bluuebunny/crossref_metadata_2025_split huggingface dataset:
Identification of an alternative triglyceride biosynthesis pathway
Authors: McLelland Gian-Luca , Lopez-Osias Marta , Verzijl Cristy R. C. , Ellenbroek Brecht D. , Oliveira Rafaela A. , Boon Nicolaas J. , Dekker Marleen , van den Hengel Lisa G. , Ali Rahmen , Janssen Hans , Song Ji-Ying , Krimpenfort Paul , van Zutphen Tim , Jonker Johan W. , Brummelkamp Thijn R. 
Published: August 2023

AbstractTriacylglycerols (TAGs) are the main source of stored energy in the body, providing an important substrate pool for mitochondrial beta-oxidation. Imbalances in the amount of TAGs are associated with obesity, cardiac disease and various other pathologies1,2. In humans, TAGs are synthesized from excess, coenzyme A-conjugated fatty acids by diacylglycerol O-acyltransferases (DGAT1 and DGAT2)3. In other organisms, this activity is complemented by additional enzymes4, but whether such alternative pathways exist in humans remains unknown. Here we disrupt the DGAT pathway in haploid human cells and use iterative genetics to reveal an unrelated TAG-synthesizing system composed of a protein we called DIESL (also known as TMEM68, an acyltransferase of previously unknown function) and its regulator TMX1. Mechanistically, TMX1 binds to and controls DIESL at the endoplasmic reticulum, and loss of TMX1 leads to the unconstrained formation of DIESL-dependent lipid droplets. DIESL is an autonomous TAG synthase, and expression of human DIESL in Escherichiacoli endows this organism with the ability to synthesize TAG. Although both DIESL and the DGATs function as diacylglycerol acyltransferases, they contribute to the cellular TAG pool under specific conditions. Functionally, DIESL synthesizes TAG at the expense of membrane phospholipids and maintains mitochondrial function during periods of extracellular lipid starvation. In mice, DIESL deficiency impedes rapid postnatal growth and affects energy homeostasis during changes in nutrient availability. We have therefore identified an alternative TAG biosynthetic pathway driven by DIESL under potent control by TMX1.
DNA-PK and the TRF2 iDDR inhibit MRN-initiated resection at leading-end telomeres
Authors: Myler Logan R. , Toia Beatrice , Vaughan Cara K. , Takai Kaori , Matei Andreea M. , Wu Peng , Paull Tanya T. , de Lange Titia , Lottersberger Francisca 
Published: August 2023

AbstractTelomeres replicated by leading-strand synthesis lack the 3′ overhang required for telomere protection. Surprisingly, resection of these blunt telomeres is initiated by the telomere-specific 5′ exonuclease Apollo rather than the Mre11–Rad50–Nbs1 (MRN) complex, the nuclease that acts at DNA breaks. Without Apollo, leading-end telomeres undergo fusion, which, as demonstrated here, is mediated by alternative end joining. Here, we show that DNA-PK and TRF2 coordinate the repression of MRN at blunt mouse telomeres. DNA-PK represses an MRN-dependent long-range resection, while the endonuclease activity of MRN–CtIP, which could cleave DNA-PK off of blunt telomere ends, is inhibited in vitro and in vivo by the iDDR of TRF2. AlphaFold-Multimer predicts a conserved association of the iDDR with Rad50, potentially interfering with CtIP binding and MRN endonuclease activation. We propose that repression of MRN-mediated resection is a conserved aspect of telomere maintenance and represents an ancient feature of DNA-PK and the iDDR.
A randomized vagus nerve stimulation study demonstrates that serum aldosterone levels decrease with age in women, but not in men
Authors: Veiz Elisabeth , Kieslich Susann-Kristin , Czesnik Dirk , Herrmann-Lingen Christoph , Meyer Thomas , Staab Julia 
Published: August 2023

