Miracle-dz/UniFAR-FTUs huggingface dataset:
The ε Subunit of DNA Polymerase III Is Involved in the Nalidixic Acid-Induced SOS Response in Escherichia coli

ABSTRACT Quinolone antibacterial drugs such as nalidixic acid target DNA gyrase in Escherichia coli. These inhibitors bind to and stabilize a normally transient covalent protein-DNA intermediate in the gyrase reaction cycle, referred to as the cleavage complex. Stabilization of the cleavage complex is necessary but not sufficient for cell killing—cytotoxicity apparently results from the conversion of cleavage complexes into overt DNA breaks by an as-yet-unknown mechanism(s). Quinolone treatment induces the bacterial SOS response in a RecBC-dependent manner, arguing that cleavage complexes are somehow converted into double-stranded breaks. However, the only proteins known to be required for SOS induction by nalidixic acid are RecA and RecBC. In hopes of identifying additional proteins involved in the cytotoxic response to nalidixic acid, we screened for E. coli mutants specifically deficient in SOS induction upon nalidixic acid treatment by using a dinD::lacZ reporter construct. From a collection of SOS partially constitutive mutants with disruptions of 47 different genes, we found that dnaQ insertion mutants are specifically deficient in the SOS response to nalidixic acid. dnaQ encodes DNA polymerase III ε subunit, the proofreading subunit of the replicative polymerase. The deficient response to nalidixic acid was rescued by the presence of the wild-type dnaQ gene, confirming involvement of the ε subunit. To further characterize the SOS deficiency of dnaQ mutants, we analyzed the expression of several additional SOS genes in response to nalidixic acid using real-time PCR. A subset of SOS genes lost their response to nalidixic acid in the dnaQ mutant strain, while two tested SOS genes (recA and recN) continued to exhibit induction. These results argue that the replication complex plays a role in modulating the SOS response to nalidixic acid and that the response is more complex than a simple on/off switch.
Synchrotron- and laboratory-based X-ray phase-contrast imaging for imaging mouse articular cartilage in the absence of radiopaque contrast agents

The mouse model of osteoarthritis (OA) has been recognized as the most promising research tool for the identification of new OA therapeutic targets. However, this model is currently limited by poor throughput, dependent on the extremely time-consuming histopathology assessment of the articular cartilage (AC). We have recently shown that AC in the rat tibia can be imaged both in air and in saline solution using a laboratory system based on coded-aperture X-ray phase-contrast imaging (CAXPCi). Here, we explore ways to extend the methodology for imaging the much thinner AC of the mouse, by means of gold-standard synchrotron-based phase-contrast methods. Specifically, we have used analyser-based phase-contrast micro-computed tomography (micro-CT) for its high sensitivity to faint phase changes, coupled with a high-resolution (4.5 μm pixel) detector. Healthy, diseased (four weeks post induction of OA) and artificially damaged mouse AC was imaged at the Elettra synchrotron in Trieste, Italy, using the above method. For validation, we used conventional micro-CT combined with radiopaque soft-tissue staining and standard histomorphometry. We show that mouse cartilage can be visualized correctly by means of the synchrotron method. This suggests that: (i) further developments of the laboratory-based CAXPCi system, especially in terms of pushing the resolution limits, might have the potential to resolve mouse AC ex vivo and (ii) additional improvements may lead to a new generation of CAXPCi micro-CT scanners which could be used for in vivo longitudinal pre-clinical imaging of soft tissue at resolutions impossible to achieve by current MRI technology.
Decode-and-forward relaying with full-duplex wireless information and power transfer

