bluuebunny/crossref_metadata_2025 huggingface dataset:
Late gene therapy limits the restoration of retinal function in a mouse model of retinitis pigmentosa
Authors: Scalabrino Miranda L. , Thapa Mishek , Wang Tian , Sampath Alapakkam P. , Chen Jeannie , Field Greg D.
Published: December 2023

Retinitis pigmentosa is an inherited photoreceptor degeneration that begins with rod loss followed by cone loss. This cell loss greatly diminishes vision, with most patients becoming legally blind. Gene therapies are being developed, but it is unknown how retinal function depends on the time of intervention. To uncover this dependence, we utilize a mouse model of retinitis pigmentosa capable of artificial genetic rescue. This model enables a benchmark of best-case gene therapy by removing variables that complicate answering this question. Complete genetic rescue was performed at 25%, 50%, and 70% rod loss (early, mid and late, respectively). Early and mid treatment restore retinal output to near wild-type levels. Late treatment retinas exhibit continued, albeit slowed, loss of sensitivity and signal fidelity among retinal ganglion cells, as well as persistent gliosis. We conclude that gene replacement therapies delivered after 50% rod loss are unlikely to restore visual function to normal. This is critical information for administering gene therapies to rescue vision.
Temperature-related death burden of various neurodegenerative diseases under climate warming: a nationwide modelling study
Authors: Yin Peng , Gao Ya , Chen Renjie , Liu Wei , He Cheng , Hao Junwei , Zhou Maigeng , Kan Haidong
Published: December 2023

Limited knowledge exists regarding the ramifications of climate warming on death burden from neurodegenerative diseases. Here, we conducted a nationwide, individual-level, case-crossover study between 2013 and 2019 to investigate the effects of non-optimal temperatures on various neurodegenerative diseases and to predict the potential death burden under different climate change scenarios. Our findings reveal that both low and high temperatures are linked to increased risks of neurodegenerative diseases death. We project that heat-related neurodegenerative disease deaths would increase, while cold-related deaths would decrease. This is characterized by a steeper slope in the high-emission scenario, but a less pronounced trend in the scenarios involving mitigation strategies. Furthermore, we predict that the net changes in attributable death would increase after the mid-21st century, especially under the unrestricted-emission scenario. These results highlight the urgent need for effective climate and public health policies to address the growing challenges of neurodegenerative diseases associated with global warming.
Phylogeny and molecular evolution of the first local monkeypox virus cluster in Guangdong Province, China
Authors: Yu Jianhai , Zhang Xin , Liu Jiajun , Xiang Linlin , Huang Shen , Xie Xiaoting , Fang Ling , Lin Yifan , Zhang Meng , Wang Linqing , He Jianfeng , Zhang Bao , Di Biao , Peng Bo , Liang Jingtao , Shen Chenguang , Zhao Wei , Li Baisheng
Published: December 2023

The first local mpox outbreak in Guangdong Province, China occurred in June 2023. However, epidemiological data have failed to quickly identify the source and transmission of the outbreak. Here, phylogeny and molecular evolution of 10 monkeypox virus (MPXV) genome sequences from the Guangdong outbreak were characterized, revealing local silent transmissions that may have occurred in Guangdong whose mpox outbreaks suggested a molecular epidemiological correlation with Portugal and several regions of China during the same period. The lineage IIb C.1, which includes all 10 MPXV from Guangdong, shows consistent temporal continuity in both phylogenetic characteristics and unique molecular evolutionary mutation spectrum, reflected in the continuous increase of single nucleotide polymorphisms (SNPs) and shared mutations over time. Compared with the Japan MPXV, the Guangdong MPXV showed higher genomic nucleotide differences and separated 14 shared mutations from the B.1 lineage, comprising 6 non-synonymous mutations in genes linked to host regulation, virus infection, and virus life cycle. The unique mutation spectrum with temporal continuity in IIb C.1, related to apolipoprotein B mRNA-editing catalytic polypeptide-like 3, promotes rapid viral evolution and diversification. The findings contribute to understanding the ongoing mpox outbreak in China and offer insights for developing joint prevention and control strategies.
Unconventional polarization fatigue in van der Waals layered ferroelectric ionic conductor CuInP2S6
Authors: Zhou Ziwen , Wang Shun , Zhou Zhou , Hu Yiqi , Li Qiankun , Xue Jinshuo , Feng Zhijian , Yan Qingyu , Luo Zhongshen , Weng Yuyan , Tang Rujun , Su Xiaodong , Zheng Fengang , Okamoto Kazuki , Funakubo Hiroshi , Kang Lixing , Fang Liang , You Lu
Published: December 2023

Recent progress in two-dimensional ferroelectrics greatly expands the versatility and tunability in van der Waals heterostructure based electronics. However, the switching endurance issue that widely plagues conventional ferroelectrics in practical applications is hitherto unexplored for van der Waals layered ferroelectrics. Herein, we report the observation of unusual polarization fatigue behaviors in van der Waals layered CuInP2S6, which also possesses finite ionic conductivity at room temperature. The strong intertwinement of the short-range polarization switching and long-range ionic movement in conjunction with the van der Waals layered structure gives rise to unique morphological and polarization evolutions under repetitive electric cycles. With the help of concerted chemical, structural, lattice vibrational and dielectric analyses, we unravel the critical role of the synergy of ionic migration and surface oxidation on the anomalous polarization enhancement and the eventual polarization degradation. This work provides a general insight into the polarization fatigue characteristics in ionically-active van der Waals ferroelectrics and delivers potential solutions for the realization of fatigue-free capacitors.
Resource-efficient fault-tolerant one-way quantum repeater with code concatenation
Authors: Wo Kah Jen , Avis Guus , Rozpędek Filip , Mor-Ruiz Maria Flors , Pieplow Gregor , Schröder Tim , Jiang Liang , Sørensen Anders S. , Borregaard Johannes
Published: December 2023

