bluuebunny/crossref_metadata_2025_split huggingface dataset:
Dopamine and glutamate regulate striatal acetylcholine in decision-making
Authors: Chantranupong Lynne , Beron Celia C. , Zimmer Joshua A. , Wen Michelle J. , Wang Wengang , Sabatini Bernardo L. 
Published: August 2023

AbstractStriatal dopamine and acetylcholine are essential for the selection and reinforcement of motor actions and decision-making1. In vitro studies have revealed an intrastriatal circuit in which acetylcholine, released by cholinergic interneurons (CINs), drives the release of dopamine, and dopamine, in turn, inhibits the activity of CINs through dopamine D2 receptors (D2Rs). Whether and how this circuit contributes to striatal function in vivo is largely unknown. Here, to define the role of this circuit in a living system, we monitored acetylcholine and dopamine signals in the ventrolateral striatum of mice performing a reward-based decision-making task. We establish that dopamine and acetylcholine exhibit multiphasic and anticorrelated transients that are modulated by decision history and reward outcome. Dopamine dynamics and reward encoding do not require the release of acetylcholine by CINs. However, dopamine inhibits acetylcholine transients in a D2R-dependent manner, and loss of this regulation impairs decision-making. To determine how other striatal inputs shape acetylcholine signals, we assessed the contribution of cortical and thalamic projections, and found that glutamate release from both sources is required for acetylcholine release. Altogether, we uncover a dynamic relationship between dopamine and acetylcholine during decision-making, and reveal multiple modes of CIN regulation. These findings deepen our understanding of the neurochemical basis of decision-making and behaviour.
R-loop-dependent promoter-proximal termination ensures genome stability
Authors: Xu Congling , Li Chengyu , Chen Jiwei , Xiong Yan , Qiao Zhibin , Fan Pengyu , Li Conghui , Ma Shuangyu , Liu Jin , Song Aixia , Tao Bolin , Xu Tao , Xu Wei , Chi Yayun , Xue Jingyan , Wang Pu , Ye Dan , Gu Hongzhou , Zhang Peng , Wang Qiong , Xiao Ruijing , Cheng Jingdong , Zheng Hai , Yu Xiaoli , Zhang Zhen , Wu Jiong , Liang Kaiwei , Liu Yan-Jun , Lu Huasong , Chen Fei Xavier 
Published: August 2023

Abstract
The proper regulation of transcription is essential for maintaining genome integrity and executing other downstream cellular functions1,2. Here we identify a stable association between the genome-stability regulator sensor of single-stranded DNA (SOSS)3 and the transcription regulator Integrator-PP2A (INTAC)4–6. Through SSB1-mediated recognition of single-stranded DNA, SOSS–INTAC stimulates promoter-proximal termination of transcription and attenuates R-loops associated with paused RNA polymerase II to prevent R-loop-induced genome instability. SOSS–INTAC-dependent attenuation of R-loops is enhanced by the ability of SSB1 to form liquid-like condensates. Deletion of NABP2 (encoding SSB1) or introduction of cancer-associated mutations into its intrinsically disordered region leads to a pervasive accumulation of R-loops, highlighting a genome surveillance function of SOSS–INTAC that enables timely termination of transcription at promoters to constrain R-loop accumulation and ensure genome stability.
Lactobacillus oris improves non-alcoholic fatty liver in mice and inhibits endogenous cholesterol biosynthesis
Authors: Zhao Yiming , Li Congyong , Luan Zhe , Chen Jun , Wang Cong , Jing Yujia , Qi Shirui , Zhao Zhizhuang , Zhang Hanwen , Wu Junling , Chen Yi , Li Zhuanyu , Zhao Bowen , Wang Shufang , Yang Yunsheng , Sun Gang 
Published: August 2023

