The V5A13.1 envelope glycoprotein deletion mutant of mouse hepatitis virus type-4 is neuroattenuated by its reduced rate of spread in the central nervous system.

Following intracerebral inoculation of adult Balb/c Byj mice, the MHV-4 strain of mouse hepatitis virus (MHV) had an LD50 of less than 0.1 PFU, whereas its monoclonal antibody resistant variant V5A13.1 had an LD50 of 10(4.2) PFU. To determine the basis for this difference in neurovirulence we have studied the acute central nervous system (CNS) infection of these two viruses by in situ hybridization. Both viruses infected the same, specific neuroanatomical areas, predominantly neurons, and spread via the cerebrospinal fluid, along neuronal pathways and between adjacent cells. The neuronal nuclei infected and the spread of virus within the brain are described. The main difference between the parental and variant viruses was the rate at which the infection spread. MHV-4 spread rapidly, destroying large numbers of neurons and the animals died within 4 days of infection. The variant virus spread to the same areas of the brain but at a slower rate. This difference in the rate of virus spread was also apparent from the brain virus titers. The slower rate of spread of the variant virus appears to allow intervention by the immune response. Consistent with this, the variant virus spread slowly in athymic nu/nu mice, but in the absence of an intact immune response, infection and destruction of neurons eventually reached the same extent as that of the parental virus and the mice died within 6 days of infection. We conclude that the V5A13.1 variant of MHV-4 is neuroattenuated by its slower rate of spread in the CNS

Defect chemistry of Ti and Fe impurities and aggregates in Al2O3

We report a theoretical evaluation of the properties of iron and titanium impurities in sapphire (corundum structured α-Al2O3). Calculations using analytical force fields have been performed on the defect structure with the metals present in isolated, co-doped and tri-cluster configurations. Crystal field parameters have been calculated with good agreement to available experimental data. When titanium and iron are present in neighbouring face and edge-sharing orientations, the overlap of the d-orbitals facilitates an intervalence charge transfer (FeIII/TiIII → FeII/TiIV) with an associated optical excitation energy of 1.85 eV and 1.76 eV in the respective configurations. Electronic structure calculations based on density functional theory confirm that FeIII/TiIII is the ground-state configuration for the nearest-neighbour pairs, in contrast to the often considered FeII/TiIV pair. Homonuclear intervalence charge transfer energies between both FeIII/FeII and TiIV/TiIII species have also been calculated, with the energy lying in the infra-red region. Investigation of multiple tri-clusters of iron and titanium identified one stable configuration, TiIII–(TiIV/FeII), with the energy of electron transfer remaining unchanged

Microscopic origin of the optical processes in blue sapphire

Al2O3 changes from transparent to a range of intense colours depending on the chemical impurities present. In blue sapphire, Fe and Ti are incorporated; however, the chemical process that gives rise to the colour has long been debated. Atomistic modelling identifies charge transfer from Ti(III) to Fe(III) as being responsible for the characteristic blue appearance

Supplemental peri-operative intravenous crystalloids for postoperative nausea and vomiting: an abridged Cochrane systematic review.

We conducted a Cochrane systematic review on the effectiveness of supplemental intravenous crystalloid administration in preventing postoperative nausea and vomiting. We included randomised controlled trials of patients undergoing surgery under general anaesthesia and given supplemental peri-operative intravenous crystalloid. Our primary outcomes were the risk of postoperative nausea and the risk of postoperative vomiting. We assessed the risk of bias for each included study and applied the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) framework for the certainty of evidence. We included 41 studies. We found that the intervention probably reduces the overall risk of postoperative nausea, the risk ratio (95%CI) being 0.62 (0.51-0.75) (I2  = 57%, p < 0.00001, 18 studies; 1766 participants; moderate-certainty evidence). It also probably reduces the risk of postoperative nausea within 6 h of surgery, with a risk ratio (95%CI) of 0.67 (0.58 to 0.78) (I2  = 9%, p < 0.00001, 20 studies; 2310 participants; moderate-certainty evidence) and by around 24 h, the risk ratio (95%CI) being 0.47 (0.32-0.69) (I2  = 38%, p = 0.0001, 17 studies; 1682 participants; moderate-certainty evidence). Supplemental intravenous crystalloid probably also reduces the overall risk of postoperative vomiting, with a risk ratio (95%CI) of 0.50 (0.40-0.63) (I2  = 31%, p < 0.00001, 20 studies; 1970 participants; moderate-certainty evidence). The beneficial effect on vomiting was seen both within 6 h and by around 24 h postoperatively