One-way quantum repeaters where loss and operational errors are counteracted by quantum error-correcting codes can ensure fast and reliable qubit transmission in quantum networks. It is crucial that the resource requirements of such repeaters, for example, the number of qubits per repeater node and the complexity of the quantum error-correcting operations are kept to a minimum to allow for near-future implementations. To this end, we propose a one-way quantum repeater that targets both the loss and operational error rates in a communication channel in a resource-efficient manner using code concatenation. Specifically, we consider a tree-cluster code as an inner loss-tolerant code concatenated with an outer 5-qubit code for protection against Pauli errors. Adopting flag-based stabilizer measurements, we show that intercontinental distances of up to 10,000 km can be bridged with a minimized resource overhead by interspersing repeater nodes that each specialize in suppressing either loss or operational errors. Our work demonstrates how tailored error-correcting codes can significantly lower the experimental requirements for long-distance quantum communication.
Mesenchymal ovarian cancer cells promote CD8+ T cell exhaustion through the LGALS3-LAG3 axis
Authors: Yakubovich Edward , Cook David P. , Rodriguez Galaxia M. , Vanderhyden Barbara C.
Published: December 2023

Cancer cells often metastasize by undergoing an epithelial-mesenchymal transition (EMT). Although abundance of CD8+ T-cells in the tumor microenvironment correlates with improved survival, mesenchymal cancer cells acquire greater resistance to antitumor immunity in some cancers. We hypothesized the EMT modulates the immune response to ovarian cancer. Here we show that cancer cells from infiltrated/inflamed tumors possess more mesenchymal cells, than excluded and desert tumors. We also noted high expression of LGALS3 is associated with EMT in vivo, a finding validated with in vitro EMT models. Dissecting the cellular communications among populations in the tumor revealed that mesenchymal cancer cells in infiltrated tumors communicate through LGALS3 to LAG3 receptor expressed by CD8+ T cells. We found CD8+ T cells express high levels of LAG3, a marker of T cell exhaustion. The results indicate that EMT in ovarian cancer cells promotes interactions between cancer cells and T cells through the LGALS3 - LAG3 axis, which could increase T cell exhaustion in infiltrated tumors, dampening antitumor immunity.
Deep learning downscaled high-resolution daily near surface meteorological datasets over East Asia
Authors: Lin Hai , Tang Jianping , Wang Shuyu , Wang Shuguang , Dong Guangtao
Published: December 2023

U-Net, a deep-learning convolutional neural network, is used to downscale coarse meteorological data. Based on 19 models from the Coupled Model Intercomparison Project Phase 6 and the Multi-Source Weather (MSWX) dataset, bias correction and UNet downscaling approaches are used to develop high resolution dataset over the East Asian region, referred to as Climate Change for East Asia with Bias corrected UNet Dataset (CLIMEA-BCUD). CLIMEA-BCUD provides nine meteorological variables including 2-m air temperature, 2-m daily maximum air temperature, 2-m daily minimum air temperature, precipitation, 10-m wind speed, 2-m relative humidity, 2-m specific humidity, downward shortwave radiation and downward longwave radiation with 0.1° horizontal resolution at daily intervals over the historical period of 1950–2014 and three future scenarios (SSP1-2.6, SSP2-4.5 and SSP5-8.5) of 2015–2100. Validation against MSWX indicates that CLIMEA-BCUD shows reasonable performance in terms of climatology, and it is capable of simulating seasonal cycles and future changes well. It is suggested that CLIMEA-BCUD can promote the application of deep learning in climate research in the areas of climate change, hydrology, etc.
Chromosome-level genome assembly and annotation of the Antarctica whitefin plunderfish Pogonophryne albipinna
Authors: Jo Euna , Choi Soyun , Lee Seung Jae , Kim Jinmu , Choi Eun Kyung , Cho Minjoo , Kim Jangyeon , Chung Sangdeok , Lee Jaebong , Kim Jeong-Hoon , Park Hyun
Published: December 2023

The Antarctic whitefin plunderfish Pogonophryne albipinna belongs to the family Artedidraconidae, a key component of Antarctic benthic ecosystems within the order Perciformes and the suborder Notothenioidei. While genome research on P. albipinna using short-read sequencing is available, high-quality genome assembly and annotation employing long-read sequencing have yet to be performed. This study presents a chromosome-scale genome assembly and annotation for P. albipinna, utilizing a combination of Illumina short-read, PacBio long-read, and Hi-C sequencing technologies. The resulting genome assembly spans approximately 1.07 Gb, with a longest scaffold measuring 59.39 Mb and an N50 length of 41.76 Mb. Of the 1,111 Hi-C scaffolds, 23 exceeded 10 Mb and were thus classified as chromosome-level. BUSCO completeness was assessed at 95.6%. The assembled genome comprises 50.68% repeat sequences, and a total of 31,128 protein-coding genes were predicted. This study will enhance our understanding of the genomic characteristics of cryonotothenioids and facilitate comparative analyses of their adaptation and evolution in extreme environments.
Blood-based DNA methylation in advanced Nasopharyngeal Carcinoma exhibited distinct CpG methylation signature
Authors: Chatterjee Koustav , Mal Sudipa , Ghosh Monalisha , Chattopadhyay Nabanita Roy , Roy Sankar Deb , Chakraborty Koushik , Mukherjee Syamantak , Aier Moatoshi , Choudhuri Tathagata
Published: December 2023