AbstractWe previously confirmed that a strain of Lactobacillus oris isolated from the fecal samples of healthy Hainan centenarian having potent lipid-lowering ability in HepG2 cells; and this study was to investigate the effect of the stain on non-alcoholic fatty liver in mice in vivio. The Lactobacillus oris strain isolated from Hainan centenarian fecal samples were frozen stored in our laboratory. Thirty ob/ob mice (10 in each group) were orally gavaged with Lactobacillus oris (Lactobacillus, 5 × 109 cfu), mixed probiotics (Mixed, 5 × 109 cfu, a mixture with known lipid-lowering ability), or culture medium (Control) respectively. Lactobacillus oris isolated from fecal samples of Hainan centenarians showed significantly in vivo lipid lowering ability compared with the controls, and the ability was comparable with mixed probiotics strains in mice The possible mechanisms of lipid-lowering of probiotics and Lactobacillus oris may be associated with HMGR inhibition to suppress the synthesis of endogenous cholesterol; bile acids reabsorption, and intestinal FXR-FGF15 signaling pathways promoting the cholesterol conversion into bile acids secretion.
Foreign DNA detection in genome-edited potatoes by high-throughput sequencing
Authors: Yasumoto Shuhei , Muranaka Toshiya 
Published: August 2023

AbstractGenome editing is a powerful breeding technique that introduces mutations into specific gene sequences in genomes. For genome editing in higher plants, nucleotides for artificial nuclease (e.g. TALEN or CRISPR-Cas9) are transiently or stably introduced into the plant cells. After the introduction of mutations by artificial nucleases, it is necessary to select lines that do not contain the foreign nucleotides to overcome GMO regulation; however, there is still no widely legally authorized and approved method for detecting foreign genes in genome-edited crops. Recently, k-mer analysis based on next-generation sequencing (NGS) was proposed as a new method for detecting foreign DNA in genome-edited agricultural products. Compared to conventional methods, such as PCR and Southern hybridization, in principle, this method can detect short DNA fragments with high accuracy. However, this method has not yet been applied to genome-edited potatoes. In this study, we evaluated the feasibility of k-mer analysis in tetraploid potatoes by computer simulation, and also evaluated whether the k-mer method can detect foreign genes with high accuracy by analyzing samples of genome-edited potatoes. We show that when NGS data (at a depth of × 30 the genome size) are used, the k-mer method can correctly detect foreign genes in the potato genome even with the insertion of DNA fragments of 20 nt in length. Based on these findings, we expect that k-mer analysis will be one of the main methods for detecting foreign genes in genome-edited potatoes.
Long- and short-term history effects in a spiking network model of statistical learning
Authors: Maes Amadeus , Barahona Mauricio , Clopath Claudia 
Published: August 2023

AbstractThe statistical structure of the environment is often important when making decisions. There are multiple theories of how the brain represents statistical structure. One such theory states that neural activity spontaneously samples from probability distributions. In other words, the network spends more time in states which encode high-probability stimuli. Starting from the neural assembly, increasingly thought of to be the building block for computation in the brain, we focus on how arbitrary prior knowledge about the external world can both be learned and spontaneously recollected. We present a model based upon learning the inverse of the cumulative distribution function. Learning is entirely unsupervised using biophysical neurons and biologically plausible learning rules. We show how this prior knowledge can then be accessed to compute expectations and signal surprise in downstream networks. Sensory history effects emerge from the model as a consequence of ongoing learning.
An analysis of interactions between three structurally diverse anthocyanidins, as well as their glucosides, and model biological membranes, albumin, and plasmid DNA
Authors: Dudek Anita , Strugała-Danak Paulina , Kral Teresa , Hof Martin , Pruchnik Hanna 
Published: August 2023

AbstractThe aim of the study is to investigate the differences in the interaction of three structurally diverse anthocyanidins, namely peonidin, petunidin, and delphinidin, as well as their glucosides with model biological membranes, human albumin, and plasmid DNA in order to look into their structure–activity relationships. Fluorimetric studies, as well as ATR-FTIR analyses, were jointly used in order to determine the changes observed in both the hydrophilic and hydrophobic layers of cell-mimic membranes (MM) which reflected the membrane lipid composition of tumour cells and red blood cell membranes (RBCM). Our results showed that anthocyanins and anthocyanidins can cause an increase in the packing order of the polar heads of lipids, as well as interact with their deeper layers by reducing the fluidity of lipid chains. The results presented here indicate that all compounds tested here possessed the ability to bind to human serum albumin (HSA) and the presence of a glucose molecule within the structures formed by anthocyanidin reduces their ability to bind to proteins. Using fluorescence correlation spectroscopy, it was demonstrated that the compounds tested here were capable of forming stable complexes with plasmid DNA and, particularly, strong DNA conformational changes were observed in the presence of petunidin and corresponding glucoside, as well as delphinidin. The results we obtained can be useful in comprehending the anthocyanins therapeutic action as molecular antioxidants and provide a valuable insight into their mechanism of action.
RNase E biomolecular condensates stimulate PNPase activity
Authors: Collins Michael J. , Tomares Dylan T. , Nandana Vidhyadhar , Schrader Jared M. , Childers W. Seth 
Published: August 2023

