bluuebunny/crossref_metadata_2025 huggingface dataset:
Stacking correlation length in single-stranded DNA
Authors: Viader-Godoy Xavier , Manosas Maria , Ritort Felix
Published: October 2024

Base stacking is crucial in nucleic acid stabilization, from DNA duplex hybridization to single-stranded DNA (ssDNA) protein binding. While stacking energies are tiny in ssDNA, they are inextricably mixed with hydrogen bonding in DNA base pairing, making their measurement challenging. We conduct unzipping experiments with optical tweezers of short poly-purine (dA and alternating dG and dA) sequences of 20–40 bases. We introduce a helix-coil model of the stacking–unstacking transition that includes finite length effects and reproduces the force-extension curves. Fitting the model to the experimental data, we derive the stacking energy per base, finding the salt-independent value $\Delta G_0^{ST}=0.14(3)$ kcal/mol for poly-dA and $\Delta G_0^{ST}=0.07(3)$ kcal/mol for poly-dGdA. Stacking in these polymeric sequences is predominantly cooperative with a correlation length of ∼4 bases at zero force . The correlation length reaches a maximum of ∼10 and 5 bases at the stacking–unstacking transition force of ∼10 and 20 pN for poly-dA and poly-dGdA, respectively. The salt dependencies of the cooperativity parameter in ssDNA and the energy of DNA hybridization are in agreement, suggesting that double-helix stability is primarily due to stacking. Analysis of poly-rA and poly-rC RNA sequences shows a larger stacking stability but a lower stacking correlation length of ∼2 bases.
Insertion sequence elements and unique symmetrical genomic regions mediate chromosomal inversions in Streptococcus pyogenes
Authors: Jespersen Magnus G , Hayes Andrew J , Tong Steven Y C , Davies Mark R
Published: October 2024

Chromosomal inversions are a phenomenon in many bacterial species, often across the axis of replication. Inversions have been shown to alter gene expression, changing persistence of colonisation and infection following environmental stresses. In Streptococcus pyogenes, inversions have been reported. However, frequency and molecular markers of inversions have not been systematically examined. Here, 249 complete S.pyogenes genomes were analysed using a pangenomic core gene synteny framework to identify sequences associated with inversions. 47% of genomes (118/249) contained at least one inversion, from 23 unique inversion locations. Chromosomal locations enabling inversions were usually associated with mobile elements (insertion sequences n = 9 and prophages n = 7). Two insertion sequences, IS1548 and IS1239, accounted for >80% of insertion sequences and were the only insertion sequences associated with inversions. The most observed inversion location (n = 104 genomes, 88% of genomes with an inversion) occurs between two conserved regions encoding rRNAs, tRNAs and sigma factor genes. The regions are symmetrically placed around the origin of replication forming a unique chromosomal structure in S. pyogenes, relative to other streptococci. Cataloging of the chromosomal location and frequency of inversions can direct dissection of phenotypic changes following chromosomal inversions. The framework used here can be transferred to other bacterial species to characterise chromosomal inversions.
YY1 is a transcriptional activator of the mouse LINE-1 Tf subfamily
Authors: Saha Karabi , Nielsen Grace I , Nandani Raj , Zhang Yizi , Kong Lingqi , Ye Ping , An Wenfeng
Published: October 2024

Long interspersed element type 1 (LINE-1, L1) is an active autonomous transposable element in human and mouse genomes. L1 transcription is controlled by an internal RNA polymerase II promoter in the 5′ untranslated region (5′UTR) of a full-length L1. It has been shown that transcription factor YY1 binds to a conserved sequence at the 5′ end of the human L1 5′UTR and primarily dictates where transcription initiates. Putative YY1-binding motifs have been predicted in the 5′UTRs of two distinct mouse L1 subfamilies, Tf and Gf. Using site-directed mutagenesis, in vitro binding and gene knockdown assays, we experimentally tested the role of YY1 in mouse L1 transcription. Our results indicate that Tf, but not Gf subfamily, harbors functional YY1-binding sites in 5′UTR monomers and YY1 functions as a transcriptional activator for the mouse Tf subfamily. Activation of Tf transcription by YY1 during early embryogenesis is also supported by a reanalysis of published zygotic knockdown data. Furthermore, YY1-binding motifs are solely responsible for the synergistic interaction between Tf monomers, consistent with a model wherein distant monomers act as enhancers for mouse L1 transcription. The abundance of YY1-binding sites in Tf elements also raise important implications for gene regulation across the genome.
RPS 2.0: an updated database of RNAs involved in liquid–liquid phase separation
Authors: He Yongxin , Bao Xiaoqiong , Chen Tianjian , Jiang Qi , Zhang Luowanyue , He Li-Na , Zheng Jian , Zhao An , Ren Jian , Zuo Zhixiang
Published: October 2024

