bluuebunny/crossref_metadata_2025_split huggingface dataset:
Thermal Characterization and Preclinical Validation of an Accessible, Carbon Dioxide-Based Cryotherapy System
Authors: Hu Yixin , Gordon Naomi , Ogg Katherine , Kraitchman Dara L. , Durr Nicholas J. , Surtees Bailey 
Published: March 2024

AbstractTo investigate the potential of an affordable cryotherapy device for accessible treatment of breast cancer, the performance of a novel carbon dioxide-based device was evaluated through both benchtop and in vivo canine models. This novel device was quantitatively compared to a commercial device that utilizes argon gas as the cryogen. The thermal behavior of each device was characterized through calorimetry and by measuring the temperature profiles of iceballs generated in tissue phantoms. A 45-minute treatment from the carbon dioxide device in a tissue phantom produced a 1.67 ± 0.06 cm diameter lethal isotherm that was equivalent to a 7-minute treatment from the commercial argon-based device which produced a 1.53 ± 0.15 cm diameter lethal isotherm. In vivo validation was performed with the carbon dioxide-based device in one spontaneously occurring canine mammary mass with two standard 10-minutes freezes. Following cryotherapy, this mass was surgically resected and analyzed for necrosis margins via histopathology. The histopathology margin of necrosis from the in vivo treatment with the carbon dioxide device at 14 days post cryoablation was 1.57 cm. While carbon dioxide gas has historically been considered an impractical cryogen due to its low working pressure and high boiling point, this study shows that carbon dioxide-based cryotherapy may be equivalent to conventional argon-based cryotherapy in the size of the ablation zone in a standard treatment time. The validation of the carbon dioxide device performed in this study is an important step towards bringing accessible breast cancer treatment to women in low-resource settings.
Human brain aging heterogeneity observed from multi-region omics data reveals a subtype closely related to Alzheimer’s disease
Authors: Peng Shouneng , Wang Erming , Wang Minghui , Wang Xusheng , Yu Kaiwen , Fu Yingxue , Poudel Suresh , Ho Lap , Narayan Sushma , Huffman Derek M. , Gaiteri Chris , Bennet David A. , Ehrlich Michelle E. , Haroutunian Vahram , Peng Junmin , Zhang Bin , Tu Zhidong 
Published: March 2024

AbstractINTRODUCTION: The interconnection between brain aging and Alzheimer’s disease (AD) remain to be elucidated. METHODS: We investigated multi-omics (transcriptomics and proteomics) data from multiple brain regions (i.e., the hippocampus (HIPP), prefrontal cortex (PFC), and cerebellum (CRBL)) in cognitively normal individuals. RESULTS: We found that brain samples could be divided into ADL (AD-like) and NL (normal) subtypes which were correlated across brain regions. The differentially expressed genes in the ADL samples highly overlapped with AD gene signatures and the changes were consistent across brain regions (PFC and HIPP) in the multi-omics data. Intriguingly, the ADL subtype in PFC showed more differentially expressed genes than other brain regions, which could be explained by the baseline gene expression differences in the PFC NL samples. DISCUSSION: We conclude that brain aging heterogeneity widely exists, and our findings corroborate with the hypothesis that AD-related changes occur decades before the clinical manifestation of cognitive impairment in a sub-population.
Formamide denaturation of double-stranded DNA for fluorescencein situhybridization (FISH) distorts nanoscale chromatin structure
Authors: Shim Anne R. , Frederick Jane , Pujadas Emily M. , Kuo Tiffany , Ye I Chae , Pritchard Joshua A. , Dunton Cody L. , Gonzalez Paola Carrillo , Acosta Nicolas , Jain Surbhi , Anthony Nicholas M. , Almassalha Luay M. , Szleifer Igal , Backman Vadim 
Published: March 2024

AbstractAs imaging techniques rapidly evolve to probe nanoscale genome organization at higher resolution, it is critical to consider how the reagents and procedures involved in sample preparation affect chromatin at the relevant length scales. Here, we investigate the effects of fluorescent labeling of DNA sequences within chromatin using the gold standard technique of three-dimensional fluorescencein situhybridization (3D FISH). The chemical reagents involved in the 3D FISH protocol, specifically formamide, cause significant alterations to the sub-200 nm (sub-Mbp) chromatin structure. Alternatively, two labeling methods that do not rely on formamide denaturation, resolution after single-strand exonuclease resection (RASER)-FISH and clustered regularly interspaced short palindromic repeats (CRISPR)-Sirius, had minimal impact on the three-dimensional organization of chromatin. We present a polymer physics-based analysis of these protocols with guidelines for their interpretation when assessing chromatin structure using currently available techniques.
Synthesis and Biological Assessment of Chalcone and Pyrazoline Derivatives as Novel Inhibitor for ELF3-MED23 Interaction
Authors: Hwang Soo-Yeon , Jeon Kyung-Hwa , Lee Hwa-Jong , Moon Inhye , Jung Sehyun , Kim Seul-Ah , Jo Hyunji , Park Seojeong , Ahn Misun , Kwak Soo-Yeon , Na Younghwa , Kwon Youngjoo 
Published: March 2024

