bluuebunny/crossref_metadata_2025_split huggingface dataset:
Adverse events following immunization during COVID-19 mass vaccination campaigns in the Democratic Republic of Congo: Findings from active safety surveillance
Authors: Kayumba Kizito , Duga Alemayehu Duga , Papa Fallah Mosoka , Tshidibi Claire , Lubaki Nicky , Coulibaly Barnabas , Djoudalbaye Benjamin , Nora Sylvana Efire , Sembuche Senga Lucy , Tilahun Tedi , Jibril Murtala , Kilowe Carlos , Kuba Aminu , Mafwila Lusala Antoine , Dereje Nebiyu , Ndembi Nicaise , Raji Tajudeen , Ngongo Ngashi 
Published: August 2024

Introduction: Post-marketing safety surveillance is indispensable for ensuring safety and public trust in vaccines, particularly in African settings where evidence of COVID–19 vaccine safety is less documented. We aimed to identify the types of adverse events following immunization (AEFIs), the overall incidence, and factors associated with AEFIs during mass vaccination campaigns in The Democratic Republic of Congo (DRC). Methods: From December 1 to 29, 2023, a prospective safety surveillance study was conducted on 4,766 individuals in Kinshasa Province in DRC. They were surveyed through phone calls from day 1 to 28 following the administration of the COVID-19 vaccine. We calculated AEFI incidence rates by type of vaccine, sex, and age group. We identified factors associated with AEFIs using multivariable logistic regression models, which were expressed by adjusted odds ratio (aOR) and its 95% confidence interval (CI). Results: A total of 4766 participants were included in the study. The median age of the participants was 36 years, with an interquartile range of 27 to 48 years and 2503 (53%) were females. Most of the participants (94.6%) received the Johnson & Johnson (J&J) vaccine, while 256 (5.4%) received the Pfizer vaccine. Nearly a quarter of participants (23.75%, 95% CI: 22.54%-24.99%) reported AEFIs. The most common AEFIs reported were fever (9.61%, 95%CI: 8.88%-10.48%), injection site pain (9.00%, 95%CI: 8.20%-9.85%), headache (4.11%, 95%CI: 3.57%-4.72%), stiffness (1.51%, 95%CI: 1.18%-1.89 %) and myalgia (1.15%, 95%CI: 0.87%-1.49%). The incidence of AEFIs was higher for the Pfizer vaccine at 34.48% (95% CI: 28.57%-40.54%) compared to 23.15% (95% CI: 21.92%-24.41%) for the J&J vaccine. Participants aged 36 years and above were associated with increased odds of reporting any adverse event (aOR=1.17, 95%CI: 1.02-1.33), injection site pain (aOR=1.36, 95% CI: 1.11-1.66), and two or more signs (aOR=1.46, 95%CI: 1.10-1.94), compared to those below 36 years of age. Conclusions: AEFI reported by about a quarter of participants and its association with vaccine type and older age underscores the need for systematic vaccine safety monitoring in the population. This is critical for developing future vaccination strategies tailored to individuals more susceptible to AEFIs.
Engineering rice Nramp5 modifies cadmium and manganese uptake selectivity using yeast assay system
Authors: Inoue Junji , Teramoto Takamasa , Kazama Tomohiko , Nakamura Takahiro 
Published: August 2024

