A spatial covariance (123)I-5IA-85380 SPECT study of α4β2 nicotinic receptors in Alzheimer's disease

Alzheimer's disease (AD) is characterized by widespread degeneration of cholinergic neurons, particularly in the basal forebrain. However, the pattern of these deficits and relationship with known brain networks is unknown. In this study, we sought to clarify this and used 123I-5-iodo-3-[2(S)-2-azetidinylmethoxy] pyridine (1235IA-85380) single photon emission computed tomography to investigate spatial covariance of α4β2 nicotinic acetylcholine receptors in AD and healthy controls. Thirteen AD and 16 controls underwent 1235IA-85380 and regional cerebral blood flow (99mTc-exametazime) single photon emission computed tomography scanning. We applied voxel principal component (PC) analysis, generating series of principal component images representing common intercorrelated voxels across subjects. Linear regression generated specific α4β2 and regional cerebral blood flow covariance patterns that differentiated AD from controls. The α4β2 pattern showed relative decreased uptake in numerous brain regions implicating several networks including default mode, salience, and Papez hubs. Thus, as well as basal forebrain and brainstem cholinergic system dysfunction, cholinergic deficits mediated through nicotinic acetylcholine receptors could be evident within key networks in AD. These findings may be important for the pathophysiology of AD and its associated cognitive and behavioral phenotypes

Earths in Other Solar Systems N-body simulations: the Role of Orbital Damping in Reproducing the Kepler Planetary Systems

The population of exoplanetary systems detected by Kepler provides opportunities to refine our understanding of planet formation. Unraveling the conditions needed to produce the observed exoplanets will sallow us to make informed predictions as to where habitable worlds exist within the galaxy. In this paper, we examine using N-body simulations how the properties of planetary systems are determined during the final stages of assembly. While accretion is a chaotic process, trends in the ensemble properties of planetary systems provide a memory of the initial distribution of solid mass around a star prior to accretion. We also use EPOS, the Exoplanet Population Observation Simulator, to account for detection biases and show that different accretion scenarios can be distinguished from observations of the Kepler systems. We show that the period of the innermost planet, the ratio of orbital periods of adjacent planets, and masses of the planets are determined by the total mass and radial distribution of embryos and planetesimals at the beginning of accretion. In general, some amount of orbital damping, either via planetesimals or gas, during accretion is needed to match the whole population of exoplanets. Surprisingly, all simulated planetary systems have planets that are similar in size, showing that the "peas in a pod" pattern can be consistent with both a giant impact scenario and a planet migration scenario. The inclusion of material at distances larger than what Kepler observes has a profound impact on the observed planetary architectures, and thus on the formation and delivery of volatiles to possible habitable worlds.Comment: Resubmitted to ApJ. Planet formation models available online at http://eos-nexus.org/genesis-database

Water Delivery and Giant Impacts in the 'Grand Tack' Scenario

A new model for terrestrial planet formation (Hansen 2009, Walsh et al. 2011) has explored accretion in a truncated protoplanetary disk, and found that such a configuration is able to reproduce the distribution of mass among the planets in the Solar System, especially the Earth/Mars mass ratio, which earlier simulations have generally not been able to match. Walsh et al. tested a possible mechanism to truncate the disk--a two-stage, inward-then-outward migration of Jupiter and Saturn, as found in numerous hydrodynamical simulations of giant planet formation. In addition to truncating the disk and producing a more realistic Earth/Mars mass ratio, the migration of the giant planets also populates the asteroid belt with two distinct populations of bodies--the inner belt is filled by bodies originating inside of 3 AU, and the outer belt is filled with bodies originating from between and beyond the giant planets (which are hereafter referred to as `primitive' bodies). We find here that the planets will accrete on order 1-2% of their total mass from primitive planetesimals scattered onto planet-crossing orbits during the formation of the planets. For an assumed value of 10% for the water mass fraction of the primitive planetesimals, this model delivers a total amount of water comparable to that estimated to be on the Earth today. While the radial distribution of the planetary masses and the dynamical excitation of their orbits are a good match to the observed system, we find that the last giant impact is typically earlier than 20 Myr, and a substantial amount of mass is accreted after that event. However, 5 of the 27 planets larger than half an Earth mass formed in all simulations do experience large late impacts and subsequent accretion consistent with the dating of the Moon-forming impact and the estimated amount of mass accreted by Earth following that event

Social evolution of toxic metal bioremediation in Pseudomonas aeruginosa

This is the final version. Available on open access from the Royal Society via the DOI in this recordThere is another ORE record for this publication: http://hdl.handle.net/10871/39858Bacteria are often iron-limited, and hence produce extracellular iron-scavenging siderophores. A crucial feature of siderophore production is that it can be an altruistic behaviour (individually costly but benefitting neighbouring cells), thus siderophore producers can be invaded by non-producing social ‘cheats’. Recent studies have shown that siderophores can also bind other heavy metals (such as Cu and Zn), but in this case siderophore chelation actually reduces metal uptake by bacteria. These complexes reduce heavy metal toxicity, hence siderophore production may contribute to toxic metal bioremediation. Here, we show that siderophore production in the context of bioremediation is also an altruistic trait and can be exploited by cheating phenotypes in the opportunistic pathogen Pseudomonas aeruginosa. Specifically, we show that in toxic copper concentrations (i) siderophore non-producers evolve de novo and reach high frequencies, and (ii) producing strains are fitter than isogenic non-producing strains in monoculture, and vice versa in co-culture. Moreover, we show that the evolutionary effect copper has on reducing siderophore production is greater than the reduction observed under iron-limited conditions. We discuss the relevance of these results to the evolution of siderophore production in natural communities and heavy metal bioremediation.AXANERCUniversity of Exete