AbstractHER2 overexpression significantly contributes to the aggressive nature and recurrent patterns observed in various solid tumors, notably gastric cancers. Trastuzumab, HER2-targeting monoclonal antibody drug, has shown considerable clinical success, however, readily emerging drug resistance emphasizes the pressing need for improved interventions in HER2-overexpressing cancers. To address this, we proposed targeting the protein-protein interaction (PPI) between ELF3 and MED23 as an alternative therapeutic approach to trastuzumab. In this study, we synthesized a total of 26 compounds consisting of 10 chalcones, 7 pyrazoline acetyl, and 9 pyrazoline propionyl derivatives, and evaluated their biological activity as potential ELF3-MED23 PPI inhibitors. Upon systematic analysis, candidate compound10was selected due to its potency in downregulating reporter gene activity ofERBB2promoter confirmed by SEAP activity and its effect on HER2 protein and mRNA levels. Compound10effectively disrupted the binding interface between the ELF3 TAD domain and the 391-582 amino acid region of MED23, resulting in successful inhibition of the ELF3-MED23 PPI. This intervention led to a substantial reduction in HER2 levels and its downstream signals in the HER2-positive gastric cancer cell line. Subsequently, compound10induced significant apoptosis and anti-proliferative effects, demonstrating superiorin vitroandin vivoanticancer activity overall. We found that the anticancer activity of compound10was not only restricted to trastuzumab-sensitive cases, but was also valid for trastuzumab-refractory clones. This suggests its potential as a viable therapeutic option for trastuzumab-resistant gastric cancers. In summary, compound10could be a novel alternative therapeutic strategy for HER2-overexpressing cancers, overcoming the limitations of trastuzumab.
Evaluation of a Machine Learning-guided Strategy for Elevated Lipoprotein(a) Screening in Health Systems
Authors: Aminorroaya Arya , Dhingra Lovedeep S , Oikonomou Evangelos K , Khera Rohan 
Published: March 2024

ABSTRACTBackgroundWhile universal screening for Lp(a) is increasingly recommended, fewer than 0.5% of the patients undergo Lp(a) testing. Here, we assessed the feasibility of deploying Algorithmic Risk Inspection for Screening Elevated Lp(a) (ARISE), a validated machine learning tool, to health system EHRs to increase the yield of Lp(a) testing.MethodsWe randomly sampled 100,000 patients from the Yale-New Haven Health System (YNHHS) to evaluate the feasibility of ARISE deployment. We also evaluated Lp(a) tested populations in the YNHHS (N=7,981) and the Vanderbilt University Medical Center (VUMC) (N=10,635) to assess the association of ARISE score with elevated Lp(a). To compare the representativeness of the Lp(a) tested population, we included 456,815 participants from the UK Biobank and 23,280 from three US-based cohorts of ARIC, CARDIA, and MESA.ResultsAmong 100,000 randomly selected YNHHS patients, 413 (0.4%) had undergone Lp(a) measurement. ARISE score could be computed for 31,586 patients based on existing data, identifying 2,376 (7.5%) patients with a high probability of elevated Lp(a). A positive ARISE score was associated with significantly higher odds of elevated Lp(a) in the YNHHS (OR 1.87, 95% CI, 1.65-2.12) and the VUMC (OR 1.41, 95% CI, 1.24-1.60). The Lp(a) tested population significantly differed from other study cohorts in terms of ARISE features.ConclusionsWe demonstrate the feasibility of deployment of ARISE in US health systems to define the risk of elevated Lp(a), enabling a high-yield testing strategy. We also confirm the very low adoption of Lp(a) testing, which is also being restricted to a highly selected population.
Unveiling the Intricate Sinking behavior of Large Diatoms: Insights from Time-Frequency Analysis ofPalmerina hardmanianaSinking under Silicate-Depleted Conditions
Authors: Zhang Ping , Lu Jiachang , Li Lang , Zhuang Junlian , Lai Junxiang , Shi Tianying , Li Jie 
Published: March 2024

