bluuebunny/crossref_metadata_2025 huggingface dataset:
Reading; through the eyes of a university student: A double-masked randomised placebo-controlled cross-over protocol investigating coloured spectacle lens efficacy in adults with visual stress.
Authors: Harkin Darragh Liam , Little Julie-Anne , McCullough Sara J.
Published: August 2024

Background: Visual stress is a reading disorder characterised by perceptual distortions, asthenopia and headache whilst reading, alongside increased sensitivity to repeated striped patterns (‘pattern glare’), in the absence of underlying ocular pathology. Coloured filters including tinted spectacle lenses and coloured overlays/acetates have been reported to ameliorate visual stress symptoms. However, evidence on coloured spectacle lenses efficacy at managing symptoms of visual stress, particularly in adults, is lacking, with two recent systematic reviews advocating the need for large-scale randomised control trials.   Methods: This is a double-masked randomised placebo-controlled trial. University students identified with symptoms of visual stress, through use of a reading symptom questionnaire and mid-spatial frequency pattern glare test, will be recruited. Sample size for power of 90% at 5% significance, accounting for 10% dropout will be 65. Participants will be randomly assigned experimental and control coloured spectacle lenses to wear for six weeks followed by a two week washout period, prior to wear of the alternate lenses for a further six weeks with a two week washout period. Participants will compare both sets of spectacle lenses in a ‘head-to-head’ comparison after the secondary washout period, prior to choosing the preferred lenses for voluntary future wear. Long-term adherence to the preferred lenses will be assessed three months post-comparison. Researchers and participants will be masked to spectacle lenses worn throughout the duration of the trial.  Reading performance will be assessed with both sets of lenses at various time points within the trial. A range of reading tests, reading symptoms and pattern glare evaluation will be used to monitor change in reading performance and visual stress symptoms during the trial.   Discussion: The study will evaluate the hypothesis that coloured spectacle lenses increase reading speed and reduce severity and frequency of reading symptoms in adults with visual stress.    Trial Registration: The trial is registered at clinicaltrials.gov:NCT04318106
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

Cd 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

Microvascular 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

Generalization 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

Gene 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.
Task-related activity in auditory cortex enhances sound representation
Authors: Polterovich Ana , Jankowski Maciej M , Niediek Johannes , Kazakov Alex , Nelken Israel
Published: August 2024

In auditory-guided tasks, sound presentations often occupy a small fraction of the total task time. We studied here neuronal dynamics that spanned trial duration. Many neurons had large, slow, firing rate modulations, which were not driven by sounds, were larger than the sound evoked responses, and were locked to specific time points during the task, similar to responses of hippocampal time-sensitive neurons. Concurrently, responses to sounds differed between active behavior and passive listening conditions: in the active sessions, the on-going activity just before sound presentations was higher and the responses to target stimuli were weaker but more informative about the task-relevant sounds. We show that the slow firing rate modulations caused the increased on-going activity. Using a model, we demonstrate that higher on-going activity led to more synaptic depression of the cortico-cortical synapses, reducing the tendency to produce population spikes and resulting in weaker but more informative responses.
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

Nutrient 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

Shelterin 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.

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Dietary Bioactive Compounds Trigger Distinct Epigenetic and Metabolic Reprogramming inLactobacillus acidophilus
Authors: Kong Yanzhuo , Adejoro Damola O. , Wescombe Philip A. , Winefield Christopher , On Stephen L.W. , Mitchell Nadia L. , Subbaraj Arvind , Saunders Andrew , Maes Evelyne , Chelikani Venkata
Published: August 2024

