Miracle-dz/UniFAR-FTUs huggingface dataset:
Involvement of the cardiac ryanodine receptor/calcium release channel in catecholaminergic polymorphic ventricular tachycardia

The cardiac ryanodine receptor (RyR2), the major calcium release channel on the sarcoplasmic reticulum (SR) in cardiomyocytes, has recently been shown to be involved in at least two forms of sudden cardiac death (SCD): (1) Catecholaminergic polymorphic ventricular tachycardia (CPVT) or familial polymorphic VT (FPVT); and (2) Arrhythmogenic right ventricular dysplasia type 2 (ARVD2). Eleven RyR2 missense mutations have been linked to these diseases. All eleven RyR2 mutations cluster into 3 regions of RyR2 that are homologous to the three malignant hyperthermia (MH)/central core disease (CCD) mutation regions of the skeletal muscle ryanodine receptor/calcium release channel RyR1. MH/CCD RyR1 mutations have been shown to alter calcium‐induced calcium release. Sympathetic nervous system stimulation leads to phosphorylation of RyR2 by protein kinase A (PKA). PKA phosphorylation of RyR2 activates the channel. In conditions associated with high rates of SCD such as heart failure RyR2 is PKA hyperphosphorylated resulting in “leaky” channels. SR calcium leak during diastole can generate “delayed after depolarizations” that can trigger fatal cardiac arrhythmias (e.g., VT). We propose that RyR2 mutations linked to genetic forms of catecholaminergic‐induced SCD may alter the regulation of the channel resulting in increased SR calcium leak during sympathetic stimulation. J. Cell. Physiol. 190: 1–6, 2002. © 2002 Wiley‐Liss, Inc.
Crystal and NMR structures of a Trp-cage mini-protein benchmark for computational fold prediction

To provide high-resolution X-ray crystallographic structures of a peptide with the Trp-cage fold, we prepared a cyclized version of this motif. Cyclized Trp-cage is remarkably stable and afforded two crystal forms suitable for X-ray diffraction. The resulting higher resolution crystal structures validate the prior NMR models and provide explanations for experimental observations that could not be rationalized by NMR structural data, including the structural basis for the increase in fold stability associated with motif cyclization and the manner in which a polar serine side chain is accommodated in the hydrophobic interior. A hexameric oligomer of the cyclic peptide is found in both crystal forms and indicates that under appropriate conditions, this minimized system may also serve as a model for protein–protein interactions.
Digital stereoscopic video system with embedded high resolution images

We developed a stereoscopic video system, which has high-resolution images for central vision and it is called the Q system. The Q system uses a compound image that is a wide-angle image with an embedded high-resolution image. However, the Q system could not be used under situations where many robots work at the same time. This is because it needs four channels of video signals and the available channels could be limited under such situations. Thus, we have developed a digital Q system. The system can be used under such restricted situations, because the required data transfer rate is adjustable by changing the compression rates for a high-resolution image and a wide-angle image. In addition, an experiment confirmed that even though the systems used the same data transfer rate, digital Q system could make teleoperation more efficient and more precise than a conventional stereoscopic video system.
Intrinsic biocontainment: Multiplex genome safeguards combine transcriptional and recombinational control of essential yeast genes

Significance The advance of biotechnology opens up greater possibilities of bioterror and bioerror. Here, we propose multiplexed safeguard switches rooted in the development of foundational genomic, regulatory, and metabolic technologies. Safeguard switches can be regulated by submicromolar small molecule(s) and combined in a modular fashion. The resulting safeguard strains show high fitness and low reversion rates. Moreover, two distinct classes of safeguard switches are orthogonal, providing a potential fail-safe mechanism. The safeguard technologies provide a practical and generic approach to containing engineered microbes within defined laboratory and/or industrial environments, and can in principle be used in the field as well. Biocontainment may be required in a wide variety of situations such as work with pathogens, field release applications of engineered organisms, and protection of intellectual properties. Here, we describe the control of growth of the brewer’s yeast, Saccharomyces cerevisiae, using both transcriptional and recombinational “safeguard” control of essential gene function. Practical biocontainment strategies dependent on the presence of small molecules require them to be active at very low concentrations, rendering them inexpensive and difficult to detect. Histone genes were controlled by an inducible promoter and controlled by 30 nM estradiol. The stability of the engineered genes was separately regulated by the expression of a site-specific recombinase. The combined frequency of generating viable derivatives when both systems were active was below detection (<10−10), consistent with their orthogonal nature and the individual escape frequencies of <10−6. Evaluation of escaper mutants suggests strategies for reducing their emergence. Transcript profiling and growth test suggest high fitness of safeguarded strains, an important characteristic for wide acceptance.
An Atomistic Study of Perfluoropolyether Lubricant Thermal Stability in Heat Assisted Magnetic Recording

