Miracle-dz/UniFAR-FTUs huggingface dataset:
Modulation of Ca2+‐dependent intercellular adhesion in bovine aortic and human umbilical vein endothelial cells by heparin‐binding growth factors

Cultured endothelial cells have been shown to possess two mechanisms of intercellular adhesion: Ca2+‐dependent and Ca2+‐independent. We report here that growth of bovine aortic endothelial cells (BAEC) in complete medium containing purified basic fibroblast growth factor (bFGF, 6 ng/ml) results in loss of Ca2+‐dependent intercellular adhesion. In the presence of heparin (90 μg/ml), this effect is reproduced upon treatment with acidic fibroblast growth factor (aFGF, 6 ng/ml) or endothelial cell growth supplement (ECGS, 100 μg/ml), in both human umbilical vein endothelial cells (HUVEC) and BAEC. Treatment at these doses with aFGF in the absence of heparin or with heparin alone is without significant effect. Loss of Ca2+‐dependent adhesion following treatment of cells with heparin‐binding growth factors (HBGFs) is prevented by pre‐treatment of cell layers with cycloheximide. The Ca2+‐independent adhesion mechanism is unaffected by HBGF treatment. Exposure of endothelial cells to HBGFs, moreover, prevents the eventual establishment of quiescence in growing cultures and restimulates replication in confluent cultures that have reached a final density‐inhibited state. Addition of bFGF alone or aFGF + heparin at these doses results in a 4‐fold increase in DNA synthesis over untreated control cultures at saturation density as reflected by thymidine index. A single addition of bFGF (6 ng/ml) to untreated quiescent confluent BAEC monolayers results in an increase in 3H‐TdR incorporation reaching a peak at 22 hours with a parallel loss of Ca2+‐dependent adhesiveness. Fluorescent staining with rhodamine‐phalloidin demonstrates an altered distribution of polymerized F‐actin in the bFGF‐treated monolayers, marked by disruption of the dense peripheral microfilament bands retained by untreated confluent monolayers. Together, these results indicate that the mitogenic effect of HBGFs in cultured endothelial cells is associated with a “morphogenic” set of responses, perhaps dependent on breakdown of calcium‐dependent cell‐cell contacts.
Identification of differentially transcribed genes in human lymphoblastoid cells irradiated with 0.5 Gy of γ-ray and the involvement of low dose radiation inducible CHD6 gene in cell proliferation and radiosensitivity

Purpose: To identify candidate genes specifically involved in response to low-dose irradiation in human lymphoblastoid cells; to better clarify the role of the human chromodomain helicase DNA binding protein 6 gene (CHD6), one of these genes, in cell proliferation and radiosensitivity. Materials and methods: DNA microarray technology was used to analyse global transcriptional profile in human lymphoblastoid AHH-1 cells at 4 h after exposure to 0.5 Gy of γ-ray. Gene expression changes were confirmed by semi-quantitative reverse transcription – polymerase chain reaction (RT-PCR) and Northern blot. RNA interfering technology was employed to knock-down the CHD6 gene in A549 cells. Colony-forming ability was used to analyse radiosensitivity. Results: The microarray assay revealed a set of 0.5 Gy-responsive genes, including 30 up-regulated genes and 45 down-regulated genes. The up-regulated genes include a number of genes involved in: signal transduction pathways, e.g., STAT3, CAMKK2, SIRT1, CREM, MAPK3K7IP2 and GPR56; transcription or DNA-binding, e.g., CHD6, CRSP3, SNURF, SH2 domain binding protein 1 and MIZF. Some of the down-regulated genes are involved in: cytoskeleton and cell movement (WASF2, LCP1, MSN, NIPSNAP1, KIF2C); DNA replication and repair (MCM2, MCM3, MCM7 and XRCC-4). Radiation-increased expression of CHD6 was also found in A549 cells and HeLa cells. The sustained CHD6 induction was restricted to relatively low doses (0.2 Gy or 0.5 Gy), no change occurring after 4 Gy irradiation. Silencing of CHD6 mediated by siRNA increased the growth rate of A549 cells by 40 ∼ 60%. Most importantly, silencing CHD6 led to an increased radioresistance of A459 cells to radiation doses up to 2 Gy, but barely affected the sensitivity of cells at 4 and 8 Gy. Conclusion: This study has identified a set of genes responsive to 0.5 Gy of γ-rays. CDH6 gene can be specifically up-regulated by low dose irradiation, and its inducible expression could be involved in a low dose hypersensitive response.
Optimized temperature and deadspace correction improve analysis of multiple breath washout measurements by ultrasonic flowmeter in infants