Labour efficiency on-farm

End of project reportImprovements in milking efficiency have a greater influence than any other aspect of the dairy farmers work on overall farm labour inputs (Whipp, 1992). In order to facilitate the examination of milking process labour inputs, the milking process may be divided into the following three components: herding pre and post milking (transfer of cows to and from the milking parlour); milking (milking tasks / work routines within the parlour); and washing (washing of milking machine and yard). Meanwhile, within milking specifically, the number of cows milked per operator per hour is the best measure of both the performance of the operator and the milking installation (Clough, 1978). This is affected by the following three factors: the milking times of the cows, the number and arrangement of the milking units, and the operator’s work routine (Whipp, 1992). The addition of extra milking units will only increase milking performance if the operator has idle time during milking (Hansen, 1999)

Measuring labor input on pasture-based dairy farms using a smartphone

peer-reviewedWith the cessation of milk quotas in the European Union, dairy herd sizes increased in some countries, including Ireland, with an associated increase in labor requirement. Second to feed costs, labor has been identified as one of the highest costs on pasture-based dairy farms. Compared with other European Union countries, Ireland has historically had low milk production per labor unit; thus, optimization of labor efficiency on farm should be addressed before or concurrently with herd expansion. The objective of this study was to quantify current levels of labor input and labor efficiency on commercial pasture-based dairy farms and to identify the facilities and management practices associated with increased labor efficiency. Thirty-eight dairy farms of varying herd sizes, previously identified as labor-efficient farms, were enrolled on the study and data were collected over 3 consecutive days each month over a 12-mo period, starting in May 2015 and finishing in August of 2016. This was achieved through the use of a smartphone application. For analysis purposes, farms were categorized into 1 of 3 herd size categories (HSC): farms with <150 cows (HSC 1), 150–249 cows (HSC 2), or ≥250 cows (HSC 3). Overall farm labor input increased with HSC with 3,015, 4,499, and 6,023 h worked on HSC 1, 2, and 3, respectively. A higher proportion of work was carried out by hired staff as herd size increased. Labor efficiency was measured as total hours input to the dairy enterprise divided by herd size. Labor efficiency improved as herd size increased above 250 cows with 17.3 h/cow per yr observed for HSC 3; labor efficiency was similar for HSC 1 and 2, at 23.8 and 23.3 h/cow per yr, respectively. A large range of efficiency was observed within HSC. The labor requirements had a distinct seasonal pattern across the 3 HSC with the highest input observed in springtime (February to April) primarily due to calving and calf-care duties, milking, and winter feeding. The lowest input was observed in wintertime (November to January) when cows were dry. Particular facilities and management practices were associated with efficiency within certain tasks, the most notable in regard to milking and winter feeding practices. Additionally, the most efficient farms used contractors to perform a higher proportion of machinery work on farm than the least efficient farms

Cholinergic and perfusion brain networks in Parkinson disease dementia.

OBJECTIVE: To investigate muscarinic M1/M4 cholinergic networks in Parkinson disease dementia (PDD) and their association with changes in Mini-Mental State Examination (MMSE) after 12 weeks of treatment with donepezil. METHODS: Forty-nine participants (25 PDD and 24 elderly controls) underwent (123)I-QNB and (99m)Tc-exametazime SPECT scanning. We implemented voxel principal components (PC) analysis, producing a series of PC images of patterns of interrelated voxels across individuals. Linear regression analyses derived specific M1/M4 and perfusion spatial covariance patterns (SCPs). RESULTS: We found an M1/M4 SCP of relative decreased binding in basal forebrain, temporal, striatum, insula, and anterior cingulate (F1,47 = 31.9, p < 0.001) in cholinesterase inhibitor-naive patients with PDD, implicating limbic-paralimbic and salience cholinergic networks. The corresponding regional cerebral blood flow SCP showed relative decreased uptake in temporoparietal and prefrontal areas (F1,47 = 177.5, p < 0.001) and nodes of the frontoparietal and default mode networks (DMN). The M1/M4 pattern that correlated with an improvement in MMSE (r = 0.58, p = 0.005) revealed relatively preserved/increased pre/medial/orbitofrontal, parietal, and posterior cingulate areas coinciding with the DMN and frontoparietal networks. CONCLUSION: Dysfunctional limbic-paralimbic and salience cholinergic networks were associated with PDD. Established cholinergic maintenance of the DMN and frontoparietal networks may be prerequisite for cognitive remediation following cholinergic treatment in this condition.Medical Research Council UK [grant number G9817682], and by the National Institute for Health Research (NIHR) Research for Public Benefit, Wellcome Trust (WT088441MA Fellowship funding J-P.T). NIHR Dementia Biomedical Research Unit at Cambridge University Hospitals NHS Foundation Trust and the University of Cambridge. The NIHR Newcastle Biomedical Research Centre in Ageing and Chronic Disease and Biomedical Research Unit in Lewy Body Dementia based at Newcastle upon Tyne Hospitals NHS Foundation Trust and Newcastle University.This is the final version of the article. It first appeared from Wolters Kluwer via http://dx.doi.org/10.​1212/​WNL.​000000000000283