Lactobacillus acidophilusATCC 4356 (LA), a key probiotic in the human gut microbiota, offers several health benefits. While dietary bioactive compounds are known to influence gut microbiota, their specific mechanisms remain unclear. This study investigated how certain dietary bioactive compounds impact LA gene expression and metabolism. Results showed each compound produces unique transcriptional, metabolic, proteomic, and epigenetic profiles in LA. Notably, dietary compounds altered the epigenetic landscape through N4-methylcytosine (4mC) modification, a relatively underexplored form of methyl modification that may play a role in regulating gene transcription. For instance, genistein treatment up-regulated 76 genes and the down-regulated 130 genes in LA. A gene involved in mucus-binding proteins, crucial for bacterial adhesion, was up-regulated 38-fold, likely due to 4mC modifications. Additionally, the gene coding for the melibiose operon regulatory protein increased 78-fold, enhancing melibiose (a prebiotic) production with genistein, but only 1.1-fold with sodium butyrate. This study highlights the potential of dietary compounds for microbial metabolic engineering, offering a non-GMO method for modulating bacterial performance and other biotechnology applications.
Loss of Zmiz1 in mice leads to impaired cortical development and autistic-like behaviors
Authors: K C Rajan , Patel Nehal R , Thurmon Abbigail N , Lorino Maryann G , Tiemroth Alina S , Kulstad Isabella , Morrison Vivianne , Akumuo Mauren , Shenoy Anoushka , Meadows Stryder M , Galazo Maria J
Published: August 2024

De novo mutations in transcriptional regulators are emerging as key risk factors contributing to the etiology of neurodevelopmental disorders. Human genetic studies have recently identified ZMIZ1 and its de novo mutations as causal of a neurodevelopmental syndrome strongly associated with intellectual disability, autism, ADHD, microcephaly, and other developmental anomalies. However, the role of ZMIZ in brain development or how ZMIZ1 mutations cause neurological phenotypes is unknown. Here, we generated a forebrain-specific Zmiz1 mutant mouse model that develops brain abnormalities, including cortical microcephaly, corpus callosum dysgenesis, and abnormal differentiation of upper-layer cortical neurons. Behaviorally, Zmiz1 mutant mice show alterations in motor activity, anxiety, communication, and social interactions with strong sex differences, resembling phenotypes associated with autism. Molecularly, Zmiz1 deficiency leads to transcriptomic changes disrupting neurogenesis, neuron differentiation programs, and synaptic signaling. We identified Zmiz1-mediated downstream regulation of key neurodevelopmental factors, including Lhx2, Auts2, and EfnB2. Importantly, reactivation of the EfnB2 pathway by exogenous EFNB2 recombinant protein rescues the dendritic outgrowth deficits in Zmiz1 mutant cortical neurons. Overall, our in vivo findings provide insight into Zmiz1 function in cortical development and reveal mechanistic underpinnings of ZMIZ1 syndrome, thereby providing valuable information relevant to future studies on this neurodevelopmental disorder.
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

Background

Dietary 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.

Methods

A 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.

Results

Stimulation 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.

Conclusion

3-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.
Head-to-head comparison of [18F]florbetapir and [18F]FDG PET for the early detection of amyloidosis in systemic amyloidosis and plasma cell dyscrasias
Authors: Kong Yanyan , Cao Lei , He Boyan , Zhou Zhongwen , Zhang Minmin , Zhang Qian , Wang Qian , Wang Wei , Zhu Haoxiang , Xiao Jianfei , Rominger Axel , Guan Yihui , Tan Haibo , Ni Ruiqing
Published: August 2024

