bluuebunny/crossref_metadata_2025_split huggingface dataset:
Multiple Horizontal Mini-chromosome Transfers Drive Genome Evolution of Clonal Blast Fungus Lineages
Authors: Barragan Ana Cristina , Latorre Sergio M , Malmgren Angus , Harant Adeline , Win Joe , Sugihara Yu , Burbano Hernán A , Kamoun Sophien , Langner Thorsten 
Published: August 2024

Abstract
Crop disease pandemics are often driven by asexually reproducing clonal lineages of plant pathogens that reproduce asexually. How these clonal pathogens continuously adapt to their hosts despite harboring limited genetic variation, and in absence of sexual recombination remains elusive. Here, we reveal multiple instances of horizontal chromosome transfer within pandemic clonal lineages of the blast fungus Magnaporthe (Syn. Pyricularia) oryzae. We identified a horizontally transferred 1.2Mb accessory mini-chromosome which is remarkably conserved between M. oryzae isolates from both the rice blast fungus lineage and the lineage infecting Indian goosegrass (Eleusine indica), a wild grass that often grows in the proximity of cultivated cereal crops. Furthermore, we show that this mini-chromosome was horizontally acquired by clonal rice blast isolates through at least nine distinct transfer events over the past three centuries. These findings establish horizontal mini-chromosome transfer as a mechanism facilitating genetic exchange among different host-associated blast fungus lineages. We propose that blast fungus populations infecting wild grasses act as genetic reservoirs that drive genome evolution of pandemic clonal lineages that afflict cereal crops.
Phylogenetic distribution of DNA topoisomerase VI and its distinction from SPO11
Authors: Allen Adam M B , Maxwell Anthony 
Published: August 2024

Abstract
DNA topoisomerases (topos) are major targets for antimicrobial and chemotherapeutic drugs due to their fundamental roles in regulating DNA topology. Type II topos are essential for chromosome segregation and relaxing positive DNA supercoils, and are exemplified by topo II in eukaryotes, topo IV and DNA gyrase in bacteria, and topo VI in archaea. Topo VI occurs ubiquitously in plants and sporadically in bacteria, algae, and other protists and is highly homologous to Spo11, which initiates eukaryotic homologous recombination. This homology makes the two complexes difficult to distinguish by sequence and leads to discrepancies such as the identity of the putative topo VI in malarial Plasmodium species. A lack of understanding of the role and distribution of topo VI outside of archaea hampers its pursuit as a potential drug target, and the present study addresses this with an up-to-date and extensive phylogenetic analysis. We show that the A and B subunits of topo VI and Spo11 can be distinguished using phylogenetics and structural modelling, and that topo VI is not present in Plasmodium nor other members of the phylum Apicomplexa. These findings provide insights into the evolutionary relationships between topo VI and Spo11, and their adoption alongside other type II topos.
SIRV: spatial inference of RNA velocity at the single-cell resolution
Authors: Abdelaal Tamim , Grossouw Laurens M , Pasterkamp R Jeroen , Lelieveldt Boudewijn P F , Reinders Marcel J T , Mahfouz Ahmed 
Published: August 2024

Abstract
RNA Velocity allows the inference of cellular differentiation trajectories from single-cell RNA sequencing (scRNA-seq) data. It would be highly interesting to study these differentiation dynamics in the spatial context of tissues. Estimating spatial RNA velocities is, however, limited by the inability to spatially capture spliced and unspliced mRNA molecules in high-resolution spatial transcriptomics. We present SIRV, a method to spatially infer RNA velocities at the single-cell resolution by enriching spatial transcriptomics data with the expression of spliced and unspliced mRNA from reference scRNA-seq data. We used SIRV to infer spatial differentiation trajectories in the developing mouse brain, including the differentiation of midbrain-hindbrain boundary cells and marking the forebrain origin of the cortical hem and diencephalon cells. Our results show that SIRV reveals spatial differentiation patterns not identifiable with scRNA-seq data alone. Additionally, we applied SIRV to mouse organogenesis data and obtained robust spatial differentiation trajectories. Finally, we verified the spatial RNA velocities obtained by SIRV using 10x Visium data of the developing chicken heart and MERFISH data from human osteosarcoma cells. Altogether, SIRV allows the inference of spatial RNA velocities at the single-cell resolution to facilitate studying tissue development.
Targeted radionuclide therapy for gliomas: Emerging clinical trial landscape
Authors: Weller Michael , Albert Nathalie L , Galldiks Norbert , Bink Andrea , Preusser Matthias , Sulman Erik P , Treyer Valerie , Wen Patrick Y , Tonn Joerg C , Le Rhun Emilie 
Published: August 2024