The TNM staging system is currently used to detect cancer stages. Regardless, a small proportion of cancer patients recur even after therapy, suggesting more specific molecular tools are required to justify the stage-specific detection and prompt cancer diagnosis. Thus, we aimed to explore the blood-based DNA methylation signature of metastatic nasopharyngeal carcinoma (NPC) to establish a holistic methylation biomarker panel. For the identification of methylation signature, the EPIC BeadChip-based array was performed. Comparative analysis for identifying unique probes, validation, and functional studies was investigated by analyzing GEO and TCGA datasets. We observed 4093 differentially methylated probes (DMPs), 1232 hydroxymethylated probes, and 25 CpG islands. Gene expression study revealed both upregulated and downregulated genes. Correlation analysis suggested a positive (with a positive r, p ≤ 0.05) and negative (with a negative r, p ≤ 0.05) association with different cancers. TFBS analysis exhibited the binding site for many TFs. Furthermore, gene enrichment analysis indicated the involvement of those identified genes in biological pathways. However, blood-based DNA methylation data uncovered a distinct DNA methylation pattern, which might have an additive role in NPC progression by altering the TFs binding. Moreover, based on tissue-specificity, a variation of correlation between methylation and gene expression was noted in different cancers.
The Prevalence of Behavioural Symptoms and Psychiatric Disorders in Hadza Children
Authors: Ougrin Dennis , Woodhouse Emma , Tucker Gavin , Ronaldson Amy , Bakolis Ioannis
Published: December 2023

The worldwide pooled prevalence of psychiatric disorders in children is 13.4%. Studying the prevalence of childhood psychiatric disorders across radically different economic systems and social structures could indicate universal factors leading to their development. The prevalence of childhood psychiatric disorders in a mixed-subsistence foraging society has not been studied. The Strengths and Difficulties Questionnaire and the Development and Well-Being Assessment were used to compare the prevalence of behavioural symptoms and psychiatric disorders in Hadza children aged 5–16 years (n = 113) to a nationally representative sample from England (n = 18,029) using a cross-sectional study design. Emotional problems, conduct problems and hyperactivity were lower in the Hadza children. Prosocial behaviour and peer problems were higher in Hadza children. 3.6% of Hadza children met the criteria for a psychiatric disorder compared to 11.8% of English children. All psychiatric disorders in Hadza children were co-morbid with autism spectrum disorder. No child from the Hadza group met the criteria for an emotional, behaviour or eating disorder. Further work should study the factors which lead to the different prevalence of psychiatric disorders in Hadza children.
Experimental study on the effect of room temperature pre-oxidized time on spontaneous combustion characteristics of coal
Authors: Zhang Xun , Liang Huimin , Huang Ge , Lu Bing , Yu Chen , Zou Jiahui
Published: December 2023

The presence of different types of coal at room temperature can lead to self-heating of coal, potentially resulting in spontaneous combustion. To investigate the effect of ambient temperature pre-oxidation (BL) time on the self-combustion characteristics of different coal types, synchronous thermal analysis (STA) and Fourier-transform infrared spectroscopy (FTIR) experiments were conducted. The results of the synchronous thermal analysis experiments indicate that ambient temperature pre-oxidation for 3 months (BL3), BL6, and BL9 coals exhibit faster oxidation reactions compared to the original coal, while BL12 coal shows slower oxidation than the original coal. Among these, BL9 coal demonstrates the most significant changes in oxidation reaction characteristics, with the fastest oxidation reaction time being 35.36 min, which is 1.38 min faster than the original coal. To support this observation, a comparison was made between the relative content of active functional groups in the original coal and BL coal. The study revealed that the BL process affects the relative content of hydroxyl groups, aromatic hydrocarbons, aliphatic hydrocarbons, and oxygen-containing functional groups, thereby influencing the coal-oxygen reaction process. This suggests that pre-oxidized coal, compared to the original coal, has a larger pore structure, which plays a dominant role in promoting coal self-combustion in the first 9 months of the BL process. As BL time continues to increase, the continuous reaction of active functional groups at room temperature leads to excessive consumption, resulting in a more significant role in inhibiting coal self-combustion. The research results provide valuable insights for predicting the spontaneous combustion risk of oxidized coal.
Insecticidal roof barriers mounted on untreated bed nets can be as effective against Anopheles gambiae as regular insecticide-treated bed nets
Authors: Abbott Anthony J. , Matope Agnes , Jones Jeff , Voloshin Vitaly , Towers Catherine E. , Towers David , McCall Philip J.
Published: December 2023

Barrier bednets (BBnets), regular bednets with a vertical insecticidal panel to target mosquitoes above the bednet roof, where they are most active, have the potential to improve existing Insecticidal Treated Bednets (ITNs), by reducing the quantity of insecticide required per net, reducing the toxic risks to those using the net, potentially increasing insecticide choice. We evaluated the performance of PermaNet 3.0 (P3) and untreated (Ut) bed nets with and without pyrethroid and piperonyl butoxide roof barriers in killing pyrethroid-resistant and susceptible Anopheles gambiae, simultaneously video-recording mosquito flight tracks. Bioassay results showed that treated roof barriers, particularly the longitudinal P3 barrier (P3L) could be an effective addition to a bed net: P3 + P3L were consistently significantly more effective than the reference P3 bednet while performance of untreated nets could be raised to equal that of the reference P3 following the addition of a P3 barrier. The BBnet’s potential to augment existing bednets and enhance their performance is considered.
Metabolic brain imaging with glucosamine CEST MRI: in vivo characterization and first insights
Authors: Rivlin Michal , Perlman Or , Navon Gil
Published: December 2023

