484 research outputs found
Reversible DNA micro-patterning using the fluorous effect
We describe a new method for the immobilisation of DNA into defined patterns with sub-micron resolution, using the fluorous effect. The method is fully reversible via a simple solvent wash, allowing the patterning, regeneration and re-patterning of surfaces with no degradation in binding efficiency following multiple removal/attachment cycles of different DNA sequences
nNOS-expressing neurons in the ventral tegmental area and substantia nigra pars compacta
GABA neurons in the VTA and SNc play key roles in reward and aversion through their local inhibitory control of dopamine neuron activity and through long-range projections to several target regions including the nucleus accumbens. It is not clear whether some of these GABA neurons are dedicated local interneurons or if they all collateralize and send projections externally as well as making local synaptic connections. Testing between these possibilities has been challenging in the absence of interneuron-specific molecular markers. We hypothesized that one potential candidate might be neuronal nitric oxide synthase (nNOS), a common interneuronal marker in other brain regions. To test this, we used a combination of immunolabelling (including antibodies for nNOS that we validated in tissue from nNOS-deficient mice) and cell type-specific virus-based anterograde tracing in mice. We found that nNOS-expressing neurons, in the parabrachial pigmented (PBP) part of the VTA and the SNc were GABAergic and did not make detectable projections, suggesting they may be interneurons. In contrast, nNOS-expressing neurons in the rostral linear nucleus (RLi) were mostly glutamatergic and projected to a number of regions, including the lateral hypothalamus (LH), the ventral pallidum (VP), and the median raphe (MnR) nucleus. Taken together, these findings indicate that nNOS is expressed by neurochemically- and anatomically-distinct neuronal sub-groups in a sub-region-specific manner in the VTA and SNc
Comparative physiology of Australian quolls (Dasyurus; Marsupialia)
Quolls (Dasyurus) are medium-sized carnivorous dasyurid marsupials. Tiger (3,840 g) and eastern quolls (780 g) are mesic zone species, northern quolls (516 g) are tropical zone, and chuditch (1,385 g) were once widespread through the Australian arid zone. We found that standard physiological variables of these quolls are consistent with allometric expectations for marsupials. Nevertheless, inter-specific patterns amongst the quolls are consistent with their different environments. The lower T ^sub b^ of northern quolls (34°C) may provide scope for adaptive hyperthermia in the tropics, and they use torpor for energy/water conservation, whereas the larger mesic species (eastern and tiger quolls) do not appear to. Thermolability varied from little in eastern (0.035°C °C^sup -1^) and tiger quolls (0.051°C ºC^sup -1^) to substantial in northern quolls (0.100°C ºC^sup -1^) and chuditch (0.146°C ºC^sup -1^), reflecting body mass and environment. Basal metabolic rate was higher for eastern quolls (0.662 ± 0.033 ml O^sub 2^ g^sup -1^ h^sup -1^), presumably reflecting their naturally cool environment. Respiratory ventilation closely matched metabolic demand, except at high ambient temperatures where quolls hyperventilated to facilitate evaporative heat loss; tiger and eastern quolls also salivated. A higher evaporative water loss for eastern quolls (1.43 ± 0.212 mg H^sub 2^O g^sup -1^ h^sup -1^) presumably reflects their more mesic distribution. The point of relative water economy was low for tiger (-1.3°C), eastern (-12.5°C) and northern (+3.3) quolls, and highest for the chuditch (+22.6°C). We suggest that these differences in water economy reflect lower expired air temperatures and hence lower respiratory evaporative water loss for the arid-zone chuditch relative to tropical and mesic quolls
Metabolic, hygric and ventilatory physiology of a hypermetabolic marsupial, the honey possum (Tarsipes rostratus)
The honey possum is the only non-volant mammal to feed exclusively on a diet of nectar and pollen. Like other mammalian and avian nectarivores, previous studies indicated that the honey possum's basal metabolic rate was higher than predicted for a marsupial of equivalent body mass. However, these early measurements have been questioned. We re-examined the basal metabolic rate (2.52 +/- A 0.222 ml O(2) g(-1) h(-1)) of the honey possum and confirm that it is indeed higher (162%) than predicted for other marsupials both before and after accounting for phylogenetic history. This, together with its small body mass (5.4 +/- A 0.14 g; 1.3% of that predicted by phylogeny) may be attributed to its nectarivorous diet and mesic distribution. Its high-basal metabolic rate is associated with a high-standard body temperature (36.6 +/- A 0.48A degrees C) and oxygen extraction (19.4%), but interestingly the honey possum has a high point of relative water economy (17.0A degrees C) and its standard evaporative water loss (4.33 +/- A 0.394 mg H(2)O g(-1) h(-1)) is not elevated above that of other marsupials, despite its mesic habitat and high dietary water intake.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP
Validation of the SCID-hu Thy/Liv mouse model with four classes of licensed antiretrovirals.