At the head disk interface (HDI), the stability of the perfluoropolyether (PFPE) lubricant and carbon overcoat (COC) materials must be preserved under HAMR conditions. In this work, we investigate this issue by comparing the effects of transient versus steady heating of Zdol to replicate the precise pulsed heating of the HAMR system. These effects include changes in intermolecular lubricant bonding, molecular decomposition and desorption. In order to accurately account for potential changes in covalent and intermolecular bonds, we utilize the cutting-edge molecular simulation method of ab initio molecular dynamics. To simulate constant heating, a series of constant temperature simulations are performed at temperatures ranging from 300 K-700 K where the temperature is maintained via the Nose Hoover thermostat. For the transient heating simulations, the temperature is ramped over 100 K intervals with initial temperatures ranging from 300 K to 700 K. These heating studies are performed for bulk PFPE systems as well as PFPE-COC configurations to highlight the effect of PFPE-COC adhesion on lubricant thermal stability at the HDI. In the PFPE-COC simulations, we evaluate the amount of desorption versus decomposition as a function of initial temperature. Through our analysis, we are able to reveal the molecular mechanism of PFPE depletion as a function of functional group composition and, thereby, provide design criteria for lubricant molecular architecture in HAMR applications.
Psychometric Comparison of the PHQ-9 and BDI-II for Measuring Response during Treatment of Depression

The Patient Health Questionnaire-9 Item (PHQ-9) and Beck Depression Inventory–II (BDI-II) are frequently used measures of depression severity, but little is known about their relative psychometric properties. The authors assessed psychometric properties of both measures during treatment for depression. The PHQ-9 and BDI-II scores from 172 depressed participants in two randomized controlled trials of treatment for depression were assessed and combined. Tests of internal consistency (Cronbach's α), factor analyses, correlational analyses, estimates of clinically significant change, and effect sizes (Cohen's d) were calculated after treatment and follow-up. Both scales demonstrated adequate internal consistency at pre- and posttreatment (PHQ-9 α = .74 and .81; BDI-II α = .87 and .90, respectively). Factor analysis failed to confirm the one-factor model previously reported for the PHQ-9, but two factors evidenced good fit for the BDI-II. Both scales converged more with each other than with the Sheehan Disability Scale at pre- but not at posttreatment. Responsiveness to change of PHQ-9 and BDI-II was similar at both posttreatment and follow-up. The consistency of agreement on indices of clinical significance was fair to moderate, but the BDI-II categorised a greater proportion of participants with severe depression than the PHQ-9. The BDI-II and PHQ-9 demonstrated adequate reliability, convergent/discriminant validity, and similar responsiveness to change. Differences were found in how they categorised severity. Pending the results of further studies, the attributes of the PHQ-9, of being shorter and based on the diagnostic criteria for depression, may indicate an advantage over the BDI-II.
Beneficial Effects of Mini-Cardiopulmonary Bypass on Hemostasis in Coronary Artery Bypass Grafting: Analysis of Inflammatory Response and Hemodilution