The utility of chemical exchange saturation transfer (CEST) MRI for monitoring the uptake of glucosamine (GlcN), a safe dietary supplement, has been previously demonstrated in detecting breast cancer in both murine and human subjects. Here, we studied and characterized the detectability of GlcN uptake and metabolism in the brain. Following intravenous GlcN administration in mice, CEST brain signals calculated by magnetization transfer ratio asymmetry (MTRasym) analysis, were significantly elevated, mainly in the cortex, hippocampus, and thalamus. The in vivo contrast remained stable during 40 min of examination, which can be attributed to GlcN uptake and its metabolic products accumulation as confirmed using 13C NMR spectroscopic studies of brain extracts. A Lorentzian multi-pool fitting analysis revealed an increase in the hydroxyl, amide, and relayed nuclear Overhauser effect (rNOE) signal components after GlcN treatment. With its ability to cross the blood-brain barrier (BBB), the GlcN CEST technique has the potential to serve as a metabolic biomarker for the diagnosis and monitoring various brain disorders.
Unlocking geothermal energy for sustainable greenhouse farming in arid regions: a remote-sensed assessment in Egypt’s New Delta
Authors: Hegazy Anwar , Mohamed Sami Z.
Published: December 2023

This study introduces a novel approach for assessing geothermal potential in arid regions, specifically Egypt’s New Delta Agriculture Mega Project area. The challenge of limited sub-soil temperature profile data was addressed by integrating Global Land Data Assimilation System (GLDAS) weather data. Using the Earth-to-Air Heat Exchanger (EAHE) model, the extracted air and sub-soil temperature profiles the potential for geothermal energy production was estimated. We modeled the annual sinusoidal soil surface periodic heating pattern by utilizing GLDAS ambient air temperature (AAT) and land surface temperature (LST). Using either AAT or LST yielded a Root-Mean-Square Error (RSME) of 0.2°C. The generated sub-soil profiles for the New Delta region showed a temperature variation of no more than 1.5°C at a 4-m depth, making it an optimal depth for EAHE installation. One-pipe EAHE demonstrated a cooling/heating capacity ranging from 400 W (cooling) to −300 W (heating). The study highlights the New Delta region’s strong geothermal potential for greenhouse cooling and heating, underlining its suitability as a sustainable energy source in arid areas. It also offers a practical guide for the EAHE application and it emphasizes the global potential for geothermal energy exploration, using innovative GLDAS data to expand sub-soil temperature profile accessibility.
Clinical efficacy of the mulligan maneuver for cervicogenic headache: a randomized controlled trial
Authors: Jin Xin , Du Hong-Gen , Kong Ning , Shen Jian-Liang , Chen Wen-Jun
Published: December 2023

Cervicogenic headache is an often observed secondary headache in clinical settings, with patients who endure prolonged and persistent pain being particularly susceptible to mood changes. Currently, the Mulligan is one of the effective methods for CEH. However, there is a lack of evaluation about the strength and frequency of headaches, as well as the assessment of pain-induced emotions, in individuals with CEH using this particular procedure. Herein, we aimed to evaluate the effectiveness of the Mulligan maneuver from a multidimensional perspective of pain intensity and mood. A total of forty patients diagnosed with CEH who satisfied the specified inclusion criteria were recruited and allocated randomly into two groups: the control group and the treatment group, with each group consisting of twenty cases. The control group received health education, while the treatment group received the Mulligan maneuver once daily over a course of 10 treatment sessions.The clinical outcome of patients with CEH in two groups was assessed using the Visual Analog Scale (VAS), Hamilton Anxiety Scale (HAMA), and Hamilton Depression Scale (HAMD). Resting-state functional magnetic resonance imaging was employed to examine variations in brain function activities between the two CEH groups. Brain regions showing differences were identified as regions of interest and subsequently correlated with clinical behavioral measures using Pearson’s correlation analysis. The differences in VAS, HAMA and HAMD between the two groups of CEH patients were also statistically significant. The brain regions that showed differences in the ReHo scores between the two groups of CEH patients included the left cerebellum, the frontal gyrus, and the middle temporal gyrus. There was a positive correlation between the left frontal gyrus and VAS, HAMA and HAMD. The left middle temporal gyrus had a negative correlation with VAS, HAMA, and HAMD and the left cerebellum had a positive correlation with VAS correlation. The Mulligan maneuver may improve pain levels and have a moderating effect on pain-related negative emotions by regulating the function of relevant brain regions in CEH patients.
A laboratory ice machine as a cold oligotrophic artificial microbial niche for biodiscovery
Authors: Satari Leila , Torrent Daniel , Ortega-Legarreta Asier , Latorre-Pérez Adriel , Pascual Javier , Porcar Manuel , Iglesias Alba
Published: December 2023