Assessment of lung volume (FRC) and ventilation inhomogeneities with ultrasonic flowmeter and multiple breath washout (MBW) has been used to provide important information about lung disease in infants. Sub‐optimal adjustment of the mainstream molar mass (MM) signal for temperature and external deadspace may lead to analysis errors in infants with critically small tidal volume changes during breathing.
Expression and distribution of octopus gonadotropin‐releasing hormone in the central nervous system and peripheral organs of the octopus (Octopus vulgaris) by in situ hybridization and immunohistochemistry

We recently purified a peptide with structural features similar to vertebrate gonadotropin‐releasing hormone (GnRH) from the brain of Octopus vulgaris, cloned a cDNA encoding the precursor protein, and named it oct‐GnRH. In the current study, we investigated the expression and distribution of oct‐GnRH throughout the central nervous system (CNS) and peripheral organs of Octopus by in situ hybridization on the basis of the cDNA sequence and by immunohistochemistry using a specific antiserum against oct‐GnRH. Oct‐GnRH mRNA‐expressing cell bodies were located in 10 of 19 lobes in the supraesophageal and subesophageal parts of the CNS. Several oct‐GnRH–like immunoreactive fibers were seen in all the neuropils of the CNS lobes. The sites of oct‐GnRH mRNA expression and the mature peptide distribution were consistent with each other as judged by in situ hybridization and immunohistochemistry. In addition, many immunoreactive fibers were distributed in peripheral organs such as the heart, the oviduct, and the oviducal gland. Modulatory effects of oct‐GnRH on the contractions of the heart and the oviduct were demonstrated. The results suggested that, in the context of reproduction, oct‐GnRH is a key peptide in the subpedunculate lobe and/or posterior olfactory lobe–optic gland–gonadal axis, an octopus analogue of the hypothalamo–hypophysial–gonadal axis. It may also act as a modulatory factor in controlling higher brain functions such as feeding, memory, movement, maturation, and autonomic functions. J. Comp. Neurol. 477:310–323, 2004. © 2004 Wiley‐Liss, Inc.
Evidence-based medicine and myocardial protection — where is the evidence?

Objective: Myocardial protection with cardioplegia is an integral component of most cardiac surgical procedures, providing protection of the heart by limiting metabolic activity and increasing the myocardium’s capacity to withstand ischemia for prolonged periods of time. Cardioplegia has greatly affected the landscape of cardiothoracic surgery since its introduction in the 1960s, but, to this day, there continues to be a debate over what the ideal cardioplegic solution should be. The goal of this analysis is to describe current practices in cardioplegia and to point out the lack of quality human research and subsequent publications that prevent best practices from being utilized. Methods: This study is a systematic review of journal publications pertaining to the composition of commonly used cardioplegic solutions. Four main types of cardioplegia were assessed to give a narrower field of examination; specifically, microplegia, del Nido, Custodiol HTK, and 4:1 blood cardioplegia. Other combinations of cardioplegia, including St. Thomas’s Solution and the University of Wisconsin (UW) Solution, were considered when applicable according to the context of the publication being reviewed. Factors being assessed consisted of scientific validity, nature of the test subject (isolated organ vs. animal vs. human studies), experimental setup (retrospective trials vs. randomized clinical trials) and patient outcomes. Results: There are very few randomized clinical trials with human subjects comparing commonly used cardioplegic solutions. Numerous retrospective studies exist, but often show similar intraoperative and postoperative outcomes between the solutions. Some solutions, del Nido cardioplegia in particular, were found to have few or no significant human trials to back the rigor required in such a highly specialized field as cardiovascular surgery. A wide variation in the types of surgeries and primary outcomes were included in the publications, so it is difficult to perform an accurate systematic review of the topic. Conclusion: Uniform variables among different studies would be preferable for analysis of this topic; thus, it is the researchers’ recommendation that the collection of multicenter data be undertaken in order to more fully answer this research question. Comparative effectiveness studies to associate commonly used solutions are needed. Without this research, surgeon preference remains the primary determining factor for deciding which cardioplegic solution to use. Cardioplegia selection should rely more on higher scientific research, using evidenced-based medicine and ranking of clinical studies.
A Systematic Overview of Radiation Therapy Effects in Non-Small Cell Lung Cancer

