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The open access movement has drastically reconfigured the financial burdens of scholarly publishing. Yet, the influence of a marketized scholarly publishing system on doctoral education remains unexplored. I reflect on my own PhD candidature to illustrate how article processing charges disempower doctoral candidates. I argue that the current open access publishing model unfairly advantages candidates with personal, familial and/or institutional wealth. The inequalities imposed on doctoral students by our sectors’ current publishing habits ultimately bias who will be paid to produce and safeguard knowledge in the future. Doctoral students can no longer be ignored in debates over open access publishing.

Background Coproduction is defined as patients and clinicians collaborating equally and reciprocally in healthcare and is a crucial concept for quality improvement (QI) of health services. Learning Health Networks (LHNs) provide insights to integrate coproduction with QI efforts from programmes from various health systems.Objective We describe interventions to develop and maintain patient and family partner (PFP) coproduction, measured by PFP-reported and programme-reported scales. We aim to increase percentage of programmes with PFPs reporting active QI work within their programme, while maintaining satisfaction in PFP-clinician relationships.Methods Conducted in the Cystic Fibrosis Learning Network (CFLN), an LHN comprising over 30 cystic fibrosis (CF) programmes, people with CF, caregivers and clinicians cocreated interventions in readiness awareness, inclusive PFP recruitment, onboarding process, partnership development and leadership opportunities. Interventions were adapted by CFLN programmes and summarised in a change package for existing programmes and the orientation of new ones. We collected monthly assessments for PFP and programme perceptions of coproduction and PFP self-rated competency of QI skills and satisfaction with programme QI efforts. We used control charts to analyse coproduction scales and run charts for PFP self-ratings.Results Between 2018 and 2022, the CFLN expanded to 34 programmes with 52% having ≥1 PFP reporting active QI participation. Clinicians from 76% of programmes reported PFPs were actively participating or leading QI efforts. PFPs reported increased QI skills competency (17%–32%) and consistently high satisfaction and feeling valued in their work.Conclusions Implementing system-level programmatic strategies to engage and sustain partnerships between clinicians and patients and families with CF improved perceptions of coproduction to conduct QI work. Key adaptable strategies for programmes included onboarding and QI training, supporting multiple PFPs simultaneously and developing financial recognition processes. Interventions may be applicable in other health conditions beyond CF seeking to foster the practice of coproduction.

Book review of The Pernicious PhD Supervisor, written and narrated by Tara Brabazon.

Irrigation schemes across sub-Saharan Africa are constructed with the intention of increasing agricultural production to increase food security, reduce poverty and improve economic growth. However, most of these schemes are not performing as expected. This study therefore, diagnosed performance gaps in the pilot irrigation schemes of Mubuku and Doho in Uganda and analysed sustainable improvement options. Data was collected through systematic review of literature and scheme data, direct measurements at the schemes, field surveys, inspections, and key informant interviews. For each scheme, data for climate, irrigation, flow measurements, crop yields and farm gate prices were collected. Comparative indicators of agricultural output, water supply, financial and physical sustainability were used to assess scheme performance using standard approaches by International Water Management Institute (IWMI). The findings showed that the schemes were not performing optimally with crop yields being far below the attainable potential. The major contributing factors to the low performance were low water use efficiency and low agricultural output. Poor flow control, poor water distribution, and poor on-farm water application contributed to low water use efficiency. Low agricultural production was attributed to poor crop yields resulting from poor agronomic practices, poor irrigation scheduling and low produce prices. The financial self-sufficiency indicator pointed to farmers’ inability to operate and maintain irrigation schemes effectively. Improving the irrigation schemes performance requires a multidisciplinary approach targeting the improvement water use efficiency and agricultural output.

