689 research outputs found
Quantitative proteomic analysis reveals concurrent RNA-protein interactions and identifies new RNA-binding proteins in Saccharomyces cerevisiae
A growing body of evidence supports the existence of an extensive network of RNA-binding proteins (RBPs) whose combinatorial binding affects the post-transcriptional fate of every mRNA in the cell-yet we still do not have a complete understanding of which proteins bind to mRNA, which of these bind concurrently, and when and where in the cell they bind. We describe here a method to identify the proteins that bind to RNA concurrently with an RBP of interest, using quantitative mass spectrometry combined with RNase treatment of affinity-purified RNA-protein complexes. We applied this method to the known RBPs Pab1, Nab2, and Puf3. Our method significantly enriched for known RBPs and is a clear improvement upon previous approaches in yeast. Our data reveal that some reported protein-protein interactions may instead reflect simultaneous binding to shared RNA targets. We also discovered more than 100 candidate RBPs, and we independently confirmed that 77% (23/30) bind directly to RNA. The previously recognized functions of the confirmed novel RBPs were remarkably diverse, and we mapped the RNA-binding region of one of these proteins, the transcriptional coactivator Mbf1, to a region distinct from its DNA-binding domain. Our results also provided new insights into the roles of Nab2 and Puf3 in post-transcriptional regulation by identifying other RBPs that bind simultaneously to the same mRNAs. While existing methods can identify sets of RBPs that interact with common RNA targets, our approach can determine which of those interactions are concurrent-a crucial distinction for understanding post-transcriptional regulation
Thermoelectric Response of an Interacting Two-Dimensional Electron Gas in Quantizing Magnetic Field
We present a discussion of the linear thermoelectric response of an
interacting electron gas in a quantizing magnetic field. Boundary currents can
carry a significant fraction of the net current passing through the system. We
derive general expressions for the bulk and boundary components of the number
and energy currents. We show that the local current density may be described in
terms of ``transport'' and ``internal magnetization'' contributions. The latter
carry no net current and are not observable in standard transport experiments.
We show that although Onsager relations cannot be applied to the local current,
they are valid for the transport currents and hence for the currents observed
in standard transport experiments. We relate three of the four thermoelectric
response coefficients of a disorder-free interacting two-dimensional electron
gas to equilibrium thermodynamic quantities. In particular, we show that the
diffusion thermopower is proportional to the entropy per particle, and we
compare this result with recent experimental observations.Comment: 18 pages, 2 postscript figures included. Revtex with epsf.tex and
multicol.sty. In the revised version, the comparison with experimental
observations at is extended to include the possibility of
corrections due to weak impurity scattering. The conclusions that we reach
regarding the applicability of the composite fermion model at these filling
fractions are not affecte
Runaway Events Dominate the Heavy Tail of Citation Distributions
Statistical distributions with heavy tails are ubiquitous in natural and
social phenomena. Since the entries in heavy tail have disproportional
significance, the knowledge of its exact shape is very important. Citations of
scientific papers form one of the best-known heavy tail distributions. Even in
this case there is a considerable debate whether citation distribution follows
the log-normal or power-law fit. The goal of our study is to solve this debate
by measuring citation distribution for a very large and homogeneous data. We
measured citation distribution for 418,438 Physics papers published in
1980-1989 and cited by 2008. While the log-normal fit deviates too strong from
the data, the discrete power-law function with the exponent does
better and fits 99.955% of the data. However, the extreme tail of the
distribution deviates upward even from the power-law fit and exhibits a
dramatic "runaway" behavior. The onset of the runaway regime is revealed
macroscopically as the paper garners 1000-1500 citations, however the
microscopic measurements of autocorrelation in citation rates are able to
predict this behavior in advance.Comment: 6 pages, 5 Figure
Phenotypic covariance of longevity, immunity and stress resistance in the Caenorhabditis nematodes
Background \ud