Purpose: Amyloidosis is underdiagnosed in light-chain amyloidosis (AL) and hereditary transthyretin amyloidosis (hATTR), as well as plasma cell dyscrasias (PCD). We aimed to investigate the utility of [18F]florbetapir (FBP) and [18F]fluorodeoxyglucose (FDG) positron emission tomography (PET) for the early detection and evaluation of organ involvement in systemic amyloidosis. Methods: We retrospectively included 83 participants, including 38 AL patients, 8 hATTR polyneuropathy patients, 28 PCD patients and 9 healthy controls. Whole-body PET/CT using [18F]FBP was performed in all participants, [18F]FDG PET was performed in 37 patients with AL and PCD, and the results were analyzed by visual and quantitative assessment. Biochemical, serum, and urine assays and histological analysis of tissue biopsies were performed. Results: [18F]FBP SUV and TBR analysis showed comparable uptake in AL and hATTR-PN patients (p.A117S, p.V50M, p.K55N, p.T69AM, or p.H76R mutation carriers) and greater uptake than in PCD patients and control patients. Different regional [18F]FBP and [18F]FDG distributions were observed among the PCD, AL, and hATTR-PN groups. Both [18F]FBP and [18F]FDG enabled the detection of amyloidosis in patients with PCD before clinical detection of AL. [18F]FBP SUV and visual analysis provide comparable measures of organ involvement and were comparable to [18F]FDG and clinical assessment. Conclusions: [18F]FBP PET detected organ amyloidosis in PCD, AL and hATTR-PN patients with high sensitivity and specificity and was more sensitive than [18F]FDG. Visual analysis and SUV analysis of [18F]FBP PET data provide comparable methods for evaluating organ involvement and are useful for noninvasively assisting in the early and accurate detection of systemic amyloidosis.
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

Complexes 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

Glucocorticoids (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 study

Our 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 Methods

HEI-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.

Results

Treatment 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.

Conclusion

This 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.
Single-layer tensor network approach for three-dimensional quantum systems
Authors: Lukin I. V. , Sotnikov A. G.
Published: August 2024

Calculation of observables with three-dimensional projected entangled pair states is generally hard, as it requires a contraction of complex multi-layer tensor networks. We utilize the multi-layer structure of these tensor networks to largely simplify the contraction. The proposed approach involves the usage of the layer structure both to simplify the search for the boundary projected entangled pair states and the single-layer mapping of the final corner transfer matrix renormalization group contraction. We benchmark our results on the cubic lattice Heisenberg model, reaching the bond dimension D=7, and find a good agreement with the previous results.

Published by the American Physical Society
2024
Refined determination of the weak mixing angle at low energy
Authors: Corona M. Atzori , Cadeddu M. , Cargioli N. , Dordei F. , Giunti C.
Published: August 2024

The weak mixing angle is a fundamental parameter of the electroweak theory of the standard model whose measurement in the low-energy regime is still not precisely determined. Different probes are sensitive to its value, including atomic parity violation, coherent elastic neutrino-nucleus scattering, and parity-violating electron scattering on different nuclei. In this work, we attempt for the first time to combine all these various determinations by performing a global fit that also takes into account the unavoidable dependence on the experimentally poorly known neutron distribution radius of the nuclei employed, for which a new measurement using proton-cesium elastic scattering became available. By using all present direct determinations of the neutron distribution radius of cesium, we find sin2ϑW=0.2396−0.0019+0.0020, which should supersede the previous value determined from atomic parity violation on cesium. When including electroweak only, but also indirect, determinations of the neutron distribution radius of cesium, the uncertainty reduces to 0.0017, maintaining the same central value and showing excellent agreement independently of the method used.

Published by the American Physical Society
2024
Revealing nanoscale sorption mechanisms of gases in a highly porous silica aerogel
Authors: Vu Phung Nhu Hao , Radlinski Andrzej P. , Blach Tomasz , Schweins Ralf , Lemmel Hartmut , Daniels John , Regenauer-Lieb Klaus
Published: August 2024