AbstractIn this randomized, sham-controlled study, we explored the effects of acute transcutaneous vagus nerve stimulation (tVNS) on serum aldosterone in 20 younger (21–26 years) and 19 older (40–70 years) healthy participants. Blood samples were collected on two different days before and after a 20-min application of active tVNS at the inner tragus or sham stimulation of the earlobe. Irrespective of the stimulation mode, aldosterone levels decreased from pre- to post-stimulation in both the young (active: β = − 1.610 (− 2.855, − 0.365), p = 0.022; sham: β = − 0.857 (− 2.102, 0.388), p = 0.257) and the old cohort (active: β = − 1.969 (− 3.234, − 0.703), p = 0.005; sham: β = − 1.334 (− 2.600, − 0.069), p = 0.063). Although this decline was significant during active tVNS, the difference in estimated β-coefficients between active and sham stimulation was not statistically significant in either cohort. Nevertheless, aldosterone concentrations showed a significant interaction effect between sex and age (p = 0.001). Among all study participants, younger women (23.3 ± 1.6 years) had the highest mineralocorticoid levels (pre active: 172.1 ± 102.0 pg/ml, pre sham: 214.3 ± 82.3 pg/ml), whereas the lowest were observed in older females (59.4 ± 9.4 years) (pre active: 104.9 ± 85.8 pg/ml, pre sham: 81.1 ± 53.8 pg/ml). This post hoc analysis did not suggest that active auricular tVNS reduces serum aldosterone levels compared to sham stimulation in healthy subjects. However, serum aldosterone levels differed among subjects depending on their age and sex, irrespective of tVNS.
X-ray free electron laser observation of ultrafast lattice behaviour under femtosecond laser-driven shock compression in iron
Authors: Sano Tomokazu , Matsuda Tomoki , Hirose Akio , Ohata Mitsuru , Terai Tomoyuki , Kakeshita Tomoyuki , Inubushi Yuichi , Sato Takahiro , Miyanishi Kohei , Yabashi Makina , Togashi Tadashi , Tono Kensuke , Sakata Osami , Tange Yoshinori , Arakawa Kazuto , Ito Yusuke , Okuchi Takuo , Sato Tomoko , Sekine Toshimori , Mashimo Tsutomu , Nakanii Nobuhiko , Seto Yusuke , Shigeta Masaya , Shobu Takahisa , Sano Yuji , Hosokai Tomonao , Matsuoka Takeshi , Yabuuchi Toshinori , Tanaka Kazuo A. , Ozaki Norimasa , Kodama Ryosuke 
Published: August 2023

AbstractOver the past century, understanding the nature of shock compression of condensed matter has been a major topic. About 20 years ago, a femtosecond laser emerged as a new shock-driver. Unlike conventional shock waves, a femtosecond laser-driven shock wave creates unique microstructures in materials. Therefore, the properties of this shock wave may be different from those of conventional shock waves. However, the lattice behaviour under femtosecond laser-driven shock compression has never been elucidated. Here we report the ultrafast lattice behaviour in iron shocked by direct irradiation of a femtosecond laser pulse, diagnosed using X-ray free electron laser diffraction. We found that the initial compression state caused by the femtosecond laser-driven shock wave is the same as that caused by conventional shock waves. We also found, for the first time experimentally, the temporal deviation of peaks of stress and strain waves predicted theoretically. Furthermore, the existence of a plastic wave peak between the stress and strain wave peaks is a new finding that has not been predicted even theoretically. Our findings will open up new avenues for designing novel materials that combine strength and toughness in a trade-off relationship.
High N availability decreases N uptake and yield under limited water availability in maize
Authors: Flynn Nora E. , Comas Louise H. , Stewart Catherine E. , Fonte Steven J. 
Published: August 2023

AbstractWater and nitrogen (N) are the most limiting factors to plant productivity globally, but we lack a critical understanding of how water availability impacts N dynamics in agricultural systems. Plant N requirements are particularly uncertain when water is limited because of the interactive effect of water and N on plant growth, N demand, and plant uptake. We investigated impacts of N application and water availability on plant growth and N movement, including above and belowground growth, water productivity, N productivity, N uptake, N recovery, and greenhouse gas emissions within a semi-arid system in northeastern Colorado, USA. Moderately high soil N availability depressed grain yield and shoot growth under both limited and full water availability, despite no indication of physical toxicity, and came with additional risk of deleterious N losses. Under low N availability, plant N concentrations in aboveground tissues showed greater recovery of N than what was applied in the low N treatments under both full and limited water availability. This enhanced recovery underscores the need to better understand both plant soil foraging and processes governing resource availability under these conditions. Finally, limited water availability reduced N uptake across all N treatments and left 30% more soil nitrate (NO3−) deep in the soil profile at the end of the season than under full water availability. Our results show that plant N needs are not linearly related to water use and emphasize the need for an integrated understanding of water and N interactions, plant foraging for these resources, and the dynamics of processes that make N available to plants.
Enhancing the accuracies by performing pooling decisions adjacent to the output layer
Authors: Meir Yuval , Tzach Yarden , Gross Ronit D. , Tevet Ofek , Vardi Roni , Kanter Ido 
Published: August 2023