AbstractNutrient limits impact diatom sinking in time domain, but response in time-frequency domain is unclear. Studying the response of large diatoms to nutrients exclusively in the time domain fails to fully capture the complete impact of nutrient limitations on sinking behavior due to the absence of crucial information, including period and frequency. Wavelet analysis provides valuable insights into the period and frequency of signals and unveils their positions in the time. This study investigated the sinking behavior response of the large diatomPalmerina hardmanianato silicate-depleted conditions in the time-frequency domain using wavelet analysis. The results showed thatP. hardmanianawas capable of regulating its sinking speed, and this regulation occurred intermittently in time. The predominant frequency of intermittent regulation fell within the range of 0.13-0.50 Hz (equivalent to a period of 2-8 s) for both control and silicate-depleted conditions. The similarity in the frequency range of regulation between the two groups suggests the involvement of shared physiological mechanisms.P. hardmanianaresponded to silicate depletion by intensifying the regulation of 0.13-0.50 Hz, which was reflected in the time domain as a change in the proportion of different instantaneous sinking speeds and consequently lead to a significant increase or decrease in the mean sinking speed(p<0.05). Additionally, the regulation ofP. hardmanianasinking behavior was also influenced by the physiological state of the cells. Short-term silicate stress (30 min) enhanced the oscillation power of sinking regulation, while prolonged silicate stress (≥ 3 d) led to a decline in oscillation power.
Overexpression ofPpGL2fromPrunus persicaenhanced soybean drought tolerance
Authors: Wei Li , Li Zhao , Dahong Li , Hong-yan Li 
Published: March 2024

AbstractThe HD-ZIP transcription factor family plays crucial roles in plant growth and abiotic stress responses. While its diverse functions and regulatory mechanisms are well-documented, its role in conferring abiotic stress tolerance in peaches remains largely unexplored. Here, we report the bioinformatics profile of PpGL2, a member of the HD-ZIP transcription factor family, and its integration into the soybean genome to assess its potential impact on drought tolerance. Localization studies in onion cells revealed nuclear localization of PpGL2-GFP fusion protein, while yeast hybridization experiments demonstrated its transactivation and DNA binding abilities.PpGL2overexpression under drought conditions led to reduced accumulation of reactive oxygen species and malondialdehyde compared to wild-type, decreased water loss rate, and increased chlorophyll content and relative water content. Additionally,PpGL2overexpression promoted plant height and root length under drought stress, accompanied by altered transcription levels of stress-related genes across different plant genotypes. Furthermore,PpGL2overexpression enhanced oxidative tolerance. Therefore, our findings suggest thatPpGL2overexpression holds promise for enhancing soybean drought resistance, offering a novel approach to improving soybean drought resistance.
The flavohemoglobin Yhb1 is a new interacting partner of the heme transporter Str3
Authors: Lo Ying Ping Florie , Vahsen Tobias , Brault Ariane , Néré Raphaël , Labbé Simon 
Published: March 2024

SummaryNitric oxide (NO) is a gaseous molecule that induces nitrosative stress, which can jeopardize cell viability. Yeasts have evolved diverse detoxification mechanisms to effectively counteract NO-mediated toxicity. One mechanism relies on the flavohemoglobin Yhb1, whereas a second one requires the S-nitrosoglutathione reductase Fmd2. However, in this study, we eliminate any contribution from Fmd2 by using strains deleted for this gene. To investigate heme-dependent activation of Yhb1 in response to NO, we usehem1Δ-derivativeSchizosaccharomyces pombestrains lacking the initial enzyme in heme biosynthesis, forcing cells to assimilate heme from external sources. Under these conditions,yhb1+mRNA levels are repressed in the presence of iron through a mechanism involving the GATA-type transcriptional repressor Fep1. In contrast, when iron levels are low, the transcription ofyhb1+is derepressed and further induced in the presence of the NO donor DETANONOate. Cells lacking Yhb1 or expressing inactive forms of Yhb1 fail to grow in a hemin-dependent manner when exposed to DETANONOate. Similarly, loss of function of the heme transporter Str3 phenocopies the effects of Yhb1 disruption by causing hypersensitivity to DETANONOate under hemin-dependent culture conditions. Coimmunoprecipitation and bimolecular fluorescence complementation assays demonstrate the interaction between Yhb1 and the heme transporter Str3. Collectively, our findings unveil a novel pathway for activating Yhb1, fortifying yeast cells against nitrosative stress.
Detection of pathogens and antimicrobial resistant genes from urine within 5 hours using Nanopore sequencing
Authors: Bellankimath Anurag Basavaraj , Chapagain Crystal , Branders Sverre , Ali Jawad , Wilson Robert C , Bjerklund Johansen Truls E. , Ahmad Rafi 
Published: March 2024

