198 research outputs found
The human gC1qR/p32 gene, C1qBP. Genomic organization and promoter analysis
gC1qR is an ubiquitously expressed cell protein that interacts with the globular heads of C1q (gC1q) and many other ligands. In this study, the 7.8-kilobase pair (kb) human gC1qPJp32 (C1qBP) gene was cloned and found to consist of 6 exons and 5 introns. Analysis of a 1.3-kb DNA fragment at the 5âČ-flanking region of this gene revealed the presence of multiple TATA, CCAAT, and Sp1 binding sites. Luciferase reporter assays performed in different human cell lines demonstrated that the reporter gene was ubiquitously driven by this 1.3-kb fragment. Subsequent 5âČ and 3âČ deletion of this fragment confined promoter elements to within 400 base pairs (bp) upstream of the translational start site. Because the removal of the 8-bp consensus TATATATA at -399 to -406 and CCAAT at -410 to -414 did not significantly affect the transcription efficiency of the promoter, GC-rich sequences between this TATA box and the translation start site may be very important for the promoter activity of the C1qBP gene. One of seven GC-rich sequences in this region binds specifically to PANC-1 nuclear extracts, and the transcription factor Sp1 was shown to bind to this GC-rich sequence by the supershift assay. Primer extension analysis mapped three major transcription start regions. The farthest transcription start site is 49 bp upstream of the ATG translation initiation codon and is in close proximity of the specific SP1 binding site.postprin
Sea anemones may thrive in a high CO2 world
Increased seawater pCO 2, and in turn 'ocean acidification' (OA), is predicted to profoundly impact marine ecosystem diversity and function this century. Much research has already focussed on calcifying reef-forming corals (Class: Anthozoa) that appear particularly susceptible to OA via reduced net calcification. However, here we show that OA-like conditions can simultaneously enhance the ecological success of non-calcifying anthozoans, which not only play key ecological and biogeochemical roles in present day benthic ecosystems but also represent a model organism should calcifying anthozoans exist as less calcified (soft-bodied) forms in future oceans. Increased growth (abundance and size) of the sea anemone (Anemonia viridis) population was observed along a natural CO 2 gradient at Vulcano, Italy. Both gross photosynthesis (P G) and respiration (R) increased with pCO 2 indicating that the increased growth was, at least in part, fuelled by bottom up (CO 2 stimulation) of metabolism. The increase of P G outweighed that of R and the genetic identity of the symbiotic microalgae (Symbiodinium spp.) remained unchanged (type A19) suggesting proximity to the vent site relieved CO 2 limitation of the anemones' symbiotic microalgal population. Our observations of enhanced productivity with pCO 2, which are consistent with previous reports for some calcifying corals, convey an increase in fitness that may enable non-calcifying anthozoans to thrive in future environments, i.e. higher seawater pCO 2. Understanding how CO 2-enhanced productivity of non- (and less-) calcifying anthozoans applies more widely to tropical ecosystems is a priority where such organisms can dominate benthic ecosystems, in particular following localized anthropogenic stress. © 2012 Blackwell Publishing Ltd
Inflation on the Brane with Vanishing Gravity
Many existing models of brane inflation suffer from a steep irreducible
gravitational potential between the branes that causes inflation to end too
early. Inspired by the fact that point masses in 2+1 D exert no gravitational
force, we propose a novel unwarped and non-supersymmetric setup for inflation,
consisting of 3-branes in two extra dimensions compactified on a sphere. The
size of the sphere is stabilized by a combination of a bulk cosmological
constant and a magnetic flux. Computing the 4D effective potential between
probe branes in this background, we find a non-zero contribution only from
exchange of level-1 KK modes of the graviton and radion. Identifying antipodal
points on the 2-sphere projects out these modes, eliminating entirely the
troublesome gravitational contribution to the inflationary potential.Comment: 19 pages, 11 figures, JHEP forma
Effective theories of single field inflation when heavy fields matter
We compute the low energy effective field theory (EFT) expansion for
single-field inflationary models that descend from a parent theory containing
multiple other scalar fields. By assuming that all other degrees of freedom in
the parent theory are sufficiently massive relative to the inflaton, it is
possible to derive an EFT valid to arbitrary order in perturbations, provided
certain generalized adiabaticity conditions are respected. These conditions