A systematic review of radiation therapy trials in several tumour types was performed by The Swedish Council of Technology Assessment in Health Care (SBU). The procedures for evaluation of the scientific literature are described separately (Acta Oncol 2003; 42: 357-365). This synthesis of the literature on radiation therapy for non-small cell lung cancer (NSCLC) is based on data from 4 meta-analyses and 31 randomized trials. Moreover, data from 12 prospective studies, 12 retrospective studies and 6 other articles were used. In toal, 65 scientific articles are included, involving 18 310 patients. The results were compared with those of a similar overview from 1996 including 28 172 patients. The conclusions reached can be summarized as follows: <list id="l1" type="5"> <item>Extensive clinical experience indicates that radiotherapy for medically inoperable patients or patients refusing surgery with NSCLC stage I/II prolongs survival, 15-20% of these patients reaching long-term (5-year) survival. However, no randomized trials have addressed this issue. </item><item>There is strong evidence that postoperative radiotherapy in radically resected stage I/II NSCLC does not prolong survival compared with observation alone. </item><item>There is some evidence that continuous hyperfractionated accelerated radiotherapy (CHART) is associated with increased survival compared to conventional radiotherapy in locally advanced NSCLC and also in medically unfit patients with stage I/II NSCLC. However, the benefit is limited to squamous cell histology. </item><item>There is strong evidence that combined modality treatment with platinum-based chemotherapy and radiotherapy, either neoadjuvant or concomitant, is superior to radiotherapy alone in terms of survival in locally advanced unresectable NSCLC and should be the standard of care in patients with good performance status. </item><item>There is some evidence that concomitant chemo-radiotherapy is associated with increased survival compared with sequential chemo-radiotherapy, albeit at the price of increased toxicity. </item></list> Comment: Combined chemo-radiotherapy of primary non-resectable stage III NSCLC followed by surgery in responders lacks evidence from prospective randomized trials and cannot be recommended for routine use. <list id="l2" type="5"> <item>There is strong evidence that radiotherapy can palliate symptoms associated with the intrathoracic tumour burden. </item><item>There is some evidence that two large fractions may be as effective as conventional schedules consisting of 10-13 smaller fractions in terms of palliation of symptoms. </item><item>There is some evidence that endobronchial brachytherapy for palliation of symptoms associated with endobronchial tumours is not superior to external beam radiotherapy. </item></list>
Compulsive Social Behavior Emerges after Selective Ablation of Striatal Cholinergic Interneurons

The mechanisms underlying social dysfunction in neuropsychiatric conditions such as obsessive-compulsive disorder and Tourette syndrome remain uncertain. However, it is known that dysfunctions in basal ganglia, including a reduced number of striatal cholinergic interneurons (SCIN), are involved in their pathophysiology. To explore the role of SCIN in relation to perseverative behaviors, we characterized a new transgenic mouse model in which inducible ablation of SCIN is achieved with high efficiency in a cell-type- and region-specific manner. Mice were subjected to extensive behavioral testing, including assessment of social behaviors, and corticostriatal functional connectivity was evaluated in vivo. Selective SCIN ablation leads to altered social interactions together with exacerbated spontaneously emitted repetitive behaviors. Lesioned mice showed normal motor coordination, balance, and general locomotion. Interestingly, only environmentally driven, but not self-directed, repetitive behaviors were exacerbated in lesioned mice. Remarkably, in mice with SCIN ablation, the normal pattern of social exploration was replayed continuously. The emerging pattern of social interactions is highly predictable and invariant across time. In vivo electrophysiological recordings indicate that SCIN ablation results in an increase of the functional connectivity between different cortical areas and the motor, but not associative, region of the striatum. Our results identify a role of SCIN in suppressing perseverative behaviors, including socially related ones. In sum, SCIN ablation in mice leads to exacerbated ritualistic-like behaviors that affect social performance, providing a link between SCIN dysfunction and the social impairments present in psychiatric disorders. SIGNIFICANCE STATEMENT We sought to uncover the impact of striatal cholinergic interneuron (SCIN) degeneration on perseverative behaviors related to obsessive-compulsive disorder (OCD) and Tourette syndrome (TS). We found that extensive SCIN ablation results in exacerbated social interactions, in which normal social contacts were replayed continuously in a highly stereotyped, ritualistic pattern. SCIN ablation also leads to an increase in other spontaneously emitted repetitive behaviors without alteration of motor coordination, balance, or locomotion. Moreover, we identify an increase of functional connectivity between frontal cortical areas and the motor region of the striatum as a putative substrate for the observed behavioral alterations. Therefore, perseveration induced by SCIN ablation extends to social performance as occurs in neuropsychiatric conditions such as OCD and TS.
Comparative analysis of Gata3 and Gata2 expression during chicken inner ear development