We compared the inflammatory response, hemodilution, and blood loss in patients who underwent mini-cardiopulmonary bypass (CPB) or conventional CPB during coronary artery bypass grafting (CABG). Ninety-eight consecutive patients with ischemic heart disease were randomly assigned to mini-CPB (n = 34) or conventional CPB (n = 64). Interleukin (IL) −8 and neutrophil elastase levels were measured before and after surgery. Hemodilution during CPB, blood loss during and after surgery were also evaluated. Compared with the conventional group, the mini-CPB group had lower levels of IL-8 on postoperative day 1 (8.3 ± 6.4 vs. 19 ± 11 pg/mL, p = 0.016) and of neutrophil elastase on postoperative days 1 (127 ± 52 vs. 240 ± 100 &mgr;g/L, p = 0.013) and 2 (107 ± 17 vs. 170 ± 45 &mgr;/L, p = 0.0001). The mini-CPB group also has less blood loss during (620 ± 595 vs. 978 ± 658 mL, p = 0.012) and after the operation (578 ± 310 vs. 1,002 ± 651 mL, p = 0.0034) and a hemodilution ratio of 14 ± 2 vs. 25% ± 3%, p < 0.0001. Thus, mini-CPB attenuated the inflammatory response and hemodilution, resulting in blood conservation in patients undergoing CABG.
Individual mediodorsal thalamic neurons project to multiple areas of the rat prefrontal cortex: A single neuron‐tracing study using virus vectors

The prefrontal cortex has an important role in a variety of cognitive and executive processes, and is generally defined by its reciprocal connections with the mediodorsal thalamic nucleus (MD). The rat MD is mainly subdivided into three segments, the medial (MDm), central (MDc), and lateral (MDl) divisions, on the basis of the cytoarchitecture and chemoarchitecture. The MD segments are known to topographically project to multiple prefrontal areas at the population level: the MDm mainly to the prelimbic, infralimbic, and agranular insular areas; the MDc to the orbital and agranular insular areas; and the MDl to the prelimbic and anterior cingulate areas. However, it is unknown whether individual MD neurons project to single or multiple prefrontal cortical areas. In the present study, we visualized individual MD neurons with Sindbis virus vectors, and reconstructed whole structures of MD neurons. While the main cortical projection targets of MDm, MDc, and MDl neurons were generally consistent with those of previous results, it was found that individual MD neurons sent their axon fibers to multiple prefrontal areas, and displayed various projection patterns in the target areas. Furthermore, the axons of single MD neurons were not homogeneously spread, but were rather distributed to form patchy axon arbors approximately 1 mm in diameter. The multiple‐area projections and patchy axon arbors of single MD neurons might be able to coactivate cortical neuron groups in distant prefrontal areas simultaneously. Furthermore, considerable heterogeneity of the projection patterns is likely, to recruit the different sets of cortical neurons, and thus contributes to a variety of prefrontal functions. J. Comp. Neurol. 525:166–185, 2017. © 2016 Wiley Periodicals, Inc.
Community Leaders' Perceptions of Single, Low-Income Mothers' Needs and Concerns for Social Support

Purposes of this study were to (a) assess and describe needs and concerns of single, low-income mothers during their transition to parenthood from the perspective of 16 Midwestern community leaders working closely with families and (b) evaluate social support mechanisms that are available for families. Focus group questions were organized around social support theory to gather information. The following themes evolved from focus group discussions: (a) social support issues (emotional, tangible, informational, and appraisal support; positive and negative support); (b) personal barriers to success (stress, low self-esteem, isolation, and inadequate parenting competence); and (c) system barriers (fear of the system and insensitive and ineffective services). Community health nursing strategies were identified that include assessment and interventions for this vulnerable population throughout their infants' 1st year of life and beyond.
Exploring Health and Social Exclusion Within Hidden Homeless

Homelessness and poverty are extreme forms of social exclusion which extend beyond the lack of physical or material needs. Using Brunner and Marmot’s social determinants of health model (1999, 2004), this secondary analysis explored the everyday living conditions of a hidden homeless population. The purpose of this study was to explore and expand the understanding of the physical, psychological and social health impacts associated with material and social deprivation. The study aimed to expand the concept of social exclusion within the social determinants of health perspective. Health professionals who understand health behaviours as coping mechanisms for poor quality social environments can provide more comprehensive and holistic care. The findings of this study should be used to show that the need for a national housing policy is a key factor in the health and well being of people who experience poverty, homelessness and social exclusion. SOCIAL DETERMINANTS OF HEALTH v
Fibroblast growth factor‐2 deficiency affects hippocampal spine morphology, but not hippocampal catecholaminergic or cholinergic innervation