Liquid–liquid phase separation (LLPS) is a crucial process for the formation of biomolecular condensates such as coacervate droplets, P-bodies and stress granules, which play critical roles in many physiological and pathological processes. Increasing studies have shown that not only proteins but also RNAs play a critical role in LLPS. To host LLPS-associated RNAs, we previously developed a database named ‘RPS’ in 2021. In this study, we present an updated version RPS 2.0 (https://rps.renlab.cn/) to incorporate the newly generated data and to host new LLPS-associated RNAs driven by post-transcriptional regulatory mechanisms. Currently, RPS 2.0 hosts 171 301 entries of LLPS-associated RNAs in 24 different biomolecular condensates with four evidence types, including ‘Reviewed’, ‘High-throughput (LLPS enrichment)’, ‘High-throughput (LLPS perturbation)’ and ‘Predicted’, and five event types, including ‘Expression’, ‘APA’, ‘AS’, ‘A-to-I’ and ‘Modification’. Additionally, extensive annotations of LLPS-associated RNAs are provided in RPS 2.0, including RNA sequence and structure features, RNA–protein/RNA–RNA interactions, RNA modifications, as well as diseases related annotations. We expect that RPS 2.0 will further promote research of LLPS-associated RNAs and deepen our understanding of the biological functions and regulatory mechanisms of LLPS.
CancerSCEM 2.0: an updated data resource of single-cell expression map across various human cancers
Authors: Zeng Jingyao , Nie Zhi , Shang Yunfei , Mai Jialin , Zhang Yadong , Yang Yuntian , Xu Chenle , Zhao Jing , Fan Zhuojing , Xiao Jingfa
Published: October 2024

The field of single-cell RNA sequencing (scRNA-seq) has advanced rapidly in the past decade, generating significant amounts of valuable data for researchers to study complex tumor profiles. This data is crucial for gaining innovative insights into cancer biology. CancerSCEM (https://ngdc.cncb.ac.cn/cancerscem) is a public resource that integrates, analyzes and visualizes scRNA-seq data related to cancer, and it provides invaluable support to numerous cancer-related studies. With CancerSCEM 2.0, scRNA-seq data have increased from 208 to 1466 datasets, covering tumor, matching-normal and peripheral blood samples across 127 research projects and 74 cancer types. The new version of this resource enhances transcriptome analysis by adding copy number variation evaluation, transcription factor enrichment, pseudotime trajectory construction, and diverse biological feature scoring. It also introduces a new cancer metabolic map at the single-cell level, providing an intuitive understanding of metabolic regulation across different cancer types. CancerSCEM 2.0 has a more interactive analysis platform, including four modules and 14 analytical functions, allowing researchers to perform cancer scRNA-seq data analyses in various dimensions. These enhancements are expected to expand the usability of CancerSCEM 2.0 to a broader range of cancer research and clinical applications, potentially revolutionizing our understanding of cancer mechanisms and treatments.
Differential redox sensitivity of tRNA dihydrouridylation
Authors: Kilz Lea-Marie , Zimmermann Simone , Marchand Virginie , Bourguignon Valérie , Sudol Claudia , Brégeon Damien , Hamdane Djemel , Motorin Yuri , Helm Mark
Published: October 2024

Various transfer RNA (tRNA) modifications have recently been shown to regulate stress-dependent gene expression by modulating messenger RNA translation. Among these modifications, dihydrouridine stands out for its increase of tRNA structural flexibility. However, whether and how dihydrouridine synthesis reacts to environmental stimuli is largely unknown. In this study, we manipulated the intracellular redox state of Escherichia coli using paraquat, revealing differential sensitivities of the three tRNA-dihydrouridine synthases towards oxidative stress. Using liquid chromatography–mass spectrometry quantification of dihydrouridine in various knockout strains, we validated the use of a specific RNA sequencing method, namely AlkAnilineSeq, for the precise mapping of dihydrouridines throughout E. coli tRNAs. We found DusA showing high activity, followed by DusB and DusC, whose activity was decreased under paraquat treatment. The relative sensitivity is most plausibly explained by a paraquat-dependent drop of NADPH availability. These findings are substantiated by in vitro kinetics, revealing DusA as the most active enzyme, followed by DusB, while DusC showed little activity, likely related to the efficacy of the redox reaction of the flavin coenzyme with NADPH. Overall, our study underscores the intricate interplay between redox dynamics and tRNA modification processes, revealing a new facet of the regulatory mechanisms influencing cellular responses to oxidative stress.
Understanding the Crucial Role of Phosphate and Iron Availability in Regulating Root Nodule Symbiosis
Authors: Isidra-Arellano Mariel C , Valdés-López Oswaldo
Published: October 2024

The symbiosis between legumes and nitrogen-fixing bacteria (rhizobia) is instrumental in sustaining the nitrogen cycle and providing fixed nitrogen to the food chain. Both partners must maintain an efficient nutrient exchange to ensure a successful symbiosis. This mini-review highlights the intricate phosphate and iron uptake and homeostasis processes taking place in legumes during their interactions with rhizobia. The coordination of transport and homeostasis of these nutrients in host plants and rhizobia ensures an efficient nitrogen fixation process and nutrient use. We discuss the genetic machinery controlling the uptake and homeostasis of these nutrients in the absence of rhizobia and under symbiotic conditions with this soil bacterium. We also highlight the genetic impact of the availability of phosphate and iron to coordinate the activation of the genetic programs that allow legumes to engage in symbiosis with rhizobia. Finally, we discuss how the transcription factor phosphate starvation response might be a crucial genetic element to integrate the plant’s needs of nitrogen, iron and phosphate while interacting with rhizobia. Understanding the coordination of the iron and phosphate uptake and homeostasis can lead us to better harness the ecological benefits of the legume-rhizobia symbiosis, even under adverse environmental conditions.
LinkedOut? A Field Experiment on Discrimination in Job Network Formation
Authors: Evsyukova® Yulia , Rusche® Felix , Mill Wladislaw
Published: October 2024