The adoption of Fourth Industrial Revolution (4IR) technologies has revolutionized agricultural practices worldwide. However, their application in the context of sub-Saharan Africa remains a critical challenge. This study presents a systematic review that investigates the potential of 4IR technologies in smart irrigation. Sub-Saharan Africa faces multiple agricultural challenges, exacerbated by climate change, water scarcity, and inefficient irrigation practices. The need for sustainable, water-efficient, and data-driven irrigation systems is urgent to ensure food security and economic development in the region. This study addresses a crucial knowledge gap by assessing the constraints, opportunities, and prospects of implementing 4IR technologies for smart irrigation in sub-Saharan Africa. A systematic review methodology was employed, utilizing reputable databases including Web of Science, Google Scholar, Science Direct, Institute of Electrical and Electronics Engineers (IEEE) Xplore, and PubMed. A comprehensive search strategy was designed to identify peer-reviewed articles, conference papers, and reports related to the application of Internet of Things, Artificial Intelligence, Unmanned Aerial Vehicles, Big Data, and Blockchain technology in smart irrigation. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) approach was used to arrive at 95 articles included in this research. The review reveals promising trends in the integration of 4IR technologies for smart irrigation. 4IR technologies including Artificial Intelligence, Internet of Things, Big Data technology, Blockchain and drones are widely used in smart irrigation. These technologies have facilitated real time monitoring of soil moisture and weather conditions, precision irrigation scheduling, water allocation optimization, rapid data collection, insights in real time crop water use and transparency and trust in agricultural water management among others. While the potential of 4IR technologies is evident, challenges including limited infrastructure, access to technology, and technical expertise pose significant barriers for the adoption in sub-Saharan Africa. Additionally, the high initial costs associated with these technologies can impede widespread adoption. The study highlights the potential to leverage existing mobile phone penetration for IoT data collection, collaborative partnerships, and innovative financing models to overcome financial constraints. Capacity-building initiatives and knowledge transfer can empower local communities to embrace these technologies. The future of smart irrigation in sub-Saharan Africa relies on policy support, investments, and technology diffusion strategies. It is imperative to create an enabling environment that fosters innovation and addresses the unique needs of the region. Collaboration between governments, academia, industry, and international organizations can catalyze the transformative impact of 4IR technologies, ultimately enhancing irrigation sustainability and food security.

Increasing obesity rates are an enduring concern for the health sector globally. By the beginning of the 21st century, neuroscientists began to assert that obesity is primarily a brain disorder. The resulting field of obesity neuroscience has become an influential lens through which to research the pathogenesis of diet-induced obesity, with important implications for both public health and bioethics. This historical analysis aims to trace the intellectual origins of the obesity neuroscience discipline by examining two historical events: the United States’ war on drugs, and the nutrition transition. Major historical milestones associated with each of these events are analyzed. Then, the convergence of these events is characterized, by an analysis of how this transformed neuroscience research on hunger. This analysis demonstrates how the US war on drugs discovered new neurobehavioral epistemologies, predominately around addiction, that were then grafted onto the existing neuroscience of hunger. The resulting analysis provides an illustrative explanation of the close epistemological relationship between obesity neuroscience and addiction.

Degenerative disc disease (DDD) is a pervasive condition that limits quality of life and burdens economies worldwide. Conventional pharmacological treatments primarily aimed at slowing the progression of degeneration have demonstrated limited long-term efficacy and often do not address the underlying causes of the disease. On the other hand, orthobiologics are regenerative agents derived from the patient’s own tissue and represent a promising emerging therapy for degenerative disc disease. This review comprehensively outlines the pathophysiology of DDD, highlighting the inadequacies of existing pharmacological therapies and detailing the potential of orthobiologic approaches. It explores advanced tools such as platelet-rich plasma and mesenchymal stem cells, providing a historical overview of their development within regenerative medicine, from foundational in vitro studies to preclinical animal models. Moreover, the manuscript delves into clinical trials that assess the effectiveness of these therapies in managing DDD. While the current clinical evidence is promising, it remains insufficient for routine clinical adoption due to limitations in study designs. The review emphasizes the need for further research to optimize these therapies for consistent and effective clinical outcomes, potentially revolutionizing the management of DDD and offering renewed hope for patients.

Psychiatric disorders like major depressive disorder (MDD), schizophrenia (SCZ), and bipolar disorder (BPD), represent a significant global public health concern. Sex differences in the prevalence and presentation of psychiatric disorders, and the association of a psychiatric diagnosis with increased risk of suicide, are well-established. However, the neurobiology underlying these features of disease are not well understood. Dysfunction of the orbitofrontal cortex (OFC), a brain region responsible for decision-making and sensory processing, has been implicated in psychiatric disorders but remains understudied compared to other frontocortical brain regions. In this study we investigated sexual dimorphism in psychiatric illnesses and suicide by analyzing publicly available OFC transcriptional profiles (RNAseq data obtained from the Stanley Neuropathology Consortium) from individuals with SCZ, BPD, MDD, and non-psychiatric controls (n=15/group). Gene set enrichment analysis (GSEA) revealed significant differences in immune-related processes in male and female comparisons and in psychiatric disorders relative to controls. Analysis of top differentially expressed genes found changes in P2RY12 in males and females who died by suicide. Additionally, downregulation of protein folding processes was observed in female suicide subjects, suggesting an association between dysregulated protein metabolism and suicide. Our results further our understanding of the shared and unique molecular pathways underlying psychiatric disorders and suicide.

