936 research outputs found
Hepatic cell mobilization for protection against ischemic myocardial injury
The heart is capable of activating protective mechanisms in response to ischemic injury to support myocardial survival and performance. These mechanisms have been recognized primarily in the ischemic heart, involving paracrine signaling processes. Here, we report a distant cardioprotective mechanism involving hepatic cell mobilization to the ischemic myocardium in response to experimental myocardial ischemiaâreperfusion (MI-R) injury. A parabiotic mouse model was generated by surgical skin-union of two mice and used to induce bilateral MI-R injury with unilateral hepatectomy, establishing concurrent gain- and loss-of-hepatic cell mobilization conditions. Hepatic cells, identified based on the cell-specific expression of enhanced YFP, were found in the ischemic myocardium of parabiotic mice with intact liver (0.2 ± 0.1%, 1.1 ± 0.3%, 2.7 ± 0.6, and 0.7 ± 0.4% at 1, 3, 5, and 10 days, respectively, in reference to the total cell nuclei), but not significantly in the ischemic myocardium of parabiotic mice with hepatectomy (0 ± 0%, 0.1 ± 0.1%, 0.3 ± 0.2%, and 0.08 ± 0.08% at the same time points). The mobilized hepatic cells were able to express and release trefoil factor 3 (TFF3), a protein mitigating MI-R injury as demonstrated in TFF3â/â mice (myocardium infarcts 17.6 ± 2.3%, 20.7 ± 2.6%, and 15.3 ± 3.8% at 1, 5, and 10 days, respectively) in reference to wildtype mice (11.7 ± 1.9%, 13.8 ± 2.3%, and 11.0 ± 1.8% at the same time points). These observations suggest that MI-R injury can induce hepatic cell mobilization to support myocardial survival by releasing TFF3
MigrĂąnea com Aura, Qualidade de Vida e Tratamento: um relato de caso
A migrĂąnea Ă© uma cefaleia primĂĄria de etiologia multifatorial que acomete cerca de 15% da população. Afeta mais as mulheres do que os homens e gera um impacto significativo na qualidade de vida. A crise de cefalĂ©ia migranosa apresenta quatro fases: prodrĂŽmica, de aura, cefalĂ©ia e fase de recuperação. Um plano terapĂȘutico para migrĂąnea inclui tratamento agudo da crise para melhora da dor e do prejuĂzo funcional, e a terapia profilĂĄtica de longo prazo para diminuir a frequĂȘncia, a intensidade e a duração das crises. No presente trabalho, os autores correlacionaram o relato de caso de uma paciente do Hospital UniversitĂĄrio Sul Fluminense com a literatura atual
Centralized Inverted Decoupling Control
This paper presents a new methodology of multivariable centralized control based on the structure of inverted decoupling. The method is presented for general nĂn processes, obtaining very simple general expressions for the controller elements with a complexity independent of the system size. The possible configurations and realizability conditions are stated. Then, the specification of performance requirements is carried out from simple open loop transfer functions for three common cases. As a particular case, it is shown that the resulting controller elements have PI structure or filtered derivative action plus a time delay when the process elements are given by first order plus time delay systems. Comparisons with other works demonstrate the effectiveness of this methodology through the use of several simulation examples and an experimental lab process
Fast response electromagnetic follow-ups from low latency GW triggers
© Published under licence by IOP Publishing Ltd. We investigate joint low-latency gravitational wave (GW) detection and prompt electromagnetic (EM) follow-up observations of coalescing binary neutron stars (BNSs). Assuming that BNS mergers are associated with short duration gamma ray bursts (SGRBs), we evaluate if rapid EM follow-ups can capture the prompt emission, early engine activity or reveal any potential by-products such as magnetars or fast radio bursts. To examine the expected performance of extreme low-latency search pipelines, we simulate a population of coalescing BNSs and use these to estimate the detectability and localisation efficiency at different times before merger. Using observational SGRB flux data corrected to the range of the advanced GW interferometric detectors, we determine what EM observations could be achieved from low-frequency radio up to high energy ?-ray. We show that while challenging, breakthrough multi-messenger science is possible through low latency pipelines
Analyzing the forces binding a restriction endonuclease to DNA using a synthetic nanopore
Restriction endonucleases are used prevalently in recombinant DNA technology because they bind so stably to a specific target sequence and, in the presence of cofactors, cleave double-helical DNA specifically at a target sequence at a high rate. Using synthetic nanopores along with molecular dynamics (MD), we have analyzed with atomic resolution how a prototypical restriction endonuclease, EcoRI, binds to the DNA target sequenceâGAATTCâin the absence of a Mg2+ ion cofactor. We have previously shown that there is a voltage threshold for permeation of DNA bound to restriction enzymes through a nanopore that is associated with a nanonewton force required to rupture the complex. By introducing mutations in the DNA, we now show that this threshold depends on the recognition sequence and scales linearly with the dissociation energy, independent of the pore geometry. To predict the effect of mutation in a base pair on the free energy of dissociation, MD is used to qualitatively rank the stability of bonds in the EcoRIâDNA complex. We find that the second base in the target sequence exhibits the strongest binding to the protein, followed by the third and first bases, with even the flanking sequence affecting the binding, corroborating our experiments
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Author Correction: MiR-31 promotes mammary stem cell expansion and breast tumorigenesis by suppressing Wnt signaling antagonists.
An amendment to this paper has been published and can be accessed via a link at the top of the paper
MiR-31 promotes mammary stem cell expansion and breast tumorigenesis by suppressing Wnt signaling antagonists
MicroRNA-mediated post-transcriptional regulation plays key roles in stem cell self-renewal and tumorigenesis. However, the in vivo functions of specific microRNAs in controlling mammary stem cell (MaSC) activity and breast cancer formation remain poorly understood. Here we show that miR-31 is highly expressed in MaSC-enriched mammary basal cell population and in mammary tumors, and is regulated by NF-ÎșB signaling. We demonstrate that miR-31 promotes mammary epithelial proliferation and MaSC expansion at the expense of differentiation in vivo. Loss of miR-31 compromises mammary tumor growth, reduces the number of cancer stem cells, as well as decreases tumor-initiating ability and metastasis to the lung, supporting its pro-oncogenic function. MiR-31 modulates multiple signaling pathways, including Prlr/Stat5, TGFÎČ and Wnt/ÎČ-catenin. Particularly, it activates Wnt/ÎČ-catenin signaling by directly targeting Wnt antagonists, including Dkk1. Importantly, Dkk1 overexpression partially rescues miR31-induced mammary defects. Together, these findings identify miR-31 as the key regulator of MaSC activity and breast tumorigenesis
Correlation of the leptin:adiponectin ratio with measures of insulin resistance in non-diabetic individuals
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