Computation of molecular Hartree–Fock Wigner intracules

The computation of molecular Wigner intracules from Hartree–Fock wave functions using Gaussian basis functions is described. The Wigner intracule is a new type of intracule that contains information about both the relative position and momentum of the electrons. Two methods for evaluating the required integrals are presented. The first approach uses quadrature while the second requires summation of an infinite series.This research was partly supported by the Engineering and Physical Sciences Research Council through a project studentship (GR/R81121) to D.P.O. and an Advanced Research Fellowship (GR/R77636) to N.A.B

miR-132/212 knockout mice reveal roles for these miRNAs in regulating cortical synaptic transmission and plasticity

miR-132 and miR-212 are two closely related miRNAs encoded in the same intron of a small non-coding gene, which have been suggested to play roles in both immune and neuronal function. We describe here the generation and initial characterisation of a miR-132/212 double knockout mouse. These mice were viable and fertile with no overt adverse phenotype. Analysis of innate immune responses, including TLR-induced cytokine production and IFNβ induction in response to viral infection of primary fibroblasts did not reveal any phenotype in the knockouts. In contrast, the loss of miR-132 and miR-212, while not overtly affecting neuronal morphology, did affect synaptic function. In both hippocampal and neocortical slices miR-132/212 knockout reduced basal synaptic transmission, without affecting paired-pulse facilitation. Hippocampal long-term potentiation (LTP) induced by tetanic stimulation was not affected by miR-132/212 deletion, whilst theta burst LTP was enhanced. In contrast, neocortical theta burst-induced LTP was inhibited by loss of miR-132/212. Together these results indicate that miR-132 and/or miR-212 play a significant role in synaptic function, possibly by regulating the number of postsynaptic AMPA receptors under basal conditions and during activity-dependent synaptic plasticity

Advances in methods and algorithms in a modern quantum chemistry program package

Advances in theory and algorithms for electronic structure calculations must be incorporated into program packages to enable them to become routinely used by the broader chemical community. This work reviews advances made over the past five years or so that constitute the major improvements contained in a new release of the Q-Chem quantum chemistry package, together with illustrative timings and applications. Specific developments discussed include fast methods for density functional theory calculations, linear scaling evaluation of energies, NMR chemical shifts and electric properties, fast auxiliary basis function methods for correlated energies and gradients, equation-of-motion coupled cluster methods for ground and excited states, geminal wavefunctions, embedding methods and techniques for exploring potential energy surfaces

Effectiveness of a biopsychosocial e-learning intervention on the clinical judgements of medical students and GP trainees regarding future risk of disability in patients with chronic lower back pain: study protocol for a randomised controlled trial

Introduction Chronic lower back pain (CLBP) is a major healthcare problem with wide ranging effects. It is a priority for appropriate management of CLBP to get individuals back to work as early as possible. Interventions that identify biopsychosocial barriers to recovery have been observed to lead to successfully reduced pain-related work absences and increased return to work for individuals with CLBP. Modern conceptualisations of pain adopt a biopsychosocial approach, such as the flags approach. Biopsychosocial perspectives have been applied to judgements about future adjustment, recovery from pain and risk of long-term disability; and provide a helpful model for understanding the importance of contextual interactions between psychosocial and biological variables in the experience of pain. Medical students and general practitioner (GP) trainees are important groups to target with education about biopsychosocial conceptualisations of pain and related clinical implications. Aim The current study will compare the effects of an e-learning intervention that focuses on a biopsychosocial model of pain, on the clinical judgements of medical students and trainees. Methods and analysis Medical student and GP trainee participants will be randomised to 1 of 2 study conditions: (1) a 20 min e-learning intervention focused on the fundamentals of the flags approach to clinical judgement-making regarding risk of future pain-related disability; compared with a (2) wait-list control group on judgement accuracy and weighting (ie, primary outcomes); flags approach knowledge, attitudes and beliefs towards pain, judgement speed and empathy (ie, secondary outcomes). Participants will be assessed at preintervention and postintervention.peer-reviewe

Tailored adsorption of His6-tagged protein onto nickel(II)–cyclam grafted mesoporous silica

The specific immobilisation of a histidine tagged protein, Spi, onto mono-anchored nickel(II) cyclam functionalised SBA-15 is reported.Science Foundation Irelan

Environmental and genetic drivers of population differences in SARS-CoV-2 immune responses

The RNA sequencing data generated and analyzed in this study have been deposited in the Institut Pasteur data repository, OWEY, which can be accessed via the following link: https://doi.org/XXXX. The genome-wide genotyping data generated or used in this study have been deposited in OWEY and can be accessed at the following URL: https://doi.org/XXXX. Data access and use is restricted to academic research related to the variability of the human immune response.Humans display vast clinical variability upon SARS-CoV-2 infection 1–3 , partly due to genetic and immunological factors 4 . However, the magnitude of population differences in immune responses to SARS-CoV-2 and the mechanisms underlying such variation remain unknown. Here we report single-cell RNA-sequencing data for peripheral blood mononuclear cells from 222 healthy donors of various ancestries stimulated with SARS-CoV-2 or influenza A virus. We show that SARS-CoV-2 induces a weaker, but more heterogeneous interferon-stimulated gene activity than influenza A virus, and a unique pro-inflammatory signature in myeloid cells. We observe marked population differences in transcriptional responses to viral exposure that reflect environmentally induced cellular heterogeneity, as illustrated by higher rates of cytomegalovirus infection, affecting lymphoid cells, in African-descent individuals. Expression quantitative trait loci and mediation analyses reveal a broad effect of cell proportions on population differences in immune responses, with genetic variants having a narrower but stronger effect on specific loci. Additionally, natural selection has increased immune response differentiation across populations, particularly for variants associated with SARS-CoV-2 responses in East Asians. We document the cellular and molecular mechanisms through which Neanderthal introgression has altered immune functions, such as its impact on the myeloid response in Europeans. Finally, colocalization analyses reveal an overlap between the genetic architecture of immune responses to SARS-CoV-2 and COVID-19 severity. Collectively, these findings suggest that adaptive evolution targeting immunity has also contributed to current disparities in COVID-19 risk