The adverse effects of climate change and climate variability are hindering agricultural productivity in developing countries. When combined with the laborious nature of irrigated agriculture, many smallholder farmers in these countries abandon irrigation systems or occasionally fail to implement an irrigation event due to other commitments. Therefore, this necessitates smart technology advances in agriculture to deal with irrigated agriculture problems of energy use efficiency, cost, water conservation, and drudgery. This study aimed at developing a mobile solar-powered control system for real-time scheduling using feedback from soil moisture sensors. A smart solar-powered irrigation control system (Smart Irri-Kit) was developed to schedule and automate water delivery to crops based on soil moisture levels. Itincorporates an automated tank water level control system that triggers pump activation during irrigation. The Kit was designed, fabricated, programmed, and field tested at Makerere University Agricultural Research Station Kabanyolo, using sandy clay loam soil. In this study, efficient irrigation scheduling and relay of soil moisture updates to the farmers were achieved. The Smart Irri-Kit soil moisture sensors were able to detect soil moisture with no significant difference from the gravimetric method. The development of the solar-powered Smart Irri-Kit presents a sustainable and automated solution for optimizing irrigation practices, contributing to water conservation and improved crop yield. The integration of solar power enhances its autonomy and reduces operational costs. Future research directions include the incorporation of weather parameters and advanced communication capabilities for remote monitoring and control. Overall, the Smart Irri-Kit holds great potential in promoting efficient and sustainable irrigation practices in agriculture

There is information paucity on response of Napier production to different irrigation water management strategies. The study aimed at assessing the response of dry matter Napier yields (ton/ha) to different irrigation regimes. A single factor experiment was arranged in a completely randomized design under drip irrigation with three treatments: (T1) full irrigation, and two deficit treatments at 50% (T2) and 25% (T3) of full irrigation. The control was rainfed (T0). Results indicated that T2 saved over 48% of irrigation water with minimal yield reductions (14%) compared to T1. During peak dry season, T2 water productivity was higher by 20% compared to T1. Over 40% yield increase was observed in Treatment T3 at peak dry season. In comparison with T0, there was 132% average yield increase under T2 during the first, second, and third growth cycles. Thus, irrigation at 50% total available water is critical in addressing the fodder gap and contributes to minimizing livestock movement in search of pasture, hence, increased productivity.

Background: The standard treatment for patients with large brain metastases and limited intracranial disease is surgical resection and post-operative stereotactic radiosurgery (SRS). However, post-operative SRS still has elevated rates of local failure (LF) and is complicated by radiation necrosis (RN), and meningeal disease (MD). Pre-operative SRS may reduce the risk of RN and MD, while fractionated therapy may improve local control through delivering a higher biological effective dose. We hypothesize that pre-operative fractionated stereotactic radiation therapy (FSRT) will have less toxicity compared to patients who receive post-operative SRS or FSRT. Methods: A multi-institutional analysis was conducted and included patients who had surgical resection and stereotactic radiation therapy to treat at least one brain metastasis. Pertinent demographic, clinical, radiation, surgical, and follow up data were collected for each patient. The primary outcome was a composite endpoint defined as patients with one of the following adverse events: 1) LF, 2) MD, and/or 3) Grade 2 or higher (symptomatic) RN. Results: 279 patients were eligible for analysis. The median follow-up time was 9 months. 87 % of patients received fractionated treatment. 29 % of patients received pre-operative treatment. The composite endpoint incidences for post-operative SRS (n = 10), post-operative FSRT (n = 189), pre-operative SRS (n = 27), and pre-operative FSRT (n = 53) were 0 %, 17 %, 15 %, and 7.5 %, respectively. Conclusions: In our study, the composite endpoint of 7.5% for pre-operative FSRT compares favorably to our post-operative FSRT rate of 17%. Pre-operative FSRT was observed to have low rates of LF, MD, and RN. Prospective validation is needed.

