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 ischemia–reperfusion (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 TFF3−/− 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

Migrânea com Aura, Qualidade de Vida e Tratamento: um relato de caso

A migrânea é uma cefaleia primária 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 cefaléia migranosa apresenta quatro fases: prodrômica, de aura, cefaléia e fase de recuperação. Um plano terapêutico para migrânea inclui tratamento agudo da crise para melhora da dor e do prejuízo funcional, e a terapia profilática de longo prazo para diminuir a frequência, a intensidade e a duração das crises. No presente trabalho, os autores correlacionaram o relato de caso de uma paciente do Hospital Universitário 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 n×n 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

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 sequence—GAATTC—in 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 EcoRI–DNA 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

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

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-κB 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, TGFβ and Wnt/β-catenin. Particularly, it activates Wnt/β-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

αV Integrin Induces Multicellular Radioresistance in Human Nasopharyngeal Carcinoma via Activating SAPK/JNK Pathway

BACKGROUND:Tumor cells acquire the capacity of resistance to chemotherapy or radiotherapy via cell-matrix and cell-cell crosstalk. Integrins are the most important cell adhesion molecules, in which αV integrin mainly mediating the tight contact between tumor cells. METHODOLOGY/PRINCIPAL FINDINGS:To investigate the role of αV integrin in multi-cellular radioresistance (MCR) of human nasopharyngeal carcinoma (NPC), we performed immunohistochemistry and Western blotting to find that the expression of αV integrin in the tumor tissue of radioresistant patients is much higher than that in radiosensitive patients. In vitro, we cultured human NPC cell line CNE-2 cells as multi-cellular spheroids (MCSs) or as monolayer cells (MCs), and found that the expression of αV integrin in MCSs is significantly higher than that in MCs. MTT, flow cytometry and clonogenic survival assays showed that MCSs are less sensitive to X-ray irradiation than MCs while blocking of αV integrin in MCSs dramatically reversed their radioresistance. Furthermore, as detected by Western blotting, MCSs displayed sustained activation of the stress-activated protein kinase/c-Jun NH2-terminal kinase (SAPK/JNK) pathway in presence of irradiation. Blocking of αV integrin in MCSs decreased the expression of phosphorylated JNK. Additionally, blocking of SAPK/JNK signaling pathway synergistically induced apoptosis of MCSs exposed to irradiation by increasing the expression of cleaved caspase-3. In vivo, we found that irradiation combined with αV integrin blocking treatment significantly enhanced the radiosensitivity of NPC xenografts. CONCLUSIONS:Our results indicate a novel role of αV integrin in multi-cellular radioresistance of NPCs