The association between maternal childhood trauma and offspring childhood psychopathology: a mediation analysis from the ALSPAC cohort

Background: Studies have shown that a mother’s history of child maltreatment is associated with her child’s experience of internalising and externalising difficulties. Aims: To characterise the mediating pathways that underpin this association. Method: Data on a mother’s history of child maltreatment, depression during pregnancy, postnatal depression, maladaptive parenting practices and her child’s experience of maltreatment and internalising and externalising difficulties were analysed in an ALSPAC sample of 9,397 mother-child dyads followed prospectively from pregnancy to age 13. Results: Maternal history of child maltreatment was significantly associated with offspring internalising and externalising difficulties. Maternal antenatal depression, postnatal depression and offspring child maltreatment were observed to significantly mediate this association independently. Conclusions: Psychological and psychosocial interventions focused around treating maternal depression, particularly during pregnancy, and safeguarding against adverse childhood experiences could be offered to mothers with traumatic childhood histories to help protect against psychopathology in the next generation

SUMOylation determines the voltage required to activate cardiac IKs channels.

IKs channels open in response to depolarization of the membrane voltage during the cardiac action potential, passing potassium ions outward to repolarize ventricular myocytes and end each beat. Here, we show that the voltage required to activate IKs channels depends on their covalent modification by small ubiquitin-like modifier (SUMO) proteins. IKs channels are comprised of four KCNQ1 pore-forming subunits, two KCNE1 accessory subunits, and up to four SUMOs, one on Lys424 of each KCNQ1 subunit. Each SUMO shifts the half-maximal activation voltage (V1/2) of IKs ∼ +8 mV, producing a maximal +34-mV shift in neonatal mouse cardiac myocytes or Chinese hamster ovary (CHO) cells expressing the mouse or human subunits. Unexpectedly, channels formed without KCNE1 carry at most two SUMOs despite having four available KCNQ1-Lys424 sites. SUMOylation of KCNQ1 is KCNE1 dependent and determines the native attributes of cardiac IKs in vivo

Diethylcarbamazine activity against Brugia malayi microfilariae is dependent on inducible nitric-oxide synthase and the cyclooxygenase pathway

BACKGROUND: Diethylcarbamazine (DEC) has been used for many years in the treatment of human lymphatic filariasis. Its mode of action is not well understood, but it is known to interact with the arachidonic acid pathway. Here we have investigated the contribution of the nitric oxide and cyclooxygenase (COX) pathways to the activity of DEC against B. malayi microfilariae in mice. METHODS: B. malayi microfilariae were injected intravenously into mice and parasitaemia was measured 24 hours later. DEC was then administered to BALB/c mice with and without pre-treatment with indomethacin or dexamethasone and the parasitaemia monitored. To investigate a role for inducible nitric oxide in DEC's activity, DEC and ivermectin were administered to microfilaraemic iNOS(-/- )mice and their background strain (129/SV). Western blot analysis was used to determine any effect of DEC on the production of COX and inducible nitric-oxide synthase (iNOS) proteins. RESULTS: DEC administered alone to BALB/c mice resulted in a rapid and profound reduction in circulating microfilariae within five minutes of treatment. Microfilarial levels began to recover after 24 hours and returned to near pre-treatment levels two weeks later, suggesting that the sequestration of microfilariae occurs independently of parasite killing. Pre-treatment of animals with dexamethasone or indomethacin reduced DEC's efficacy by almost 90% or 56%, respectively, supporting a role for the arachidonic acid and cyclooxygenase pathways in vivo. Furthermore, experiments showed that treatment with DEC results in a reduction in the amount of COX-1 protein in peritoneal exudate cells. Additionally, in iNOS(-/- )mice infected with B. malayi microfilariae, DEC showed no activity, whereas the efficacy of another antifilarial drug, ivermectin, was unaffected. CONCLUSION: These results confirm the important role of the arachidonic acid metabolic pathway in DEC's mechanism of action in vivo and show that in addition to its effects on the 5-lipoxygenase pathway, it targets the cyclooxygenase pathway and COX-1. Moreover, we show for the first time that inducible nitric oxide is essential for the rapid sequestration of microfilariae by DEC

The UTMOST Survey for Magnetars, Intermittent pulsars, RRATs and FRBs I: System description and overview

We describe the ongoing `Survey for Magnetars, Intermittent pulsars, Rotating radio transients and Fast radio bursts' (SMIRF), performed using the newly refurbished UTMOST telescope. SMIRF repeatedly sweeps the southern Galactic plane performing real-time periodicity and single-pulse searches, and is the first survey of its kind carried out with an interferometer. SMIRF is facilitated by a robotic scheduler which is capable of fully autonomous commensal operations. We report on the SMIRF observational parameters, the data analysis methods, the survey's sensitivities to pulsars, techniques to mitigate radio frequency interference and present some early survey results. UTMOST's wide field of view permits a full sweep of the Galactic plane to be performed every fortnight, two orders of magnitude faster than previous surveys. In the six months of operations from January to June 2018, we have performed $\sim 10$ sweeps of the Galactic plane with SMIRF. Notable blind re-detections include the magnetar PSR J1622$-$4950, the RRAT PSR J0941$-$3942 and the eclipsing pulsar PSR J1748$-$2446A. We also report the discovery of a new pulsar, PSR J1705$-$54. Our follow-up of this pulsar with the UTMOST and Parkes telescopes at an average flux limit of $\leq 20$ mJy and $\leq 0.16$ mJy respectively, categorizes this as an intermittent pulsar with a high nulling fraction of $< 0.002$Comment: Submitted to MNRAS, comments welcom

Broken-symmetry-adapted Green function theory of condensed matter systems:towards a vector spin-density-functional theory

The group theory framework developed by Fukutome for a systematic analysis of the various broken symmetry types of Hartree-Fock solutions exhibiting spin structures is here extended to the general many body context using spinor-Green function formalism for describing magnetic systems. Consequences of this theory are discussed for examining the magnetism of itinerant electrons in nanometric systems of current interest as well as bulk systems where a vector spin-density form is required, by specializing our work to spin-density-functional formalism. We also formulate the linear response theory for such a system and compare and contrast them with the recent results obtained for localized electron systems. The various phenomenological treatments of itinerant magnetic systems are here unified in this group-theoretical description.Comment: 17 page

Basic concepts for convection parameterization in weather forecast and climate models: COST Action ES0905 final report

The research network “Basic Concepts for Convection Parameterization in Weather Forecast and Climate Models” was organized with European funding (COST Action ES0905) for the period of 2010–2014. Its extensive brainstorming suggests how the subgrid-scale parameterization problem in atmospheric modeling, especially for convection, can be examined and developed from the point of view of a robust theoretical basis. Our main cautions are current emphasis on massive observational data analyses and process studies. The closure and the entrainment–detrainment problems are identified as the two highest priorities for convection parameterization under the mass–flux formulation. The need for a drastic change of the current European research culture as concerns policies and funding in order not to further deplete the visions of the European researchers focusing on those basic issues is emphasized