Microorganisms are ubiquitously distributed in nature and usually appear as biofilms attached to a variety of surfaces. Here, we report the development of a thick biofilm in the drain pipe of several standard laboratory ice machines, and we describe and characterise, through culture-dependent and -independent techniques, the composition of this oligotrophic microbial community. By using culturomics, 25 different microbial strains were isolated and taxonomically identified. The 16S rRNA high-throughput sequencing analysis revealed that Bacteroidota and Proteobacteria were the most abundant bacterial phyla in the sample, followed by Acidobacteriota and Planctomycetota, while ITS high-throughput sequencing uncovered the fungal community was clearly dominated by the presence of a yet-unidentified genus from the Didymellaceae family. Alpha and beta diversity comparisons of the ice machine microbial community against that of other similar cold oligotrophic and/or artificial environments revealed a low similarity between samples, highlighting the ice machine could be considered a cold and oligotrophic niche with a unique selective pressure for colonisation of particular microorganisms. The recovery and analysis of high-quality metagenome-assembled genomes (MAGs) yielded a strikingly high rate of new species. The functional profiling of the metagenome sequences uncovered the presence of proteins involved in extracellular polymeric substance (EPS) and fimbriae biosynthesis and also allowed us to detect the key proteins involved in the cold adaptation mechanisms and oligotrophic metabolic pathways. The metabolic functions in the recovered MAGs confirmed that all MAGs have the genes involved in psychrophilic protein biosynthesis. In addition, the highest number of genes for EPS biosynthesis was presented in MAGs associated with the genus Sphingomonas, which was also recovered by culture-based method. Further, the MAGs with the highest potential gene number for oligotrophic protein production were closely affiliated with the genera Chryseoglobus and Mycobacterium. Our results reveal the surprising potential of a cold oligotrophic microecosystem within a machine as a source of new microbial taxa and provide the scientific community with clues about which microorganisms are able to colonise this ecological niche and what physiological mechanisms they develop. These results pave the way to understand how and why certain microorganisms can colonise similar anthropogenic environments.
Genetic, metabolic and clinical delineation of an MRPS23-associated mitochondrial disorder
Authors: Ittiwut Chupong , Ittiwut Rungnapa , Kuptanon Chulaluck , Matsuhashi Tetsuro , Shimura Masaru , Sugiyama Yohei , Onuki Takanori , Ohtake Akira , Murayama Kei , Vatanavicharn Nithiwat , Dejputtawat Waralee , Tantisirivit Nitchanund , Kor-anantakul Phawin , Kamolvisit Wuttichart , Suphapeetiporn Kanya , Shotelersuk Vorasuk
Published: December 2023

MRPS23 is a nuclear gene encoding a mitochondrial ribosomal protein. A patient with a mitochondrial disorder was found to carry a variant in MRPS23. More cases are necessary to establish MRPS23 as a mitochondrial disease gene. Of 5134 exomes performed in our center, we identified five independent patients who had similar clinical manifestations and were homozygous for the same germline variant c.119C>T; p.P40L in MRPS23. Detailed clinical findings, mitochondrial enzyme activity assays from cultured skin fibroblasts, PCR-Sanger-sequencing, and variant age estimation were performed. Their available family members were also studied. Eight members homozygous for the MRPS23 p.P40L were identified. All were from Hmong hilltribe. Seven presented with alteration of consciousness and recurrent vomiting, while the eighth who was a younger brother of a proband was found pre-symptomatically. Patients showed delayed growth and development, hearing impairment, hypoglycemia, lactic acidosis, and liver dysfunction. In vitro assays of cultured fibroblasts showed combined respiratory chain complex deficiency with low activities of complexes I and IV. PCR-Sanger-sequencing confirmed the variant, which was estimated to have occurred 1550 years ago. These results establish the MRPS23-associated mitochondrial disorder inherited in an autosomal recessive pattern and provide insight into its clinical and metabolic features.
Visualization and data exploration of chromosome conformation capture data using Voronoi diagrams with v3c-viz
Authors: Race Alan M. , Fuchs Alisa , Chung Ho-Ryun
Published: December 2023

Chromosome conformation capture (3C) sequencing approaches, like Hi-C or micro-C, allow for an unbiased view of chromatin interactions. Most analysis methods rely on so-called interaction matrices, which are derived from counting read pairs in bins of fixed size. Here, we propose the Voronoi diagram, as implemented in Voronoi for chromosome conformation capture data visualization (v3c-viz) to visualize 3C data. The Voronoi diagram corresponds to an adaptive-binning strategy that adapts to the local densities of points. In this way, visualization of data obtained by moderate sequencing depth pinpoint many, if not most, interesting features such as high frequency contacts. The favorable visualization properties of the Voronoi diagram indicate that the Voronoi diagram as density estimator can be used to identify high frequency contacts at a resolution approaching the typical size of enhancers and promoters.v3c-vizis available athttps://github.com/imbbLab/v3c-viz.
Unexpected appetitive events promote positive affective state in juvenile European sea bass
Authors: Alvarado M. V. , Felip A. , Espigares F. , Oliveira R. F.
Published: December 2023

Some animal species exhibit considerable physiological and behavioural alterations in response to captivity. It has been hypothesized, but rarely tested, that such changes reflect a negative affective state that is associated to this specific context. In the last years, judgement bias measures have emerged as reliable indicators of animal affective state, under the assumption that individuals in a negative affective state are more likely to evaluate ambiguous stimuli as negative and display therefore pessimistic behaviours. Here, we have developed a judgement bias task for juvenile European sea bass (Dicentrarchus labrax) aiming to measure optimism/pessimism in this marine species, which have previously been reported to show important dysregulations in captive settings. Our results show that juvenile sea bass exhibit a considerable bias towards pessimistic behaviours in laboratory settings. Furthermore, juveniles that received an unexpected positive event during the judgement bias test displayed more optimistic responses toward ambiguous stimuli as compared to control fish, indicating a positive change in their affective state induced by the appetitive experience. These results reveal a direct interaction of the internal affective state with decision-making processing under ambiguity in juvenile European sea bass, highlighting therefore the potential of judgement bias tests as a tool for the advancement and improvement of our understanding of welfare in finfish aquaculture.
Enlarging the scenario of site directed 19F labeling for NMR spectroscopy of biomolecules
Authors: Vitali Valentina , Torricella Francesco , Massai Lara , Messori Luigi , Banci Lucia
Published: December 2023