Geological formations provide a promising environment for the long-term and short-term storage of gases, including carbon dioxide, hydrogen and hydrocarbons, controlled by the rock-specific small-scale pore structure. This study investigates the nanoscale structure and gas uptake in a highly porous silica aerogel (a synthetic proxy for natural rocks) using transmission electron microscopy, X-ray diffraction, and small-angle and ultra-small-angle neutron scattering with a tracer of deuterated methane (CD4) at pressures up to 1000 bar. The results show that the adsorption of CD4 in the porous silica matrix is scale dependent. The pore space of the silica aerogel is fully accessible to the invading gas, which quickly equilibrates with the external pressure and shows no condensation on the sub-nanometre scale. In the 2.5–50 nm pore size region a classical two-phase adsorption behaviour is observed. The structure of the aerogel returns to its original state after the CD4 pressure has been released.
Ptychographic phase retrieval via a deep-learning-assisted iterative algorithm
Authors: Yamada Koki , Akaishi Natsuki , Yatabe Kohei , Takayama Yuki
Published: August 2024

Ptychography is a powerful computational imaging technique with microscopic imaging capability and adaptability to various specimens. To obtain an imaging result, it requires a phase-retrieval algorithm whose performance directly determines the imaging quality. Recently, deep neural network (DNN)-based phase retrieval has been proposed to improve the imaging quality from the ordinary model-based iterative algorithms. However, the DNN-based methods have some limitations because of the sensitivity to changes in experimental conditions and the difficulty of collecting enough measured specimen images for training the DNN. To overcome these limitations, a ptychographic phase-retrieval algorithm that combines model-based and DNN-based approaches is proposed. This method exploits a DNN-based denoiser to assist an iterative algorithm like ePIE in finding better reconstruction images. This combination of DNN and iterative algorithms allows the measurement model to be explicitly incorporated into the DNN-based approach, improving its robustness to changes in experimental conditions. Furthermore, to circumvent the difficulty of collecting the training data, it is proposed that the DNN-based denoiser be trained without using actual measured specimen images but using a formula-driven supervised approach that systemically generates synthetic images. In experiments using simulation based on a hard X-ray ptychographic measurement system, the imaging capability of the proposed method was evaluated by comparing it with ePIE and rPIE. These results demonstrated that the proposed method was able to reconstruct higher-spatial-resolution images with half the number of iterations required by ePIE and rPIE, even for data with low illumination intensity. Also, the proposed method was shown to be robust to its hyperparameters. In addition, the proposed method was applied to ptychographic datasets of a Simens star chart and ink toner particles measured at SPring-8 BL24XU, which confirmed that it can successfully reconstruct images from measurement scans with a lower overlap ratio of the illumination regions than is required by ePIE and rPIE.
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

Purpose

There 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/approach

17 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.

Findings

Regional 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/value

The 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.
An approach for fault-related monitoring variables selection based on dual-layer correlation networks
Authors: Zhang Zhenjie , Chen Xinjiu , Xu Xiaobin , Li Yi , Hou Pingzhi , Zhang Zehui , Guo Haohao
Published: August 2024

Purpose

Fault-related monitoring variables selection is a process of obtaining a subset of variables from the original set, which is of great significance for reducing information redundancy and improving the performance of the fault diagnosis models. This paper aims to propose a novel variables selection approach based on complex networks.

Design/methodology/approach

Firstly, a dual-layer correlation networks (DlCN) which consists of mechanism-oriented correlation sub-network (MoCSN) and data-oriented correlation sub-network (DoCSN) is constructed. Secondly, an algorithm for identifying critical fault-related monitoring variables based on dual correlations is introduced. In the algorithm, the topological attributes of the MoCSN and correlation threshold of the DoCSN are used successively.

Findings

In the experiments of vertical elevator fault diagnosis, the critical fault-related monitoring variables selected by the DlCN-based approach is more effective than the traditional approaches. It indicates that fusion mechanism-oriented correlation can enhance the comprehensiveness of variable correlation analysis. Moreover, the approach has been proved to be adaptable to different fault diagnosis models.