Abstract
According to the new WHO classification of 2021, gliomas are a heterogeneous group of tumors with very different histology, molecular genetics, and prognoses. In addition to glioblastomas, the most common gliomas, there are also numerous less common gliomas, some of which have a very favorable prognosis. Targeted radionuclide therapy is a therapeutic option that can be attractive if a tumor can be targeted based on its molecular characteristics. It is particularly useful when tumors cannot be completely resected or when conventional imaging does not fully capture the extent of the tumor. Numerous approaches to radionuclide therapy for gliomas are in early development. The most advanced approaches for patients with gliomas in the clinic employ L-type amino acid transporter 1 as an uptake mechanism for radiolabeled amino acids or target somatostatin receptor 2 or gastrin-releasing peptide receptor. Here, we discuss the various target structures of radionuclide therapy in gliomas and provide an outlook for which glioma entities radionuclide therapy could most likely provide a therapeutic alternative.
Insights into interrupted rolling strategy as post-processing impact on dual phase tribological behaviour properties of Mg-8%Li doped bagasse nanoparticles composite
Authors: Aigbodion Victor Sunday 
Published: August 2024

Abstract
A combined effect of percentage reduction in rolling and weight percentage bagasse nanoparticles were used to improved the wear behaviour of Mg-8% Li/bagasse nanoparticle composites for the first time. The composites were produced using the double stir casting method by varying bagasse nanoparticles from 1 to 3%. The interrupted rolling process was used to reduce the samples to 50, 70, and 90%. The microstructural, hardness, and wear properties of the rolled composite were investigated. The results show that interrupted rolling lessen macrocracking and increase the rolled sample's formability. At 90% rolled reduction and 3% bagasse addition, the sample's hardness values improved to 74%. The coefficient of friction and wear resistance improved; with 90% rolled work exhibiting the highest wear resistance. Adhesion and delamination were the main wear processes in the as-cast samples; in the rolled samples, abrasion was the predominant wear mechanism. This study showed how to make Mg-8% Li-bagasse nanoparticle composites more resistant to wear by combining the effects of bagasse nanoparticles and rolling reduction.
N6-methyladenosine RNA modification regulates photoperiod sensitivity in cotton
Authors: He Ying , Si Zhanfeng , Mei Gaofu , Cheng Yu , Zhang Jun , Jiang Tao , Chen Jiani , Xiong Huifang , Zhang Tianzhen , Hu Yan 
Published: August 2024

Abstract
The methylation of N6-methyladenosine (m6A) involves writers, erasers, and readers, acting synergistically in posttranscriptional regulation. These processes influence various biological processes, including plant floral transition. However, the specific role of m6A modifications in photoperiod sensitivity in cotton (Gossypium hirsutum) remains obscure. To elucidate this, in this study, we conducted transcriptome-wide m6A sequencing during critical flowering transition stages in the photoperiod-sensitive wild G. hirsutum var. yucatanense (yucatanense) and the photoperiod-insensitive cultivated cotton G. hirsutum acc. TM-1 (TM-1). Our results revealed significant variations in m6A methylation of 2 cotton varieties, with yucatanense exhibiting elevated m6A modification levels compared with TM-1 under long-day conditions. Notably, distinct m6A peaks between TM-1 and yucatanense correlated significantly with photoperiod sensitivity. Moreover, our study highlighted the role of the demethylase G. hirsutum ALKB homolog 5 (GhALKBH5) in modulating m6A modification levels. Silencing GhALKBH5 led to a decreased mRNA level of key photoperiodic flowering genes (GhADO3, GhAGL24, and GhFT1), resulting in delayed bud emergence and flowering. Reverse transcription quantitative PCR analyses confirmed that silencing GhADO3 and GhAGL24 significantly downregulated the expression of the floral integrator GhFT1. Collectively, our findings unveiled a transcriptional regulatory mechanism in which GhALKBH5-mediated m6A demethylation of crucial photoperiodic flowering transcripts modulated photoperiod sensitivity in cotton.
Ocean weather, biological rates, and unexplained global ecological patterns
Authors: Li Shing Hiung Darren L C Y , Schuster Jasmin M , Duncan Murray I , Payne Nicholas L , Helmuth Brian , Chu Jackson W F , Baum Julia K , Brambilla Viviana , Bruno John , Davies Sarah W , Dornelas Maria , Gagnon Patrick , Guy-Haim Tamar , Jackson Jennifer M , Leichter James J , Madin Joshua S , Monteith Zachary L , Queirós Ana M , Schneider Eric V C , Starko Samuel , Talwar Brendan S , Wyatt Alex S J , Aichelman Hannah E , Bensoussan Nathaniel , Caruso Carlo , Castillo Karl , Choi Francis , Dong Yun-Wei , Garrabou Joaquim , Guillemain Dorian , Higgs Nicholas , Jiang Yuwu , Kersting Diego K , Kushner David J , Longo Guilherme O , Neufeld Christopher , Peirache Marion , Smyth Tim , Sprague Joshua L , Urvoy Gaëlle , Zuberer Frederic , Bates Amanda E 
Published: August 2024