AbstractCd is a seriously hazardous heavy metal for both plants and humans and international regulations regarding Cd intake have become stricter in recent years. Three-quarters of the Cd intake comes from plant-based foods, half of which comes from cereals. Therefore, it is anticipated that the Cd uptake efficiency of cereals, including rice, a staple crop in Asia, will be reduced. Natural resistance-associated macrophage protein (Nramp) is the principal transporter involved in the uptake and translocation of metal ions in various plants. In rice, OsNramp5 is a transporter of Mn, which is an essential micronutrient for plant growth, and is responsible for Cd uptake. Although several attempts have been made to engineer the metal uptake characteristics of OsNramp5, in many cases, both Cd and Mn uptake efficiencies are impaired. Therefore, in this study, we engineered OsNramp5 to reduce Cd uptake while retaining Mn uptake efficiency for low-Cd rice production. OsNramp5 was engineered using amino acid substitution(s) at the 232ndAla and 235thMet of OsNramp5, which have been suggested to be key residues for metal uptake efficiency and/or selectivity by structural analyses of bacterial Nramps. The metal uptake efficiency was first analyzed using a yeast model assay system. Several mutants showed less than 8.6% Cd and more than 64.1% Mn uptake efficiency compared to the original OsNramp5. The improved metal uptake characteristics were confirmed by direct measurement of the metal content in the yeast using inductively coupled plasma optical emission spectroscopy. Notably, several mutants reduced Cd uptake efficiency to the background level while retaining more than 64.7% Mn uptake efficiency under conditions mimicking heavily polluted soils in the world. In addition, computational structural modeling suggested requirements for the spatial and chemical properties of the metal transport tunnel and metal-binding site, respectively, for Cd/Mn uptake efficiency.
Endothelial β1 Integrins are Necessary for Microvascular Function and Glucose Uptake
Authors: Winn Nathan C. , Roby Deborah A. , McClatchey P. Mason , Williams Ian M. , Bracy Deanna P. , Bedenbaugh Michelle N. , Lantier Louise , Plosa Erin J. , Pozzi Ambra , Zent Roy , Wasserman David H. 
Published: August 2024

AbstractMicrovascular insulin delivery to myocytes is rate limiting for the onset of insulin-stimulated muscle glucose uptake. The structural integrity of capillaries of the microvasculature is regulated, in part, by a family of transmembrane adhesion receptors known as integrins, which are composed of an α and β subunit. The integrin β1 (itgβ1) subunit is highly expressed in endothelial cells (EC). EC itgβ1 is necessary for the formation of capillary networks during embryonic during development and its knockdown in adult mice blunts the reactive hyperemia that manifests during ischemia reperfusion. In this study we investigated the contribution of skeletal muscle EC itgβ1 in microcirculatory function and glucose uptake. We hypothesized that loss of EC itgβ1 would impair microvascular hemodynamics and glucose uptake during insulin stimulation, creating ‘delivery’-mediated insulin resistance. An itgβ1 knockdown mouse model was developed to avoid lethality of embryonic gene knockout and the deteriorating health resulting from early post-natal inducible gene deletion. We found that mice with (itgβ1fl/flSCLcre) and without (itgβ1fl/fl) inducible stem cell leukemia cre recombinase (SLCcre) expression at 10 days post cre induction have comparable exercise tolerance and pulmonary and cardiac functions. We quantified microcirculatory hemodynamics using intravital microscopy and the ability of mice to respond to the high metabolic demands of insulin-stimulated muscle using a hyperinsulinemic-euglycemia clamp. We show that itgβ1fl/flSCLcre mice compared to itgβ1fl/fllittermates have, i) deficits in capillary flow rate, flow heterogeneity, and capillary density; ii) impaired insulin-stimulated glucose uptake despite sufficient transcapillary insulin efflux; and iii) reduced insulin-stimulated glucose uptake due to perfusion-limited glucose delivery. Thus, EC itgβ1 is necessary for microcirculatory function and to meet the metabolic challenge of insulin stimulation.
An infralimbic cortex neuronal ensemble encoded during learning attenuates fear generalization expression
Authors: Subramanian Rajani , Bauman Avery , Carpenter Olivia , Cho Chris , Coste Gabrielle , Dam Ahona , Drake Kasey , Ehnstrom Sara , Fitzgerald Naomi , Jenkins Abigail , Koolpe Hannah , Liu Runqi , Paserman Tamar , Petersen David , Chavez Diego Scala , Rozental Stefano , Thompson Hannah , Tsukuda Tyler , Zweig Sasha , Gall Megan , Zupan Bojana , Bergstrom Hadley 
Published: August 2024