Originality/value

In the DlCN-based variables selection approach, the mechanism-oriented correlation and data-oriented correlation are comprehensively considered. It improves the precision of variables selection. Meanwhile, it is an unsupervised and model-agnostic approach which addresses the shortcomings of some conventional approaches that require data labels and have insufficient adaptability for fault diagnosis models.
Research on the key techniques of composite processing of EDM and vibration ultrasonic drilling
Authors: Liu Jianyong , Luo Xueke , Li Long , Liu Fangyuan , Qiu Chuanyang , Fan Xinghao , Dong Haoran , Li Ruobing , Liu Jiahao
Published: August 2024

Purpose

Utilizing electrical discharge machining (EDM) to process micro-holes in superalloys may lead to the formation of remelting layers and micro-cracks on the machined surface. This work proposes a method of composite processing of EDM and ultrasonic vibration drilling for machining precision micro-holes in complex positions of superalloys.

Design/methodology/approach

A six-axis computer numerical control (CNC) machine tool was developed, whose software control system adopted a real-time control architecture that integrates electrical discharge and ultrasonic vibration drilling. Among them, the CNC system software was developed based on Windows + RTX architecture, which could process the real-time processing state received by the hardware terminal and adjust the processing state. Based on the SoC (System on Chip) technology, an architecture for a pulse generator was developed. The circuit of the pulse generator was designed and implemented. Additionally, a composite mechanical system was engineered for both drilling and EDM. Two sets of control boards were designed for the hardware terminal. One set was the EDM discharge control board, which detected the discharge state and provided the pulse waveform for turning on the transistor. The other was a relay control card based on STM32, which could meet the switch between EDM and ultrasonic vibration, and used the Modbus protocol to communicate with the machining control software.

Findings

The mechanical structure of the designed composite machine tool can effectively avoid interference between the EDM spindle and the drilling spindle. The removal rate of the remelting layer on 1.5 mm single crystal superalloys after composite processing can reach over 90%. The average processing time per millimeter was 55 s, and the measured inner surface roughness of the hole was less than 1.6 µm, which realized the  micro-hole machining without remelting layer, heat affected zone and micro-cracks in the single crystal superalloy.

Originality/value

The test results proved that the key techniques developed in this paper were suite for micro-hole machining of special materials.
When digital transformation meets supply chain needs in emerging markets: contributions for social and economic performance
Authors: Lerman Laura V. , Benitez Guilherme B. , Müller Julian M. , de Sousa Paulo Renato , Frank Alejandro Germán
Published: August 2024

Purpose

Supply chains are increasingly incorporating social perspectives into their activities. It is often argued that social initiatives in supply chain management (SCM) are a response to external pressures. However, it is still undetermined whether these initiatives can improve economic performance. Additionally, it is proposed that digital transformation in supply chains, also described as Smart Supply Chain, can support social performance. Therefore, this study aims to analyze the association between digital transformation, social performance in SCM and economic performance.

Design/methodology/approach

The study is based on a survey of 473 companies in Brazil, a country where social needs create high pressures on companies to respond to the country’s challenges. The data collected underwent testing using ordinary least squares regression and bootstrapping techniques to examine the mediation effects between Smart Supply Chain, social performance and economic performance.

Findings

The findings indicate that digital transformation supports social performance. Additionally, adopting social initiatives helps to increase firm performance in the context of an emerging economy, while social initiatives mediate between digital transformation and firm performance.

Originality/value

This paper provides a new perspective on the social side of supply chains by demonstrating the close relationship between digital transformation and social engagement initiatives. It argues that aligning digital transformation strategies and technologies with social performance is crucial for companies to establish stronger connections with stakeholders.
From waste to worth: a mediation analysis of lean manufacturing and operational performance in developing country
Authors: Bashar Abul , Hasin Ahsan Akhtar , Ray Samrat , Sakib Md. Nazmus , Rahman Md. Mahbubur , Bashar Nabila Binta
Published: August 2024

Purpose

Lean Manufacturing Systems (LMS) gained popularity among manufacturers globally. However, their efficacy in developing and least-developed countries remained noticeably understudied. Motivated by this research gap, the researchers of this study designed a quantitative study with a structured survey technique to investigate its context-specific impact on the apparel industry of a developing country. Hence, this study aimed to examine the relationship between LMS and elimination of waste (EOW) and operational performance (OP) and comprehend how the EOW mediates the relationship between an LMS and OP within the apparel industry of a developing economy.