BackgroundThe SCID-hu Thy/Liv mouse model of HIV-1 infection is a useful platform for the preclinical evaluation of antiviral efficacy in vivo. We performed this study to validate the model with representatives of all four classes of licensed antiretrovirals.Methodology/principal findingsEndpoint analyses for quantification of Thy/Liv implant viral load included ELISA for cell-associated p24, branched DNA assay for HIV-1 RNA, and detection of infected thymocytes by intracellular staining for Gag-p24. Antiviral protection from HIV-1-mediated thymocyte depletion was assessed by multicolor flow cytometric analysis of thymocyte subpopulations based on surface expression of CD3, CD4, and CD8. These mice can be productively infected with molecular clones of HIV-1 (e.g., the X4 clone NL4-3) as well as with primary R5 and R5X4 isolates. To determine whether results in this model are concordant with those found in humans, we performed direct comparisons of two drugs in the same class, each of which has known potency and dosing levels in humans. Here we show that second-generation antiretrovirals were, as expected, more potent than their first-generation predecessors: emtricitabine was more potent than lamivudine, efavirenz was more potent than nevirapine, and atazanavir was more potent than indinavir. After interspecies pharmacodynamic scaling, the dose ranges found to inhibit viral replication in the SCID-hu Thy/Liv mouse were similar to those used in humans. Moreover, HIV-1 replication in these mice was genetically stable; treatment of the mice with lamivudine did not result in the M184V substitution in reverse transcriptase, and the multidrug-resistant NY index case HIV-1 retained its drug-resistance substitutions.ConclusionGiven the fidelity of such comparisons, we conclude that this highly reproducible mouse model is likely to predict clinical antiviral efficacy in humans
A soliton menagerie in AdS
We explore the behaviour of charged scalar solitons in asymptotically global
AdS4 spacetimes. This is motivated in part by attempting to identify under what
circumstances such objects can become large relative to the AdS length scale.
We demonstrate that such solitons generically do get large and in fact in the
planar limit smoothly connect up with the zero temperature limit of planar
scalar hair black holes. In particular, for given Lagrangian parameters we
encounter multiple branches of solitons: some which are perturbatively
connected to the AdS vacuum and surprisingly, some which are not. We explore
the phase space of solutions by tuning the charge of the scalar field and
changing scalar boundary conditions at AdS asymptopia, finding intriguing
critical behaviour as a function of these parameters. We demonstrate these
features not only for phenomenologically motivated gravitational Abelian-Higgs
models, but also for models that can be consistently embedded into eleven
dimensional supergravity.Comment: 62 pages, 21 figures. v2: added refs and comments and updated
appendice
Doping the holographic Mott insulator
Mott insulators form because of strong electron repulsions, being at the
heart of strongly correlated electron physics. Conventionally these are
understood as classical "traffic jams" of electrons described by a short-ranged
entangled product ground state. Exploiting the holographic duality, which maps
the physics of densely entangled matter onto gravitational black hole physics,
we show how Mott-insulators can be constructed departing from entangled
non-Fermi liquid metallic states, such as the strange metals found in cuprate
superconductors. These "entangled Mott insulators" have traits in common with
the "classical" Mott insulators, such as the formation of Mott gap in the
optical conductivity, super-exchange-like interactions, and form "stripes" when
doped. They also exhibit new properties: the ordering wave vectors are detached
from the number of electrons in the unit cell, and the DC resistivity diverges
algebraically instead of exponentially as function of temperature. These
results may shed light on the mysterious ordering phenomena observed in
underdoped cuprates.Comment: 27 pages, 9 figures. Accepted in Nature Physic
Employing Participatory Methods to Engage an Under-Researched Group: opportunities and challenges
In this article, we report on our experience of working on an exploratory project where the primary objective was to involve homeless service users with food-based participatory qualitative approaches. The project FLM aimed to explore food experiences and behaviours in a sample of users of homelessness services in a south west UK coastal city, in order to create solutions to improve their wellbeing. A mixture of qualitative methods was used, including observations, photo-elicitation and focus group discussions. We aimed to be participatory and ‘creative’ in our approach and in our analysis. Here, we focus on detailing and critiquing our approach to the collection and analysis of data.</jats:p
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