ABSTRACTGeneralization allows previous experience to adaptively guide behavior when conditions change. The infralimbic (IL) subregion of the ventral medial prefrontal cortex plays a known role in generalization processes, although mechanisms remain unclear. A basic physical unit of memory storage and expression in the brain are sparse, distributed groups of neurons known as ensembles (i.e., the engram). Here, we set out to determine whether neuronal ensembles established in the IL during learning contribute to generalized responses. Generalization was tested in male and female mice by presenting a novel, ambiguous, tone generalization stimulus following Pavlovian defensive (fear) conditioning. The first experiment was designed to test a role for IL in generalization using chemogenetic manipulations. Results show IL regulates defensive behavior in response to ambiguous stimuli. IL silencing led to a switch in defensive state, from vigilant scanning to generalized freezing, while IL stimulation reduced freezing in favor of scanning. Leveraging activity-dependent “tagging” technology (ArcCreERT2x eYFP system), a neuronal ensemble, preferentially located in IL Layer 2/3, was associated with the generalization stimulus. Remarkably, in the identical discrete location, fewer reactivated neurons were associated with the generalization stimulus at the remote timepoint (30 days) following learning. When an IL neuronal ensemble established during learning was selectively chemogenetically silenced, generalization increased. Conversely, IL neuronal ensemble stimulation reduced generalization. Overall, these data identify a crucial role for IL in suppressing generalized responses. Further, an IL neuronal ensemble, formed during learning, functions to later attenuate the expression of generalization in the presence of ambiguous threat stimuli.
Congruence between noise and plasticity in protein expression
Authors: Tsuru Saburo , Furusawa Chikara 
Published: August 2024

AbstractGene expression responds to various perturbations, such as mutations, environmental changes, and stochastic perturbations. The variability in gene expression levels differs among genes, influencing the availability of adaptive variants or mutants and thereby affecting nongenetic and genetic adaptations. Different types of variability are interdependent, suggesting global canalization/decanalization against different perturbations and a common underlying mechanism. Despite this, the relationship between plasticity (variability in response to environmental changes) and noise (variability among cells under the same conditions) in gene expression remains debatable. Previous studies reported a positive correlation between plasticity and noise, but these variabilities are often measured at different levels: plasticity at the mRNA level and noise at the protein level. This methodological discrepancy complicates the understanding of their relationship. We investigated this by measuring protein expression levels of essential and nonessential genes inEscherichia coli. Using flow cytometry, we quantified noise and plasticity from the same dataset. Essential genes exhibited lower noise and plasticity than nonessential genes. Nonessential genes showed a positive correlation between noise and plasticity, while essential genes did not. This study provides empirical evidence of essentiality-dependent coupling between noise and plasticity in protein expression, highlighting the organization of different types of variabilities.
2-monopalmitin, but not 1-monopalmitin, enhances hypothalamic leptin responsiveness, energy balance, and glucose homeostasis under overnutrition
Authors: Takahashi Nozomi , Ikeda Mutsumi , Yamazaki Yukiko , Funatsu Yui , Shiino Tamae , Hosokawa Aoi , Kaneko Kentaro 
Published: August 2024

AbstractNutrient excess, a major driver of obesity, diminishes hypothalamic responses to exogenously administered leptin, a critical hormone for energy balance. Here, we found that 2-monopalmitin, but not 1-monopalmitin or palmitic acid, enhances hypothalamic leptin responsiveness inex vivobrain slices. Centrally administered 2-monopalmitin markedly restored the leptin-induced suppression of food intake and reduction of body weight in diet-induced obese mice. Peripherally administered 2-monopalmitin also enhanced the anorectic effect of centrally administered leptin. Furthermore, daily 2-monopalmitin treatment protected against diet-induced body weight gain, and the energy expenditure of 2-monopalmitin-treated mice was significantly enhanced in a leptin-dependent manner. We also demonstrated that 2-monopalmitin lowered blood glucose levels, improved glucose and insulin tolerance, and protected mice against HFD-induced peripheral insulin resistance at the cellular and whole-body levels. Finally, treatment with 2-monopalmitin protected against LPS-induced leptin resistance, and decreased the hypothalamic levels of SOCS3, an inhibitor of leptin actions, and inflammatory cytokines. Altogether, our results showed that 2-monopalmitin in the brain, but not 1-monopalmitin or palmitic acid, is critical for linking overnutrition to the control of neural leptin actions.
Protection of the Telomeric Junction by the Shelterin Complex
Authors: Shiekh Sajad , Feldt Darion , Jack Amanda , Kodikara Sineth G. , Alfehaid Janan , Pasha Sabaha , Yildiz Ahmet , Balci Hamza 
Published: August 2024

