1) a checklist for definitions to encourage explicit definitions; (2) implementation of a hierarchy of hypotheses (HoH), where general hypotheses branch into specific and precisely testable hypotheses; and (3) platforms for improved communication. These measures may significantly increase conceptual clarity and enhance communication, thus advancing invasion ecology

Genome-wide structural variant analysis identifies risk loci for non-Alzheimer's dementias

We characterized the role of structural variants, a largely unexplored type of genetic variation, in two non-Alzheimer's dementias, namely Lewy body dementia (LBD) and frontotemporal dementia (FTD)/amyotrophic lateral sclerosis (ALS). To do this, we applied an advanced structural variant calling pipeline (GATK-SV) to short-read whole-genome sequence data from 5,213 European-ancestry cases and 4,132 controls. We discovered, replicated, and validated a deletion in TPCN1 as a novel risk locus for LBD and detected the known structural variants at the C9orf72 and MAPT loci as associated with FTD/ALS. We also identified rare pathogenic structural variants in both LBD and FTD/ALS. Finally, we assembled a catalog of structural variants that can be mined for new insights into the pathogenesis of these understudied forms of dementia

Cysteinyl leukotrienes: multi-functional mediators in allergic rhinitis

Cysteinyl leukotrienes (CysLTs) are a family of inflammatory lipid mediators synthesized from arachidonic acid by a variety of cells, including mast cells, eosinophils, basophils, and macrophages. This article reviews the data for the role of CysLTs as multi-functional mediators in allergic rhinitis (AR). We review the evidence that: (1) CysLTs are released from inflammatory cells that participate in AR, (2) receptors for CysLTs are located in nasal tissue, (3) CysLTs are increased in patients with AR and are released following allergen exposure, (4) administration of CysLTs reproduces the symptoms of AR, (5) CysLTs play roles in the maturation, as well as tissue recruitment, of inflammatory cells, and (6) a complex inter-regulation between CysLTs and a variety of other inflammatory mediators exists.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/75432/1/j.1365-2222.2006.02498.x.pd

Genome sequencing analysis identifies new loci associated with Lewy body dementia and provides insights into its genetic architecture

The genetic basis of Lewy body dementia (LBD) is not well understood. Here, we performed whole-genome sequencing in large cohorts of LBD cases and neurologically healthy controls to study the genetic architecture of this understudied form of dementia, and to generate a resource for the scientific community. Genome-wide association analysis identified five independent risk loci, whereas genome-wide gene-aggregation tests implicated mutations in the gene GBA. Genetic risk scores demonstrate that LBD shares risk profiles and pathways with Alzheimer's disease and Parkinson's disease, providing a deeper molecular understanding of the complex genetic architecture of this age-related neurodegenerative condition