Design/methodology/approach

The researchers collected data from 227 garment companies in Bangladesh. These organization-level data were then analyzed using the structural equation modeling approach with AMOS 20.0 software to examine the direct and indirect effects among EOW, LMS and OP.

Findings

The findings of this study suggest that EOW has a direct and significant effect on OP. This research also revealed that EOW has a partial mediating effect on the relationship between LMS and OP.

Research limitations/implications

This research focused on a single industry administering self-reported data and cross-sectional design, limiting generalizability and causal inference.

Practical implications

LMS and directing efforts towards EOW can significantly improve the operational performance of apparel companies by reducing lead times and costs, improving quality and increasing productivity.

Originality/value

These findings can provide useful insight to managers, practitioners and future researchers to understand the relationship between EOW, LMS and OP to optimize their production processes and improve OP in the apparel industry.
Attenuation of renal fibrosis in mice due to lack of bombesin receptor‐activated protein homologue
Authors: Peng Zhi , Wang Hui , Zheng Jiaoyun , Chen Hui , Wang Jie , Weber Horst Christian , Yuan Lin , Qin Xiaoqun , Xiang Yang , Liu Chi , Ji Ming , Liu Huijun , Qu Xiangping
Published: August 2024

Bombesin receptor‐activated protein (BRAP), encoded by the C6orf89 gene in humans, is expressed in various cells with undefined functions. BC004004, the mouse homologue of C6orf89, has been shown to play a role in bleomycin‐induced pulmonary fibrosis through the use of a BC004004 gene knockout mouse (BC004004−/−). In this study, we investigated the potential involvement of BRAP in renal fibrosis using two mouse models: unilateral ureteral obstruction (UUO) and type 2 diabetes mellitus induced by combination of a high‐fat diet (HFD) and streptozocin (STZ). BRAP or its homologue was expressed in tubular epithelial cells (TECs) in the kidneys of patients with chronic kidney disease (CKD) and in BC004004+/+ mice. Compared to control mice, BC004004−/− mice exhibited attenuated renal injury and renal fibrosis after UUO or after HFD/STZ treatment. Immunohistochemistry and immunoblot analyses of the kidneys of BC004004+/+ mice after UUO surgery showed a more significant decrease in E‐cadherin expression and a more significant increase in both α smooth muscle actin (α‐SMA) and vimentin expression compared to BC004004−/− mice. Additionally, stimulation with transforming growth factor‐β1 (TGF‐β1) led to a more significant decrease in E‐cadherin expression and a more significant increase in α‐SMA and vimentin expression in isolated TECs from BC004004+/+ than in those from BC004004−/− mice. These results suggest that an enhanced epithelial‐mesenchymal transition (EMT) process occurred in TECs in BC004004+/+ mice during renal injury, which might contribute to renal fibrosis. The loss of the BRAP homologue in BC004004−/− mice suppressed EMT activation in kidneys and contributed to the suppression of fibrosis during renal injury.
The European Union's involvement in global migration management: Possibilities and limitations
Authors: Nitszke Agnieszka
Published: August 2024

Climate migration will be one of the most important challenges in the coming decades, and although many international institutions are beginning to recognise this challenge, there is no coordinator for these efforts. The EU, because of the resources at its disposal and the fact that it is a world leader in the fight against climate change, can play this role. It can also be one of the elements of building and strengthening the EU's partnerships in the international arena, and it could strengthen the flagship political project of recent years, i.e. strategic autonomy. The aim of this article is to analyse the EU agenda and the actions taken so far to prepare the EU and the international community to manage climate migration on a global scale.