The rising competition for scarce land and water resources and the need to satisfy the global food demand from an ever-growing population necessitates novel methods to monitor irrigation scheme performance for improved water use efficiency. The traditional methods employed in sub-Saharan Africa to assess irrigation performance are point-based, expensive, and time-consuming, making monitoring and evaluation of these capital-intensive projects difficult. This study aimed at employing satellite data with high spatial and temporal resolution in assessing the performance of Doho Rice Irrigation Scheme through estimations of actual evapotranspiration. Actual evapotranspiration (ETa) was modelled from Landsat 7 imagery using the surface energy balance system algorithm on five clear days between January and April 2020. Using equity and adequacy metrics, the derived ETa was used to assess the irrigation performance of the scheme. Results showed that the equity indicator was generally fair, with the coefficient of variation between 0.11 and 0.08, close to the 0.10 threshold implying irrigation water is fairly distributed within the scheme. The average adequacy was 0.87, above the 0.65 threshold, indicating adequate water supply throughout the scheme. The study's findings can be used in future research and benchmarking with other irrigation schemes to address the country's water resource management challenges.

Background & Aims: Although basal cell hyperplasia is a histologic hallmark of eosinophilic esophagitis (EoE), little is known about the capabilities of epithelial renewal and differentiation in the EoE inflammatory milieu. In murine esophageal epithelium, there are self-renewing and slowly proliferating basal stem-like cells characterized by concurrent expression of CD73 (5'-nucleotidase ecto) and CD104 (integrin β4). Here, we investigated CD73+CD104+ cells within the basal population of human esophageal epithelium and clarified the biological significance of these cells in the EoE epithelium. Methods: We performed flow cytometry on esophageal biopsy samples from EoE and non-EoE patients to determine the quantity of CD73+CD104+ cells in the epithelium. Simulating the EoE milieu we stimulated primary patient-derived and immortalized cell line–derived esophageal organoids with interleukin (IL)4 and IL13 and analyzed by flow cytometry, immunohistochemistry, and quantitative reverse-transcription polymerase chain reaction. We performed single-cell RNA sequencing on primary organoids in the setting of IL13 stimulation and evaluated the CD73+CD104+ population. We performed fluorescent-activated cell sorting to purify CD73+CD104+ and CD73- CD104+ populations and seeded these groups in organoid culture to evaluate the organoid formation rate and organoid size. We used RNA interference to knock down CD73 in esophageal organoids to evaluate organoid formation rates and size. We evaluated the effects of signal transducer and activator of transcription 6 (STAT6) signaling inhibition by RNA interference, a STAT6 inhibitor, AS1517499, as well as the proton pump inhibitor omeprazole. Results: EoE patients showed decreased epithelial CD73+CD104+ cell content. IL4 and IL13 stimulation depleted this population in 3-dimensional organoids with a recapitulation of basal cell hyperplasia as corroborated by single-cell RNA sequencing of the organoids, which suggests depletion of CD73+CD104+ cells. The CD73+CD104+ population had enhanced organoid formation compared with the CD73-CD104+ population. Similarly, knock-down of CD73 resulted in decreased organoid formation rate. Genetic and pharmacologic inhibition of STAT6 prevented T helper 2 cytokine-induced depletion of CD73+CD104+ cells. Lastly, omeprazole treatment prevented the effects of IL4 and IL13 on the CD73+CD104+ population. Conclusions: This study addressed the role of CD73+CD104+ cells in epithelial renewal and homeostasis in the context of EoE. The depletion of the CD73+CD104+ self-renewal population by helper T cell 2 cytokines in EoE milieu may be perpetuating epithelial injury. Future therapies targeting epithelial restitution in EoE could decrease the need for immune modulation and steroid therapy.

Development of local technologies is crucial to the sustainable energy agenda in resource-limited countries and the world. Strengthening local green technologies and promoting local utilization will reduce carbon emissions that could be generated during transportation and delivery of green products from one country to another. In this paper we developed bio-oil/diesel blends using a low-tech pyrolysis system designed for smallholder farmers in developing countries and tested their appropriateness for diesel engines using standard ASTM methods. Corn stover retrieved from smallholder farmers in Gayaza, Uganda were pyrolyzed in a batch rocket stove reactor at 350 °C and liquid bio-oil harvested. Bio-oil chemical composition was analyzed by Gas Chromatography equipped with Flame Ionization Detector (GC-FID). Bio-oil/diesel emulsions in ternary concentrations 5%, 10% and 20% bio-oil weight were developed with 1% concentration of sorbitan monolaurate as an emulsifier. The bio-oil/diesel emulsions and distillates had property ranges: specific gravities at 15 °C 827.4–830.7 kg m−3, specific gravities at 20 °C 823.9–827.2 kg m −3, kinematic viscosities at 40 °C 3.01–3.22 mm2/s, initial boiling points 140–160 °C, final boiling points 354–368 °C, and calculated cetane indexes 56.80–57.63. These properties of the bio-oil/diesel blends and their distillates compare well with standard transportation diesel fuel. The emulsion distillates meet the standard requirements for automotive diesel in East Africa.