The possibility of using selectively incorporated 19F nuclei for NMR spectroscopic studies has retrieved increasing interest in recent years. The high gyromagnetic ratio of 19F and its absence in native biomolecular systems make this nucleus an interesting alternative to standard 1H NMR spectroscopy. Here we show how we can attach a label, carrying a 19F atom, to protein tyrosines, through the use of a specific three component Mannich-type reaction. To validate the efficacy and the specificity of the approach, we tested it on two selected systems with the aid of ESI MS measurements.
Associations of tissue damage induced inflammatory plasticity in masseter muscle with the resolution of chronic myalgia
Authors: Lindquist Karen A. , Shein Sergey A. , Hovhannisyan Anahit H. , Mecklenburg Jennifer , Zou Yi , Lai Zhao , Tumanov Alexei V. , Akopian Armen N.
Published: December 2023

Gene plasticity during myogenous temporomandibular disorder (TMDM) development is largely unknown. TMDM could be modeled by intramuscular inflammation or tissue damage. To model inflammation induced TMDM we injected complete Freund’s adjuvant (CFA) into masseter muscle (MM). To model tissue damage induced TMDM we injected extracellular matrix degrading collagenase type 2 (Col). CFA and Col produced distinct myalgia development trajectories. We performed bulk RNA-seq of MM to generate gene plasticity time course. CFA initiated TMDM (1d post-injection) was mainly linked to chemo-tacticity of monocytes and neutrophils. At CFA-induced hypersensitivity post-resolution (5d post-injection), tissue repair processes were pronounced, while inflammation was absent. Col (0.2U) produced acute hypersensitivity linked to tissue repair without inflammatory processes. Col (10U) generated prolonged hypersensitivity with inflammatory processes dominating initiation phase (1d). Pre-resolution phase (6d) was accompanied with acceleration of expressions for tissue repair and pro-inflammatory genes. Flow cytometry showed that immune processes in MM was associated with accumulations of macrophages, natural killer, dendritic and T-cells, further confirming our RNA-seq findings. Altogether, CFA and Col treatments induced different immune processes in MM. Importantly, TMDM resolution was preceded with muscle cell and extracellular matrix repairs, an elevation in immune system gene expressions and distinct immune cell accumulations in MM.
Alleviation of calcium hydroxide nanoparticles induced genotoxicity and gastritis by coadministration of calcium titanate and yttrium oxide nanoparticles in mice
Authors: Mohamed Hanan R. H. , Elbasiouni Salma H. , Farouk Ahmed H. , Nasif Kirolls A. , Nasraldin Karima , Safwat Gehan
Published: December 2023

Diverse applications of nanoparticles due to their unique properties has rapidly increased human exposure to numerous nanoparticles such as calcium hydroxide (Ca(OH)2), calcium titanate (CaTiO3), and yttrium oxide (Y2O3) nanoparticles almost in all aspect of daily life. However, very limited data are available on the effect of these nanoparticles on genomic DNA integrity and inflammation induction in the gastric tissues. Hence, this study estimated the effect of Ca(OH)2, CaTiO3, or/and Y2O3 nanoparticles multiple oral administration on the genomic DNA damage and inflammation induction in the mice gastric tissues. A suspension containing 50 mg/kg b.w of Ca(OH)2, CaTiO3, or Y2O3 nanoparticles were given orally to male mice separately or together simultaneously three times a week for two consecutive weeks. Multiple oral administration of Ca(OH)2 nanoparticles led to significant elevations in DNA damage induction and ROS generation, in contrast to the non-significant changes observed in the level of induced DNA damage and generated ROS after administration of CaTiO3 or Y2O3 nanoparticles separately or in combination with Ca(OH)2 nanoparticles. Oral administration of Ca(OH)2 nanoparticles alone also highly upregulated INOS and COX-2 genes expression and extremely decreased eNOS gene expression. However, high elevations in eNOS gene expression were detected after multiple administration of CaTiO3 and Y2O3 nanoparticles separately or together simultaneously with Ca(OH)2 nanoparticles. Meanwhile, non-remarkable changes were noticed in the expression level of INOS and COX-2 genes after administration of CaTiO3 and Y2O3 nanoparticles separately or simultaneously together with Ca(OH)2 nanoparticles. In conclusion: genomic DNA damage and inflammation induced by administration of Ca(OH)2 nanoparticles alone at a dose of 50 mg/kg were mitigated by about 100% when CaTiO3 and Y2O3 nanoparticles were coadministered with Ca(OH)2 nanoparticles until they reached the negative control level through altering the expression level of eNOS, INOS and COX-2 genes and scavenging gastric ROS. Therefore, further studies are recommended to investigate the toxicological properties of Ca(OH)2, CaTiO3 and Y2O3 nanoparticles and possibility of using CaTiO3 and Y2O3 nanoparticles to mitigate genotoxicity and inflammation induction by Ca(OH)2 nanoparticles.
Progression of retinitis pigmentosa on static perimetry, optical coherence tomography, and fundus autofluorescence
Authors: Iga Yuhei , Hasegawa Tomoko , Ikeda Hanako Ohashi , Hirota Yoshimichi , Miyata Manabu , Numa Shogo , Otsuka Yuki , Tsujikawa Akitaka
Published: December 2023