We assess the impact of discrimination on Black individuals’ job networks across the United States using a two-stage field experiment with 400+ fictitious LinkedIn profiles. In the first stage, we vary race via AI-generated images only and find that Black profiles’ connection requests are 13% less likely to be accepted. Based on users’ CVs, we find widespread discrimination across social groups. In the second stage, we exogenously endow Black and white profiles with the same networks and ask connected users for career advice. We find no evidence of direct discrimination in information provision. However, when taking into account differences in the composition and size of networks, Black profiles receive substantially fewer replies. Our findings suggest that gatekeeping is a key driver of Black–white disparities.
Quantification of myocardial oxygen extraction fraction on noncontrast MRI enabled by deep learning
Authors: Li Ran , Eldeniz Cihat , Wang Keyan , Nguyen Natalie , Schindler Thomas H , Huang Qi , Peterson Linda R , Yang Yang , Yan Yan , Cheng Jingliang , Woodard Pamela K , Zheng Jie
Published: October 2024

Purpose

To develop a new deep learning enabled cardiovascular magnetic resonance (CMR) approach for noncontrast quantification of myocardial oxygen extraction fraction (mOEF) and myocardial blood volume (MBV) in vivo.

Materials and Methods

An asymmetric spin-echo prepared CMR sequence was created in a 3 T MRI clinical system. A UNet-based fully connected neural network was developed based on a theoretical model of CMR signals to calculate mOEF and MBV. Twenty healthy volunteers (20–30 years old, 11 females) underwent CMR scans at 3 short-axial slices (16 myocardial segments) on 2 different days. The reproducibility was assessed by the coefficient of variation. Ten patients with chronic myocardial infarction were examined to evaluate the feasibility of this CMR method to detect abnormality of mOEF and MBV.

Results

Among the volunteers, the average global mOEF and MBV on both days was 0.58 ± 0.07 and 9.5% ± 1.5%, respectively, which agreed well with data measured by other imaging modalities. The coefficient of variation of mOEF was 8.4%, 4.5%, and 2.6%, on a basis of segment, slice, and participant, respectively. No significant difference in mOEF was shown among 3 slices or among different myocardial segments. Female participants showed significantly higher segmental mOEF than male participants (P < .001). Regional mOEF decrease 40% in CMR-confirmed myocardial infarction core, compared to normal myocardial regions.

Conclusion

The new deep learning–enabled CMR approach allows noncontrast quantification of mOEF and MBV with good to excellent reproducibility. This technique could provide an objective contrast-free means to assess and serially measure hypoxia-relief effects of therapeutic interventional strategies to save viable myocardial tissues.
Nanoarchitectonics of copper sulfide nanoplating for improvement of computed tomography efficacy of bismuth oxide constructs toward drugless theranostics
Authors: Meng Ruo-Yin , Xia Hong-Ying , Zhao Ying , Ye Ying-Tong , Wang Shi-Bin , Chen Ai-Zheng , Kankala Ranjith Kumar
Published: October 2024

Triple-negative breast cancer (TNBC) has emerged as one of the dreadful metastatic tumors in women due to complexity, specificity and high recurrence, resulting in poor therapeutic outcomes and requiring real-time monitoring for improved theranostics. Despite the success as efficient radiosensitizers and computed tomography (CT)-based contrast agents, bismuth (Bi)-based composites suffer from poor colloidal stability, dose-dependent toxicity and pharmacokinetic shortcomings, leading to poor therapeutic monitoring. In addition, several small molecule-based therapeutics, including nanoparticle-based delivery systems, suffer from several limitations of poor therapeutic delivery and acquired multidrug resistance by cancer cells, depriving the therapeutic needs. To overcome this aspect, this study demonstrates the fabrication of drug-like/drugless nanoarchitectures based on copper sulfide-nanoplated bismuth oxide (Bi2O3@CuS, shortly BC) composites for improved theranostic efficacy against TNBC. These systematically characterized BC nanocomposites exhibited pH-/near-infrared (NIR, 808 nm) light-responsive degradability toward dual modal therapies. Due to the band transition of Cu species, the designed BC composites displayed exceptional photothermal (PTT) conversion efficiency toward localized PTT effects. In addition to pH-/NIR-responsiveness, the internally overexpressed glutathione (GSH)-responsiveness facilitated the release of Cu2+ species for chemodynamic therapy (CDT)-based effects. To this end, the Bi3+ species in the core could be fully hydrated in the acidic tumor microenvironment, resulting in GSH depletion and reducing CDT-induced reactive oxygen species clearance, thereby ablating tumors. The acid-responsive degradability of CuS resulted in the intratumoral enrichment of BC, demonstrating remarkable CT imaging efficacy in vivo. Together, these pH-/NIR-/GSH-responsive biodegradable BC composites could realize the integrated PTT/CDT/CT theranostics against breast carcinoma.
Revisiting R&I policy assessment in the EU: a semantic analysis of ERAWATCH and RIO reports
Authors: Zacharewicz Thomas , García-Flores Victor , González-Vázquez Ignacio , Palma-Martos Luis-Antonio
Published: October 2024