CELF6 (CUGBP Elav-Like Family Member 6), a canonical RNA binding protein (RBP), plays important roles in post-transcriptional regulation of pre-mRNAs. However, the underlying mechanism of lower expressed CELF6 in lung cancer tissues is still unclear. In this study, we increased CELF6 manually in lung cancer cell line (A549) and utilized transcriptome sequencing (RNA-seq) technology to screen out differentially expressed genes (DEGs) and alternative splicing events (ASEs) after CELF6 over-expression (CELF6-OE). We found that CELF6-OE induced 417 up-regulated and 1,351 down-regulated DEGs. Functional analysis of down-regulated DEGs showed that they were highly enriched in immune/inflammation response- related pathways and cell adhesion molecules (CAMs). We also found that CELF6 inhibited the expression of many immune-related genes, including TNFSF10, CCL5, JUNB, BIRC3, MLKL, PIK3R2, CCL20, STAT1, MYD88, and CFS1, which mainly promote tumorigenesis in lung cancer. The dysregulated DEGs were also validated by reverse transcriptase quantitative polymerase chain reaction (RT-qPCR) experiment. In addition, CELF6 regulates the splicing pattern of large number of genes that are enriched in p53 signaling pathway and apoptosis, including TP53 and CD44. In summary, we made an extensive analysis of the transcriptome profile of gene expression and alternative splicing by CELF6-OE, providing a global understanding of the target genes and underlying regulation mechanisms mediated by CELF6 in the pathogenesis and development of lung cancer.

Background: Induced abortion is defined as a procedure done to end pregnancy [ACOG], and most induced abortions are done in the first 12 weeks of pregnancy. Methodology: The study was cross-sectional in design. This is so because it yields results in a short time. A simple random sampling technique was used to select 60 respondents who participated in the study. Results: The majority 35(58%) of the respondents were Bagisu and the least 4(7%) were Bagwere. Most 33(55%) of the respondents had attained secondary 12(40%) of the respondents had attained primary level, 9(15%) attained tertiary level and the least 6(10%) had attained none. The majority (43)72% of the respondents were in the age range of 16-26 years due to fact that this is the reproductive age group, still attending school, more sexually active, and are exposed to sexual and reproduction information and articles; of which most are not married having fear to sustain pregnancy and the least (17) 28% were 30-44 years as most of them are married thus with no fear for sustaining the pregnancy once they conceived. Conclusion: The study showed that most women of reproductive age had some knowledge of induced abortion but a few knew about safe induced abortion and the majority knew at least one method of induced abortion. Recommendations: This study highlighted the need for policymakers and health administrators to implement measures that would increase the knowledge of people on safe induced abortion including legal rights.

Immune checkpoint therapies (ICT) are promising for treating various cancers, but response rates vary. Here the authors show, in mouse models, that tumor-infiltrating mast cells colocalize with regulatory T cells, coincide with local reduction of MHC-I and CD8 T cells, and is associated with resistance to ICT, which can be reversed by c-kit inhibitor treatment.

The rise in obesity prevalence has been linked to overconsumption of high-sugar containing food and beverages. Recent evidence suggests that chronic sucrose consumption leads to changes in serotonergic neuroplasticity within the neural circuits involved in feeding control. Although there is a relationship between serotonin signalling in the brain and diet-induced obesity, the specific serotonin (5-HT) receptors or pathways involved remain unknown. The 5-HT1A receptor subtype plays a role in regulating mood, anxiety, and appetite, and has been associated with reversing addiction to substances of abuse. However, the respective role of 5-HT1A auto- vs heteroreceptors in sucrose consumption has not been examined. Mice were given controlled access to either 5%, 10% or 25% w/v sucrose, or water as a control, for 12 weeks using the well-established “drinking in the dark” protocol (n = 6–8 mice per group). Ligands selectively targeting 5-HT1A auto- and/or heteroreceptors (NLX-112, unbiased 5-HT1A receptor agonist; NLX-101, preferential heteroreceptor agonist; F13714, preferential autoreceptor agonist) were administered i.p. acutely after 6 and 12 weeks of sucrose consumption. The specific involvement of 5-HT1A receptors in these effects was verified by blockade with the selective 5-HT1A receptors antagonist WAY-100,635. The specific subpopulation of 5-HT1A receptors involved in sucrose consumption was dependent on the concentration of sucrose solution and the duration of exposure to sucrose (6 weeks vs 12 weeks). Long-term sucrose consumption leads to accentuated 5-HT1A autoreceptor function. Thus, targeting 5-HT1A autoreceptors might represent an effective therapeutic strategy to combat the rise in obesity resulting from the overconsumption of high-sugar diet.

