159 research outputs found
Demography of male reproductive queues in cooperatively breeding superb fairy-wrens Malurus cyaneus
1. Subordinate helpers in cooperative societies may gain both immediate and future benefits, including paternity and territorial inheritance. However, if such opportunities correlate with rank in the queue, it is unclear why such queues should be stable
A53T-alpha-synuclein overexpression impairs dopamine signaling and striatal synaptic plasticity in old mice
BACKGROUND: Parkinson's disease (PD), the second most frequent neurodegenerative disorder at old age, can be caused by elevated expression or the A53T missense mutation of the presynaptic protein alpha-synuclein (SNCA). PD is characterized pathologically by the preferential vulnerability of the dopaminergic nigrostriatal projection neurons. METHODOLOGY/PRINCIPAL FINDINGS: Here, we used two mouse lines overexpressing human A53T-SNCA and studied striatal dysfunction in the absence of neurodegeneration to understand early disease mechanisms. To characterize the progression, we employed young adult as well as old mice. Analysis of striatal neurotransmitter content demonstrated that dopamine (DA) levels correlated directly with the level of expression of SNCA, an observation also made in SNCA-deficient (knockout, KO) mice. However, the elevated DA levels in the striatum of old A53T-SNCA overexpressing mice may not be transmitted appropriately, in view of three observations. First, a transcriptional downregulation of the extraneural DA degradation enzyme catechol-ortho-methytransferase (COMT) was found. Second, an upregulation of DA receptors was detected by immunoblots and autoradiography. Third, extensive transcriptome studies via microarrays and quantitative real-time RT-PCR (qPCR) of altered transcript levels of the DA-inducible genes Atf2, Cb1, Freq, Homer1 and Pde7b indicated a progressive and genotype-dependent reduction in the postsynaptic DA response. As a functional consequence, long term depression (LTD) was absent in corticostriatal slices from old transgenic mice. CONCLUSIONS/SIGNIFICANCE: Taken together, the dysfunctional neurotransmission and impaired synaptic plasticity seen in the A53T-SNCA overexpressing mice reflect early changes within the basal ganglia prior to frank neurodegeneration. As a model of preclinical stages of PD, such insights may help to develop neuroprotective therapeutic approaches
Freedom and indoctrination
It has been alleged that compatibilists are committed to the view that agents act freely and responsibly even when subject to certain forms of radical manipulation. In this paper I identify and elucidate a form of compatibilist freedom, social autonomy, that is essential to understanding what is wrong with ordinary indoctrination and argue that it also holds the key to understanding what goes wrong in more fanciful manipulation cases
Red-list status and extinction risk of the world’s whales, dolphins and porpoises
To understand the scope and scale of the loss of biodiversity, tools are required that can be applied in a standardized manner to all species globally, spanning realms from land to the open ocean. We used data from the International Union for the Conservation of Nature Red List to provide a synthesis of the conservation status and extinction risk of cetaceans. One in 4 cetacean species (26% of 92 species) was threatened with extinction (i.e., critically endangered, endangered, or vulnerable) and 11% were near threatened. Ten percent of cetacean species were data deficient, and we predicted that 2–3 of these species may also be threatened. The proportion of threatened cetaceans has increased: 15% in 1991, 19% in 2008, and 26% in 2021. The assessed conservation status of 20% of species has worsened from 2008 to 2021, and only 3 moved into categories of lesser threat. Cetacean species with small geographic ranges were more likely to be listed as threatened than those with large ranges, and those that occur in freshwater (100% of species) and coastal (60% of species) habitats were under the greatest threat. Analysis of odontocete species distributions revealed a global hotspot of threatened small cetaceans in Southeast Asia, in an area encompassing the Coral Triangle and extending through nearshore waters of the Bay of Bengal, northern Australia, and Papua New Guinea and into the coastal waters of China. Improved management of fisheries to limit overfishing and reduce bycatch is urgently needed to avoid extinctions or further declines, especially in coastal areas of Asia, Africa, and South America.Publisher PDFPeer reviewe