AbstractLearning classification tasks of $$({2}^{n}\times {2}^{n})$$

(

2

n

×

2

n

)

inputs typically consist of $$\le n(2\times 2$$

≤
n
(
2
×
2

) max-pooling (MP) operators along the entire feedforward deep architecture. Here we show, using the CIFAR-10 database, that pooling decisions adjacent to the last convolutional layer significantly enhance accuracies. In particular, average accuracies of the advanced-VGG with $$m$$
m
layers (A-VGGm) architectures are 0.936, 0.940, 0.954, 0.955, and 0.955 for m = 6, 8, 14, 13, and 16, respectively. The results indicate A-VGG8’s accuracy is superior to VGG16’s, and that the accuracies of A-VGG13 and A-VGG16 are equal, and comparable to that of Wide-ResNet16. In addition, replacing the three fully connected (FC) layers with one FC layer, A-VGG6 and A-VGG14, or with several linear activation FC layers, yielded similar accuracies. These significantly enhanced accuracies stem from training the most influential input–output routes, in comparison to the inferior routes selected following multiple MP decisions along the deep architecture. In addition, accuracies are sensitive to the order of the non-commutative MP and average pooling operators adjacent to the output layer, varying the number and location of training routes. The results call for the reexamination of previously proposed deep architectures and their accuracies by utilizing the proposed pooling strategy adjacent to the output layer.
Food additives and PAHO’s nutrient profile model as contributors’ elements to the identification of ultra-processed food products
Authors: Canella Daniela Silva , Pereira Montera Vanessa dos Santos , Oliveira Natália , Mais Laís Amaral , Andrade Giovanna Calixto , Martins Ana Paula Bortoletto 
Published: August 2023

AbstractThe NOVA classification system categorizes foods according to the extent and purpose of industrial processing. Ultra-processed food products (UPF) are frequently composed of excessive amounts of sugars, salt, oils, and fats, and cosmetic additives designed to make them palatable and/or appealing. We aimed to describe the presence of critical nutrients in excess and cosmetic additives in packaged foods and beverages and to evaluate the proportion of UPF that can be correctly identified through the presence of critical nutrients in excess or the presence of cosmetic additives in food products. A total of 9851 items available in Brazilian supermarkets containing lists of ingredients and nutrition facts panels were analyzed. Cosmetic additives and critical nutrients in excess, according to Pan American Health Organization (PAHO)’s nutrient profile model, were assessed. All food items were categorized into the four NOVA classification groups. Relative frequencies of items with at least one critical nutrient in excess and one type of cosmetic additive were estimated. For UPF, 82.1% had some cosmetic additive, and 98.8% had some cosmetic additive or a nutrient in excess. This combined criterion allowed the identification of 100.0% of sweet cookies, salted biscuits, margarine, cakes and sweet pies, chocolate, dairy beverages, and ice cream. Combining the presence of cosmetic additives and the PAHO’s nutrient profile model contributes to the identification of UPF.
Benchmarking of force fields to characterize the intrinsically disordered R2-FUS-LC region
Authors: Chan-Yao-Chong Maud , Chan Justin , Kono Hidetoshi 
Published: August 2023

AbstractIntrinsically Disordered Proteins (IDPs) play crucial roles in numerous diseases like Alzheimer's and ALS by forming irreversible amyloid fibrils. The effectiveness of force fields (FFs) developed for globular proteins and their modified versions for IDPs varies depending on the specific protein. This study assesses 13 FFs, including AMBER and CHARMM, by simulating the R2 region of the FUS-LC domain (R2-FUS-LC region), an IDP implicated in ALS. Due to the flexibility of the region, we show that utilizing multiple measures, which evaluate the local and global conformations, and combining them together into a final score are important for a comprehensive evaluation of force fields. The results suggest c36m2021s3p with mTIP3p water model is the most balanced FF, capable of generating various conformations compatible with known ones. In addition, the mTIP3P water model is computationally more efficient than those of top-ranked AMBER FFs with four-site water models. The evaluation also reveals that AMBER FFs tend to generate more compact conformations compared to CHARMM FFs but also more non-native contacts. The top-ranking AMBER and CHARMM FFs can reproduce intra-peptide contacts but underperform for inter-peptide contacts, indicating there is room for improvement.
Intercellular cross-talk through lineage-specific gap junction of cancer-associated fibroblasts related to stromal fibrosis and prognosis
Authors: Cho Seong Ju , Oh Ji-Hye , Baek Jaehoon , Shin Yunsu , Kim Wonkyung , Ko Junsu , Jun Eunsung , Lee Dakeun , Kim Seok-Hyung , Sohn Insuk , Sung Chang Ohk 
Published: August 2023