AbstractPurposeUrinary Tract Infection (UTI) is a prevalent global health concern accounting for 1-3% of primary healthcare visits. The current methods for UTI diagnosis have a high turnaround time of 3-5 days for pathogen identification and susceptibility testing. This work is a proof-of-concept study aimed at determining the detection limit by establishing a culture and amplification-free DNA extraction methodology from spiked urine samples followed by real-time Nanopore sequencing and data analysis.MethodsThis study first establishes an optical density culture-based method for spiking healthy urine samples with the six most prevalent uropathogens. Pathogens were spiked at two clinically significant concentrations of 103and 105CFU/ml. Three commercial DNA extraction kits were investigated based on the quantity of isolated DNA, average processing time, elution volume and the average cost incurred per extraction. The outperforming kit was used for direct DNA extraction and subsequent sequencing on MinION and Flongle flowcells.ResultsThe Blood and Tissue kit outperformed the other kits. All pathogens were identified at a concentration of 105CFU/ml within ten minutes, and the corresponding AMR genes were detected within three hours of the sequencing start. The overall turnaround time including the DNA extraction and sequencing steps was five hours. Moreover, we also demonstrate that the identification of some pathogens and antibiotic-resistance genes was possible at a spike concentration of 103CFU/mL.ConclusionThis study shows great promise toward reducing the time required for making an informed antibiotic administration from approximately 48 hours to five hours thereby reducing the number of empirical doses and saving lives.
Regulation of Arabidopsis polyamine acetylation by NATA1 and NATA2
Authors: Hameed Umar F. Shahul , Lou Yann-Ru , Yan Jian , Guzman Vega Francisco Javier , Aleksenko Ekaterina , Briozzo Pierre , Morera Solange , Jander Georg , Arold Stefan T. 
Published: March 2024

ABSTRACTPolyamines have vital functions in organisms, including bacteria, plants, and animals, with key roles in growth, development, and stress responses. Spermine/spermidineN1-acetyl transferases (SSATs) regulate polyamine abundance by catalysing theirN-acetylation, thereby reducing the pool of polyamines and producing other bioactive components. The regulatory mechanisms controlling SSAT enzymes are incompletely understood. Here, we investigate the biological role and regulation of the two SSAT isoforms present inArabidopsis thaliana,N-ACETYLTRANSFERASE ACTIVITY (NATA) 1 and 2. We show that NATA2 is a heat-stable isoform, induced in response to heat. Intriguingly, anata2knockout mutation proved beneficial for growth and pathogen defence under heat stress in Arabidopsis, aligning with the stress-mitigating effect of polyamines. In contrast, the double knockout ofnata1andnata2was lethal, highlighting the essential role of basal SSAT activity. Our numerous crystal structures of both NATAs, supported by functional assays, revealed that stress-produced acidic metabolites can selectively inhibit polyamine acetylation by occupying the NATA substrate-binding pocket. This environment-responsive regulation mechanism may allow Arabidopsis to adjust the deleterious action of NATAs under stress conditions, without eliminating the enzyme. More generally, metabolite-ensemble inhibition may be a novel paradigm for non-genetic feedback regulation of plant enzymes.
Involvement of ArlI, ArlJ, and CirA in Archaeal Type-IV Pilin-Mediated Motility Regulation
Authors: Chatterjee Priyanka , Garcia Marco A. , Cote Jacob A. , Yun Kun , Legerme Georgio P. , Habib Rumi , Tripepi Manuela , Young Criston , Kulp Daniel , Dyall-Smith Mike , Pohlschroder Mecky 
Published: March 2024