The availability of fibroblast growth factor‐2 (FGF‐2) ‐deficient mice has permitted studying the role of endogenous FGF‐2. Several studies have reported that neocortical but not hippocampal neurons are lost in FGF‐2–deficient mice. Here, we show that neuronal densities within the basolateral amygdala are unaltered in FGF‐2−/− mice. Moreover, we provide evidence that FGF‐2 mutant mice display no obvious alterations in the catecholaminergic or cholinergic innervation of the hippocampus. With regard to the formation of dendritic spines, our studies reveal that endogenous FGF‐2 is not essential for hippocampal spinogenesis; however, FGF‐2 affects the length of individual spines. Such alterations in spine morphology may be related to disturbances in mental capacities or alterations in neuronal plasticity. Of interest, in this context, animal models of mental retardation develop no alterations in hippocampal spine densities, but display higher numbers of long dendritic spines. Thus, FGF‐2 may also affect learning and memory by altering spine morphology. Developmental Dynamics 238:343–350, 2009. © 2009 Wiley‐Liss, Inc.
Construction of a dictionary of sequence motifs that characterize groups of related proteins

Abstract An automatic procedure is proposed to identify, from the protein sequence database, conserved amino acid patterns (or sequence motifs) that are exclusive to a group of functionally related proteins. This procedure is applied to the PIR database and a dictionary of sequence motifs that relate to specific superfamilies constructed. The motifs have a practical relevance in identifying the membership of specific superfamilies without the need to perform sequence database searches in 20% of newly determined sequences. The sequence motifs identified represent functionally important sites on protein molecules. When multiple blocks exist in a single motif they are often close together in the 3-D structure. Furthermore, occasionally these motif blocks were found to be split by introns when the correlation with exon structures was examined.
Voltage Gated Ion Channel Function: Gating, Conduction, and the Role of Water and Protons

Ion channels, which are found in every biological cell, regulate the concentration of electrolytes, and are responsible for multiple biological functions, including in particular the propagation of nerve impulses. The channels with the latter function are gated (opened) by a voltage signal, which allows Na+ into the cell and K+ out. These channels have several positively charged amino acids on a transmembrane domain of their voltage sensor, and it is generally considered, based primarily on two lines of experimental evidence, that these charges move with respect to the membrane to open the channel. At least three forms of motion, with greatly differing extents and mechanisms of motion, have been proposed. There is a “gating current”, a capacitative current preceding the channel opening, that corresponds to several charges (for one class of channel typically 12–13) crossing the membrane field, which may not require protein physically crossing a large fraction of the membrane. The coupling to the opening of the channel would in these models depend on the motion. The conduction itself is usually assumed to require the “gate” of the channel to be pulled apart to allow ions to enter as a section of the protein partially crosses the membrane, and a selectivity filter at the opposite end of the channel determines the ion which is allowed to pass through. We will here primarily consider K+ channels, although Na+ channels are similar. We propose that the mechanism of gating differs from that which is generally accepted, in that the positively charged residues need not move (there may be some motion, but not as gating current). Instead, protons may constitute the gating current, causing the gate to open; opening consists of only increasing the diameter at the gate from approximately 6 Å to approximately 12 Å. We propose in addition that the gate oscillates rather than simply opens, and the ion experiences a barrier to its motion across the channel that is tuned by the water present within the channel. Our own quantum calculations as well as numerous experiments of others are interpreted in terms of this hypothesis. It is also shown that the evidence that supports the motion of the sensor as the gating current can also be consistent with the hypothesis we present.
Productive and nonproductive binding to ribonuclease A: X‐ray structure of two complexes with uridylyl(2′,5′)guanosine