The monitoring and evaluation of R&I policies relies on quantitative and qualitative methods with important methodological shortcomings. Quantitative assessments rely on standardized indicators that do not capture context-specific challenges, while qualitative approaches lack comparability. Both approaches are complementary but not always analyzed in combination, thereby considerably limiting their validity. In this study, we propose an alternative approach by using semantic analysis to analyze the large body of evidence available in the 189 annual country-specific qualitative assessments developed between 2011 and 2019 for all EU Member States in the European Commission’s ERAWATCH and RIO reports. We show that the semantic analysis of recurrent qualitative reviews of R&I policies can overcome the limitations of both quantitative scoreboards and ad hoc qualitative reviews, by taking into account country-specific challenges while allowing comparisons across countries. In our analysis, we first identify the main R&I challenges highlighted in all EU countries. Secondly, we focus on a set of four EU Member States to identify structural commonalities and contextual differences across countries. Finally, we focus on the case of Spain to compare the findings from the ERAWATCH and RIO reports with the European Innovation Scoreboard as the main quantitative assessment instrument used in the EU to assess Member States’ R&I performance. By showing that semantic analysis of recurrent and cross-country qualitative assessments of EU R&I policies provide a clear added value to the understanding of the main challenges faced in this field, we recommend the creation of a renewed EU research and innovation observatory.
Predictors of irreversible renal dysfunction in patients with idiopathic retroperitoneal fibrosis
Authors: Ji Zongfei , Sun Ying , Zhang Lijuan , Kong Xiufang , Jiang Lindi
Published: October 2024

Objectives

Idiopathic retroperitoneal fibrosis (iRPF) can lead to irreversible kidney damage. This study aimed to investigate predictors of irreversible renal dysfunction in patients with iRPF.

Methods

Eighty-three patients with newly diagnosed iRPF were enrolled between January 2010 and September 2022 at Zhongshan Hospital of Fudan University, including 60 in the training set and 23 in the validation set. They were regularly contacted or followed up via outpatient examinations by specialist doctors, who documented their condition and treatment progress. Predictors of irreversible renal dysfunction were identified using univariate and multivariate regression, logistic model, and receiver operating curve analyses.

Results

In the training set, over a median follow-up of 29 months, 16.7% of patients had an estimated glomerular filtration rate (eGFR) of <60 ml/min/1.73 m2 at the last follow-up, and 25% had hydronephrosis or required prolonged double-J stents. A prognostic score was developed by assigning 1, 1, and 2 points for peripheral CD19+ B cells <9.3%, serum creatinine (sCr) ≥120 µmol/L, and no response at 6 months, respectively. A score of ≥2 for predicting irreversible renal dysfunction had sensitivity and specificity of 100% and 92%, respectively. In the validation set, 21.7% of patients suffered from irreversible renal dysfunction. The sensitivity and specificity for predicting irreversible renal dysfunction were 100% and 94.4%, respectively.

Conclusions

A prognostic score based on factors including CD19+ B cells <9.3% and sCr ≥120 µmol/L at baseline, and no response at 6 months, is suitable for predicting irreversible renal dysfunction in iRPF.
Contributors to organ damage in childhood lupus: corticosteroid use and disease activity
Authors: Hanif Maria , Sarker Chandni , Al-Abadi Eslam , Armon Kate , Bailey Kathryn , Bohm Marek , Brennan Mary , Ciurtin Coziana , Gardner-Medwin Janet , Hawley Daniel P , Kinder Alison , Leahy Alice , Malik Gulshan , McLaren Zoe , Moraitis Elena , Mosley Ellen , Ramanan Athimalaipet V , Rangaraj Satyapal , Ratcliffe Annie , Riley Philip , Rostron Heather , Sen Ethan , Beresford Michael W , Smith Eve M D
Published: October 2024

Objectives

Awareness of paediatric-specific predictors of damage in childhood lupus is needed to inform mitigation measures. The objective of this study was to ascertain how clinical and demographic variables correlate with damage accrual and identify predictors of damage.

Methods

This analysis included UK JSLE Cohort Study participants. Univariable and multivariable Prentice-Williams-Peterson models investigated how demographic and clinical factors influenced the hazards of new damage. Analyses were performed across the entire cohort, in patients with minimal disease activity marked by a time-adjusted average SLEDAI-2K score (AMS) of ≤2, in patients with low activity (AMS of ≤4), patients with moderate-to-high activity (AMS of >4) and patients with no CS use.

Results

Within the entire cohort (n = 430), factors associated with damage included: any methylprednisolone [hazard ratio, HR 2.20 (CI 1.33–3.62)], time-adjusted mean Physician’s Global Assessment (PGA) [HR 2.87 (CI 1.48–5.56)] and AMS score [HR 1.13 (CI 1.03–1.24), all P < 0.05]. Within the low activity subgroup, any methylprednisolone [HR 2.61 (CI 1.04–6.53)] and time-adjusted mean PGA [HR 3.41 (CI 1.52–7.76)] were associated with damage (both P < 0.05). Within the moderate-to-high activity subgroup, any methylprednisolone [HR 2.29 (CI 1.31–4.00)], time-adjusted mean PGA [HR 2.66, (CI 1.20–5.87)] and AMS score [HR 1.15 (CI 1.03–1.29)] were predictive of damage (all P < 0.05). Baseline organ damage was predictive of subsequent damage accrual in the minimal disease activity subgroup [HR 1.33 (CI 1.78–8.08)] and the no CSs subgroup [HR 3.64 (CI 1.83–7.24), both P < 0.005].

