303 research outputs found
Simultaneous whole-animal 3D-imaging of neuronal activity using light field microscopy
3D functional imaging of neuronal activity in entire organisms at single cell
level and physiologically relevant time scales faces major obstacles due to
trade-offs between the size of the imaged volumes, and spatial and temporal
resolution. Here, using light-field microscopy in combination with 3D
deconvolution, we demonstrate intrinsically simultaneous volumetric functional
imaging of neuronal population activity at single neuron resolution for an
entire organism, the nematode Caenorhabditis elegans. The simplicity of our
technique and possibility of the integration into epi-fluoresence microscopes
makes it an attractive tool for high-speed volumetric calcium imaging.Comment: 25 pages, 7 figures, incl. supplementary informatio
Composite Higgs Search at the LHC
The Higgs boson production cross-sections and decay rates depend, within the
Standard Model (SM), on a single unknown parameter, the Higgs mass. In
composite Higgs models where the Higgs boson emerges as a pseudo-Goldstone
boson from a strongly-interacting sector, additional parameters control the
Higgs properties which then deviate from the SM ones. These deviations modify
the LEP and Tevatron exclusion bounds and significantly affect the searches for
the Higgs boson at the LHC. In some cases, all the Higgs couplings are reduced,
which results in deterioration of the Higgs searches but the deviations of the
Higgs couplings can also allow for an enhancement of the gluon-fusion
production channel, leading to higher statistical significances. The search in
the H to gamma gamma channel can also be substantially improved due to an
enhancement of the branching fraction for the decay of the Higgs boson into a
pair of photons.Comment: 32 pages, 16 figure
Correlation between three assay systems for anti-Mullerian hormone (AMH) determination
PURPOSE: Analysis of anti-MΓΌllerian hormone (AMH) is becoming of recognized importance in reproductive medicine, but assays are not standardized. We have evaluated the correlation between the new Gen II ELISA kit (Beckman-Coutler) and the older ELISA kits by Immunotech (IOT) and Diagnostic Systems Laboratories (DSL). METHODS: A total of 56 archived serum samples from patients with subfertility or reproductive endocrine disorders were retrieved and assayed in duplicate using the three AMH ELISA kits . The samples covered a wide range of AMH concentrations (1.9 to 142.5 pmol/L). RESULTS: We observed good correlations between the new (AMH Gen II) and old AMH assay kits by IOT and DSL (R(2)β=β0.971 and 0.930 respectively). The regression equations were AMH (Gen II)β=β1.353 Γ AMH (IOT)β+β0.051 and AMH (Gen II)β=β1.223 Γ AMH (DSL) β 1.270 respectively. CONCLUSIONS: AMH concentrations using the Gen II kit are slightly higher than those from the IOT and DSL kits. Standardization of assay results worldwide is urgently required but this analysis facilitates the interpretation of values obtained historically and in future studies using any of the 3 assays available. Meanwhile, adapting clinical cut-offs from previously published work by direct conversion is not recommended
Predictions for Higgs production at the Tevatron and the associated uncertainties
We update the theoretical predictions for the production cross sections of
the Standard Model Higgs boson at the Fermilab Tevatron collider, focusing on
the two main search channels, the gluon-gluon fusion mechanism and
the Higgs-strahlung processes with , including all
relevant higher order QCD and electroweak corrections in perturbation theory.
We then estimate the various uncertainties affecting these predictions: the
scale uncertainties which are viewed as a measure of the unknown higher order
effects, the uncertainties from the parton distribution functions and the
related errors on the strong coupling constant, as well as the uncertainties
due to the use of an effective theory approach in the determination of the
radiative corrections in the process at next-to-next-to-leading
order. We find that while the cross sections are well under control in the
Higgs--strahlung processes, the theoretical uncertainties are rather large in
the case of the gluon-gluon fusion channel, possibly shifting the central
values of the next-to-next-to-leading order cross sections by more than
. These uncertainties are thus significantly larger than the
error assumed by the CDF and D0 experiments in their recent
analysis that has excluded the Higgs mass range 162-166 GeV at the 95%
confidence level. These exclusion limits should be, therefore, reconsidered in
the light of these large theoretical uncertainties.Comment: 40 pages, 12 figures. A few typos are corrected and some updated
numbers are provide
NLO QCD corrections to pseudoscalar Higgs production in the MSSM
We present a calculation of the two-loop quark-squark-gluino contributions to
pseudoscalar Higgs boson production via gluon fusion in the MSSM. We regularize
the loop integrals using the Pauli-Villars method, and obtain explicit and
compact analytic results based on an expansion in the heavy particle masses.