Guanine‐containing mono‐ and dinucleotides bind to the active site of ribonuclease A in a nonproductive mode (retro‐binding) (Aguilar CF, Thomas PJ, Mills A, Moss DS, Palmer RA, 1992, J Mol Biol 224:265‐267). Guanine binds to the highly specific pyrimidine site by forming hydrogen bonds with Thr45 and with the sulfate anion located in the P1 site. To investigate the influence of the anion present in the P1 site on retro‐binding, we determined the structure of two new complexes of RNase A with uridylyl(2′,5′)guanosine obtained by soaking two different forms of pre‐grown RNase A crystals. In one case, RNase A was crystallized without removing the sulfate anion strongly bound to the active site; in the other, the protein was first equilibrated with a basic solution to displace the anion from the P1 site. The X‐ray structures of the complexes with and without sulfate in P1 were refined using diffraction data up to 1.8 Å (R‐factor 0.192) and 2.0 Å (R‐factor 0.178), respectively. The binding mode of the substrate analogue to the protein differs markedly in the two complexes. When the sulfate is located in P1, we observe retro‐binding; whereas when the anion is removed from the active site, the uridine is productively bound at the B1 site. In the productive complex, the electron density is very well defined for the uridine moiety, whereas the downstream guanine is disordered. This finding indicates that the interactions of guanine in the B2 site are rather weak and that this site is essentially adenine preferring. In this crystal form, there are two molecules per asymmetric unit, and due to crystal packing, only the active site of one molecule is accessible to the ligand. Thus, in the same crystal we have a ligand‐bound and a ligand‐free RNase A molecule. The comparison of these two structures furnishes a detailed and reliable picture of the structural alterations induced by the binding of the substrate. These results provide structural information to support the hypotheses on the role of RNase A active site residues that have recently emerged from site‐directed mutagenesis studies.
Global health, foreign policy, and agenda setting processes : the European Union as a global health actor

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Evaluation of photoscreener instruments in a childhood population. 1. Otago photoscreener and Dortmans videophotorefractor.

OBJECTIVE To evaluate two photoscreeners in a childhood population. STUDY DESIGN Double-masked study. SUBJECTS AND METHOD One hundred and thirteen children aged between 11 and 44 months with either normal vision or known visual disorders were photoscreened without cycloplegia by the Otago and Dortmans (prototype) photoscreeners. Each child had a full ophthalmological examination either on the day of screening or in the proceeding six months. Photoscreen images were reviewed by an independent observer for indicators of amblyopiogenic risk factors, and compared to the full ophthalmological examination to determine sensitivity and specificity for each instrument. RESULTS The Otago photoscreener returned a sensitivity of 70% and specificity of 82% for the detection of amblyopiogenic risk factors. The Dortmans photoscreener returned a sensitivity of 70% and specificity of 90%. Both photoscreeners were portable and easily operated. CONCLUSION Children can be screened successfully for amblyopiogenic risk factors with these photoscreening systems. Further evaluation is required to determine specificity in a normal population. This would also provide information on the potential usefulness of photoscreeners in a cost effective childhood vision screening program.
Expression of an Activation Antigen, Mo3e, Associated With the Cellular Response to Migration Inhibitory Factor by HL‐60 Promyelocytes Undergoing Monocyte‐Macrophage Differentiation

HL‐60 promyelocytic cells acquire the surface expression of the Mo3e antigenic determinant after exposure to PMA or compounds that raise intracellular concentrations of cyclic AMP (dibutyryl cyclic AMP or a combination of cholera toxin and IBMX). The expression of Mo3e by these stimulated HL‐60 cells coincides with the development of features of monocyte‐macrophage differentiation (characteristic morphology, nonspecific esterase activity, and respiratory burst activity). During in vitro monocyte‐macrophage differentiation, HL‐60 cells become responsive to migration inhibitory factor (MIF); the MIF responsiveness of differentiated HL‐60 cells is blocked by anti‐Mo3e monoclonal antibody. These findings further support the relationship between the expression of Mo3e and the cellular response to MIF.