The inner ear is a complex sensory organ with hearing and balance functions. Gata3 and Gata2 are expressed in the inner ear, and to gain more insight into their roles in otic development, we made a detailed expression analysis in chicken embryos. At early stages, their expression was highly overlapping. At later stages, Gata2 expression became prominent in vestibular and cochlear nonsensory epithelia. In contrast to Gata2, Gata3 was mainly expressed in the developing sensory epithelia, reflecting the importance of this factor in the sensory–neural development of the inner ear. While the later expression patterns of both Gata3 and Gata2 were highly conserved between chicken and mouse, important differences were observed especially with Gata3 during early otic development, providing indications of divergent molecular control during placode invagination in mice and chickens. We also found indications that the regulatory hierarchy observed in mouse, where Gata3 is upstream of Gata2 and Fgf10, could be conserved in chicken. Developmental Dynamics 236:306–313, 2007. © 2006 Wiley‐Liss, Inc.
Impact on postoperative bleeding and cost of recombinant activated factor VII in patients undergoing heart transplantation

Background: Cardiac transplantation can be complicated by refractory hemorrhage particularly in cases where explantation of a ventricular assist device is necessary. Recombinant activated factor VII (rFVIIa) has been used to treat refractory bleeding in cardiac surgery patients, but little information is available on its efficacy or cost in heart transplant patients. Methods: Patients who had orthotopic heart transplantation between January 2009 and December 2014 at a single center were reviewed. Postoperative bleeding and the total costs of hemostatic therapies were compared between patients who received rFVIIa and those who did not. Propensity scores were created and used to control for the likelihood of receiving rFVIIa in order to reduce bias in our risk estimates. Results: Seventy-six patients underwent heart transplantation during the study period. Twenty-one patients (27.6%) received rFVIIa for refractory intraoperative bleeding. There was no difference in postoperative red blood cell transfusion, chest tube output, or surgical re-exploration between patients who received rFVIIa and those who did not, even after adjusting with the propensity score (P = 0.94, P = 0.60, and P = 0.10, respectively). The total cost for hemostatic therapies was significantly higher in the rFVIIa group (median $10,819 vs. $1,985; P < 0.0001). Subgroup analysis of patients who underwent redo-sternotomy with left ventricular assist device explantation did not show any benefit for rFVIIa either. Conclusions: In this relatively small cohort, rFVIIa use was not associated with decreased postoperative bleeding in patients undergoing heart transplantation; however, it led to significantly higher cost.
The Inflammation-associated Protein TSG-6 Cross-links Hyaluronan via Hyaluronan-induced TSG-6 Oligomers

Tumor necrosis factor-stimulated gene-6 (TSG-6) is a hyaluronan (HA)-binding protein that plays important roles in inflammation and ovulation. TSG-6-mediated cross-linking of HA has been proposed as a functional mechanism (e.g. for regulating leukocyte adhesion), but direct evidence for cross-linking is lacking, and we know very little about its impact on HA ultrastructure. Here we used films of polymeric and oligomeric HA chains, end-grafted to a solid support, and a combination of surface-sensitive biophysical techniques to quantify the binding of TSG-6 into HA films and to correlate binding to morphological changes. We find that full-length TSG-6 binds with pronounced positive cooperativity and demonstrate that it can cross-link HA at physiologically relevant concentrations. Our data indicate that cooperative binding of full-length TSG-6 arises from HA-induced protein oligomerization and that the TSG-6 oligomers act as cross-linkers. In contrast, the HA-binding domain of TSG-6 (the Link module) alone binds without positive cooperativity and weaker than the full-length protein. Both the Link module and full-length TSG-6 condensed and rigidified HA films, and the degree of condensation scaled with the affinity between the TSG-6 constructs and HA. We propose that condensation is the result of protein-mediated HA cross-linking. Our findings firmly establish that TSG-6 is a potent HA cross-linking agent and might hence have important implications for the mechanistic understanding of the biological function of TSG-6 (e.g. in inflammation).
The Dbf4-Cdc7 Kinase Promotes Mcm2-7 Ring Opening to Allow for Single-stranded DNA Extrusion and Helicase Assembly*