AbstractBacterial Ribonucleoprotein bodies (BR-bodies) play an essential role in organizing RNA degradation via phase separation in the cytoplasm of bacteria. BR-bodies mediate multi-step mRNA decay through the concerted activity of the endoribonuclease RNase E coupled with the 3′-5′ exoribonuclease Polynucleotide Phosphorylase (PNPase). In vivo, studies indicated that the loss of PNPase recruitment into BR-bodies led to a significant build-up of RNA decay intermediates in Caulobacter crescentus. However, it remained unclear whether this is due to a lack of colocalized PNPase and RNase E within BR-bodies or whether PNPase’s activity is stimulated within the BR-body. We reconstituted RNase E’s C-terminal domain with PNPase towards a minimal BR-body in vitro to distinguish these possibilities. We found that PNPase’s catalytic activity is accelerated when colocalized within the RNase E biomolecular condensates, partly due to scaffolding and mass action effects. In contrast, disruption of the RNase E-PNPase protein–protein interaction led to a loss of PNPase recruitment into the RNase E condensates and a loss of ribonuclease rate enhancement. We also found that RNase E’s unique biomolecular condensate environment tuned PNPase’s substrate specificity for poly(A) over poly(U). Intriguingly, a critical PNPase reactant, phosphate, reduces RNase E phase separation both in vitro and in vivo. This regulatory feedback ensures that under limited phosphate resources, PNPase activity is enhanced by recruitment into RNase E’s biomolecular condensates.
Associations between fatty acid intake and diabetic retinopathy in a Japanese population
Authors: Sasaki Mariko , Yuki Kenya , Hanyuda Akiko , Yamagishi Kazumasa , Motomura Kaoru , Kurihara Toshihide , Tomita Yohei , Mori Kiwako , Ozawa Nobuhiro , Ozawa Yoko , Sawada Norie , Negishi Kazuno , Tsubota Kazuo , Tsugane Shoichiro , Iso Hiroyasu 
Published: August 2023

AbstractResidents of Chikusei City, aged 40–74 years, underwent systemic and ophthalmological screening, and participants with diabetes were included in this analysis. Dietary intake was assessed using a food frequency questionnaire and calculated as a percentage of the total energy. The presence of diabetic retinopathy (DR) was defined as Early Treatment Diabetic Retinopathy Study levels ≥ 20 in either eye. The association between dietary fatty acid intake and DR has been examined in a cross-sectional study. Among the 647 diabetic participants, 100 had DR. The mean total fat and saturated fatty acid (SFA) intakes were 22.0% and 7.3% of the total energy intake, respectively. After adjusting for potential confounders, the highest quartiles of total fat and SFA intake were positively associated with the presence of DR compared with the lowest quartiles (odds ratios (95% confidence intervals), 2.61 (1.07–6.39), p for trend = 0.025, and 2.40 (1.12–5.17), p for trend = 0.013, respectively). No significant associations were found between DR prevalence and monounsaturated or unsaturated fatty acid intake. These results suggest that a high intake of fat and SFA may affect the development of DR, even in individuals whose total fat intake is generally much lower than that of Westerners.
Development and validation of a disease-specific quality of life measure QLICD-HY (V2.0) for patients with hypertension
Authors: Liu Yuxi , Chang Yue , Wan Dandan , Li Weiqiang , Xu Chuanzhi , Wan Chonghua 
Published: August 2023

AbstractThe purpose of the present study is to develop and validate the hypertension scale of the Quality of Life Instruments (QoL) for Chronic Diseases system, QLICD-HY (V2.0). The QLICD-HY (V2.0) was developed via a programmed decision method with several focus groups, nominal discussions and pilot testing. The data was collected from 370 hypertensive inpatients and measured their QoL three times before and after treatment. Using correlation, factor analyses, as well as t-tests, the psychometric properties of the scale were assessed with regard to validity, reliability and responsiveness. Correlation and factor analysis supported good construct validity and criterion-related validity when using Short Form 36 as a criterion. Test–retest reliability coefficients for the overall scale score and all domains, with the exception of the psychological and social domain (0.77, 0.78), were greater than 0.80, with a range of 0.77–0.92. The internal consistency for all domains was higher than 0.70. With the exception of the psychological domain and social domain, the overall score and scores for the majority of aspects within each domain underwent statistically significant changes (t-tests) after the treatment. The QLICD-HY (V2.0) has good validity, reliability and responsiveness and can be used as a QoL measure for hypertensive patients.
Disease-associated astrocytes and microglia markers are upregulated in mice fed high fat diet
Authors: Lin Li , Basu Rashmita , Chatterjee Debolina , Templin Andrew T. , Flak Jonathan N. , Johnson Travis S. 
Published: August 2023