In this study, the authors consider a decode-and-forward (DF) relaying protocol with full-duplex wireless information and power transfer, and investigate its outage performance. In this protocol, a cooperative relay can transmit the information to the destination and harvest the energy from the source simultaneously. Thus, part of the energy used by the relay can be recycled through the self-loop channel that exists in the relay's full-duplex operation. An approximated expression for the outage probability is derived under the scenario where the self-loop channel is fading, and then the authors derive an exact closed-form expression for the outage probability under a scenario where the self-loop channel is non-fading. Moreover, to optimise the outage performance, a power allocation scheme is also provided. The authors analyse the effect of self-loop channel on the outage performance, and show that, benefiting from the full-duplex operation and self-energy recycling, the considered protocol is superior to the existing power splitting-based and time switching-based DF relaying protocols, in terms of outage performance. Simulations are provided to validate the authors' results.
New Diagnostics for Mycobacterium tuberculosis

Mycobacterium tuberculosis (Mtb) infection is one of the leading causes of morbidity and mortality worldwide with an estimated one third of the world’s population infected by Mtb resulting in about two million deaths per year (Lonnroth and Raviglione, 2008; Wallis et al., 2010). Developing countries are burdened with the highest levels of Mtb infections and conversely have the lowest financial resources available to improve this situation (Figures 1 and 2). High rates of infection are associated with poverty, low levels of public hygiene and often with a high prevalence of HIV+ individuals who are at particular risk of infection, all factors that contribute to an uncontrolled spread of Mtb infection (Corbett et al., 2006; Wright et al., 2009).
Emerging Role of Multimodality Imaging to Evaluate Patients at Risk for Sudden Cardiac Death

Accurate identification of patients at high risk for sudden cardiac death (SCD) has been one of the objectives of research in the last years. With an annual incidence between 184 000 and 462000, SCD is a major public-health problem.The most common cause of SCD is a malignant ventricular arrhythmia and, in the majority of patients with SCD, the underlying anatomic substrate can be identified.2,3 Ischemic heart disease, idiopathic dilated cardiomyopathy (DCM), and hypertrophic cardiomyopathy are the most frequent structural heart diseases associated with SCD. Regardless of the underlying structural heart disease, the use of implantable cardioverter defibrillators (ICD) for secondary prevention of SCD is supported by extensive evidence demonstrating the superiority of ICD over antiarrhythmic drug therapy in reducing SCD and all-cause mortality of patients resuscitated from cardiac arrest.4 Furthermore, in patients with ischemic and nonischemic heart failure, the superior efficacy of ICD over antiarrhythmic therapy for primary prevention of SCD has been demonstrated in multiple randomized controlled trials with >6000 patients included.4 However, recommendations for ICD implantation for primary prevention in patients with other structural heart diseases such as hypertrophic cardiomyopathy or right ventricular arrhythmogenic dysplasia rely on prospective registries or retrospectively analyzed series and predictive markers of SCD have not been definitively established. Based on inclusion criteria of multicenter ICD trials for primary prevention, left ventricular ejection fraction (LVEF) ≤35% is one of the major criteria for ICD implantation.However, patients with reduced LVEF constitute a small proportion of the individuals who die suddenly and most of the SCD events occur in patients who do not have symptoms or signs of cardiac disease yet.6 In addition, in the Multicenter Automatic Defibrillator Implantation Trial II (MADIT II), only 35% of patients randomized to the ICD arm received appropriate therapy during 3 years’ follow-up.7 …
Hierarchical Error Representation: A Computational Model of Anterior Cingulate and Dorsolateral Prefrontal Cortex

Anterior cingulate and dorsolateral prefrontal cortex (ACC and dlPFC, respectively) are core components of the cognitive control network. Activation of these regions is routinely observed in tasks that involve monitoring the external environment and maintaining information in order to generate appropriate responses. Despite the ubiquity of studies reporting coactivation of these two regions, a consensus on how they interact to support cognitive control has yet to emerge. In this letter, we present a new hypothesis and computational model of ACC and dlPFC. The error representation hypothesis states that multidimensional error signals generated by ACC in response to surprising outcomes are used to train representations of expected error in dlPFC, which are then associated with relevant task stimuli. Error representations maintained in dlPFC are in turn used to modulate predictive activity in ACC in order to generate better estimates of the likely outcomes of actions. We formalize the error representation hypothesis in a new computational model based on our previous model of ACC. The hierarchical error representation (HER) model of ACC/dlPFC suggests a mechanism by which hierarchically organized layers within ACC and dlPFC interact in order to solve sophisticated cognitive tasks. In a series of simulations, we demonstrate the ability of the HER model to autonomously learn to perform structured tasks in a manner comparable to human performance, and we show that the HER model outperforms current deep learning networks by an order of magnitude.
High-resolution gamma ray spectroscopy measurements of the fast ion energy distribution in JET 4He plasmas

