3,696 research outputs found
A quantitative comparison of sRNA-based and protein-based gene regulation
Small, non-coding RNAs (sRNAs) play important roles as genetic regulators in
prokaryotes. sRNAs act post-transcriptionally via complementary pairing with
target mRNAs to regulate protein expression. We use a quantitative approach to
compare and contrast sRNAs with conventional transcription factors (TFs) to
better understand the advantages of each form of regulation. In particular, we
calculate the steady-state behavior, noise properties, frequency-dependent gain
(amplification), and dynamical response to large input signals of both forms of
regulation. While the mean steady-state behavior of sRNA-regulated proteins
exhibits a distinctive tunable threshold-linear behavior, our analysis shows
that transcriptional bursting leads to significantly higher intrinsic noise in
sRNA-based regulation than in TF-based regulation in a large range of
expression levels and limits the ability of sRNAs to perform quantitative
signaling. Nonetheless, we find that sRNAs are better than TFs at filtering
noise in input signals. Additionally, we find that sRNAs allow cells to respond
rapidly to large changes in input signals. These features suggest a niche for
sRNAs in allowing cells to transition quickly yet reliably between distinct
states. This functional niche is consistent with the widespread appearance of
sRNAs in stress-response and quasi-developmental networks in prokaryotes.Comment: 26 pages, 8 figures; accepted for publication in Molecular Systems
Biolog
COVID-19, SARS and MERS:A neurological perspective
Central to COVID-19 pathophysiology is an acute respiratory infection primarily manifesting as pneumonia. Two months into the COVID-19 outbreak, however, a retrospective study in China involving more than 200 participants revealed a neurological component to COVID-19 in a subset of patients. The observed symptoms, the cause of which remains unclear, included impaired consciousness, skeletal muscle injury and acute cerebrovascular disease, and appeared more frequently in severe disease. Since then, findings from several studies have hinted at various possible neurological outcomes in COVID-19 patients. Here, we review the historical association between neurological complications and highly pathological coronaviruses including SARS-CoV, MERS-CoV and SARS-CoV-2. We draw from evidence derived from past coronavirus outbreaks, noting the similarities and differences between SARS and MERS, and the current COVID-19 pandemic. We end by briefly discussing possible mechanisms by which the coronavirus impacts on the human nervous system, as well as neurology-specific considerations that arise from the repercussions of COVID-19.</p
Assessing Household Solid Fuel Use: Multiple Implications for the Millennium Development Goals
OBJECTIVE: The World Health Organization is the agency responsible for reporting the Millennium Development Goal (MDG) indicator āpercentage of population using solid fuels.ā In this article, we present the results of a comprehensive assessment of solid fuel use, conducted in 2005, and discuss the implications of our findings in the context of achieving the MDGs. METHODS: For 93 countries, solid fuel use data were compiled from recent national censuses or household surveys. For the 36 countries where no data were available, the indicator was modeled. For 52 upper-middle or high-income countries, the indicator was assumed to be < 5%. RESULTS: According to our assessment, 52% of the worldās population uses solid fuels. This percentage varies widely between countries and regions, ranging from 77%, 74%, and 74% in Sub-Saharan Africa, Southeast Asia, and the Western Pacific Region, respectively, to 36% in the Eastern Mediterranean Region, 16% in Latin America and the Caribbean and in Central and Eastern Europe. In most industrialized countries, solid fuel use falls to the < 5% mark. DISCUSSION: Although the āpercentage of population using solid fuelsā is classified as an indicator to measure progress towards MDG 7, reliance on traditional household energy practices has distinct implications for most of the MDGs, notably MDGs 4 and 5. There is an urgent need for development agendas to recognize the fundamental role that household energy plays in improving child and maternal health and fostering economic and social development
Functional central limit theorems for vicious walkers
We consider the diffusion scaling limit of the vicious walker model that is a
system of nonintersecting random walks. We prove a functional central limit
theorem for the model and derive two types of nonintersecting Brownian motions,