Should IUI replace IVF as first-line treatment for unexplained infertility? A literature review

Background Unexplained infertility accounts for 25% of infertility causes in the UK. Active intervention methods, such as intrauterine insemination (IUI) or in vitro fertilisation (IVF), are often sought. Despite the National Institute for Health and Care Excellence (NICE) recommending IVF for unexplained infertility, this recommendation has generated an ongoing debate, with few fertility clinics discontinuing the use of IUI as the first-line management of choice. In contrast to NICE, recent guidance released from the European Society for Human Reproduction and Embryology (ESHRE) in August 2023 supports the use of IUI as first-line. High-quality evidence behind such interventions is lacking, with current literature providing conflicting results. Aims This review aims to provide a literature overview exploring whether IUI or IVF should be used as first-line treatment for couples with unexplained infertility, in the context of current guidelines. Methods The primary outcome used to assess efficacy of both treatment methods is live birth (LB) rates. Secondary outcomes used are clinical pregnancy (CP) and ongoing pregnancy (OP) rates. A comprehensive literature search of 4 databases: Ovid MEDLINE, EMBASE, Maternity & Infant Care and the Cochrane Library were searched in January 2022. Upon removal of duplications, abstract screening, and full-text screening, a total of 34 papers were selected. Discussion/conclusion This review highlights a large discrepancy in the literature when examining pregnancy outcomes of IUI and IVF treatments. Evidence shows IUI increases LB and CP rates 3-fold compared to expectant management. Literature comparing IUI to IVF is less certain. The review finds the literature implies IVF should be used for first-line management but the paucity of high-quality randomised controlled trials (RCTs), coupled with heterogeneity of the identified studies and a lack of research amongst women > 40 years warrants the need for further large RCTs. The decision to offer IUI with ovarian stimulation (IUI-OS) or IVF should be based upon patient prognostic factors. We suggest that IUI-OS could be offered as first-line treatment for unexplained infertility for women  38 years. Patients should be appropriately counselled to enable informed decision making

Biases in Indian summer monsoon precipitation forecasts in the Unified Model and their relationship with BSISO index.

Abstract This study shows that the Boreal Summer Intraseasonal Oscillation (BSISO) dominates the Indian summer monsoon low‐precipitation bias in the Met Office Unified model. Analyzing a recent 9‐year period (June, July, August only), it is found that the precipitation bias is dominated by break and break‐to‐active transition BSISO phases, while some of the other phases have no bias at all over a 7‐day forecast. Evidence of a link to upstream effects is found, in that there is a delayed reduction in the moisture flux entering India from the west. It is also shown that an increase in the net flow of moisture out of India to the east is strongly linked to the low‐precipitation bias, and there is some evidence that this is related to a lack of low‐pressure systems over India. Most atmospheric models have substantial rainfall biases over India, and these results may indicate the circulation patterns responsible. Plain Language Summary The Met Office Unified Model (UM) is widely used worldwide for weather forecasting, climate prediction and environmental research. An important deficiency of the UM, in common with many other weather and climate models, is that it simulates significantly too little rainfall over India, when averaged over the summer monsoon season. Indian monsoon rainfall is important to the livelihoods of hundreds of millions of people, and these errors in the models have knock‐on consequences for weather and climate prediction around the world. This study shows that the UM's rainfall bias is dominated by periods when the general monsoon behavior is in transition from low‐activity to high‐activity, while in other periods, the rainfall forecasts perform much better. These results will help us to better understand the causes of the model bias. A systematic evaluation of the UM moisture flow has also been carried out; this suggests that a key problem in these low to high‐activity transition periods is a replacement of monsoon cyclonic systems with too much purely westerly flow out of India. The results should also be of value in weather forecasting, in identifying weather regimes where we have relatively high, and relatively low, confidence in the forecasts

Antagonism, accommodation and agonism in critical management studies: alternative organizations as allies

Critical Management Studies has long been engaged in discussions about the purpose of critique and the possibilities of engagement. A recent expression calls for Critical Management Studies to moderate its ‘negative’ critique of management and instead use words like care, engagement and affirmation in order to enable ‘progressive’ engagement with managers. This ‘performative turn’ has been poorly received by some who see it as a dilution of radical intent. We argue for a middle ground between the antagonistic versions of Critical Management Studies that appear to want to oppose management, and ‘performative’ scholars who appear to accommodate with managerialism. We do this by planting the debate firmly within an empirical setting and a crisis that the first author experienced as a ‘critical scholar’ when conducting an ethnography at a sustainable financial services firm. In order to do this, we explore Chantal Mouffe’s concept of agonism to establish a particular mode of political engagement that acknowledges a space between being ‘for’ and being ‘against’. We conclude by suggesting that the exploration of alternative forms of organization and management, themselves already involved in struggle against a hegemonic present, should be the proper task of a discipline that wishes to engage with the present and remain ‘critical

