A luminous blue kilonova and an off-axis jet from a compact binary merger at z = 0.1341.

The recent discovery of a gamma-ray burst (GRB) coincident with the gravitational-wave (GW) event GW170817 revealed the existence of a population of low-luminosity short duration gamma-ray transients produced by neutron star mergers in the nearby Universe. These events could be routinely detected by existing gamma-ray monitors, yet previous observations failed to identify them without the aid of GW triggers. Here we show that GRB150101B is an analogue of GRB170817A located at a cosmological distance. GRB150101B is a faint short burst characterized by a bright optical counterpart and a long-lived X-ray afterglow. These properties are unusual for standard short GRBs and are instead consistent with an explosion viewed off-axis: the optical light is produced by a luminous kilonova, while the observed X-rays trace the GRB afterglow viewed at an angle of ~13°. Our findings suggest that these properties could be common among future electromagnetic counterparts of GW sources.

Wind from the black-hole accretion disk driving a molecular outflow in an active galaxy.

Powerful winds driven by active galactic nuclei are often thought to affect the evolution of both supermassive black holes and their host galaxies, quenching star formation and explaining the close relationship between black holes and galaxies. Recent observations of large-scale molecular outflows in ultraluminous infrared galaxies support this quasar-feedback idea, because they directly trace the gas from which stars form. Theoretical models suggest that these outflows originate as energy-conserving flows driven by fast accretion-disk winds. Proposed connections between large-scale molecular outflows and accretion-disk activity in ultraluminous galaxies were incomplete because no accretion-disk wind had been detected. Conversely, studies of powerful accretion-disk winds have until now focused only on X-ray observations of local Seyfert galaxies and a few higher-redshift quasars. Here we report observations of a powerful accretion-disk wind with a mildly relativistic velocity (a quarter that of light) in the X-ray spectrum of IRAS F11119+3257, a nearby (redshift 0.189) optically classified type 1 ultraluminous infrared galaxy hosting a powerful molecular outflow. The active galactic nucleus is responsible for about 80 per cent of the emission, with a quasar-like luminosity of 1.5 × 10(46) ergs per second. The energetics of these two types of wide-angle outflows is consistent with the energy-conserving mechanism that is the basis of the quasar feedback in active galactic nuclei that lack powerful radio jets (such jets are an alternative way to drive molecular outflows).

A massive, cooling-flow-induced starburst in the core of a luminous cluster of galaxies.

In the cores of some clusters of galaxies the hot intracluster plasma is dense enough that it should cool radiatively in the cluster's lifetime, leading to continuous 'cooling flows' of gas sinking towards the cluster centre, yet no such cooling flow has been observed. The low observed star-formation rates and cool gas masses for these 'cool-core' clusters suggest that much of the cooling must be offset by feedback to prevent the formation of a runaway cooling flow. Here we report X-ray, optical and infrared observations of the galaxy cluster SPT-CLJ2344-4243 (ref. 11) at redshift z = 0.596. These observations reveal an exceptionally luminous (8.2 × 10(45) erg s(-1)) galaxy cluster that hosts an extremely strong cooling flow (around 3,820 solar masses a year). Further, the central galaxy in this cluster appears to be experiencing a massive starburst (formation of around 740 solar masses a year), which suggests that the feedback source responsible for preventing runaway cooling in nearby cool-core clusters may not yet be fully established in SPT-CLJ2344-4243. This large star-formation rate implies that a significant fraction of the stars in the central galaxy of this cluster may form through accretion of the intracluster medium, rather than (as is currently thought) assembling entirely via mergers.

Stimulation of DNA repair by the spermatidal TP1 protein.

The chromatin remodeling process that takes place during spermiogenesis in mammals is characterized by a transient increase in DNA single-strand breaks (SSB). The mammalian transition proteins (TPs) are expressed at a high level at mid-spermiogenesis steps coincident with chromatin remodeling and could be involved in the repair of these lesions since SSB are no longer detected in terminally differentiated spermatids. We report that TP1 can stimulate the repair of SSB in vitro and demonstrate that in vivo repair of UV-induced DNA lesions is enhanced in mammalian cells stably expressing TP1. These results suggest that, aside from its role in DNA compaction, this major transition protein may contribute to the yet unidentified enzymatic activity responsible for the repair of SSB at mid-spermiogenesis steps. These results also suggest that the TP1 proteins have the potential to participate in the repair process following genotoxic insults and therefore may play an active role in the maintenance of the integrity of the male haploid genome during spermiogenesis.