In retinitis pigmentosa (RP), photoreceptor degeneration leads to progressive visual field loss and visual impairment. Several therapeutic trials are ongoing aiming to establish effective treatments. Although functional evaluations are commonly used in clinical trials, residual ellipsoid zone (EZ) measurement on optical coherence tomography has been shown to be more sensitive to detect disease progression. Establishment of sensitive outcome measurement is essential to develop new therapeutic strategies. In the current study, we evaluated the progression rates of the disease in 76 eyes of 76 patients with RP, using the residual EZ length, ring-shaped macular hyperautofluorescent (AF), and visual field. Decrease rates measured by the residual EZ area and by the hyper-AF ring area were strongly positively correlated (P < 0.0001, r = 0.71). The reduction rates of the residual EZ length and hyper-AF ring radius were constant regardless of their baseline measurements. Faster annual reduction rates of the hyper-AF ring area or radius were significantly correlated with faster visual field progression (P = 0.03, r = 0.25 and P = 0.004, r = 0.33, respectively). These findings support the usage of morphological measurements such as EZ or hyper-AF ring measurements as outcome measurement for future clinical trials for RP.
Mechanistic insights into the anti-restenotic effects of HSP27 and HO1 modulated by reconstituted HDL on neointimal hyperplasia
Authors: Kim Ye Ji , Khaleel Zinah Hilal , Jin Myeongji , Lee Jo Woon Yi , Park Seongchan , Ga Seongmin , Kim Nam Hyeong , Sa Deok Hyang , Kang Eun Sung , Han Seul Hee , Lee Ji Yeun , Ku Hyo Jung , Kim Sang-Wook , Kim Ki Yong , Park Jeong Euy , Kim Yong Ho , Lee Bok-Soo
Published: December 2023

High-density lipoprotein (HDL) therapy has demonstrated beneficial effects in acute stroke and acute myocardial infarction models by reducing infarct size. In this study, we investigated the inhibitory effects of reconstituted HDL (rHDL) on neointimal hyperplasia and elucidated its underlying mechanism using a balloon injury rat model. Our finding revealed a significant 37% reduction in the intima to media ratio in the arteries treated with 80 mg/kg rHDL compared to those subjected to injury alone (p < 0.05), indicating a specific inhibition of neointimal hyperplasia. In vivo analysis further supported the positive effects of rHDL by demonstrating a reduction in smooth muscle cell (SMC) proliferation and an increase in endothelial cell (EC) proliferation. Additionally, rHDL treatment led to decreased infiltration of leukocytes and downregulated the expression of matrix metallopeptidase 9 (MMP9) in the neointimal area. Notably, rHDL administration resulted in decreased expression of VCAM1 and HIF1α, alongside increased expression of heme oxygenase 1 (HO1) and heat shock protein 27 (HSP27). Overexpression of HSP27 and HO1 effectively inhibited SMC proliferation. Moreover, rHDL-mediated suppression of injury-induced HIF1α coincided with upregulation of HSP27. Interestingly, HSP27 and HO1 had varying effects on the expression of chemokine receptors and rHDL did not exert significant effect on chemokine receptor expression in THP1 cells. These findings underscore the distinct roles of HSP27 and HO1 as potential regulatory factors in the progression of restenosis. Collectively, our study demonstrates that rHDL exerts a potent anti-neointimal hyperplasia effect by reducing leukocytes infiltration and SMC proliferation while promoting EC proliferation.
Manipulation of phasic arousal by auditory cues is associated with subsequent changes in visual orienting to faces in infancy
Authors: Bussu Giorgia , Portugal Ana Maria , Wilsson Lowe , Kleberg Johan Lundin , Falck-Ytter Terje
Published: December 2023

This eye-tracking study investigated the effect of sound-induced arousal on social orienting under different auditory cue conditions in 5-month-old (n = 25; n = 13 males) and 10-month-old infants (n = 21; n = 14 males) participating in a spontaneous visual search task. Results showed: (1) larger pupil dilation discriminating between high and low volume (b = 0.02, p = 0.007), but not between social and non-social sounds (b = 0.004, p = 0.64); (2) faster visual orienting (b =  − 0.09, p < 0.001) and better social orienting at older age (b = 0.94, p < 0.001); (3) a fast habituation effect on social orienting after high-volume sounds (χ2(2) = 7.39, p = 0.025); (4) a quadratic association between baseline pupil size and target selection (b =  − 1.0, SE = 0.5, χ2(1) = 4.04, p = 0.045); (5) a positive linear association between pupil dilation and social orienting (b = 0.09, p = 0.039). Findings support adaptive gain theories of arousal, extending the link between phasic pupil dilation and task performance to spontaneous social orienting in infancy.
Deriving expert-driven seismic and wind fragility functions for non-engineered residential typologies in Batanes, Philippines
Authors: Hadlos Arvin , Opdyke Aaron , Hadigheh S. Ali
Published: December 2023

Natural hazards inflict significant damage to dwellings in the Philippines where housing is often the most valued asset of households. Residential fragility functions estimate structural damage to mitigate risk but these are challenging to derive when empirical and analytical data are lacking, as is common in rural areas. Too often, conventional fragility estimates overlook the characteristics of informally built or non-engineered dwellings common in rural areas. We used a heuristic alternative of deriving fragility functions relying on experts’ judgements to understand the housing performance of non-engineered residential typologies in the Province of Batanes in the Philippines. Drawing on field surveys in the Municipality of Itbayat, we identified and defined seven prominent typologies. Based on the Applied Technology Council’s expert-driven method of deriving fragility functions, 18 experts estimated the damage states of these typologies against the impacts of earthquakes and typhoons which are the two most prominent hazards in the region. Our findings provide first-generation fragility functions for Batanes as a step towards more localised risk assessment in the Philippines. More broadly, these functions can be used for typologies identified beyond Batanes where similar structural characteristics are prevalent.
The combination of astragalus injection and ambroxol hydrochloride in the adjuvant treatment of COPD: a systematic review and meta-analysis
Authors: Zhou Zubing , Yang Lele , Hu Chao , Gao Rui , Zhang Xiaobo , Shen Tao
Published: December 2023