AbstractShelterin serves critical roles in suppressing superfluous DNA damage repair pathways on telomeres. The junction between double-stranded telomeric tracts (dsTEL) and single-stranded telomeric overhang (ssTEL) is the most accessible region of the telomeric DNA. The shelterin complex contains dsTEL and ssTEL binding proteins and can protect this junction by bridging between the ssTEL and dsTEL tracts. To test this possibility, we monitored shelterin binding to telomeric DNA substrates with varying ssTEL and dsTEL lengths and quantified its impact on telomere accessibility using single-molecule fluorescence microscopy methodsin vitro. We identified the first dsTEL repeat nearest to the junction as the preferred binding site for creating the shelterin bridge. Shelterin requires at least two ssTEL repeats while the POT1 subunit of shelterin that binds to ssTEL requires longer ssTEL tracts for stable binding to telomeres and effective protection of the junction region. The ability of POT1 to protect the junction is significantly enhanced by the 5’-phosphate at the junction. Collectively, our results show that shelterin enhances the binding stability of POT1 to ssTEL and provides more effective protection compared to POT1 alone by bridging single- and double-stranded telomeric tracts.Table of Content Graphic
Exploring 3-Aminobenzoic Acid as a Therapeutic Dietary Component for Enhancing Intestinal Barrier Integrity in Ulcerative Colitis
Authors: Tanaka Miho , Toyonaga Takahiko , Nakagawa Fumiyuki , Iwamoto Takeo , Komatsu Akira , Sumiyoshi Natsuki , Shibuya Naoki , Minemura Ayaka , Ariyoshi Tadashi , Matsumoto Asami , Oka Kentaro , Shimoda Masayuki , Saruta Masayuki 
Published: August 2024

AbstractBackgroundDietary components and their metabolites produced by intestinal bacteria play a crucial role in maintaining intestinal epithelial integrity. Disrupted epithelial integrity increases permeability and leads to chronic inflammation in the colon, known as ulcerative colitis (UC), in genetically predisposed individuals. However, the gut microbial metabolites regulating epithelial permeability remain unexplored and their metabolism in UC patients is unclear.MethodsA library of 119 gut microbial metabolites was screened for their ability to reduce epithelial permeability in Caco2 cell monolayers. The diet containing 3-aminobenzoic acid (3-ABA) was identified using liquid chromatography with quadrupole time-of-flight mass spectrometry. The abundance of fecal 3-ABA was compared between UC patients and healthy individuals followed by 16S rRNA metagenomic analysis to estimate the gut microbial function in ABA degradation. The anti-inflammatory effect of 3-ABA was examined in a mouse model of dextran sodium sulfate-induced colitis.ResultsStimulation with 3-ABA reduced epithelial permeability and enhanced barrier integrity in Caco2 cells by modulating the tight junctional regulatory pathway. 3-ABA was abundant in beans and decreased in the feces of UC patients. Functional prediction analysis of gut microbiota revealed an accelerated degradation of ABA with significant up-regulation ofmabA, a gene encoding a bacterial enzyme involved in 3-ABA degradation, in UC patients. Rectal and oral administration of 3-ABA ameliorated experimental colitis in mice.Conclusion3-ABA abundant in beans enhanced intestinal epithelial integrity and ameliorated experimental colitis in mice. Proactive intake of 3-ABA might be a novel treatment approach for UC.
Integrative structural analysis of NF45-NF90 heterodimers reveals architectural rearrangements and oligomerisation on binding dsRNA
Authors: Winterbourne Sophie , Jayachandran Uma , Zou Juan , Rappsilber Juri , Granneman Sander , Cook Atlanta G. 
Published: August 2024

AbstractComplexes of nuclear factors 45 and 90 (NF45-NF90) play a multitude of roles in co- and post-transcriptional RNA processing, including regulating adenosine-to-inosine editing, cassette exon and back splicing, and splicing fidelity. NF45-NF90 complexes recognise dsRNA and, in human cells, primarily interact with inverted Alu repeats (AluIRs) that are commonly inserted into introns and other non-coding RNA regions. Intronic AluIRs of ∼300 bp can regulate splicing outcomes, such as generation of circRNAs. We examined domain reorganisation of NF45-NF90 domains on dsRNAs exceeding 50 bp to gain insight into its RNA recognition properties on longer dsRNAs. Using a combination of phylogenetic analysis, solution methods (including small angle X-ray scattering and quantitative cross-linking mass spectrometry), machine learning and negative stain electron microscopy, we generated a model of NF45-NF90 complex formation on dsRNA. Our data reveal that different interactions of NF45-NF90 complexes allow these proteins to coat long stretches of dsRNA. This property of the NF45-NF90 complex has important implications for how long, nuclear dsRNAs are recognised in the nucleus and how this might promote (co)-regulation of specific RNA splicing and editing events that shape the mammalian transcriptome.
Tanshinone IIA potentiates the therapeutic efficacy of glucocorticoid in lipopolysaccharide-treated HEI-OC1 cells through modulation of Foxp3/Nrf2 signaling pathway
Authors: Li Jie , Zhu Xiaoyan , Ye Shiming , Dong Qi , Hou Jie , Liu Jing , She Wandong 
Published: August 2024