AbstractStromal fibrosis in cancer is usually associated with poor prognosis and chemotherapy resistance. It is thought to be caused by fibroblasts; however, the exact mechanism is not yet well understood. The study aimed to identify lineage-specific cancer-associated fibroblast (CAF) subgroup and their associations with extracellular matrix remodeling and clinical significances in various tumor types using single-cell and bulk RNA sequencing data. Through unsupervised clustering, six subclusters of CAFs were identified, including a cluster with exclusively high gap junction protein beta-2 (GJB2) expression. This cluster was named GJB2-positive CAF. It was found to be a unique subgroup of terminally differentiated CAFs associated with collagen gene expression and extracellular matrix remodeling. GJB2-positive CAFs showed higher communication frequency with vascular endothelial cells and cancer cells than GJB2-negative CAFs. Moreover, GJB2 was poorly expressed in normal tissues, indicating that its expression is dependent on interaction with other cells, including vascular endothelial cells and cancer cells. Finally, the study investigated the clinical significance of GJB2 signature score for GJB2-positive CAFs in cancer and found a correlation with poor prognosis. These results suggest that GJB2-positive CAF is a unique fibroblast subtype involved in extracellular matrix remodeling, with significant clinical implications in cancer.
The elucidation of plasma lipidome profiles during severe influenza in a mouse model
Authors: Ohno Marumi , Gowda Siddabasave Gowda B. , Sekiya Toshiki , Nomura Naoki , Shingai Masashi , Hui Shu-Ping , Kida Hiroshi 
Published: August 2023

AbstractAlthough influenza virus infection has been shown to affect lipid metabolism, details remain unknown. Therefore, we elucidated the kinetic lipid profiles of mice infected with different doses of influenza virus A/Puerto Rico/8/34 (H1N1) (PR8) by measuring multiple lipid molecular species using untargeted lipidomic analysis. C57BL/6 male mice were intranasally infected with PR8 virus at 50 or 500 plaque-forming units to cause sublethal or lethal influenza, respectively. Plasma and tissue samples were collected at 1, 3, and 6 days post-infection (dpi), and comprehensive lipidomic analysis was performed using high-performance liquid chromatography–linear trap quadrupole–Orbitrap mass spectrometry, as well as gene expression analyses. The most prominent feature of the lipid profile in lethally infected mice was the elevated plasma concentrations of phosphatidylethanolamines (PEs) containing polyunsaturated fatty acid (PUFA) at 3 dpi. Furthermore, the facilitation of PUFA-containing phospholipid production in the lungs, but not in the liver, was suggested by gene expression and lipidomic analysis of tissue samples. Given the increased plasma or serum levels of PUFA-containing PEs in patients with other viral infections, especially in severe cases, the elevation of these phospholipids in circulation could be a biomarker of infection and the severity of infectious diseases.
Genome-wide study of longitudinal brain imaging measures of multiple sclerosis progression across six clinical trials
Authors: Loomis Stephanie J. , Sadhu Nilanjana , Fisher Elizabeth , Gafson Arie R. , Huang Yunfeng , Yang Chengran , Hughes Emily E. , Marshall Eric , Herman Ann , John Sally , Runz Heiko , Jia Xiaoming , Bhangale Tushar , Bronson Paola G. 
Published: August 2023