AbstractMany prokaryotes use swimming motility to move toward favorable conditions and escape adverse surroundings. Regulatory mechanisms governing bacterial flagella-driven motility are well-established, however, little is yet known about the regulation underlying swimming motility propelled by the archaeal cell surface structure, the archaella. Previous research showed that deletion of the adhesion pilins (PilA1-6), subunits of the type IV pili cell surface structure, renders the model archaeonHaloferax volcaniinon-motile. In this study, we used EMS mutagenesis and a motility assay to identify motile suppressors of the ΔpilA[1-6] strain. Of the eight suppressors identified, six contain missense mutations in archaella biosynthesis genes,arlIandarlJ. Overexpression of thesearlIandarlJmutant constructs in the respective multi-deletion strains ΔpilA[1-6]ΔarlIand ΔpilA[1-6]ΔarlJconfirmed their role in suppressing the ΔpilA[1-6] motility defect. Additionally, three suppressors harbor co-occurring disruptive missense and nonsense mutations incirA, a gene encoding a proposed regulatory protein. A deletion ofcirAresulted in hypermotility, whilecirAoverexpression in wild-type cells led to decreased motility. Moreover, qRT-PCR analysis revealed that in wild-type cells, higher expression levels ofarlI,arlJ, and the archaellin genearlA1were observed in motile early-log phase rod-shaped cells compared to non-motile mid-log phase disk-shaped cells. Conversely, ΔcirAcells, which form rods during both early and mid-log phases, exhibited similar expression levels ofarlgenes in both growth phases. Our findings contribute to a deeper understanding of the mechanisms governing archaeal motility, highlighting the involvement of ArlI, ArlJ, and CirA in pilin- mediated motility regulation.ImportanceArchaea are close relatives of eukaryotes and play crucial ecological roles. Certain behaviors, such as swimming motility, are thought to be important for archaeal environmental adaptation. Archaella, the archaeal motility appendages, are evolutionarily distinct from bacterial flagella, and the regulatory mechanisms driving archaeal motility are largely unknown. Previous research has linked the loss of type IV pili subunits to archaeal motility suppression. This study reveals threeHaloferax volcaniiproteins involved in pilin-mediated motility regulation, offering a deeper understanding of motility regulation in this understudied domain while also paving the way for uncovering novel mechanisms that govern archaeal motility. Understanding archaeal cellular processes will help elucidate the ecological roles of archaea as well as the evolution of these processes across domains.
Identification of new resistance QTL regions in loquat cultivar ‘Champagne’ againstPseudomonas syringaepv.eriobotryaegroup C
Authors: Koga Shogo , Kawaguchi Ryusei , Tanaka Tsunami , Moriya Shigeki , Hiehata Naofumi , Kabashima Koji , Nagano Atushi J. , Nagano Yukio , Fukuda Shinji 
Published: March 2024

AbstractLoquat canker, caused byPseudomonas syringaepv.eriobotryae, is a bacterial disease that infects loquat (Eriobotrya japonica) and has been reported in several countries. Three pathotypes, A, B, and C, have been reported in Japan. The loquat cultivar ‘Champagne’ is resistant to the loquat canker group C and possesses a qualitative trait governed by a recessive homozygouspse-cgene located on Linkage Group 3 (LG3), and quantitative traits located at unidentified loci. In this study, we identified novel quantitative trait loci (QTL) regions for resistance to group C in this cultivar. A seedling population with ‘Tanaka’ (Pse-c/Pse-c) crossed with ‘Champagne’ (pse-c/pse-c) was tested. The genetic map of ‘Champagne’ includes a total of 1,016 SNP markers mapped across 17 LGs, covering a total distance of 1,301 cM and an average marker density of 1.4 cM/locus. In addition to minor potential QTLs, the major QTL for resistance to loquat canker group C was detected in the upper region of LG14, with the QTL contributing 6.9% to the disease index. The results of this study open new possibilities for resistance breeding against this disease.Highlights.A total of 1,016 SNP markers were mapped on a linkage map consisting of 17 linkage groups with a total distance of 1,301 cM.QTL analysis revealed a novel resistance QTL region in ‘Champagne’ against loquat canker group C in the upper part of the LG14.The identified QTLs in this study provide new possibilities for resistance breeding in loquat.
Pure yeasts selected from fermenting pear juice from the Lower Austrian Mostviertel region and their suitability for pear wine production
Authors: Gangl H. , Tscheik G. , Tiefenbrunner W. 
Published: March 2024

AbstractIf spontaneous fermentation is not carried out, commercially available pure yeasts, which are actually intended for the production of wines from grapes, are often used for the production of pear wines. Pear juice is clearly different from grape juice, e.g. due to the significantly greater difference in the ratio of fructose to glucose or the absence of tartaric acid. For this reason, the commercially available pure yeasts may be suboptimal for pear wine production. They were therefore compared with yeasts isolated from pear juice that had been purely cultivated with regard to their suitability for pear wine production.Overall, the yeasts isolated from fermenting pear juice proved to be more suitable for pear wine production. This is not only the result of the tasting of the wines fermented in 25-litre glass flasks, but also follows very clearly from the multivariate comparison both for the basic chemistry and for the spectrum of aroma components. Density and malic acid concentration were higher in wines produced with yeasts selected from fermenting pear juice. More substances from the "fruity" and especially "fruity-sweet" flavour groups were found in these wines in comparatively higher concentrations.For pear wine production, it is therefore advisable to isolate suitable yeasts from pear juice for pure cultivation.