Background: The Dbf4-Cdc7 kinase activates DNA replication, and the helicase is composed of Cdc45, Mcm2-7, and GINS. Results: Dbf4-Cdc7 phosphorylation of Mcm2 is required in vivo for DNA replication, single-stranded DNA accumulation, and GINS-Mcm2-7 interaction. Conclusion: The Dbf4-Cdc7 kinase promotes Mcm2-7 ring opening to allow for origin melting and helicase assembly. Significance: A mechanism for Dbf4-Cdc7 action is described. The replication fork helicase in eukaryotes is composed of Cdc45, Mcm2-7, and GINS (CMG). The Dbf4-Cdc7 kinase phosphorylates Mcm2 in vitro, but the in vivo role for Dbf4-Cdc7 phosphorylation of Mcm2 is unclear. We find that budding yeast Dbf4-Cdc7 phosphorylates Mcm2 in vivo under normal conditions during S phase. Inhibiting Dbf4-Cdc7 phosphorylation of Mcm2 confers a dominant-negative phenotype with a severe growth defect. Inhibiting Dbf4-Cdc7 phosphorylation of Mcm2 under wild-type expression conditions also results in impaired DNA replication, substantially decreased single-stranded formation at an origin, and markedly disrupted interaction between GINS and Mcm2-7 during S phase. In vitro, Dbf4-Cdc7 kinase (DDK) phosphorylation of Mcm2 substantially weakens the interaction between Mcm2 and Mcm5, and Dbf4-Cdc7 phosphorylation of Mcm2 promotes Mcm2-7 ring opening. The extrusion of ssDNA from the central channel of Mcm2-7 triggers GINS attachment to Mcm2-7. Thus, Dbf4-Cdc7 phosphorylation of Mcm2 may open the Mcm2-7 ring at the Mcm2-Mcm5 interface, allowing for single-stranded DNA extrusion and subsequent GINS assembly with Mcm2-7.
Resting energy expenditure is not increased in mildly hyperglycaemic obese diabetic patients

Resting energy expenditure (REE) is believed to be increased in type 2 diabetes, an increase that is associated with deteriorating glucose tolerance during its development. Meanwhile, insulin resistance, a state linked to obesity and observed in all type 2 diabetic patients, is associated with reduced REE. Our aim was to compare REE in obese patients with and without diabetes. REE, body composition (total body water, density, percentage fat and fat-free mass: 3-compartment model) and metabolic control were assessed in fifty obese Caucasian patients with diabetes (glycated haemoglobin level 7·6 (sd 1·5) %) and fifty obese patients who were non-diabetic. Despite being more overweight and younger, obese non-diabetic patients had an absolute REE (7·73 (sd 1·44) v. 8·12 (sd 1·37) MJ; P=0·17) and percentage fat-free mass similar to those of obese diabetic patients. Even when adjusted for differences in body composition, REE remained similar in both groups. Furthermore, REE (absolute and adjusted) was unaffected by both glucose level and control (glycated haemoglobin), with fat-free mass being the only determinant of REE. We conclude that REE is not necessarily increased by the presence of diabetes in obese people.
A new space vector modulation strategy to reduce common-mode voltage for quasi-Z-source indirect matrix converter

A new space vector modulation (SVM) strategy is proposed for quasi-Z-source indirect matrix converter (QZS-IMC) to reduce common-mode voltage and to ensure a high voltage transfer ratio. QZS-IMC's common-mode voltage is analyzed, and the subdivided sectors are employed to rearrange switching sequence in the inverter stage, which can reduce common-mode voltage and power loss. The proposed modulation method mitigates the peak value of common-mode voltage by 42% and reduces the switching losses in the inverter stage. Experimental results verify the proposed method.