Our results - valid when the pseudoscalar Higgs boson is lighter than squarks
and gluinos - can be easily implemented in computer codes for an efficient and
accurate determination of the pseudoscalar production cross section.Comment: 26 pages, 4 figures. v2: comments added in section 3, version
published in JHE
Small RNAs with 5β²-Polyphosphate Termini Associate with a Piwi-Related Protein and Regulate Gene Expression in the Single-Celled Eukaryote Entamoeba histolytica
Small interfering RNAs regulate gene expression in diverse biological processes, including heterochromatin formation and DNA elimination, developmental regulation, and cell differentiation. In the single-celled eukaryote Entamoeba histolytica, we have identified a population of small RNAs of 27 nt size that (i) have 5β²-polyphosphate termini, (ii) map antisense to genes, and (iii) associate with an E. histolytica Piwi-related protein. Whole genome microarray expression analysis revealed that essentially all genes to which antisense small RNAs map were not expressed under trophozoite conditions, the parasite stage from which the small RNAs were cloned. However, a number of these genes were expressed in other E. histolytica strains with an inverse correlation between small RNA and gene expression level, suggesting that these small RNAs mediate silencing of the cognate gene. Overall, our results demonstrate that E. histolytica has an abundant 27 nt small RNA population, with features similar to secondary siRNAs from C. elegans, and which appear to regulate gene expression. These data indicate that a silencing pathway mediated by 5β²-polyphosphate siRNAs extends to single-celled eukaryotic organisms
Mitochondrial genome deletions and minicircles are common in lice (Insecta: Phthiraptera)
Background The gene composition, gene order and structure of the mitochondrial genome are remarkably stable across bilaterian animals. Lice (Insecta: Phthiraptera) are a major exception to this genomic stability in that the canonical single chromosome with 37 genes found in almost all other bilaterians has been lost in multiple lineages in favour of multiple, minicircular chromosomes with less than 37 genes on each chromosome. Results Minicircular mt genomes are found in six of the ten louse species examined to date and three types of minicircles were identified: heteroplasmic minicircles which coexist with full sized mt genomes (type 1); multigene chromosomes with short, simple control regions, we infer that the genome consists of several such chromosomes (type 2); and multiple, single to three gene chromosomes with large, complex control regions (type 3). Mapping minicircle types onto a phylogenetic tree of lice fails to show a pattern of their occurrence consistent with an evolutionary series of minicircle types. Analysis of the nuclear-encoded, mitochondrially-targetted genes inferred from the body louse, Pediculus, suggests that the loss of mitochondrial single-stranded binding protein (mtSSB) may be responsible for the presence of minicircles in at least species with the most derived type 3 minicircles (Pediculus, Damalinia). Conclusions Minicircular mt genomes are common in lice and appear to have arisen multiple times within the group. Life history adaptive explanations which attribute minicircular mt genomes in lice to the adoption of blood-feeding in the Anoplura are not supported by this expanded data set as minicircles are found in multiple non-blood feeding louse groups but are not found in the blood-feeding genus Heterodoxus. In contrast, a mechanist explanation based on the loss of mtSSB suggests that minicircles may be selectively favoured due to the incapacity of the mt replisome to synthesize long replicative products without mtSSB and thus the loss of this gene lead to the formation of minicircles in lice
Augmented Cardiac Hypertrophy in Response to Pressure Overload in Mice Lacking ELTD1