AbstractWhile the genetics of MS risk susceptibility are well-described, and recent progress has been made on the genetics of disease severity, the genetics of disease progression remain elusive. We therefore investigated the genetic determinants of MS progression on longitudinal brain MRI: change in brain volume (BV) and change in T2 lesion volume (T2LV), reflecting progressive tissue loss and increasing disease burden, respectively. We performed genome-wide association studies of change in BV (N = 3401) and change in T2LV (N = 3513) across six randomized clinical trials from Biogen and Roche/Genentech: ADVANCE, ASCEND, DECIDE, OPERA I & II, and ORATORIO. Analyses were adjusted for randomized treatment arm, age, sex, and ancestry. Results were pooled in a meta-analysis, and were evaluated for enrichment of MS risk variants. Variant colocalization and cell-specific expression analyses were performed using published cohorts. The strongest peaks were in PTPRD (rs77321193-C/A, p = 3.9 × 10–7) for BV change, and NEDD4L (rs11398377-GC/G, p = 9.3 × 10–8) for T2LV change. Evidence of colocalization was observed for NEDD4L, and both genes showed increased expression in neuronal and/or glial populations. No association between MS risk variants and MRI outcomes was observed. In this unique, precompetitive industry partnership, we report putative regions of interest in the neurodevelopmental gene PTPRD, and the ubiquitin ligase gene NEDD4L. These findings are distinct from known MS risk genetics, indicating an added role for genetic progression analyses and informing drug discovery.
Frequency and risk factors of H. pylori infection among dental students: an observational cross-sectional study
Authors: Mikhail Christine Raouf George , Abd El Maksoud Mohamed Abeer , Shaker Olfat Gamil , EL Desouky Eman , Shalaby Rania Hassan 
Published: August 2023

AbstractDespite Helicobacter pylori infection remains asymptomatic in most people, it is associated with an increased risk of gastric cancer. Considering Egypt had the highest prevalence of H. pylori in healthy asymptomatic population in adults and pediatric age in past studies and currently salivary ELISA could be used for diagnosis of Oral H. pylori infection. Moreover, some researchers speculated that dentists and dental students might be at a higher risk for oral H. pylori infection because they are the most frequently exposed ones to saliva and dental plaque. This study aimed to determine risk factors associated with frequency of H. pylori among a sample of dental students for better management of the disease. 83 participants, with age (21–25 years), attending Faculty of Dentistry, Fayoum University were recruited. A structured questionnaire was used to collect information on sociodemographic parameters and risk factors for H. pylori. Direct inquiry about dyspeptic symptoms were done. Saliva samples were collected and tested for H. pylori antibodies. Overall seroprevalence was 22.9%. Participants in internship were more prone to be positive (p = 0.005). 32.6% of urban residents versus 10.8% of rural were H. pylori positive (p = 0.019). 75.0% of previous history of H. pylori infection versus 14.1% of those with no history were H. pylori positive p < 0.001. 70% of positive H. pylori participants reported positive clinical symptoms that were statistically significant. This study suggests that middle income, previous history of H. pylori and clinical symptoms of dyspepsia are risk factors of oral H. pylori with a decline in its prevalence in Egypt.
Reliability and performance evaluation of a solar PV-powered underground water pumping system
Authors: Ahmed Nesma Mohamed , Hassan Ahmed Mahrous , Kassem Mohamed Abdelwahab , Hegazi Ahmed Mahmoud , Elsaadawi Youssef Fayez 
Published: August 2023

AbstractThe operation and effectiveness of a solar-powered underground water pumping system are affected by many environmental and technical factors. The impact of these factors must be investigated to be considered when developing these systems and to ensure their dependability. This study evaluated the dependability and performance of photovoltaic water pumping system (PVWPS) under real operating conditions by examining the effects of solar irradiance, panels’ temperature, and components' efficiency. From December 2020 to June 2021, experiments were conducted on a 10 hp PVWPS located in Bani Salamah, Al-Qanater-Giza Governorate, Egypt, at latitude 30.3° N, longitude 30.8° E, and 19 m above sea level. The irradiance values reached 755.7, 792.7, and 805.7 W/m2at 12:00 p.m. in December, March, and June, respectively. Furthermore, the irradiance has a significant impact on the pump flow rate, as the amount of pumped water during the day reached 129, 164.1, and 181.8 m3/day, respectively. The panels' temperatures rose to 35.7 °C, 39.9 °C, and 44 °C, respectively. It was observed that when the temperature rises by 1 degree Celsius, efficiency falls by 0.48%. The average efficiency of photovoltaic solar panels reached its highest value in March (13.8%) and its lowest value in December (13%).