permit a consistent low energy EFT description even when the inflaton deviates
off its adiabatic minimum along its slowly rolling trajectory. By generalizing
the formalism that identifies the adiabatic mode with the Goldstone boson of
this spontaneously broken time translational symmetry prior to the integration
of the heavy fields, we show that this invariance of the parent theory dictates
the entire non-perturbative structure of the descendent EFT. The couplings of
this theory can be written entirely in terms of the reduced speed of sound of
adiabatic perturbations. The resulting operator expansion is distinguishable
from that of other scenarios, such as standard single inflation or DBI
inflation. In particular, we re-derive how certain operators can become
transiently strongly coupled along the inflaton trajectory, consistent with
slow-roll and the validity of the EFT expansion, imprinting features in the
primordial power spectrum, and we deduce the relevant cubic operators that
imply distinct signatures in the primordial bispectrum which may soon be
constrained by observations.Comment: (v1) 25 pages, 1 figure; (v2) references added and typos corrected,
to appear in Journal of High Energy Physic
Evaluating digital diabetic retinopathy screening in people aged 90 years and over
To evaluate the effectiveness of digital diabetic retinopathy screening in patients aged 90 years and over.MethodsThis is a retrospective analysis of 200 randomly selected patients eligible for diabetic retinopathy screening aged 90 years and over within the Birmingham, Solihull, and Black Country Screening Programme.ResultsOne hundred and seventy-nine (90%) patients attended screening at least once. 133 (74%) annual screening after their first screen, of whom 59% had no detectable diabetic retinopathy; 38 (21%) were referred for ophthalmology clinical assessment-36 for nondiabetic retinopathy reasons and two for diabetic maculopathy. Cataract accounted for 50% of all referrals for ophthalmology clinical assessment. Of the 133 patients placed on annual screening, 93 (70%) were screened at least once more. In terms of level of diabetic retinopathy, assessability or other ocular pathologies, 8 improved, 51 remained stable, and 31 deteriorated. Of the latter, 19 patients were referred for ophthalmology clinical assessment; none of these for diabetic retinopathy.ConclusionsScreening provides opportunistic identification of important nondiabetic retinopathy eye conditions. However, in view of the low identification rate of sight-threatening diabetic retinopathy in patients aged 90 years and over, and the current mission statement of the NHS Diabetic Eye Screening Programme, systematic annual diabetic retinopathy screening may not be justified in this age group of patients, but rather be performed in optometric practice
Amygdala circuitry mediating reversible and bidirectional control of anxiety
Anxietyâa sustained state of heightened apprehension in the absence of immediate threatâbecomes severely debilitating in disease states. Anxiety disorders represent the most common of psychiatric diseases (28% lifetime prevalence) and contribute to the aetiology of major depression and substance abuse. Although it has been proposed that the amygdala, a brain region important for emotional processing, has a role in anxiety, the neural mechanisms that control anxiety remain unclear. Here we explore the neural circuits underlying anxiety-related behaviours by using optogenetics with two-photon microscopy, anxiety assays in freely moving mice, and electrophysiology. With the capability of optogenetics to control not only cell types but also specific connections between cells, we observed that temporally precise optogenetic stimulation of basolateral amygdala (BLA) terminals in the central nucleus of the amygdala (CeA)âachieved by viral transduction of the BLA with a codon-optimized channelrhodopsin followed by restricted illumination in the downstream CeAâexerted an acute, reversible anxiolytic effect. Conversely, selective optogenetic inhibition of the same projection with a third-generation halorhodopsin (eNpHR3.0) increased anxiety-related behaviours. Importantly, these effects were not observed with direct optogenetic control of BLA somata, possibly owing to recruitment of antagonistic downstream structures. Together, these results implicate specific BLAâCeA projections as critical circuit elements for acute anxiety control in the mammalian brain, and demonstrate the importance of optogenetically targeting defined projections, beyond simply targeting cell types, in the study of circuit function relevant to neuropsychiatric disease
The A-B transition in superfluid helium-3 under confinement in a thin slab geometry