Mode Switching Is the Major Mechanism of Ligand Regulation of InsP3 Receptor Calcium Release Channels

The inositol 1,4,5-trisphosphate (InsP3) receptor (InsP3R) plays a critical role in generation of complex Ca2+ signals in many cell types. In patch clamp recordings of isolated nuclei from insect Sf9 cells, InsP3R channels were consistently detected with regulation by cytoplasmic InsP3 and free Ca2+ concentrations ([Ca2+]i) very similar to that observed for vertebrate InsP3R. Long channel activity durations of the Sf9-InsP3R have now enabled identification of a novel aspect of InsP3R gating: modal gating. Using a novel algorithm to analyze channel modal gating kinetics, InsP3R gating can be separated into three distinct modes: a low activity mode, a fast kinetic mode, and a burst mode with channel open probability (Po) within each mode of 0.007 ± 0.002, 0.24 ± 0.03, and 0.85 ± 0.02, respectively. Channels reside in each mode for long periods (tens of opening and closing events), and transitions between modes can be discerned with high resolution (within two channel opening and closing events). Remarkably, regulation of channel gating by [Ca2+]i and [InsP3] does not substantially alter channel Po within a mode. Instead, [Ca2+]i and [InsP3] affect overall channel Po primarily by changing the relative probability of the channel being in each mode, especially the high and low Po modes. This novel observation therefore reveals modal switching as the major mechanism of physiological regulation of InsP3R channel activity, with implications for the kinetics of Ca2+ release events in cells

Social interactions through the eyes of macaques and humans

Group-living primates frequently interact with each other to maintain social bonds as well as to compete for valuable resources. Observing such social interactions between group members provides individuals with essential information (e.g. on the fighting ability or altruistic attitude of group companions) to guide their social tactics and choice of social partners. This process requires individuals to selectively attend to the most informative content within a social scene. It is unclear how non-human primates allocate attention to social interactions in different contexts, and whether they share similar patterns of social attention to humans. Here we compared the gaze behaviour of rhesus macaques and humans when free-viewing the same set of naturalistic images. The images contained positive or negative social interactions between two conspecifics of different phylogenetic distance from the observer; i.e. affiliation or aggression exchanged by two humans, rhesus macaques, Barbary macaques, baboons or lions. Monkeys directed a variable amount of gaze at the two conspecific individuals in the images according to their roles in the interaction (i.e. giver or receiver of affiliation/aggression). Their gaze distribution to non-conspecific individuals was systematically varied according to the viewed species and the nature of interactions, suggesting a contribution of both prior experience and innate bias in guiding social attention. Furthermore, the monkeys’ gaze behavior was qualitatively similar to that of humans, especially when viewing negative interactions. Detailed analysis revealed that both species directed more gaze at the face than the body region when inspecting individuals, and attended more to the body region in negative than in positive social interactions. Our study suggests that monkeys and humans share a similar pattern of role-sensitive, species- and context-dependent social attention, implying a homologous cognitive mechanism of social attention between rhesus macaques and humans

Sperm death and dumping in Drosophila

Mating with more than one male is the norm for females of many species. In addition to generating competition between the ejaculates of different males, multiple mating may allow females to bias sperm use. In Drosophila melanogaster, the last male to inseminate a female sires approximately 80% of subsequent progeny. Both sperm displacement, where resident sperm are removed from storage by the incoming ejaculate of the copulating male, and sperm incapacitation, where incoming seminal fluids supposedly interfere with resident sperm, have been implicated in this pattern of sperm use. But the idea of incapacitation is problematic because there are no known mechanisms by which an individual could damage rival sperm and not their own. Females also influence the process of sperm use, but exactly how is unclear. Here we show that seminal fluids do not kill rival sperm and that any 'incapacitation' is probably due to sperm ageing during sperm storage. We also show that females release stored sperm from the reproductive tract (sperm dumping) after copulation with a second male and that this requires neither incoming sperm nor seminal fluids. Instead, males may cause stored sperm to be dumped or females may differentially eject sperm from the previous mating