AbstractHigh-fat diet (HFD) is associated with Alzheimer’s disease (AD) and type 2 diabetes risk, which share features such as insulin resistance and amylin deposition. We examined gene expression associated with astrocytes and microglia since dysfunction of these cell types is implicated in AD pathogenesis. We hypothesize gene expression changes in disease-associated astrocytes (DAA), disease-associated microglia and human Alzheimer’s microglia exist in diabetic and obese individuals before AD development. By analyzing bulk RNA-sequencing (RNA-seq) data generated from brains of mice fed HFD and humans with AD, 11 overlapping AD-associated differentially expressed genes were identified, including Kcnj2, C4b and Ddr1, which are upregulated in response to both HFD and AD. Analysis of single cell RNA-seq (scRNA-seq) data indicated C4b is astrocyte specific. Spatial transcriptomics (ST) revealed C4b colocalizes with Gfad, a known astrocyte marker, and the colocalization of C4b expressing cells with Gad2 expressing cells, i.e., GABAergic neurons, in mouse brain. There also exists a positive correlation between C4b and Gad2 expression in ST indicating a potential interaction between DAA and GABAergic neurons. These findings provide novel links between the pathogenesis of obesity, diabetes and AD and identify C4b as a potential early marker for AD in obese or diabetic individuals.
Intrathecal [64Cu]Cu-albumin PET reveals age-related decline of lymphatic drainage of cerebrospinal fluid
Authors: Sarker Azmal , Suh Minseok , Choi Yoori , Park Ji Yong , Lee Yun-Sang , Lee Dong Soo 
Published: August 2023

AbstractAge-related cognitive decline is associated with dysfunctional lymphatic drainage of cerebrospinal fluid (CSF) through meningeal lymphatic vessels. In this study, intrathecal [64Cu]Cu-albumin positron emission tomography (PET) was applied in mice to evaluate lymphatic drainage of CSF and its variation with age. [64Cu]Cu-albumin PET was performed at multiple time points after intrathecal injection of [64Cu]Cu-albumin at an infusion rate of 700 nl/min in adult and aged mice (15–25 months old). CSF clearance and paravertebral lymph nodes were quantified after injection and during the stationary phase. Stationary phase of the next day followed the initial perturbed state by injection of 6 ul (1/7 of total CSF volume) and CSF clearance half-time from the subarachnoid space was 93.4 ± 19.7 and 123.3 ± 15.6 min in adult and aged mice (p = 0.01), respectively. While the % injected dose of CSF space were higher, the activity of the paravertebral lymph nodes were lower in the aged mice on the next day. [64Cu]Cu-albumin PET enabled us to quantify CSF-lymphatic drainage across all levels of brain spinal cords and to visualize and quantify lymph node activity due to CSF drainage. [64Cu]Cu-albumin PET revealed the age-related decrease of the lymphatic drainage of CSF due to this decreased drainage from the subarachnoid space, especially during the stationary phase, in aged mice.
Global disease burden attributed to unsafe sex in 204 countries and territories from 1990 to 2019: results from the Global Burden of Disease Study 2019
Authors: Qiu Pei , He Hairong , Zhao Yuting , Yang Zejian , Li Shouyu , Ni Peng , Guo Yujie , Ji Chao , Zhang Chenchen , Zhang Huimin , Zhou Can , Wang Bo 
Published: August 2023