Ageing, immunity and stresstolerance are inherent characteristics of all organisms. In animals, these traits are regulated, at least in part, by forkhead transcription factors in response to upstream signals from the Insulin/Insulinβ like growth factor signalling (IIS) pathway. In the nematode Caenorhabditis elegans, these phenotypes are molecularly linked such that activation of the forkhead transcription factor DAF-16 both extends lifespan and simultaneously increases immunity and stress resistance. It is known that lifespan varies significantly among the Caenorhabditis species but, although DAF-16 signalling is highly conserved, it is unclear whether this phenotypic linkage occurs in other species. Here we investigate this phenotypic covariance by comparing longevity, stress resistance and immunity in four \ud
Caenorhabditis species. \ud
\ud
Methodology/Principal Findings \ud
We show using phenotypic analysis of DAF-16 influenced phenotypes that among four closely related Caenorhabditis nematodes, the gonochoristic species (Caenorhabditis remanei and Caenorhabditis brenneri) have diverged \ud
significantly with a longer lifespan, improved stress resistance and higher immunity than the hermaphroditic species (C. elegans and Caenorhabditis briggsae). Interestingly, we also observe significant differences in expression levels between the daf-16 homologues in these species using Real-Time PCR, which positively correlate with the observed phenotypes. Finally, we provide additional evidence in support of a role for DAF-16 in regulating phenotypic coupling by using a combination of wildtype isolates, constitutively active daf-16 mutants and bioinformatic analysis. \ud
\ud
Conclusions \ud
The gonochoristic species display a significantly longer lifespan (p < 0.0001)and more robust immune and stress response (p<0.0001, thermal stress; p<0.01, heavy metal stress; p<0.0001, pathogenic stress) than the hermaphroditic species. Our data suggests that divergence in DAF-16 mediated phenotypes may underlie many of the differences observed between these four species of Caenorhabditis nematodes. These findings are further supported by the correlative higher daf-16 expression levels among the gonochoristic species and significantly higher lifespan, immunity and stress tolerance in the constitutively active daf-16 hermaphroditic mutants
Phenotypic covariance of Longevity, Immunity and Stress Resistance in the Caenorhabditis Nematodes
Background: Ageing, immunity and stresstolerance are inherent characteristics of all organisms. In animals, these traits are regulated, at least in part, by forkhead transcription factors in response to upstream signals from the Insulin/Insulinβlike growth factor signalling (IIS) pathway. In the nematode Caenorhabditis elegans, these phenotypes are molecularly linked such that activation of the forkhead transcription factor DAF-16 both extends lifespan and simultaneously increases immunity and stress resistance. It is known that lifespan varies significantly among the Caenorhabditis species but, although DAF-16 signalling is highly conserved, it is unclear whether this phenotypic linkage occurs in other species. Here we investigate this phenotypic covariance by comparing longevity, stress resistance and immunity in four Caenorhabditis species. \ud
\ud
Methodology/Principal Findings: We show using phenotypic analysis of DAF-16 influenced phenotypes that among four closely related Caenorhabditis nematodes, the gonochoristic species (Caenorhabditis remanei and Caenorhabditis brenneri) have diverged significantly with a longer lifespan, improved stress resistance and higher immunity than the hermaphroditic species (C. elegans and Caenorhabditis briggsae). Interestingly, we also observe significant differences in expression levels between the daf-16 homologues in these species using Real-Time PCR, which positively correlate with the observed phenotypes. Finally, we provide additional evidence in support of a role for DAF-16 in regulating phenotypic coupling by using a combination of wildtype isolates, constitutively active daf-16 mutants and bioinformatic analysis. \ud
\ud
Conclusions: The gonochoristic species display a significantly longer lifespan (p<0.0001) and more robust immune and stress response (p<0.0001, thermal stress; p<0.01, heavy metal stress; p<0.0001, pathogenic stress) than the hermaphroditic species. Our data suggests that divergence in DAF-16 mediated phenotypes may underlie many of the differences observed between these four species of Caenorhabditis nematodes. These findings are further supported by the correlative higher daf-16 expression levels among the gonochoristic species and significantly higher lifespan, immunity and stress tolerance in the constitutively active daf-16 hermaphroditic mutants
Psychogenic Elaboration of Simple Partial Seizures