Conclusion

Disease activity levels (AMS/PGA) and proxy indicators (methylprednisolone exposure, baseline damage) were found to be key predictors of damage accrual. This highlights the importance of practical strategies, such as treat-to-target, for reducing disease activity and long-term treatment toxicity.
A de novo missense mutation in PPP2R5D alters dopamine pathways and morphology of iPSC-derived midbrain neurons
Authors: Carter Jasmine L , Halmai Julian A N M , Waldo Jennifer J , Vij Paula A , Anguiano Maribel , Villegas Isaac J , Du Yu Xin , Nolta Jan , Fink Kyle D
Published: October 2024

Induced pluripotent stem cell (iPSC) models of neurodevelopmental disorders (NDDs) have promoted an understanding of commonalities and differences within or across patient populations by revealing the underlying molecular and cellular mechanisms contributing to disease pathology. Here, we focus on developing a human model for PPP2R5D-related NDD, called Jordan syndrome, which has been linked to Early-Onset Parkinson’s Disease (EOPD). Here we sought to understand the underlying molecular and cellular phenotypes across multiple cell states and neuronal subtypes in order to gain insight into Jordan syndrome pathology. Our work revealed that iPSC-derived midbrain neurons from Jordan syndrome patients display significant differences in dopamine-associated pathways and neuronal architecture. We then evaluated a CRISPR-based approach for editing heterozygous dominant G-to-A mutations at the transcript level in patient-derived neural stem cells. Our findings show that site-directed RNA editing is influenced by sgRNA length and cell type. These studies support the potential for a CRISPR RNA editor system to selectively edit mutant transcripts harboring G-to-A mutations in neural stem cells while providing an alternative editing technology for those suffering from NDDs.
A comprehensive summary of eponymous awards and scholarships in sexual medicine
Authors: Alvermann Thomas A , Robertson Christopher C , Jones James M , Gross Martin S
Published: October 2024

Introduction

Numerous eponymous awards and scholarships exist within sexual medicine. This comprehensive review is intended to summarize these awards and highlight the esteemed sexual medicine experts for whom these awards are named.

Objectives

To provide historical background and context for the various eponymous awards in sexual medicine.

Methods

The websites of the International Society for Sexual Medicine (ISSM) and the regional affiliate societies, including the Sexual Medicine Society of North America (SMSNA), International Society for the Study of Women’s Sexual Health (ISSWSH), and various regional societies were identified, and all awards associated with a member of note were documented. In cases where no awards were identified within a regional society and a contact person was available, inquiries were made regarding the existence of awards. Several documents on the history of the ISSM were utilized for background on awards.

Results

A comprehensive list of current awards and their history was compiled.

Conclusion

This is the first comprehensive history of eponymous awards and scholarships available in sexual medicine.
The impact of neonicotinoid pesticides on reproductive health
Authors: Oladosu Jadesola I , Flaws Jodi A
Published: October 2024

Neonicotinoids are some of the most widely used insecticides in the world because they broadly target chewing and sucking insects. Neonicotinoids are used in commercial agricultural systems, sold for use in home gardens, and found in veterinary pharmaceuticals in the form of flea and tick preventatives for companion animals. They are also used as crop seed treatments and spread throughout crops as they mature. As a result, humans, wildlife, livestock, and pets are routinely exposed to neonicotinoids through the consumption of contaminated food and water as well as through the use of some veterinary pharmaceuticals. Although several studies indicate that neonicotinoid exposure causes genotoxicity, neurotoxicity, hepatotoxicity, and immunotoxicity in some non-target species, the impact of neonicotinoid pesticides on the male and female reproductive systems in mammals is largely understudied. This review summarizes current insights on the impact of common neonicotinoid pesticides such as acetamiprid, clothianidin, imidacloprid, and thiacloprid on male and female reproductive health in mammals. The review also summarizes the impacts of exposure to mixtures of neonicotinoids on reproductive endpoints. In addition, this review highlights where gaps in research on neonicotinoid pesticides and reproductive health exist so that future studies can be designed to fill current gaps in knowledge.
Potential of Small Molecules Piperidine and Pyrrolidine Against Copper-Resistant Xanthomonas perforans, Causal Agent of Bacterial Spot of Tomato
Authors: Pierre Ketsira , Liu Qingchun , Jibrin Mustafa Ojonuba , Jones Jeffrey B. , Zhang Shouan
Published: October 2024

Bacterial spot of tomato (BST), caused by Xanthomonas perforans, is an economically important disease of tomatoes in Florida. Due to the heavy reliance on copper-based bactericides for control of BST, copper-resistant strains of X. perforans are widely distributed in Florida, leading to reduced efficacy of copper-based bactericides for disease control. There is a need for alternative chemical control strategies to effectively manage this disease in tomato production. In this study, two small molecules, piperidine and pyrrolidine, were evaluated for their efficacy against the copper-resistant X. perforans strain GEV 485 in laboratory, greenhouse, and field experiments. In in vitro experiments, piperidine and pyrrolidine at concentrations as low as 2 mg/L and 16 mg/L, respectively, significantly (P<0.001) reduced bacterial populations within 4 h of incubation compared to the untreated control, while Kocide 3000, the grower copper-based bactericide standard, at 0.9 g/L and 2.1 g/L (full label rate) did not significantly reduce bacterial populations. When tested as foliar sprays in the greenhouse, pyrrolidine at 128 mg/L significantly (P <0.001) reduced disease severity compared to the untreated control, with an equivalent efficacy to Kocide 3000 (copper hydroxide at 2.1 g/L). Kocide 3000 at 1.0 g/L, in combination with piperidine at 64 mg/L and pyrrolidine at 64 and 128 mg/L significantly improved the efficacy in disease control compared to untreated controls and Kocide 3000 at 1.0 g/L alone. In field trials, both small molecules demonstrated equivalent or superior efficacy to ManKocide (copper hydroxide + mancozeb) against X. perforans compared to the untreated control. This study demonstrated for the first time the potential of piperidine and pyrrolidine for controlling bacterial spot of tomato.
Choroidal Infiltration in Erdheim-Chester Disease: A Case Series
Authors: Fatam El Fakih , Stéphane Abramowicz , Adélaïde Toutée , Valérie Touitou , Bahram Bodaghi
Published: October 2024