Comparative study of the coupling between topoisomerase I activity and high-mobility group proteins in E. coli and mammalian cells.

It is now well established that the HMG box DNA-binding motif can alter the topology of double-stranded DNA in several ways. Using the spermatid-specific tsHMG as a model protein of the HMG-1/-2 family, we have demonstrated that its expression in E. coli produces an increase in plasmid supercoiling density that is likely a consequence of its ability to constrain free supercoils in vivo. As demonstrated in vitro, stabilization of free DNA supercoils by tsHMG prevents topoisomerase I from gaining access to the template and could represent a mechanism for the apparent inhibition of topoisomerase I in bacteria. A similar modulation of eukaryotic topoisomerase I activity was not detected after expression of the tsHMG in mammalian cells. This differential response is discussed in terms of the marked difference in DNA packaging and accessibility of free supercoils in prokaryotic vs. eukaryotic cells.

Architectural DNA-binding properties of the spermatidal transition proteins 1 and 2.

Mammalian spermiogenesis is characterized by replacement of somatic histones by a set of basic nuclear transition proteins thought to be actively involved in the chromatin remodeling process. The two major transition proteins of the elongating spermatids, namely TP1 and TP2, were expressed and purified using a bacterial expression system. Both topoisomerase and ligase-mediated supercoiling assays demonstrated that TP1, as well as TP2, did not produce detectable changes in the twist and/or writhe of DNA molecules upon binding. Ligase-mediated circularization assay further demonstrated that neither of the transition proteins under study produced bends in linear DNA but that they both have the capacity to stimulate oligomerization of linear DNA fragments. We further established that the transition proteins are in vitro substrates for the Ca+2-phospholipid-dependent protein kinase (PKC) as well as the cAMP-dependent protein kinase (PKA). PKC phosphorylation was found to strongly weaken the DNA-condensing ability of TP2. These results suggest that the major transition proteins represent architectural factors able to stabilize DNA in a nonsupercoiled state, thereby promoting DNA condensation.

The testis-specific high-mobility-group protein, a phosphorylation-dependent DNA-packaging factor of elongating and condensing spermatids.

Mammalian spermiogenesis is characterized by a striking restructuring of the spermatid chromatin caused by the replacement of nucleohistones with transition proteins and their subsequent replacement with nucleoprotamines. The onset of nuclear elongation and chromatin condensation in spermatids is accompanied by a general decrease in the transcriptional activity of the DNA. A recently identified testis-specific high-mobility-group (tsHMG) protein, similar to the human mitochondrial transcription factor I and to the linker-associated protein delta of Tetrahymena thermophila micronuclei, is thought to play a structural role in this process. We confirm by immunoblot analysis of fractionated germ cells that the presence of tsHMG is restricted to transcriptionally quiescent elongating and condensing spermatids. Purified recombinant tsHMG protein displays preferential binding to supercoiled plasmid DNA, which reversibly protects the DNA against the DNA-relaxing activity of eukaryotic topoisomerase I and also impairs the transcriptional activity of this template when assayed in vitro. The tsHMG protein can also introduce negative supercoils into a relaxed plasmid substrate in a topoisomerase I-dependent manner. We also show that the tsHMG protein is the substrate of a Ca2+-phospholipid-dependent protein kinase (protein kinase C) present in testis extracts of adult mice and demonstrate that phosphorylation by protein kinase C is required for both the DNA-binding and the topoisomerase I-dependent supercoiling activities of tsHMG. Our results support the hypothesis that the spermatid tsHMG protein is a topological factor (transition protein) that can modulate the activity of topoisomerase I. This activity could contribute to the important transition in chromatin structure which leads to the decrease in DNA metabolism observed at the early stages of spermatid elongation.

Intramolecular recombination in polyomavirus DNA is controlled by promoter elements.

We show here that intramolecular homologous recombination in polyomavirus (Py) DNA depends upon discrete sequence elements of the viral regulatory region which are believed to regulate transcription initiation and exert little or no cis-control over replication. Either deleting the viral early promoter (EP) or inverting the viral late promoter (LP) strongly impairs viral DNA recombination under conditions allowing viral DNA replication to proceed undisturbed. These findings suggest that bi-directional transcription proceeding from the intergenic region favors intramolecular recombination.