High-resolution γ-ray measurements were carried out on the Joint European Torus (JET) in an experiment aimed at accelerating 4He ions in the MeV range by coupling third harmonic radio frequency heating to an injected 4He beam. For the first time, Doppler broadening of γ-ray peaks from the 12C(d, pγ)13C and 9Be(α, nγ)12C reactions was observed and interpreted with dedicated Monte Carlo codes based on the detailed nuclear physics of the processes. Information on the confined 4He and deuteron energy distribution was inferred, and confined 4He ions with energies as high as 6 MeV were assessed. A signature of MHD activity in γ-ray traces was also detected. The reported results have a bearing on diagnostics for fast ions in the MeV range in next step fusion devices.
The state of evolutionary medicine in undergraduate education

Abstract Background and objectives Undergraduate courses that include evolutionary medicine (EM) are increasingly available, but quantified data about such courses are lacking. In this article, we describe relevant course offerings by institution and department type, in conjunction with information on the backgrounds and experiences of associated instructors. Methodology We searched course catalogs from 196 American universities to find courses that include EM, and sent a survey to 101 EM instructors to ask about their backgrounds and teaching experiences. Results Research-focused universities (R1) were much more likely to offer at least one course that covers evolutionary applications to health and disease than universities that granted only bachelor’s or master’s degrees. A survey course on EM was offered in 56% of 116 R1 universities, but only 2% of the 80 non-R1 universities we searched. Most EM instructors have backgrounds in anthropology or biology; each instructor’s area of expertise provides clues as to how continued growth of EM may occur differently by discipline. Conclusions and implications Undergraduates are most likely to learn about EM in research-intensive universities from an anthropological or biological perspective. Responses from anthropology and biology instructors, including whom they share course materials with, highlight that courses may differ depending on the discipline in which they are taught. LAY SUMMARY Recognition of evolution’s relevance to understanding health and disease is growing, but documentation of coverage in undergraduate education is lacking. This study explores where evolutionary medicine (EM) content is taught across 196 undergraduate institutions and how 53 instructors describe their experiences teaching EM.
Applying a cognitive neuroscience perspective to the disorder of psychopathy

Four models of psychopathy (frontal lobe dysfunction, response set modulation, fear dysfunction, and violence inhibition mechanism hypotheses) are reviewed from the perspective of cognitive neuroscience. Each model is considered both with respect to the psychopathy data and, more importantly, for the present purposes, with respect to the broader cognitive neuroscience fields to which the model refers (e.g., models of attention with respect to the response set modulation account and models of emotion with respect to the fear dysfunction and violence inhibition mechanism models). The paper concludes with an articulation of the more recent integrated emotion systems model, an account inspired both by recent findings in affective cognitive neuroscience as well as in the study of psychopathy. Some directions for future work are considered.
Inhibition of serotonin of amino acid release and protein degradation in skeletal muscle.

