Differential transcription factor expression by human epithelial cells of buccal and urothelial derivation

Identification of transcription factors expressed by differentiated cells is informative not only of tissue-specific pathways, but to help identify master regulators for cellular reprogramming. If applied, such an approach could generate healthy autologous tissue-specific cells for clinical use where cells from the homologous tissue are unavailable due to disease. Normal human epithelial cells of buccal and urothelial derivation maintained in identical culture conditions that lacked significant instructive or permissive signalling cues were found to display inherent similarities and differences of phenotype. Investigation of transcription factors implicated in driving urothelial-type differentiation revealed buccal epithelial cells to have minimal or absent expression of PPARG, GATA3 and FOXA1 genes. Retroviral overexpression of GATA3 or PPARG1 coding sequences in buccal epithelial cells resulted in nuclear immunolocalisation of the respective proteins, with both transductions also inducing expression of the urothelial differentiation-associated claudin 3 tight junction protein. PPARγ1 overexpression alone entrained expression of nuclear FOXA1 and GATA3 proteins, providing objective evidence of its upstream positioning in a transcription factor network and identifying it as a candidate factor for urothelial-type transdifferentiation or reprogramming

Diverse metallicities of Fermi bubble clouds indicate dual origins in the disk and halo

The Galactic Center is surrounded by two giant plasma lobes known as the Fermi Bubbles, extending ~10 kpc both above and below the Galactic plane. Spectroscopic observations of Fermi Bubble directions at radio, ultraviolet, and optical wavelengths have detected multi-phase gas clouds thought to be embedded within the bubbles referred to as Fermi Bubble high-velocity clouds (FB HVCs). While these clouds have kinematics that can be modeled by a biconical nuclear wind launched from the Galactic center, their exact origin is unknown because, until now, there has been little information on their heavy-metal abundance (metallicity). Here we show that FB HVCs have a wide range of metallicities from <20% solar to ~320% solar. This result is based on the first metallicity survey of FB HVCs. These metallicities challenge the previously accepted tenet that all FB HVCs are launched from the Galactic center into the Fermi Bubbles with solar or super-solar metallicities. Instead, we suggest that FB HVCs originate in both the Milky Way's disk and halo. As such, some of these clouds may characterize circumgalactic medium that the Fermi Bubbles expand into, rather than material carried outward by the nuclear wind, changing the canonical picture of FB HVCs. More broadly, these results reveal that nuclear outflows from spiral galaxies can operate by sweeping up gas in their halos while simultaneously removing gas from their disks.Comment: This version of the article has been accepted for publication on Nature Astronomy after peer review. This version is not the Version of Record (https://doi.org/10.1038/s41550-022-01720-0) and does not reflect post-acceptance improvements, or any correction

Mean field analysis gives accurate predictions of the behaviour of large networks of sparsely coupled and heterogeneous neurons

Large networks of integrate-and-fire (IF) model neurons are often used to simulate and study the behaviour of biologically realistic networks. However, to fully study the large network behaviour requires an exploration of large regions of a multidimensional parameter space. Such exploration is generally not feasible with large network models, due to the computational time required to simulate a network with biologically significant size. To circumvent these difficulties we use a mean-field approach, based on the work of [1]. We consider a sparsely coupled, excitatory network of 10,000 Izhikevich model neurons [2], with Destexhe-type synapses [3]. The cellular models were fit to hippocampal CA1 pyramidal neurons and have heterogeneous applied currents with a normal distribution. We derived a mean-field system for the network which consists of differential equations for the mean of the adaptation current and the synaptic conductance. As CA1 is an area that displays prominent theta oscillations [4], we used the mean-field system to study how the frequency of bursting depends on various model parameters. Figure 1A shows an example study. These studies were successful in guiding numerical simulations of the large network. When parameter values determined from the mean-field analysis are used in a large network simulation, bursting of the predicted frequency occurs

Assessing the impact of principal’s instructional leadership, school level, and effectiveness in educational institutions

This study aimed to investigate the relationship between instructional leadership and school effectiveness in educational institutions in Toledo City Division, Philippines. A mixed-methods approach was utilized, including a survey questionnaire and focus group discussions. The survey was administered to 13 school principals, while the focus group discussions involved 14 teachers and school administrators. The quantitative results showed that instructional leadership had a significant positive effect on school effectiveness, while school level did not have a significant effect. The qualitative findings highlighted the challenges faced by school principals in implementing effective instructional leadership practices, including resistance to change and limited resources. The importance of collaboration and communication between school principals, teachers, and the community in promoting effective instructional leadership practices was also emphasized. The comparative analysis of the quantitative and qualitative results revealed that while the survey results showed a significant positive relationship between instructional leadership and school effectiveness, the focus group discussions provided valuable insights into the challenges and strategies for effective implementation of instructional leadership practices. Overall, this study suggests that instructional leadership plays a critical role in enhancing school effectiveness in educational institutions in Toledo City Division, Philippines. The findings highlight the need for collaboration and communication between school leaders, teachers, and the community to ensure the success of instructional leadership practices. These findings have implications for educational policy and practice, emphasizing the importance of investing in instructional leadership development and support to improve school effectiveness

Facet-joint injections for people with persistent non-specific low back pain (FIS) : study protocol for a randomised controlled feasibility trial