Purpose:

We describe two cases of choroidal involvement in patients with Erdheim-Chester disease (ECD), a rare non-Langerhans cell histiocytosis.

Methods:

Short case series.

Results:

The first patient was a 25-year-old man with asymptomatic ECD at the level of bones, lung, and central nervous system. Fundus examination revealed bilateral yellowish choroidal infiltration in the superior macula and nasal mid-periphery. After initial mild enlargement of the choroidal lesions, treatment with weekly subcutaneous pegylated interferon α2a (PEG-IFN) was started inducing partial regression of the lesions. The second patient was a 45-year-old man with ECD involving the left orbit, maxillary sinus, heart, blood vessels, kidney, retroperitoneum, bones and testes. Fundus examination of the left eye showed choroidal folds. Macular spectral-domain optical coherence tomography confirmed the folds and revealed underlying choroidal infiltration. Final ocular diagnosis was left choroidal, scleral, and orbital involvement. The patient was initially treated with PEG-IFN, and later with cobimetinib, a MEK inhibitor, with favorable results. Neither patient developed choroidal neovascularization (CNV) during the follow-up.

Conclusions:

ECD is a rare multisystem disorder that can present with ocular involvement, including orbital masses, xanthelasma-like lesions, and occasionally, choroidal infiltrates. Early recognition and prompt treatment can lead to improvement of ophthalmic and systemic symptoms and prevent further complications. We recommend treating patients with choroidal ECD, regardless of the presence of symptoms, considering these patients are at increased risk of developing CNV.
Changes in Clinical Competence of Novice Physical Therapists During Their First Year of Employment: A Single Center Retrospective Observational Study in Japan
Authors: Motoya Ikuo , Tanabe Shigeo , Koyama Soichiro , Hirakawa Yuichi , Iwai Masanobu , Takeda Kazuya , Kanada Yoshikiyo , Kawamura Nobutoshi , Kawamura Mami , Sakurai Hiroaki
Published: October 2024

Background and Objectives:

This study aimed to examine the development of clinical competence of novice physical therapists (PTs) during their first year of employment, following the implementation of an original in-house educational program. The educational program was designed to offer diverse training opportunities at an early stage, during the first year of employment.

Methods:

Thirty-eight novice PTs (21 males and 17 females, mean age 23.4 ± 3.2 years) participated in this study. All participants underwent educational programs and a self-assessment using the Clinical Competence Evaluation Scale in Physical Therapy (CEPT) on the first day of employment (entry-level) and after 1, 3, 6, and 12 months of employment. The total score and CEPT component-wise scores—“knowledge,” “clinical reasoning,” “skill,” “communication,” “attitude,” “self-education,” and “self-management”—at the 4 assessment points (1, 3, 6, and 12 months) were compared with values on the first day.

Results:

The total scores at 3, 6, and 12 months of employment were significantly higher than those on the first day of employment (P < .05). Among the total scores on the 7 components, those for “knowledge,” “clinical reasoning,” “skill,” and “communication” at 3, 6, and 12 months after employment were also significantly higher than those on the first day of employment (P < .05). The scores for “attitude” and “self-education” 12 months after employment were significantly higher than those on the first day of employment. However, the “self-management” scores at 1, 3, 6, and 12 months after employment did not significantly change compared with those on the first day of employment.

Conclusions:

The total score was significantly higher after 3 months. The participant’s clinical competence may have improved because they participated in an educational program related to “knowledge,” “clinical reasoning,” “skills,” and “communication” at an earlier stage in the first year. However, their progress was comparatively slower in other areas, suggesting that the content might not have been sufficient. This study revealed the effectiveness of the educational program on novice PTs’ clinical competence at a single institution in Japan. Positive outcomes were obtained for several parameters. Furthermore, the results reveal the need for content modifications within the educational program to improve PTs’ performance across all evaluated items.
Paternal genome elimination, monogenic reproduction, and the evolutionary genetics of atypical sex chromosome systems
Authors: Hitchcock Thomas J. , Baird Robert B. , Gardner Andy , Ross Laura
Published: October 2024

