microRNA-324 mediates bone homeostasis and the regulation of osteoblast and osteoclast differentiation and activity

MicroRNAs (miRNAs) modulate the expression of other RNA molecules. One miRNA can target many transcripts, allowing each miRNA to play key roles in many biological pathways. Defects in bone homeostasis result in common age-related diseases including osteoporosis. Serum levels of miR-324-3p positively correlate with several features of bone maintenance. In contrast here, using in vivo micro-computed tomography and histology, global miR-324-null mice demonstrated increased bone mineral density and both trabecular and cortical thickness, with effect magnitudes increasing with age. The bone marrow of miR-324-null mice had reduced lipid content while TRAP staining revealed a decrease in osteoclasts, with histomorphometry demonstrating an increased rate of bone formation. Ex vivo assays showed that the high bone mass phenotype of miR-324-null mice resulted from both increased osteoblast activity and decreased osteoclastogenesis. RNA-seq analysis of osteoblasts, osteoclasts and bone marrow macrophages and target validation assays identified that the osteoclast fusion regulator Pin1 and the master osteogenic regulator Runx2 were targets of miR-324-5p in osteoclast lineage cells and osteoblasts, respectively. Indeed, in vitro Runx2 overexpression recapitulated the increased osteogenesis and decreased adipogenesis phenotype observed in vivo by the loss of miR-324. Overall, these data demonstrate the importance of miR-324 in bone homeostasis by regulating aspects of both bone formation and remodelling. Elucidation of pathways regulated by miR-324 offer promise for the treatment of bone diseases such as osteoporosis

Cross-national knowledge distance and host country innovation—The mediating roles of local talents and third-country exporting

Drawing on embeddedness and learning perspectives, we examine and extend the learning-by-hiring (LBH) and learning-by-exporting (LBE) logics to better understand the innovation activities of advanced economy multinational enterprises (AEMNEs) in a dissimilar knowledge context where cross-national differences persist. We consider that the use of local talents manifests the LBH logic as a means of enhancing AEMNEs' local embeddedness. Likewise, third-country exporting is underpinned by the LBE logic as a way for MNEs to leverage third-country embeddedness. We propose that these two mechanisms act as mediators that shape and filter AEMNEs' access and integration of geographically distant knowledge for their emerging market innovation. Moreover, we predict a complementarity between employing local talents and third-country exporting. Our findings from an analysis of AEMNEs operating in China provide support for these predictions. This study offers important implications for managing multiple embeddedness across AEMNEs' global networks in order for their innovation to flourish in emerging markets

Numerical investigation of fin geometries on the effectiveness of passive, phase-change material−based thermal management systems for lithium-ion batteries

Lithium-ion battery (LIB) packs serve as the primary energy storage solution for electric vehicles (EVs), but suffer from degraded performance under non-uniform and sub-optimal operating temperatures. Passive Thermal Management Systems (TMS) based on solid–liquid Phase Change Materials (PCMs) exhibit significant potential, however PCMs’ low thermal conductivity has limited their application. Integrating fins to improve heat transfer has been proposed, but there remains a lack of knowledge regarding how the system size and discharge time scale affects thermal performance with differing fin geometries. Here, a numerical model is developed using Ansys Fluent and validated to examine the time-resolved TMS performance with differing fin geometries under thermal loading and resting conditions. Two system scales are examined, with dimensions of the order of either 10 mm or 100 mm. For small-scale systems, fins offer no meaningful improvement compared to PCM alone: the best-performing fin geometry only reduces the maximum cell temperature by 0.2 °C at the end of a 720 s (5C) discharge. However, for the large-scale system, the performance depends strongly on the discharge duration. Of all geometries, 9 vertical fins are best performing at 480 s of discharge (38.3 °C maximum cell temperature with a 2.4 °C disuniformity), but become worst performing at 720 s (44.0 °C, 7.2 °C disuniformity). At 720 s, 7 horizontal fins instead become best performing (42.5 °C, 2.6 °C disuniformity) as large thermal gradients caused by convection are suppressed. Overall, we show via a Pareto analysis which geometries offer acceptable trade-offs between thermal performance and TMS mass

Thinking about thinking: A longitudinal investigation linking developments in metacognition, inhibitory control, and theory of mind

This longitudinal study tracked the developmental relations linking metacognition, theory of mind, and inhibitory control in 52 children across a 1.5-year interval, beginning at 3 or 4 years of age. Metacognition and inhibitory control emerged before theory of mind and predicted subsequent theory of mind competence. Moreover, there was evidence of developmental mediation, whereby metacognition predicted inhibitory control, which predicted theory of mind. We suggest that metacognitive self-reflection may provide the “developmental enrichment” necessary to think about thinking, and when inhibitory control is sufficiently developed this thinking can be extended to complex reasoning about own and other minds

Is this network proper forest-based?