BACKGROUND: The role of injections of therapeutic substances into the back as treatment for low back pain is unclear. Facet joint injections are widely used despite the absence of evidence of sustained benefit. We hypothesise that facet joint injections might facilitate engagement with physiotherapist-led, best usual care (a combined physical and psychological programme) and is a clinically and cost-effective treatment for people with suspected low back pain of facet joint origin. METHODS/DESIGN: We present here the protocol for a randomised controlled feasibility trial for a main trial to test the above hypotheses. Patients referred to secondary care with persistent non-specific low back pain will be screened and invited to take part in the study. Those who meet the eligibility criteria will be invited for a physiotherapy assessment to confirm trial eligibility and for baseline data collection. All participants (n = 150) will be offered the best usual care package with physical and psychological components. Those randomised into the intervention arm (n = 75) will, in addition, receive intra-articular facet joint injections with local anaesthetic and steroids. Primary outcome data will be collected using daily and then weekly text messaging service for a pain score on a 0-10 scale. Questionnaire follow-up will be at 3, 6, and 12 months. Evaluation of trial processes and health economic analyses, including a value of information analysis, will be undertaken. The process evaluation will be mixed methods and will include the views of all stakeholders. DISCUSSION: Whilst this trial is a feasibility study it is currently one of the largest trials in this area. The outcomes will provide some evidence on the use of facet joint injections for patients with clinically diagnosed facet joint pain. TRIAL REGISTRATION: EudraCT identifier 2014-000682-50

Towards greater transparency and coherence in funding for sustainable marine fisheries and healthy oceans

This final manuscript in the special issue on “Funding for ocean conservation and sustainable fisheries” is the result of a dialogue aimed at connecting lead authors of the special issue manuscripts with relevant policymakers and practitioners. The dialogue took place over the course of a two-day workshop in December 2018, and this “coda” manuscript seeks to distil thinking around a series of key recurring topics raised throughout the workshop. These topics are collected into three broad categories, or “needs”: 1) a need for transparency, 2) a need for coherence, and 3) a need for improved monitoring of project impacts. While the special issue sought to collect new research into the latest trends and developments in the rapidly evolving world of funding for ocean conservation and sustainable fisheries, the insights collected during the workshop have helped to highlight remaining knowledge gaps. Therefore, each of the three “needs” identified within this manuscript is followed by a series of questions that the workshop participants identified as warranting further attention as part of a future research agenda. The crosscutting nature of many of the issues raised as well as the rapid pace of change that characterizes this funding landscape both pointed to a broader need for continued dialogue and study that reaches across the communities of research, policy and practice.S

Engaging stakeholders to identify gaps and develop strategies to inform evidence use for health policymaking in Nigeria

Introduction: recent efforts to bridge the evidence-policy gap in low-and middle-income countries have seen growing interest from key audiences such as government, civil society, international organizations, private sector players, academia, and media. One of such engagement was a two-day virtual participant-driven conference (the convening) in Nigeria. The aim of the convening was to develop strategies for improving evidence use in health policy. The convening witnessed a participant blend of health policymakers, researchers, political policymakers, philanthropists, global health practitioners, program officers, students, and the media. Methods: in this study, we analyzed conversations at the convening with the aim to disseminate findings to key stakeholders in Nigeria. The recordings from the convening were transcribed and analyzed inductively to identify emerging themes, which were interpreted, and inferences are drawn. Results: a total of 630 people attended the convening. Participants joined from 13 countries. Participants identified poor collaboration between researchers and policymakers, poor community involvement in research and policy processes, poor funding for research, and inequalities as key factors inhibiting the use of evidence for policymaking in Nigeria. Strategies proposed to address these challenges include the use of participatory and embedded research methods, leveraging existing systems and networks, advocating for improved funding and ownership for research, and the use of context-sensitive knowledge translation strategies. Conclusion: overall, better interaction among the various stakeholders will improve the evidence generation, translation, and use in Nigeria. A road map for the dissemination of findings from this conference has been developed for implementation across the strata of the health system

Discovery of FERM domain protein-protein interaction inhibitors for MSN and CD44 as a potential therapeutic approach for Alzheimer\u27s disease.

Proteomic studies have identified moesin (MSN), a protein containing a four-point-one, ezrin, radixin, moesin (FERM) domain, and the receptor CD44 as hub proteins found within a coexpression module strongly linked to Alzheimer\u27s disease (AD) traits and microglia. These proteins are more abundant in Alzheimer\u27s patient brains, and their levels are positively correlated with cognitive decline, amyloid plaque deposition, and neurofibrillary tangle burden. The MSN FERM domain interacts with the phospholipid phosphatidylinositol 4,5-bisphosphate (PI

On the Use of Unmanned Aerial Systems for Environmental Monitoring

Environmental monitoring plays a central role in diagnosing climate and management impacts on natural and agricultural systems; enhancing the understanding of hydrological processes; optimizing the allocation and distribution of water resources; and assessing, forecasting, and even preventing natural disasters. Nowadays, most monitoring and data collection systems are based upon a combination of ground-based measurements, manned airborne sensors, and satellite observations. These data are utilized in describing both small- and large-scale processes, but have spatiotemporal constraints inherent to each respective collection system. Bridging the unique spatial and temporal divides that limit current monitoring platforms is key to improving our understanding of environmental systems. In this context, Unmanned Aerial Systems (UAS) have considerable potential to radically improve environmental monitoring. UAS-mounted sensors offer an extraordinary opportunity to bridge the existing gap between field observations and traditional air- and space-borne remote sensing, by providing high spatial detail over relatively large areas in a cost-effective way and an entirely new capacity for enhanced temporal retrieval. As well as showcasing recent advances in the field, there is also a need to identify and understand the potential limitations of UAS technology. For these platforms to reach their monitoring potential, a wide spectrum of unresolved issues and application-specific challenges require focused community attention. Indeed, to leverage the full potential of UAS-based approaches, sensing technologies, measurement protocols, postprocessing techniques, retrieval algorithms, and evaluation techniques need to be harmonized. The aim of this paper is to provide an overview of the existing research and applications of UAS in natural and agricultural ecosystem monitoring in order to identify future directions, applications, developments, and challengespublishersversionPeer reviewe