Sex chromosomes differ from autosomes in both their ploidy and transmission genetics. Consequently, selection, mutation, and drift may act differently upon them, driving distinct patterns in genetic divergence, diversity, and gene content. Recently, researchers have begun to consider a wider set of organisms with non-standard inheritance and sex-determination systems, however in many cases we lack theory which extends to such cases. One such example is paternal genome elimination (PGE), an unusual reproductive system which has independently evolved in two fly families, the fungus gnats (Sciaridae) and gall midges (Cecidomyiidae), and one order of springtails (Symphypleona). Under PGE, males receive but do not transmit a paternal genome, such that the autosomes and X chromosomes exhibit the same transmission genetics, but with different somatic ploidy. This makes them uniquely suited to test hypotheses about the role of haploid selection in males. Additionally, repeatedly throughout these groups a novel sex determination system – monogeny – has evolved, whereby females produce broods of exclusively one sex. The genetic basis of monogeny partitions the X chromosome into three segments, all displaying distinct inheritance patterns. Here we develop a series of theoretical models adapted to the genetics of these groups, generating testable predictions as to the relative genetic diversity within populations, and divergence between populations. Our results suggest that these species are excellent systems with which to test many fundamental principles in evolutionary genetics.
Trapped ion mobility spectrometry-guided molecular discrimination between plasmalogens and other ether lipids in lipidomics experiments
Authors: Koch Jakob , Neumann Lukas , Lackner Katharina , Fernández-Quintero Monica L. , Watschinger Katrin , Keller Markus A.
Published: October 2024

Trapped Ion Mobility Spectrometry (TIMS) has demonstrated promissing potential as a powerful discriminating method when coupled with mass spectrometry, enhancing the precision of feature annotation. Such a technique is particularly valuable for lipids, where a large number of isobaric but structurally distinct molecular species often coexist within the same sample matrix. In this study we explored the potential of ion mobility for ether lipid isomer differentiation. Mammalian ether phospholipids are characterized by a fatty alcohol residue at thesn-1 position of their glycerol backbone. Ether lipids can make up to 20% of the total phospholipid mass. They are present in a broad range of tissues where they are for example crucial for nervous system function, membrane homeostasis and inter-as well as intracellular signaling.

Molecular ether lipid species are difficult to distinguish analytically, as they occur as 1-O-alkyl and 1-O-alkenyl subclasses, with the latter being also known as plasmalogens. Isomeric ether lipid pairs can be separated with reversed-phase chromatography. However, their precise identification remains challenging due to the lack of clear internal reference points, inherent to the nature of lipid profiles and the lack of sufficient commercially available standard substances.

Here, we demonstrate - with focus on phosphatidylethanolamines - that ion mobility measurements allow to discriminate between the ether lipid subclasses through distinct differences in their gas phase geometries. This approach offers significant advantages as it does not depend on the variability of chromatography. However, the current resolution in the ion mobility dimension is not sufficient to baseline separate 1-O-alkyl and 1-O-alkenyl isobars, and the observed differences are not yet accurately represented in existing collision cross section databases.

Despite these challenges, the predictable properties of the ion mobility behavior of ether lipid species can significantly support their accurate annotation and hold promise for future advancements in lipid research.
Mutagenic ligation of polβ mismatch insertion products during 8-oxoG bypass by LIG1 and LIG3α at the downstream steps of base excision repair pathway
Authors: Lee Kar Men , Castro Erick , Ratcliffe Jacob E. , Çağlayan Melike
Published: October 2024

Base excision repair (BER) maintains genome integrity by fixing oxidized bases that could be formed when reactive oxygen species attack directly on the DNA. We previously reported the importance of a proper coordination at the downstream steps involving gap filling by DNA polymerase (pol) β and subsequent nick sealing by DNA ligase (LIG) 1 or 3α. Yet, how the fidelity of 8-oxoG bypass by polβ affects the efficiency of ligation remains unclear. Here, we show that LIG1 can seal nick products of polβ after both dATP and dCTP insertions during 8- oxoG bypass, while ribonucleotide insertions completely diminish the repair coordination with both ligases, highlighting a critical role for nucleotide selectivity in maintaining BER accuracy. Furthermore, our results demonstrate that LIG3α exhibits an inability to ligate nicks of polβ dCTP:8-oxoG insertion or with preinserted 3’-dC:8-oxoG. Finally, AP-Endonuclease 1 (APE1) proofreads nick repair intermediates containing 3’-dA/rA and 3’-dC/rC mismatches templating 8-oxoG. Overall, our findings provide a mechanistic insight into how the dual coding potential of the oxidative lesion and identity of BER ligase govern mutagenicversuserror-free repair outcomes at the final steps and how the ribonucleotide challenge compromises the BER coordination leading to the formation of deleterious repair intermediates.
Linking myelin and Epstein-Barr virus specific immune responses in multiple sclerosis: insights from integrated public T cell receptor repertoires
Authors: Valkiers Sebastiaan , Dams Amber , Kuznetsova Maria , Ha My , Janssens Ibo , Willekens Barbara , Laukens Kris , Ogunjimi Benson , Cools Nathalie , Meysman Pieter
Published: October 2024

The autoimmune responses in multiple sclerosis (MS), particularly those mediated by T cells targeting CNS-derived antigens, are broadly recognized. However, the defining triggers underlying these responses remain poorly understood. Epstein-Barr virus (EBV) infection has emerged as a primary risk factor for MS, suggesting a potential role for molecular mimicry in which EBV-specific immune responses cross-react with myelin antigens.

In this study, we analyzed the T cell receptor (TCR) repertoires of MS patients (n = 129) and controls (n = 94) from public datasets, to explore the relationship between EBV-specific and myelin-specific T cell responses. Our analysis identified clusters of TCRs that were significantly depleted among MS patients, many of which were associated with cytomegalovirus (CMV). By generating a library of myelin-reactive TCRs from stimulated peripheral blood mononuclear cells (PBMCs) obtained from MS patients and mapping these sequences to the public TCR repertoire database, we also uncovered a lower frequency of myelin-reactive TCRs in MS samples compared to controls in the public datasets. In addition, epitope-specificity prediction revealed a broader response to EBV-, but not CMV-derived epitopes.