ABSTRACTIn flood hazard assessment, little attention has been given to the seasonal observation of freshwater inundation using Sentinel-1 Synthetic-Aperture Radar (SAR) images in the tropics. To assess these spatial variations, this study examined the inundation magnitudes and reflectance of riparian flora in the raining seasons (February-April and September-November) and dry-periods (May-August and December-January). The inundation areas were determined using an object-oriented classification algorithm, whilst the merits concerning the lake, riparian vegetation and shoreline were well-defined using backscatter-coefficient values. Findings indicated that the SAR images are practical to monitor inundation coverages and discern lake basin specific features such as highland areas, shoreline, water and riparian-vegetation. Seasonally, inundated sizes were comparatively higher in February (902 sq.km) and October (700 sq.km). Backscatter values of inundated parts varied from −16 dB to −19 dB, whereas those of riparian vegetation were higher in the months of May and August. This study hence displays a clear-cut correlation between riparian-vegetation, hydrology and climate variables.

There is accumulating evidence that an obesogenic Western diet causes neuroinflammatory damage to the brain, which then promotes further appetitive behaviour. Neuroinflammation has been extensively studied by analysing the translocator protein of 18 kDa (TSPO), a protein that is upregulated in the inflamed brain following a damaging stimulus. As a result, there is a rich supply of TSPO-specific agonists, antagonists and positron emission tomography ligands. One TSPO ligand, etifoxine, is also currently used clinically for the treatment of anxiety with a minimal side-effect profile. Despite the neuroinflammatory pathogenesis of diet-induced obesity, and the translational potential of targeting TSPO, there is sparse literature characterizing the effect of TSPO on appetite. Therefore, in this review, the influence of TSPO on appetite is discussed. Three putative mechanisms for TSPO's appetite-modulatory effect are then characterized: the TSPO–allopregnanolone–GABAAR signalling axis, glucosensing in tanycytes and association with the synaptic protein RIM-BP1. We highlight that, in addition to its plethora of functions, TSPO is a regulator of appetite. This review ultimately suggests that the appetite-modulating function of TSPO should be further explored due to its potential therapeutic promise.

Post-traumatic stress disorder (PTSD) is a debilitating and chronic fear-based disorder. Pavlovian fear conditioning protocols have long been utilised to manipulate and study these fear-based disorders. Contextual fear conditioning (CFC) is a particular Pavlovian conditioning procedure that pairs fear with a particular context. Studies on the neural mechanisms underlying the development of contextual fear memories have identified the medial prefrontal cortex (mPFC), or more specifically, the pre-limbic cortex (PL) of the mPFC as essential for the expression of contextual fear. Despite this, little research has explored the role of the PL in contextual fear memory maintenance or examined the role of neuronal mitogen-activated protein kinase (pMAPK; ERK 1/2), brain-derived neurotrophic factor (BDNF), and IBA-1 in microglia in the PL as a function of Pavlovian fear conditioning. The current study was designed to evaluate how the maintenance of two different long-term contextual fear memories leads to changes in the number of immune-positive cells for two well-known markers of neural activity (phosphorylation of MAPK and BDNF) and microglia (IBA-1). Therefore, the current experiment is designed to assess the number of immune-positive pMAPK and BDNF cells, microglial number, and morphology in the PL following CFC. Specifically, 2 weeks following conditioning, pMAPK, BDNF, and microglia number and morphology were evaluated using well-validated antibodies and immunohistochemistry (n = 12 rats per group). A standard CFC protocol applied to rats led to increases in pMAPK, BDNF expression and microglia number as compared to control conditions. Rats in the unpaired fear conditioning (UFC) procedure, despite having equivalent levels of fear to context, did not have any change in pMAPK, BDNF expression and microglia number in the PL compared to the control conditions. These data suggest that alterations in the expression of pMAPK, BDNF, and microglia in the PL can occur for up to 2 weeks following CFC. Together the data suggest that MAPK, BDNF, and microglia within the PL of the mPFC may play a role in contextual fear memory maintenance.