in which the nonintersecting condition is imposed in a finite time interval
for the first type and in an infinite time interval for
the second type, respectively. The limit process of the first type is a
temporally inhomogeneous diffusion, and that of the second type is a temporally
homogeneous diffusion that is identified with a Dyson's model of Brownian
motions studied in the random matrix theory. We show that these two types of
processes are related to each other by a multi-dimensional generalization of
Imhof's relation, whose original form relates the Brownian meander and the
three-dimensional Bessel process. We also study the vicious walkers with wall
restriction and prove a functional central limit theorem in the diffusion
scaling limit.Comment: AMS-LaTeX, 20 pages, 2 figures, v6: minor corrections made for
publicatio
Recommended from our members
Influence of subretinal fluid in advanced stage retinopathy of prematurity on proangiogenic response and cell proliferation
Purpose The clinical phenotype of advanced stage retinopathy of prematurity (ROP, stages 4 and 5) cannot be replicated in an animal model. To dissect the molecular events that can lead up to advanced ROP, we examined subretinal fluid (SRF) and surgically dissected retrolental membranes from patients with advanced ROP to evaluate its influences on cell proliferation, angiogenic properties, and macrophage polarity. Methods: We compared our findings to SRF collected from patients with uncomplicated rhegmatogenous retinal detachment (RD) without proliferative vitreoretinopathy and surgically dissected epiretinal membrane from eyes with macular pucker. All subretinal fluid samples were equalized for protein. The angiogenic potential of SRF from ROP eyes was measured using a combination of capillary cord formation in a fibrin clot assay, and its proliferative effect was tested with a DNA synthesis of human retinal microvascular endothelial cells. Findings were compared with SRF collected from participants with uncomplicated rhegmatogenous RD without proliferative vitreoretinopathy. The ability of SRF to induce nitric oxide production was measured in vitro using murine J774A.1 macrophages. Cytokine profiles of SRF from ROP and RD eyes were measured using a multienzyme-linked immunosorbent assay (ELISA). Fluorescent immunohistochemistry of retrolental membranes from ROP was performed to detect the presence of leukocytes and the composition of tissue macrophages using markers for M1 and M2 differentiation. Results: The cytokine composition in SRF revealed that in ROP, not only were several proangiogenic factors were preferentially elevated but also the profile of proinflammatory factors was also increased compared to the RD eyes. SRF from ROP eyes supported cell proliferation and endothelial cord formation while SRF from RD eyes had inhibitory effects. SRF from eyes with ROP but not RD robustly induced nitric oxide production in macrophages. Furthermore, fluorescent immunostaining revealed a preponderance of M1 over M2 macrophages in retrolental fibrous membranes from ROP eyes. The cytokine profile and biologic properties of SRF in ROP promote a proangiogenic environment, which supports the maintenance and proliferation of fibrous membranes associated with advanced stages of ROP. In contrast, SRF from RD eyes exhibits a suppressive environment for endothelial cell proliferation and angiogenesis. Conclusions: Our investigation demonstrates that the microenvironment in advanced ROP eyes is proangiogenic and proinflammatory. These findings suggest that management of advanced ROP should not be limited to the surgical removal of the fibrovascular membranes and antiangiogenic therapy but also directed to anti-inflammatory therapy and to promote M2 activation over M1 activity
40 Years of CSF Toxicity Studies in ALS: What Have We Learnt About ALS Pathophysiology?
AM is a Lady Edith Wolfson Clinical Fellow and is jointly funded by the Medical Research Council (MRC) and the Motor Neurone Disease Association (MR/R001162/1). He also acknowledges support from the Rowling Scholars scheme, administered by the Anne Rowling Regenerative Neurology Clinic (ARRNC), University of Edinburgh, and a seedcorn grant from The Chief Scientist Office and the RS Macdonald Charitable Trust via the Scottish Neurological Research Fund, administered by the University of St Andrews. The Hardingham and Chandran laboratories are supported by the Euan MacDonald Centre for Motor Neurone Disease Research, and the UK Dementia Research Institute (DRI), which receives its funding from UK DRI Ltd., funded by the MRC, Alzheimerās Society and Alzheimerās Research UK.Peer reviewedPublisher PD
- ā¦