Collectively, these findings underscore the complex role of chronic viral infections in MS. Particularly, they suggest that EBV-specific immune responses contribute to the dysregulation of the immune system in MS patients, potentially through mechanisms of molecular mimicry. While the broader response to EBV-derived epitopes and the lower frequency of myelin-reactive TCRs in MS samples are both associated with the disease, further research is needed to clarify the nature of this relationship. These observations suggest that viral and autoimmune mechanisms may contribute independently or interact in MS pathogenesis.
TheSaccharomyces cerevisiaecell lysis mutantcly8is a temperature-sensitive allele ofESP1
Authors: Putnam Christopher D. , Li Bin-zhong , Broderick Lori
Published: October 2024

TheSaccharomyces cerevisiaemutants designatedcly(celllysis) cause cell lysis at elevated temperatures. Thecly8mutation, previously localized to an 80 kilobase region betweenGCD2andSPT6on the right arm of chromosome VII, has been used for mutation mapping and in recombination assays, but its genetic identity has remained unknown. Whole genome sequencing ofcly8mutant andCLY8wild-type strains revealed four missense mutations specific to thecly8mutant strain in theGCD2-SPT6interval, three of these missense mutations affected essential genes. Theesp1-G543Emutation, but not the two other missense mutations, recapitulated the temperature-sensitive growth, the cell lysis phenotype, and recessive nature of thecly8mutation. TheESP1gene encodesS. cerevisiaeseparase and is required for normal chromosome segregation during mitosis. Shifting cells containing theesp1-G543Emutation to the non-permissive temperature caused chromosome missegregation based on the analysis of DNA content by flow cytometry analysis. Taken together, these results indicate that the temperature-sensitivecly8mutation is an allele of the essentialESP1gene.
β-Amyloid impairs Proteasome structure and function. Proteasome activation mitigates amyloid induced toxicity and cognitive deficits
Authors: Davidson Kanisa , Bano Mehar , Parker Danitra , Osmulski Pawel , Gaczynska Maria , Pickering Andrew M.
Published: October 2024

Background

Alzheimer’s Disease (AD) is the leading cause of dementia globally, affecting around 50 million people and marked by cognitive decline and the accumulation of β-amyloid plaques and hyperphosphorylated tau. The limited treatment options and numerous failed clinical trials targeting β-amyloid (Aβ) highlight the need for novel approaches. Lowered proteasome activity is a consistent feature in AD, particularly in the hippocampus. Impaired proteasome function in AD is hypothesized to stem from direct inhibition by β-amyloid or hyperphosphorylated tau, disrupting critical neuronal processes such as memory formation and synaptic plasticity.

Objectives

This study tests the hypothesis that AD related deficits are driven in part by impaired proteasome function as a consequence of inhibition by Aβ. We evaluated how proteasome function is modulated by Aβ and the capacity of two proteasome-activating compounds, TAT1-8,9-TOD and TAT1-DEN to rescue Aβ-induced impairment in vitro, as well as survival deficits in cell culture and Aβ-induced cognitive deficits in Drosophila and mouse models.

Results

Our study demonstrates that oligomeric β-amyloid binds to the 20S proteasome and impairs its activity and conformational stability. The oligomers also destabilize the 26S proteasome to release the free 20S proteasome. Treatment with proteasome activators TAT1-8,9TOD and TAT1-DEN rescue the 20S proteasome function and reduces cell death caused by Aβ42 toxicity in SK-N-SH cells. In Drosophila models overexpressing Aβ42, oral administration of proteasome agonists delayed mortality and restored cognitive function. Chronic treatment with TAT1-DEN protected against deficits in working memory caused by Aβ42 in mice and in hAPP(J20) mice with established deficits, acute TAT1-DEN treatment significantly improved spatial learning, with treated mice performing comparably to controls.

Conclusions

Aβ has dual impacts on 20S and 26S proteasome function and stability. Proteasome activation using TAT1-8,9TOD and TAT1-DEN shows promise in mitigating AD-like deficits by protecting against amyloid toxicity and enhancing proteasome function. These findings suggest that targeting proteasome activity could be a viable therapeutic approach for AD, warranting further investigation into the broader impacts of proteasome modulation on AD pathology.
Soil microbes influence the ecology and evolution of plant plasticity
Authors: Bolin Lana G.
Published: October 2024

Stress often induces plant trait plasticity, and microbial communities also alter plant traits. Therefore, it is unclear how much plasticity results from direct plant responses to stress versus indirect responses due to stress-induced changes to soil microbial communities.

To test how microbes and microbial community responses to stress affect the ecology and potentially the evolution of plant plasticity, I grew plants in four stress environments (salt, herbicide, herbivory, no stress) with microbes that had responded to these same environments or with sterile inoculant.

Plants delayed flowering under stress only in the presence of live microbial communities, and this plasticity was maladaptive. However, microbial communities responded to stress in ways that accelerated flowering across all environments. Microbes also affected the expression of genetic variation for plant flowering time and specific leaf area, as well as genetic variation for plasticity of both traits, and disrupted a positive genetic correlation for plasticity in response to herbicide and herbivory stress, suggesting that microbes may affect the pace of plant evolution.

Together, these results highlight an important role for soil microbes in plant plastic responses to stress and suggest that microbes may alter the evolution of plant plasticity.