AbstractUnsafe sex has become a public safety problem that endangers society, and research on deaths and disability-adjusted life years (DALYs) related to unsafe sex is valuable for global policy-making. We aimed to estimate the deaths and DALYs attributable to unsafe sex by country, gender, age group, and sociodemographic status from 1990 to 2019. We extracted data on disease burden from the Global Disease Burden 2019 (GBD 2019) database for unsafe sex, including deaths, DALYs and age-standardized rates (ASRs). Comparative analyses were performed on data about deaths, DALYs and the responding ASRs attributable to unsafe sex in different countries and regions using the Social Demographic Index (SDI). The global age-standardized mortality rate (ASMR) and age-standardized DALY rate (ASDR) attributable to unsafe sex were 11.98 (95% uncertainty intervals (UI): 10.97–13.52) per 100,000 people and 570.78 (95% UI: 510.24–658.10) per 100,000 people, respectively. Both the ASMRs and ASDRs were the highest in southern sub-Saharan Africa and lowest in Australasia and decreased with increasing SDI levels. About unsafe-sex-related disease, HIV/AIDS has the highest ASMR [8.48 (95% UI: 7.62–9.95)/100,000 people] and ASDR [447.44 (95% UI: 394.82–533.10)/100,000 people], followed by Cervical cancer [ASMR: 3.40 (95% UI: 2.90–3.81)/100,000 people and ASDR: 107.2 (95% UI: 90.52–119.43)/100,000 people] and sexually transmitted infections excluding HIV [ASMR: 0.10 (95% UI: 0.08–0.11)/100,000 people and ASDR: 16.14 (95% UI: 10.51–25.83)/100,000 people]. The death and DALY burden caused by these three diseases were more serious in the over 75 years old age group. The 40–44 age group for men and the 35–39 age group for women had the highest population of unsafe sex-related deaths and DALYs, respectively. In addition, the burden of unsafe sex in women was more serious than those in men. Unsafe sex is an important risk factor for global disease burden and a leading cause of substantial health loss. We found that the risk of ASMRs and ASDRs attributable to unsafe sex had negative correlation with SDI levels. These results demonstrate that the need for revised policies that focus on efforts to reduce overall unsafe sex worldwide.
Broadband inhomogeneous lens with conical radiation pattern
Authors: Taskhiri Mohammad Mahdi , Fakhte Saeed 
Published: August 2023

AbstractThis manuscript presents a lens antenna with simultaneous broadside and conical beams. The lens is designed for the Ku band using the ray inserting method. The proposed conical radiation pattern is broadband due to good matching with the source and surroundings. The simulation is conducted using the CST microwave studio solver. Instead of complex antenna shapes used in other works, a simple circular patch ring and RF connector are used as the lens feed to generate broadside and omnidirectional conical patterns, respectively. To validate the performance of the designed lens and its two-port feed antenna, the lens structure is realized and fabricated using the 3D printing method. Polyethylene terephthalate glycol (PETG) plastic material is utilized for constructing the lens in this work. The electromagnetic characteristics of PETG in the Ku band are accurately measured. The results of simulations and experiments demonstrate the good performance of the designed lens over a wide frequency bandwidth. The advantage of this designed structure over other works is its high gain and broad bandwidth.
Low-dose radiation induces unstable gene expression in developing human iPSC-derived retinal ganglion organoids
Authors: Katsura Mari , Urade Yoshihiro , Nansai Hiroko , Kobayashi Mika , Taguchi Akashi , Ishikawa Yukiko , Ito Tomohiro , Fukunaga Hisako , Tozawa Hideto , Chikaoka Yoko , Nakaki Ryo , Echigo Akinobu , Kohro Takahide , Sone Hideko , Wada Youichiro 
Published: August 2023

AbstractThe effects of low-dose radiation on undifferentiated cells carry important implications. However, the effects on developing retinal cells remain unclear. Here, we analyzed the gene expression characteristics of neuronal organoids containing immature human retinal cells under low-dose radiation and predicted their changes. Developing retinal cells generated from human induced pluripotent stem cells (iPSCs) were irradiated with either 30 or 180 mGy on days 4–5 of development for 24 h. Genome-wide gene expression was observed until day 35. A knowledge-based pathway analysis algorithm revealed fluctuations in Rho signaling and many other pathways. After a month, the levels of an essential transcription factor of eye development, the proportion of paired box 6 (PAX6)-positive cells, and the proportion of retinal ganglion cell (RGC)-specific transcription factor POU class 4 homeobox 2 (POU4F2)-positive cells increased with 30 mGy of irradiation. In contrast, they decreased after 180 mGy of irradiation. Activation of the “development of neurons” pathway after 180 mGy indicated the dedifferentiation and development of other neural cells. Fluctuating effects after low-dose radiation exposure suggest that developing retinal cells employ hormesis and dedifferentiation mechanisms in response to stress.