The effect of serotonin (5-hydroxytryptamine) on muscle amino acid and protein metabolism was investigated in vitro, using the isolated intact epitrochlaris preparation of rat skeletal muscle. Increasing concentrations of serotonin (1 nM-0.1 mM) produced a concentration-dependent decrease in the rate of alanine and glutamine release from muscle; intracellular levels of these amino acids were also decreased slightly by serotonin. Muscle alanine reutilization, as determined by [U-14C]alanine oxidation to 14CO2 and incorporation into protein, was unaffected by serotonin, and maximal rates of muscle protein synthesis, as judged by [3H]leucine incorporation into trichloroacetic acid-precipitable protein, were also unaltered. These effects of serotonin were blocked by cyproheptadine and methysergide, but were unaffected by morphine and tetrodotoxin (0.1 , µg/ml). None of these antagonists exhibited substantial independent effects on muscle alanine and glutamine synthesis and release. Exogenous serotonin resulted in a concentration-dependent increase in steady-state levels of intracellular cyclic 39,59-AMP in these muscle preparations. Theophylline (1 mM) or isobutylmethylxanthine (0.2 mM) potentiated the effects of submaximal concentrations of serotonin (1 µM) on muscle amino acid release, and amplified the increments in muscle cyclic AMP produced by this concentration of serotonin. Cyproheptadine and methysergide, but not morphine or tetrodotoxin, blocked the serotonin-induced increments in muscle cyclic AMP levels. The effects of serotonin on alanine and glutamine synthesis and release from muscle were reproduced by exogenous dibutyryl cyclic AMP. Serotonin did not reduce the rate of formation of alanine and glutamine from exogenous amino acid precursors such as aspartate, cysteine, leucine, and valine. Skeletal muscle proteins in the epitrochlaris preparations were partially labeled with [guanido-14C]arginine administered in vivo using pulse-chase methods. On incubation of these preparations in vitro, serotonin decreased the rate of loss of 14C label from trichloroacetic acid-precipitable protein in the muscles. Correspondingly, serotonin also decreased the appearance of 14C label in the incubation medium and in the supernatant fraction of the muscles obtained after trichloroacetic acid treatment. These data indicate that serotonin inhibits alanine and glutamine synthesis and release from intact skeletal muscle. This effect is mediated by a specific D-class serotonin receptor and appears to require the intermediary participation of muscle cyclic AMP. The mechanism of serotonin action most probably involves primary inhibition of protein degradation, which thereby results in decreased availability of precursor amino acid substrates for conversion to alanine and glutamine. These results indicate that serotonin, like norepinephrine, has direct effects on skeletal muscle metabolism, and that these effects are independent of its vasoactive properties.
The Presence of Sodium Nitrate in Generator Eluate Decreases the Radiochemical Purity of 99mTc-Sestamibi

A high radiochemical purity (RCP) is recommended for radiopharmaceutical compounds used in the clinical practice of nuclear medicine. However, some preparations of 99mTc-sestamibi contain excess impurities (>6%). To understand the origin of these impurities, we investigated the effect of sodium nitrate on the RCP of sestamibi preparations by testing eluates from 3 commercially available 99mTc generators. Methods: The sestamibi kits (Stamicis) were reconstituted with 99mTc eluate from nitrate-containing wet-column (NCWC), nitrate-free wet-column (NFWC), and nitrate-free dry-column (NFDC) generators. Sodium nitrate was 0.05 mg/mL in eluates from the NCWC generators. The RCP was determined using aluminum oxide sheets as the stationary phase and absolute ethanol as the mobile phase. Succimer, tetrofosmin, oxidronate, exametazine, albumin nanocolloid, and soluble albumin were also tested for their RCP values with eluates from the 3 different 99mTc generators. Results: The RCP assessment of 99mTc-sestamibi was performed on 127 Stamicis preparations. Significantly lower RCP values were found for Stamicis kits prepared with the NCWC generator than for Stamicis prepared with the NFWC (P < 0.0001) and NFDC (P < 0.0001) generators. The number of Stamicis preparations with an RCP under 94% was greater with the NCWC generator (32 of 53 kits) than with the NFDC (2 of 51 kits) or NFWC (0 of 23 kits) generator. Furthermore, the addition of a 0.05 mg/mL concentration of nitrate in NFWC generator eluates significantly decreased the RCP of the Stamicis preparation. In the absence of nitrate in 99mTc eluate, no difference was observed between the RCP values of Stamicis kits prepared with the NFWC and NFDC generators. The 99mTc impurities generated by nitrates did not modify the quality of myocardial imaging (normal heart-to-lung ratio, 2.2), probably because these impurities are not in the heart field of view. No other tested 99mTc-radiopharmaceutical interfered with nitrates. Conclusion: We recommend using nitrate-free generator eluates in 99mTc-sestamibi preparations to improve the product quality and prevent unnecessary exposure of the patient to radiation.
Triggering the regeneration and tissue repair programs