Sugar has become embedded in modern food and beverages. This has led to overconsumption of sugar in children, adolescents, and adults, with more than 60 countries consuming more than four times (>100 g/person/day) the WHO recommendations (25 g/person/day). Recent evidence suggests that obesity and impulsivity from poor dietary habits leads to further overconsumption of processed food and beverages. The long-term effects on cognitive processes and hyperactivity from sugar overconsumption, beginning at adolescence are not known. Using a well-validated mouse model of sugar consumption, we found that long-term sugar consumption, at a level that significantly augments weight gain, elicits an abnormal hyperlocomotor response to novelty and alters both episodic and spatial memory. Our results are similar to those reported in attention deficit and hyperactivity disorders. The deficits in hippocampal-dependent learning and memory were accompanied by altered hippocampal neurogenesis, with an overall decrease in the proliferation and differentiation of newborn neurons within the dentate gyrus. This suggests that long-term overconsumption of sugar, as that which occurs in the Western Diet might contribute to an increased risk of developing persistent hyperactivity and neurocognitive deficits in adulthood.

The overconsumption of sugar-sweetened food and beverages underpins the current rise in obesity rates. Sugar overconsumption induces maladaptive neuroplasticity to decrease dietary control. Although serotonin and glutamate co-localisation has been implicated in reward processing, it is still unknown how chronic sucrose consumption changes this transmission in regions associated with executive control over feeding—such as the prefrontal cortex (PFC) and dentate gyrus (DG) of the hippocampus. To address this, a total of 16 C57Bl6 mice received either 5% w/v sucrose or water as a control for 12 weeks using the Drinking-In-The-Dark paradigm (n = 8 mice per group). We then examined the effects of chronic sucrose consumption on the immunological distribution of serotonin (5-HT), vesicular glutamate transporter 3 (VGLUT3) and 5-HT+/VGLUT3+ co-localised axonal varicosities. Sucrose consumption over 12 weeks decreased the number of 5-HT–/VGLUT3+ and 5-HT+/VGLUT3+ varicosities within the PFC and DG. The number of 5-HT+/VGLUT3– varicosities remained unchanged within the PFC but decreased in the DG following sucrose consumption. Given that serotonin mediates DG neurogenesis through microglial migration, the number of microglia within the DG was also assessed in both experimental groups. Sucrose consumption decreased the number of DG microglia. Although the DG and PFC are associated with executive control over rewarding activities and emotional memory formation, we did not detect a subsequent change in DG neurogenesis or anxiety-like behaviour or depressive-like behaviour. Overall, these findings suggest that the chronic consumption of sugar alters serotonergic neuroplasticity within neural circuits responsible for feeding control. Although these alterations alone were not sufficient to induce changes in neurogenesis or behaviour, it is proposed that the sucrose consumption may predispose individuals to these cognitive deficits which ultimately promote further sugar intake.

In developing countries, energy demand from biomass has increased due to exponential population growth. This has translated into voluminous quantities of wood being used. The situation is exacerbated by the popular use of inefficient stoves with low thermal insulation, hence contributing to deforestation. In this study, the performance of a cooking stove improved with sawdust as an insulation material was assessed. An insulated fire stove prototype of 26 cm saucepan diameter was designed, constructed, and cast with sawdust and clay in a ratio of 1 : 1 (as the first layer) and sawdust alone as the second layer. The developed stove was tested using a water boiling test to establish its operating performance. The thermal efficiency of the stove was assessed using indigenous wood fuels used in rural Uganda (Senna spectabilis, Pinus caribaea, and Eucalyptus grandis). Computational fluid dynamics was used to simulate the temperature and velocity fields within the combustion chamber and for generating temperature contours of the stove. Obtained results indicated that S. spectabilis had the highest thermal efficiency of 35.5 ± 2.5%, followed by E. grandis (25.7 ± 1.7%) and lastly P. caribaea (19.0 ± 1.2%) in the cold start phase when compared with traditional stoves. The stove remained cold as hot air was restricted to the combustion chamber with decreasing temperature contours toward the outer wall up to the ambient temperature. The velocity flow remained constant as the chamber was colored green throughout due to the shielding of the stove with sawdust as insulation. The heat flux generated indicated that a thick layer of 6 cm or more could ensure good insulation, and this could be further reduced by introducing more sawdust. The designed stove has the potential to reduce biomass consumption and emissions when compared to traditional cookstoves. The inclusion of a chimney draught in the fire stove prototype could reduce smoke and increase thermal efficiency. Further studies should focus on minimizing the thickness of the clay-sawdust (first) layer and increasing the thickness of the sawdust layer to reduce the weight of the fire stove.