The role of p53 in the chemotherapeutic responses to cisplatin, doxorubicin and 5-fluorouracil treatment
A panel of tumour models used extensively for in vivo evaluation of new drugs was characterised for their p53 status. Basal p53 protein levels were measured by immunodetection on both formalin-fixed tumour tissue and from protein extracts of fresh tumours. High levels of nuclear-specific staining, indicative of p53 mutation, was seen in 15/25 tumours, with the remainder showing intermittent or no staining. The functional status of p53 cDNA from these tumours was assayed within the functional analysis of separated alleles in yeast (F.A.S.A.Y.) reporter system. The cDNA from those tumours with high levels of p53 protein showed 14/15 failing to activate the reporter gene. The cDNA from tumours with low or non-detectable p53 levels showed 8/10 with wild-type p53. Tumours were grown subcutaneously in mice (n=10). Each mouse was given maximum tolerated doses for either doxorubicin, 5-fluorouracil or cisplatin. Tumour volumes were measured daily, alongside untreated controls. The specific growth delay values for each tumour were separated into two groups, those with functional p53 (wild-type) and those without (mutant and null status). The Mann-Whitney U test was performed on the groups of data, to evaluate differences in their response on the basis of p53 status. Cisplatin was moderately active against tumours with wild-type and mutant p53 genes with no significant difference seen between both groups. However, a significant difference in specific growth delay was seen between the two groups when treated with doxorubicin or 5-fluorouracil (P=0.05), indicating a role for p53 protein in modulating the in vivo efficacy of these agents
Satellite derived offshore migratory movements of southern right whales (Eubalaena australis) from Australian and New Zealand wintering grounds
Funding: Australian Marine Mammal Center Grant 13/48 AIM, SDG, DH, AL http://www.marinemammals.gov.au/ The Australian Marine Mammal Center was involved in study design and anlaysis through the involvement in the project by AMMC staff, Dr Mike Double and Dr Virgina Andrews-Goff Princess Melikoff Trust Marine Mammal Conservation Program KC New Zealand Department of Conservation SC.Southern right whales (Eubalaena australis) migrate between Austral-winter calving and socialising grounds to offshore mid- to high latitude Austral-summer feeding grounds. In Australasia, winter calving grounds used by southern right whales extend from Western Australia across southern Australia to the New Zealand sub-Antarctic Islands. During the Austral-summer these whales are thought to migrate away from coastal waters to feed, but the location of these feeding grounds is only inferred from historical whaling data. We present new information on the satellite derived offshore migratory movements of six southern right whales from Australasian wintering grounds. Two whales were tagged at the Auckland Islands, New Zealand, and the remaining four at Australian wintering grounds, one at Pirates Bay, Tasmania, and three at Head of Bight, South Australia. The six whales were tracked for an average of 78.5 days (range: 29 to 150) with average individual distance of 38 km per day (range: 20 to 61 km). The length of individually derived tracks ranged from 645–6,381 km. Three likely foraging grounds were identified: south-west Western Australia, the Subtropical Front, and Antarctic waters, with the Subtropical Front appearing to be a feeding ground for both New Zealand and Australian southern right whales. In contrast, the individual tagged in Tasmania, from a sub-population that is not showing evidence of post-whaling recovery, displayed a distinct movement pattern to much higher latitude waters, potentially reflecting a different foraging strategy. Variable population growth rates between wintering grounds in Australasia could reflect fidelity to different quality feeding grounds. Unlike some species of baleen whale populations that show movement along migratory corridors, the new satellite tracking data presented here indicate variability in the migratory pathways taken by southern right whales from Australia and New Zealand, as well as differences in potential Austral summer foraging grounds.Publisher PDFPeer reviewe
A53T-Alpha-Synuclein Overexpression Impairs Dopamine Signaling and Striatal Synaptic Plasticity in Old Mice