In early October 2008, researchers from diverse backgrounds gathered at an EMBO conference entitled `The Molecular and Cellular Basis of Regeneration and Tissue Repair' to discuss the basic biology of regeneration. Topics included cell plasticity in regenerative and developmental contexts, and the link between wound healing and regeneration. The meeting also highlighted the progress made in identifying the molecular networks that underlie regeneration in a variety of model systems.
Advances in Brief Cytoplasmic HuR Expression Correlates with Poor Outcome and with Cyclooxygenase 2 Expression in Serous Ovarian Carcinoma

Cyclooxygenase-2 (COX-2) expression has been shown to associate with poor prognosis in ovarian cancer, and an mRNA stability protein HuR has been shown to enhance expression of COX-2 in tissue culture conditions. We found cytoplasmic immunoreactivity for HuR protein in 52% (233 of 445) of serous-type ovarian carcinoma specimens, and it associated with high COX-2 expression (P 0.0045) and with clinicopathological variables, including poor prognosis (P < 0.0001) and high grade (P < 0.0001). In ovarian cancer cells in vitro, a small interfering RNA against HuR and leptomycin B, an inhibitor of nucleocytoplasmic translocation of HuR, inhibited COX-2 expression. Our results show that cytoplasmic HuR expression associates with poor outcome in ovarian cancer, and one plausible explanation for this finding may be related to the ability of HuR to induce COX-2 expression.
Synaptic excitation in the thoracic spinal cord from expiratory bulbospinal neurones in the cat.

1. Synaptic actions in the thoracic spinal cord of individual expiratory bulbospinal neurones were studied in anaesthetized cats by the use of two techniques: (i) the monosynaptic connections to motoneurones were assessed by cross‐correlations between the discharges of the neurones and efferent discharges in the internal intercostal nerves of several segments bilaterally; and (ii) distributions of terminal and focal synaptic potentials were measured by extracellular spike‐triggered averaging in the thoracic ventral horn. 2. Monosynaptic connections were identified by both the durations and timings of observed cross‐correlation peaks, taking into account accurate conduction velocity measurements derived from collision tests and from spike‐triggered averaging. Discrimination was made against peaks resulting from presynaptic synchronization. 3. Monosynaptic connections to motoneurones were identified for twenty‐three out of twenty‐seven neurones. The connections to nerves on the side ipsilateral to the cell somata were, on average, about 36% of the strength of those on the contralateral side. The overall strength of the connections was about twice as strong as previous estimates for similar connections from inspiratory bulbospinal neurones to phrenic motoneurones. The monosynaptic pathway was calculated to be able to provide most of the depolarization for the motoneurones concerned and therefore was likely to be the main determinant of their firing patterns under the conditions of these experiments. 4. However, taking into account previous measurements it is considered possible that these connections may only involve a minority of motoneurones, perhaps only 10% of the expiratory population. Thus, in general, the control of the whole pool of expiratory motoneurones, despite the strong monosynaptic connections measured here, is suggested to be mainly dependent on spinal interneurones, as has been concluded previously for inspiratory motoneurones. 5. Spike‐triggered averaging revealed that nearly all neurones gave signs of collaterals in each of the segments investigated (T7, T8 or T9), as shown by the presence of terminal potentials or focal synaptic potentials, but the projection within a given thoracic segment was non‐uniform, in that large‐amplitude potentials were more common in the rostral than the caudal part of the segment. This non‐uniformity could be a factor involved in the apparently non‐heterogeneous connections to the motoneurones.