Summary: Drosophila Myb (Dm-Myb) encodes a protein that plays a key role in regulation of mitotic phase genes. Here, we further refine its role in the context of a developing tissue as a potentiator of gene expression required for proper RNA polymerase II (RNA Pol II) function and efficient H3K4 methylation at promoters. In contrast to its role in gene activation, Myb is also required for repression of many genes, although no specific mechanism for this role has been proposed. We now reveal a critical role for Myb in contributing to insulator function, in part by promoting binding of insulator proteins BEAF-32 and CP190 and stabilizing H3K27me3 Polycomb-group (PcG) domains. In the absence of Myb, H3K27me3 is markedly reduced throughout the genome, leading to H3K4me3 spreading and gene derepression. Finally, Myb is enriched at boundaries that demarcate chromatin environments, including chromatin loop anchors. These results reveal functions of Myb that extend beyond transcriptional regulation. : Myb has been considered a transcriptional activator of primarily M phase genes. Here, Santana et al. show that Myb also contributes to insulator function, in part by promoting binding of insulator factors, and is required to stabilize repressive domains in the genome. Keywords: Myb, BEAF-32, CP190, CTCF, chromatin structure, H3K27me3, topologically associating domain, TAD, chromatin loop anchors, gene expression

Aberrations in the esophageal proliferation-differentiation gradient are histologic hallmarks in eosinophilic esophagitis (EoE) and gastroesophageal reflux disease. A reliable protocol to grow 3-dimensional (3D) esophageal organoids is needed to study esophageal epithelial homeostasis under physiological and pathologic conditions. Methods: We modified keratinocyte-serum free medium to grow 3D organoids from endoscopic esophageal biopsies, immortalized human esophageal epithelial cells, and murine esophagi. Morphologic and functional characterization of 3D organoids was performed following genetic and pharmacologic modifications or exposure to EoE-relevant cytokines. The Notch pathway was evaluated by transfection assays and by gene expression analyses in vitro and in biopsies. Results: Both murine and human esophageal 3D organoids displayed an explicit proliferation-differentiation gradient. Notch inhibition accumulated undifferentiated basal keratinocytes with deregulated squamous cell differentiation in organoids. EoE patient-derived 3D organoids displayed normal epithelial structure ex vivo in the absence of the EoE inflammatory milieu. Stimulation of esophageal 3D organoids with EoE-relevant cytokines resulted in a phenocopy of Notch inhibition in organoid 3D structures with recapitulation of reactive epithelial changes in EoE biopsies, where Notch3 expression was significantly decreased in EoE compared with control subjects. Conclusions: Esophageal 3D organoids serve as a novel platform to investigate regulatory mechanisms in squamous epithelial homeostasis in the context of EoE and other diseases. Notch-mediated squamous cell differentiation is suppressed by cytokines known to be involved in EoE, suggesting that this may contribute to epithelial phenotypes associated with disease. Genetic and pharmacologic manipulations establish proof of concept for the utility of organoids for future studies and personalized medicine in EoE and other esophageal diseases.

Clinical and experimental studies have shown a clear link between diabetes, vascular dysfunction and cognitive impairment. However, the molecular underpinnings of this association remain unclear. Since vascular endothelial growth factor (VEGF) signaling is important for maintaining vascular integrity and function, we hypothesized that vascular and cognitive impairment in the diabetic brain could be related to a deficiency in VEGF signaling. Here we show that chronic hyperglycemia (~8 weeks) in a mouse model of type 1 diabetes leads to a selective reduction in the expression of VEGF and its cognate receptor (VEGF-R2) in the hippocampus. Correlating with this, diabetic mice showed selective deficits in spatial memory in the Morris water maze, increased vessel area, width and permeability in the dentate gyrus/CA1 region of the hippocampus and reduced spine densities in CA1 neurons. Chronic low dose infusion of VEGF in diabetic mice was sufficient to restore VEGF signaling, protect them from memory deficits, as well as vascular and synaptic abnormalities in the hippocampus. These findings suggest that a hippocampal specific reduction in VEGF signaling and resultant vascular/neuronal defects may underlie early manifestations of cognitive impairment commonly associated with diabetes. Furthermore, restoring VEGF signaling may be a useful strategy for preserving hippocampal-related brain circuitry in degenerative vascular diseases.