In evolutionary biology, networks are becoming increasingly used to represent evolutionary histories for species that have undergone non-treelike or reticulate evolution. Such networks are essentially directed acyclic graphs with a leaf set that corresponds to a collection of species, and in which non-leaf vertices with indegree 1 correspond to speciation events and vertices with indegree greater than 1 correspond to reticulate events such as gene transfer. Recently forest-based networks have been introduced, which are essentially (multi-rooted) networks that can be formed by adding some arcs to a collection of phylogenetic trees (or phylogenetic forest), where each arc is added in such a way that its ends always lie in two different trees in the forest. In this paper, we consider the complexity of deciding whether a given network is proper forest-based, that is, whether it can be formed by adding arcs to some underlying phylogenetic forest which contains the same number of trees as there are roots in the network. More specifically, we show that it is NP-complete to decide whether a tree-child network with m roots is proper forest-based, for each m>=2. Moreover, for binary networks the problem remains NP-complete when m>=3 but becomes polynomial-time solvable for m=2. We also give a fixed parameter tractable (FPT) algorithm, with parameters the maximum outdegree of a vertex, the number of roots, and the number of indegree 2 vertices, for deciding if a semi-binary network is proper forest-based. A key element in proving our results is a new characterization for when a network with m roots is proper forest-based in terms of certain m-colorings

Sedation and analgesia practices for less-invasive surfactant administration, elective endotracheal intubation, and mechanical ventilation: A national UK survey

Preferences for preprocedural premedication and provision of routine analgesia and sedation for ventilated babies may vary. We aimed to survey current practices in UK tertiary-level neonatal intensive care units (NICUs). In February to April 2024, we conducted a telephone questionnaire survey of tertiary-level UK NICUs using a bespoke proforma (online supplemental file 1). We asked practitioners about their unit’s practice for surfactant administration, preprocedural medication use before less invasive surfactant administration (LISA) and before elective endotracheal intubation, and whether they routinely used analgesia/sedation for mechanically ventilated infants

No Filters:A Mother and Teenage Daughter Love Story

How can we communicate when things are so painful? How can we connect when generational differences are extreme? How do parents and teenagers - and all of us - have real conversations? When Rowan was sixteen, she only tolerated communication from her mother in the form of Snapchat. Desperate to be closer to her daughter, Christie sent daily selfies of her face superimposed onto a chicken nugget. It took serious illness for them to finally talk – and truly listen. Rowan's mental health struggles revealed the chasm between their generations. They started being more honest with each other than they had ever been before: discussing identity, race and gender; opening up about disordered eating and self-harm; navigating the perils of social media. In an age of polarisation, this is how a mother and daughter find humour in the things that divide them and become more hopeful about the future of our world. A book for all parents and teenagers going through a tough time, for friends, grandparents, teachers and healthcare professionals who want to help, its bare honesty will have you laughing – and possibly crying – out loud as it shows that you are not alone

Effectiveness of a task-sharing collaborative care model for the detection and management of depression among adults receiving antiretroviral therapy in primary care facilities in South Africa: A pragmatic cluster randomised controlled trial

Background: HIV is characterised by high rates of comorbidity with mental health conditions including depression, as such, the detection and treatment of comorbid depression is critical to achieve viral load suppression. This study evaluated the effectiveness of a collaborative care intervention for depression among adults with comorbid depression symptoms receiving ART in primary health care (PHC) facilities. Methods: We conducted a pragmatic cluster-randomised trial in 40 clinics in the North West province of South Africa. PHC clinics were stratified by sub-district and randomised in a 1:1 ratio. Participants were ≥ 18 years, receiving ART, and had depression symptoms indicated by Patient Health Questionnaire-9 (PHQ-9) score ≥ 9. Intervention clinics received: i) supplementary mental health training and clinical communication skills for PHC nurses; ii) workshops for PHC doctors on treating depression; and iii) lay counselling services. Using mixed effects regression models, we assessed co-primary outcomes of PHQ-9 response at 6 months (≥50 % reduction in baseline PHQ-9 score) and viral load suppression at 12 months (viral load<1000 copies/mL). Results: The intervention had no effect in PHQ-9 response (49 % vs 57 %, risk difference (RD) = −0.08, 95 % CI = −0.19; 0.03, p = 0.184) or viral load suppression (85 % vs 84 %, RD = 0.02, 95 % CI = −0.01; 0.04, p = 0.125). Nurses referred 4298 clinic patients to counsellors, however, only 66/1008 (7 %) of intervention arm participants were referred to counsellors at any point during the study. Limitations: The highly pragmatic approach of this trial limited exposure to the counselling component of the intervention and referral to doctors for initiation of antidepressant treatment was extremely low. Conclusion: The trial showed no effect of a district-based intervention to strengthen collaborative care for depression. The trial revealed the extent of the treatment gap in the context of scaling up mental health services. Trial registration: ClinicalTrials.gov (NCT02407691); Pan African Clinical Trials Registry (201504001078347)