Typing Chlamydia trachomatis by detection of restriction fragment length polymorphism in the gene encoding the major outer membrane protein.

A method that avoids culture was devised to determine serovars of Chlamydia trachomatis. Polymerase chain reaction was used first to amplify a part of the chlamydial genome that included the leader sequence and all four variable domains of the major outer membrane protein (MOMP) of the 15 serovars of C. trachomatis. The amplified DNA was then digested simultaneously with restriction endonucleases AluI and MspI and the resulting fragments separated on 10% polyacrylamide gels. After silver staining, a total of 13 characteristic patterns were observed for the 15 serovars, leaving two ambiguities that were resolved using alternate enzymes. Analysis of 40 clinical isolates revealed patterns indistinguishable from those of the prototype serovars including, unexpectedly, 5 Ba serovars. The same PCR procedure also allowed amplification of the MOMP gene of two avian Chlamydia psittaci and one Chlamydia pneumoniae isolates.

Antidepressant and other centrally acting drugs regulate glucocorticoid receptor messenger RNA levels in rat brain.

The effect of imipramine, desipramine, ketanserin and lithium on Type II glucocorticoid receptor (GR) mRNA levels was studied in rat brain regions involved in the control of the hypothalamo-pituitary-adrenal (HPA) axis, the dysregulation of which has been implicated in the pathophysiology of major depression. Northern blot analysis of Type II GR mRNA showed that treatment of male rats with either desipramine or imipramine increased hypothalamic and hippocampal GR mRNA levels. Upregulation of GR mRNA following administration of imipramine was found in brain regions of female rats, while desipramine had no effect. Ketanserin increased levels of GR mRNA in hippocampus of male, but not female, rats. Lithium also was able to induce important increases rat brain GR mRNA; this effect was particularly marked in females. We conclude that desipramine, imipramine, ketanserin and lithium can modulate GR mRNA in regions of rat brain involved in the control of the HPA axis and may have a common mechanism of action at the level of the GR gene. Sexual dimorphism for drug regulation of brain GR mRNA content was shown and may be related to sex differences in the prevalence of certain affective disorders.

Informed consent in emergency settings.

It is often difficult for emergency physicians to comply with the doctrine of informed consent. Patients suffering true emergencies require immediate treatment, and patients who are unable to give consent, because they are either incompetent or underage, are seen frequently in emergency departments. We examine the legal requirements of informed consent in emergency settings, with specific examples illustrated by Connecticut statutes General guidelines for developing departmental policies are suggested.

Prophylactic lidocaine: uncertain benefits in emergency settings.

The need to determine whether prophylactic lidocaine has any therapeutic value is generally recognized, and further investigations have been urged: A carefully designed clinical trial of routine lidocaine administration should be carried out to provide definitive information for the physician treating patients who have had myocardial infarction. Such trials should begin immediately, in view of the magnitude of the problem and the fact that routine prophylaxis of arrhythmias after myocardial infarction is not common policy. Such a study, if well designed, can answer the question... Carefully designed trials must be conducted with patients included in the study as soon as possible after the onset of symptoms, preferably during the prehospital phase, and the medication must be administered in a random-controlled fashion. Although these requirements pose no extraordinary problems of research design and method, they lead to prohibiting ethical conflicts. Without resolving these conflicts, through the elaboration of acceptable standards which bypass traditional informed consent, the value of lidocaine prophylaxis will remain uncertain, as will the many other emergency therapeutic maneuvers of unproven effectiveness.

Errors of intuitive logic among physicians.

The effectiveness of specific training in statistics and decision-making principles upon physicians' judgmental skills was assessed by means of problems of intuitive logical reasoning. The responses of 43 statistically sophisticated physicians (SP) were compared to those of 42 practicing physicians (PP), 43 clinical nurses (CN) and 41 hospital laborers (HL). On problems evaluating use of faulty heuristics in judgments of conditional probabilities, the SP group's responses were the most biased. The proportion of subjects displaying consistent use of a particular heuristic in solving the three problems were 0.36 (SP), 0.45 (PP), 0.35 (CN) and 0.41 (HL). On problems assessing use of prevalence rate data in estimating probabilities, SP performed substantially better than the other three groups: 34% of their responses were accurate. However, 37% of their responses reflected ignorance of prevalence information concepts. We conclude that intensive statistical and decision-making training of physicians is likely to be of only limited value for improving clinicians' judgmental skills.