AbstractGlucocorticoids (GC) are commonly used to treat sudden sensorineural hearing loss (SSNHL), although some patients show resistance to this therapeutic approach. Clinical studies demonstrate the efficacy of tanshinone IIA (TA) in combination with GC for managing various human ailments. However, it remains unclear whether TA can mitigate GC resistance in SSNHL.Aim of the studyOur aim is to elucidate the role of NRF2-induced transcriptional regulation of HDAC2 in influencing GC resistance and investigate the involvement of TA-related molecular pathways in GC resistance.Materials and MethodsHEI-OC1 cells are treated with lipopolysaccharide (LPS) to establish an in vitro model for SSNHL. Subsequently, the cells are treated with dexamethasone (DXE) or DXE+TA. RT-qPCR and western blot analyses are employed to measure mRNA and protein levels of Forkhead box P3 (FOXP3), nuclear factor erythroid 2-related factor 2 (NRF2), and histone deacetylase 2 (HDAC2). Cell Counting Kit-8 (CCK-8) and 5-ethynyl-2’-deoxyuridine (EdU) assays are conducted to assess cell proliferation. Flow cytometry analysis is performed for apoptosis evaluation. Mechanistic studies involve Chromatin immunoprecipitation (ChIP), luciferase reporter, and DNA pull-down assays.ResultsTreatment with TA+DEX significantly enhances proliferation and suppresses apoptosis in LPS-treated HEI OC1 cells. TA upregulates HDAC2 expression by activating NRF2-mediated transcription of HDAC2, with the NRF2-HDAC2 binding site located at bases 419-429 (ATGACACTCCA) in the promoter sequence of HDAC2. Furthermore, TA upregulates FOXP3 expression to activate NRF2 transcription, with the predicted FOXP3-binding site located at bases 864-870 (GCAAACA) in the promoter sequence of NRF2.ConclusionThis study’s findings suggest that TA enhances the therapeutic effects of GC on proliferation and apoptosis in HEI OC1 cells by up-regulating FOXP3/Nrf2 expression. These results indicate that TA may be promising in ameliorating GC resistance in patients with SSNHL.
Improving the learning capacity of regional health systems for their transformation towards health and well-being systems: a qualitative study of ten Dutch regions
Authors: van Vooren Natascha , de Weger Esther , de Bruin Josefien , Baan Caroline 
Published: August 2024

PurposeThere is growing recognition that transformation of healthcare systems towards health and well-being systems requires a continuous learning process. This explorative study aims to gain insight into the experiences with and investment in these learning processes within regional partnerships for health and in what they need to enhance their learning capacity to use the learning for transformation.Design/methodology/approach17 interviews were held with programme managers, data scientists, trusted advisors and a citizen representative, all involved in the learning process on a regional level in ten Dutch regional partnerships. The interviews were inductively and thematically analysed, focusing on the experiences and perceptions underlying the learning processes.FindingsRegional partnerships invest in learning processes by organizing interactions between different groups of stakeholders and by reflecting on specific themes or on a region-wide level. Difficulty was found in region-wide reflection and in enhancing the learning capacity within the partnerships. Further enhancing the learning capacity required: (1) Investment in (the use of) expertise for translating learning outcomes into concrete action; (2) Leadership for change, underpinned by a shared sense of urgency to learn for transformation and (3) A facilitative environment for change which is both based on facilitative system structures and a basis of trust and commitment to learn and adapt.Originality/valueThe study highlighted the difficulty of learning on a region-wide level and the struggle to apply this learning for transformation. It provides insights into how learning processes and learning capacity can be further improved.