Chronic obstructive pulmonary disease (COPD) is a severe condition that leads to premature mortality and places a significant financial burden on healthcare systems. An adjunctive therapy in COPD includes the simultaneous administration of astragalus injection and ambroxol hydrochloride. Despite its widespread use, the effectiveness of this combined approach in COPD treatment has not been systematically evaluated. Thus, we conducted a systematic review and meta-analysis to assess the efficacy of combining astragalus injection with ambroxol hydrochloride as an adjuvant treatment for COPD. Six electronic databases were used to search for relevant randomized controlled trials, and data analysis was conducted using Review Manager 5.4. A total of 14 randomized controlled trials were included, involving 1070 patients who met the criteria. The results of the meta-analysis indicated that the combination of astragalus injection with ambroxol hydrochloride as an adjuvant treatment can improve various clinical parameters in patients with COPD compared to conventional treatment alone. These parameters include the clinical effective rate (OR = 5.44, 95% CI 3.51–8.43, I2 = 0%), partial pressure of oxygen in artery (MD = 1.12, 95% CI 0.87–1.36, I2 = 5%), partial pressure of carbon dioxide in artery (MD = − 1.43, 95% CI − 1.65 to − 1.21, I2 = 0%), forced expiratory volume in one second (MD = 0.30, 95% CI 0.18–0.42, I2 = 0%), percentage of forced expiratory volume in one second (MD = 16.18, 95% CI 12.60–19.76, I2 = 82%), forced vital capacity (MD = 0.33, 95% CI 0.21–0.45, I2 = 36%), hemoglobin (MD = − 16.17, 95% CI − 20.84 to − 11.51, I2 = 29%), and the ratio of forced expiratory volume in one second to forced vital capacity (MD = 2.51, 95% CI − 0.05 to 5.06, I2 = 0%). The combination of astragalus injection and ambroxol hydrochloride could be a selection of COPD patients as an adjuvant treatment. However, further validation is required to evaluate the effectiveness of combining astragalus injection and ambroxol hydrochloride as an adjunctive treatment for patients with COPD.
Rab7 localized on zymogen granules is involved in maturation but not in autophagy or regulated exocytosis in pancreatic acinar cells
Authors: Takahashi Kenichi , Mashima Hirosato , Sekine Masanari , Uehara Takeshi , Asano Takeharu , Sun-Wada Ge-Hong , Wada Yoh , Ohnishi Hirohide
Published: December 2023

Rab7 is known to function in the autophagy and endocytosis pathways in eukaryocytes and is related to various diseases. We recently reported that Rab7 plays a protective role against acute pancreatitis. However, its physiological function in exocytic cells remains unclear. Therefore, we investigated the role of Rab7 in pancreas-specific Rab7 knockout mice (Rab7Δpan). Immunofluorescence microscopy revealed that Rab7 colocalized with amylase in pancreatic acinar cells of wild-type mice, but not in Rab7Δpan mice. Western blotting confirmed Rab7 localization in the zymogen granule (ZG) membranes of wild-type mice. Cholecystokinin (CCK)-stimulated amylase secretion examined using isolated pancreatic acini was similar in Rab7Δpan and wild-type mice. In contrast, electron microscopy revealed that the diameters of ZGs were shorter and the number of ZGs was larger in the pancreatic acinar cells of Rab7Δpan mice than in those of wild-type mice. However, the number of ZGs decreased in both Rab7Δpan and wild-type mice after 24 h of starvation. In addition, the amount of amylase in the pancreas was decreased in both Rab7Δpan and wild-type mice. These data indicate that Rab7 localized on ZGs plays a crucial role in the maturation of ZGs but not in their autophagy or regulated exocytosis in pancreatic acinar cells.
Testing novel facial recognition technology to identify dogs during vaccination campaigns
Authors: Czupryna Anna Maria , Estepho Mike , Lugelo Ahmed , Bigambo Machunde , Sambo Maganga , Changalucha Joel , Lushasi Kennedy Selestin , Rooyakkers Philip , Hampson Katie , Lankester Felix
Published: December 2023

A lack of methods to identify individual animals can be a barrier to zoonoses control. We developed and field-tested facial recognition technology for a mobile phone application to identify dogs, which we used to assess vaccination coverage against rabies in rural Tanzania. Dogs were vaccinated, registered using the application, and microchipped. During subsequent household visits to validate vaccination, dogs were registered using the application and their vaccination status determined by operators using the application to classify dogs as vaccinated (matched) or unvaccinated (unmatched), with microchips validating classifications. From 534 classified dogs (251 vaccinated, 283 unvaccinated), the application specificity was 98.9% and sensitivity 76.2%, with positive and negative predictive values of 98.4% and 82.8% respectively. The facial recognition algorithm correctly matched 249 (99.2%) vaccinated and microchipped dogs (true positives) and failed to match two (0.8%) vaccinated dogs (false negatives). Operators correctly identified 186 (74.1%) vaccinated dogs (true positives), and 280 (98.9%) unvaccinated dogs (true negatives), but incorrectly classified 58 (23.1%) vaccinated dogs as unmatched (false negatives). Reduced application sensitivity resulted from poor quality photos and light-associated color distortion. With development and operator training, this technology has potential to be a useful tool to identify dogs and support research and intervention programs.