BACKGROUND: Epidermal growth factor (EGF), latrophilin and seven transmembrane domain-containing protein 1 (ELTD1) is developmentally upregulated in the heart. Little is known about the relationship between ELTD1 and cardiac diseases. Therefore, we aimed to clarify the role of ELTD1 in pressure overload-induced cardiac hypertrophy. METHODS AND RESULTS: C57BL/6J wild-type (WT) mice and ELTD1-knockout (KO) mice were subjected to left ventricular pressure overload by descending aortic banding (AB). KO mice exhibited more unfavorable cardiac remodeling than WT mice 28 days post AB; this remodeling was characterized by aggravated cardiomyocyte hypertrophy, thickening of the ventricular walls, dilated chambers, increased fibrosis, and blunted systolic and diastolic cardiac function. Analysis of signaling pathways revealed enhanced extracellular signal-regulated kinase (ERK) and the c-Jun amino-terminal kinase (JNK) phosphorylation in response to ELTD1 deletion. CONCLUSIONS: ELTD1 deficiency exacerbates cardiac hypertrophy and cardiac function induced by AB-induced pressure overload by promoting both cardiomyocyte hypertrophy and cardiac fibrosis. These effects are suggested to originate from the activation of the ERK and JNK pathways, suggesting that ELTD1 is a potential target for therapies that prevent the development of cardiac disease
Statistical Metamodeling for Revealing Synergistic Antimicrobial Interactions
Many bacterial pathogens are becoming drug resistant faster than we can develop new antimicrobials. To address this threat in public health, a metamodel antimicrobial cocktail optimization (MACO) scheme is demonstrated for rapid screening of potent antibiotic cocktails using uropathogenic clinical isolates as model systems. With the MACO scheme, only 18 parallel trials were required to determine a potent antimicrobial cocktail out of hundreds of possible combinations. In particular, trimethoprim and gentamicin were identified to work synergistically for inhibiting the bacterial growth. Sensitivity analysis indicated gentamicin functions as a synergist for trimethoprim, and reduces its minimum inhibitory concentration for 40-fold. Validation study also confirmed that the trimethoprim-gentamicin synergistic cocktail effectively inhibited the growths of multiple strains of uropathogenic clinical isolates. With its effectiveness and simplicity, the MACO scheme possesses the potential to serve as a generic platform for identifying synergistic antimicrobial cocktails toward management of bacterial infection in the future
Regulation of STIM1 and SOCE by the Ubiquitin-Proteasome System (UPS)
The ubiquitin proteasome system (UPS) mediates the majority of protein degradation in eukaryotic cells. The UPS has recently emerged as a key degradation pathway involved in synapse development and function. In order to better understand the function of the UPS at synapses we utilized a genetic and proteomic approach to isolate and identify novel candidate UPS substrates from biochemically purified synaptic membrane preparations. Using these methods, we have identified Stromal interacting molecule 1 (STIM1). STIM1 is as an endoplasmic reticulum (ER) calcium sensor that has been shown to regulate store-operated Ca2+ entry (SOCE). We have characterized STIM1 in neurons, finding STIM1 is expressed throughout development with stable, high expression in mature neurons. As in non-excitable cells, STIM1 is distributed in a membranous and punctate fashion in hippocampal neurons. In addition, a population of STIM1 was found to exist at synapses. Furthermore, using surface biotinylation and live-cell labeling methods, we detect a subpopulation of STIM1 on the surface of hippocampal neurons. The role of STIM1 as a regulator of SOCE has typically been examined in non-excitable cell types. Therefore, we examined the role of the UPS in STIM1 and SOCE function in HEK293 cells. While we find that STIM1 is ubiquitinated, its stability is not altered by proteasome inhibitors in cells under basal conditions or conditions that activate SOCE. However, we find that surface STIM1 levels and thapsigargin (TG)-induced SOCE are significantly increased in cells treated with proteasome inhibitors. Additionally, we find that the overexpression of POSH (Plenty of SH3β²s), an E3 ubiquitin ligase recently shown to be involved in the regulation of Ca2+ homeostasis, leads to decreased STIM1 surface levels. Together, these results provide evidence for previously undescribed roles of the UPS in the regulation of STIM1 and SOCE function
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