Parkinson's disease (PD), the second most frequent neurodegenerative disorder at old age, can be caused by elevated expression or the A53T missense mutation of the presynaptic protein alpha-synuclein (SNCA). PD is characterized pathologically by the preferential vulnerability of the dopaminergic nigrostriatal projection neurons.Here, we used two mouse lines overexpressing human A53T-SNCA and studied striatal dysfunction in the absence of neurodegeneration to understand early disease mechanisms. To characterize the progression, we employed young adult as well as old mice. Analysis of striatal neurotransmitter content demonstrated that dopamine (DA) levels correlated directly with the level of expression of SNCA, an observation also made in SNCA-deficient (knockout, KO) mice. However, the elevated DA levels in the striatum of old A53T-SNCA overexpressing mice may not be transmitted appropriately, in view of three observations. First, a transcriptional downregulation of the extraneural DA degradation enzyme catechol-ortho-methytransferase (COMT) was found. Second, an upregulation of DA receptors was detected by immunoblots and autoradiography. Third, extensive transcriptome studies via microarrays and quantitative real-time RT-PCR (qPCR) of altered transcript levels of the DA-inducible genes Atf2, Cb1, Freq, Homer1 and Pde7b indicated a progressive and genotype-dependent reduction in the postsynaptic DA response. As a functional consequence, long term depression (LTD) was absent in corticostriatal slices from old transgenic mice.Taken together, the dysfunctional neurotransmission and impaired synaptic plasticity seen in the A53T-SNCA overexpressing mice reflect early changes within the basal ganglia prior to frank neurodegeneration. As a model of preclinical stages of PD, such insights may help to develop neuroprotective therapeutic approaches
New Zealand blue whales: initial photo-identification of a little-known population
ABSTRACT Eighteen blue whales were photo-identified from coastal waters around the North and South Islands of New Zealand from 2004-2013 in five different months of the year. No photographic matches were found between locations. The photo-ID collection provides a foundation for future study on this little-known population. Fourteen of the photo-identifications were obtained in January and March 2013 during transits of the Antarctic Blue Whale Voyage from Nelson, NZ to Antarctica and return. This voyage also allowed for observations of the external morphology and behaviour of the blue whales encountered. Body length and proportion, head shape, body condition and skin condition were similar to Australian but not Antarctic blue whales. Feeding behaviour was observed off the South Island's west coast in January 2013 and strong evidence of feeding off the east coast in March 2013, the first this has been reported for these locations
Motor cortical excitability and pre-supplementary motor area neurochemistry in healthy adults with substantia nigra hyperechogenicity
Substantia nigra (SN) hyperechogenicity, viewed with transcranial ultrasound, is a risk marker for Parkinson\u27s disease. We hypothesized that SN hyperechogenicity in healthy adults aged 50 – 70 years is associated with reduced short-interval intracortical inhibition in primary motor cortex, and that the reduced intracortical inhibition is associated with neurochemical markers of activity in the pre-supplementary motor area (pre-SMA). Short-interval intracortical inhibition and intracortical facilitation in primary motor cortex was assessed with paired-pulse transcranial magnetic stimulation in 23 healthy adults with normal (n = 14; 61 ± 7 yrs) or abnormally enlarged (hyperechogenic; n = 9; 60 ± 6 yrs) area of SN echogenicity. Thirteen of these participants (7 SN − and 6 SN+) also underwent brain magnetic resonance spectroscopy to investigate pre-SMA neurochemistry. There was no relationship between area of SN echogenicity and short-interval intracortical inhibition in the ipsilateral primary motor cortex. There was a significant positive relationship, however, between area of echogenicity in the right SN and the magnitude of intracortical facilitation in the right (ipsilateral) primary motor cortex (p = .005; multivariate regression), evidenced by the amplitude of the conditioned motor evoked potential (MEP) at the 10 – 12 ms interstimulus interval. This relationship was not present on the left side. Pre-SMA glutamate did not predict primary motor cortex inhibition or facilitation. The results suggest that SN hyperechogenicity in healthy older adults may be associated with changes in excitability of motor cortical circuitry. The results advance understanding of brain changes in healthy older adults at risk of Parkinson\u27s disease
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