Seizures that cause loss of consciousness (LOC) can be classified as epileptic or nonepileptic based on evaluation of ictal semiology and analysis of changes in EEG events, recorded with continuous scalp EEG and video monitoring. We report 3 patients who had hippocampal electrographic seizures documented with intracranial EEG recording with no accompanying scalp EEG change immediately preceding psychogenic unresponsiveness. Each patient also had complex partial seizures (CPS) originating in the hippocampus. Some individuals can have complex interactions of epileptic and nonepileptic seizures.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/66184/1/j.1528-1157.1995.tb00471.x.pd
Religiosity and corporate financial reporting: evidence from a European country
Using a sample of Portuguese privately-held firms, I examine the association between religiosity and
financial reporting quality. The results suggest that firms headquartered in Portuguese areas with strong
religious adherence and in the core area of the Portuguese religious cult (the district where the FΓ‘tima
Sanctuary is located) generally experience lower incidence of earnings management. I provide further
evidence that the results are robust to alternative measures of religiosity, and that are not driven by firms
headquartered in rural areas. I also conclude that religious social norms, together with other forms of
external financial monitoring, represent a mechanism for reducing costly agency conflicts. While the
religious practice declined in the last decades in Portugal, I provide evidence that, even in a such context,
religiosity is associated with reduced acceptance of unethical business practices, in particular, with reduced
acceptance of aggressive accounting practices.I thank participants of the Second Paris Financial Management Conference (PFMC, 2014) and the 3RD
Workshop on Business Ethics (EIASM, 2015) for their helpful insights.info:eu-repo/semantics/publishedVersio
Journeying with Morrie: challenging notions of professional delivery of spiritual care at the end of life
The spiritual welfare of dying people has in recent years moved from the domain of religion to become the concern of health care professionals, particularly as part of the ideal of holism that underpins palliative care. Professional delivery of spiritual care incorporates the features of assessment, control and treatment which may involve varying degrees of intrusion into the patient's deeply personal inner self. Using a case study approach, this article explores meanings of spirituality and understandings of what is meant by the term 'spiritual care'. It argues that biographical and community approaches to spiritual care of dying people may be more congruent with the concept of the 'whole person' because this support is rooted in an intimate contextual knowledge of the dying person by the caregiver. This challenges the dominant discourses of professional expertise to embrace informal personal and collective competence in this important aspect of end of life care
Hormonal Signal Amplification Mediates Environmental Conditions during Development and Controls an Irreversible Commitment to Adulthood
Many animals can choose between different developmental fates to maximize fitness. Despite the complexity of environmental cues and life history, different developmental fates are executed in a robust fashion. The nematode Caenorhabditis elegans serves as a powerful model to examine this phenomenon because it can adopt one of two developmental fates (adulthood or diapause) depending on environmental conditions. The steroid hormone dafachronic acid (DA) directs development to adulthood by regulating the transcriptional activity of the nuclear hormone receptor DAF-12. The known role of DA suggests that it may be the molecular mediator of environmental condition effects on the developmental fate decision, although the mechanism is yet unknown. We used a combination of physiological and molecular biology techniques to demonstrate that commitment to reproductive adult development occurs when DA levels, produced in the neuroendocrine XXX cells, exceed a threshold. Furthermore, imaging and cell ablation experiments demonstrate that the XXX cells act as a source of DA, which, upon commitment to adult development, is amplified and propagated in the epidermis in a DAF-12 dependent manner. This positive feedback loop increases DA levels and drives adult programs in the gonad and epidermis, thus conferring the irreversibility of the decision. We show that the positive feedback loop canalizes development by ensuring that sufficient amounts of DA are dispersed throughout the body and serves as a robust fate-locking mechanism to enforce an organism-wide binary decision, despite noisy and complex environmental cues. These mechanisms are not only relevant to C. elegans but may be extended to other hormonal-based decision-making mechanisms in insects and mammals
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