The influence of confinement on the topological phases of superfluid 3He is
studied using the torsional pendulum method. We focus on the phase transition
between the chiral A-phase and the time-reversal-invariant B-phase, motivated
by the prediction of a spatiallymodulated (stripe) phase at the A-B phase
boundary. We confine superfluid 3He to a single 1.08 {\mu}m thick nanofluidic
cavity incorporated into a high-precision torsion pendulum, and map the phase
diagram between 0.1 and 5.6 bar. We observe only small supercooling of the
A-phase, in comparison to bulk or when confined in aerogel. This has a
non-monotonic pressure dependence, suggesting that a new intrinsic B-phase
nucleation mechanism operates under confinement, mediated by the putative
stripe phase. Both the phase diagram and the relative superfluid fraction of
the A and B phases, show that strong coupling is present at all pressures, with
implications for the stability of the stripe phase.Comment: 6 figures, 1 table + supplemental informatio
The Problem of Ethical Vagueness for Expressivism
Ethical vagueness has garnered little attention. This is rather surprising since many philosophers have remarked that the science of ethics lacks the precision that other fields of inquiry have. Of the few philosophers who have discussed ethical vagueness the majority have focused on the implications of vagueness for moral realism. Because the relevance of ethical vagueness for other metaethical positions has been underexplored, my aim in this paper is to investigate the ramifications of ethical vagueness for expressivism. Ultimately, I shall argue that expressivism does not have the resources to adequately account for ethical vagueness, while cognitivism does. This demonstrates an advantage that cognitivism holds over expressivis
Resolving the neural circuits of anxiety
Although anxiety disorders represent a major societal problem demanding new therapeutic targets, these efforts have languished in the absence of a mechanistic understanding of this subjective emotional state. While it is impossible to know with certainty the subjective experience of a rodent, rodent models hold promise in dissecting well-conserved limbic circuits. The application of modern approaches in neuroscience has already begun to unmask the neural circuit intricacies underlying anxiety by allowing direct examination of hypotheses drawn from existing psychological concepts. This information points toward an updated conceptual model for what neural circuit perturbations could give rise to pathological anxiety and thereby provides a roadmap for future therapeutic development.National Institute of Diabetes and Digestive and Kidney Diseases (U.S.) (NIH Directorâs New Innovator Award DP2-DK-102256-01)National Institute of Mental Health (U.S.) (NIH) R01-MH102441-01)JPB Foundatio
Optogenetic stimulation of a hippocampal engram activates fear memory recall
A specific memory is thought to be encoded by a sparse population of neurons. These neurons can be tagged during learning for subsequent identification3 and manipulation. Moreover, their ablation or inactivation results in reduced memory expression, suggesting their necessity in mnemonic processes. However, the question of sufficiency remains: it is unclear whether it is possible to elicit the behavioural output of a specific memory by directly activating a population of neurons that was active during learning. Here we show in mice that optogenetic reactivation of hippocampal neurons activated during fear conditioning is sufficient to induce freezing behaviour. We labelled a population of hippocampal dentate gyrus neurons activated during fear learning with channelrhodopsin-2 (ChR2) and later optically reactivated these neurons in a different context. The mice showed increased freezing only upon light stimulation, indicating light-induced fear memory recall. This freezing was not detected in non-fear-conditioned mice expressing ChR2 in a similar proportion of cells, nor in fear-conditioned mice with cells labelled by enhanced yellow fluorescent protein instead of ChR2. Finally, activation of cells labelled in a context not associated with fear did not evoke freezing in mice that were previously fear conditioned in a different context, suggesting that light-induced fear memory recall is context specific. Together, our findings indicate that activating a sparse but specific ensemble of hippocampal neurons that contribute to a memory engram is sufficient for the recall of that memory. Moreover, our experimental approach offers a general method of mapping cellular populations bearing memory engrams.RIKEN Brain Science InstituteNational Institutes of Health (U.S.) (Grant R01-MH078821)National Institutes of Health (U.S.) (Grant P50-MH58880
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