Abstract
As on land, oceans exhibit high temporal and spatial temperature variation. This “ocean weather” contributes to the physiological and ecological processes that ultimately determine the patterns of species distribution and abundance, yet is often unrecognized, especially in tropical oceans. Here, we tested the paradigm of temperature stability in shallow waters (&lt;12.5 m) across different zones of latitude. We collated hundreds of in situ, high temporal-frequency ocean temperature time series globally to produce an intuitive measure of temperature variability, ranging in scale from quarter-diurnal to annual time spans. To estimate organismal sensitivity of ectotherms (i.e. microbes, algae, and animals whose body temperatures depend upon ocean temperature), we computed the corresponding range of biological rates (such as metabolic rate or photosynthesis) for each time span, assuming an exponential relationship. We found that subtropical regions had the broadest temperature ranges at time spans equal to or shorter than a month, while temperate and tropical systems both exhibited narrow (i.e. stable) short-term temperature range estimates. However, temperature-dependent biological rates in tropical regions displayed greater ranges than in temperate systems. Hence, our results suggest that tropical ectotherms may be relatively more sensitive to short-term thermal variability. We also highlight previously unexplained macroecological patterns that may be underpinned by short-term temperature variability.
Development of a novel bacterial production system for recombinant bioactive proteins completely free from endotoxin contamination
Authors: Kamoshida Go , Yamaguchi Daiki , Kaya Yuki , Yamakado Toshiki , Yamashita Kenta , Aoyagi Moe , Nagai Saaya , Yamada Noriteru , Kawagishi Yu , Sugano Mizuki , Sakairi Yoshiaki , Ueno Mikako , Takemoto Norihiko , Morita Yuji , Ishizaka Yukihito , Yahiro Kinnosuke 
Published: August 2024

Abstract
Endotoxins, or lipopolysaccharides (LPS), are potent immunostimulatory molecules of critical concern in bacterial recombinant protein expression systems. The gram-negative bacterium Acinetobacter baumannii exhibits an interesting and unique phenotype characterized by the complete loss of LPS. In this study, we developed a novel system for producing recombinant proteins completely devoid of endotoxin contamination using LPS-deficient A. baumannii. We purified endotoxin-free functional green fluorescent protein, which reduced endotoxin contamination by approximately three orders of magnitude, and also purified the functional cytokine tumor necrosis factor (TNF)-α. Additionally, utilization of the Omp38 signal peptide of A. baumannii enabled the extracellular production of variable domain of heavy chain of heavy chain (VHH) antibodies. With these advantages, mNb6-tri-20aa, a multivalent VHH that specifically binds to the spike protein of severe acute respiratory syndrome coronavirus 2, was purified from the culture supernatant, and endotoxin contamination was reduced by a factor of approximately 2 × 105 compared with that in conventional expression systems. A virus neutralization assay demonstrated the functionality of the purified antibody in suppressing viral infections. Moreover, we applied our system to produce ozoralizumab, a multispecific VHH that binds to human TNF-α and albumin and are marketed as a rheumatoid arthritis drug. We successfully purified a functional antibody from endotoxin contamination. This system establishes a new, completely endotoxin-free platform for the expression of recombinant proteins, which distinguishes it from other bacterial expression systems, and holds promise for future applications.
A Falls Prevention Program for People After Stroke in Guyana: An International Collaboration
Authors: Pascal Maureen Romanow , Lawrence Barbara , Pires Stephanie , Newton Elton , Babulall Deoranie , Saroka Kelly , Shaver Megan , Schanzlin Mackenzie , Pearage Kristi 
Published: August 2024

Abstract

Objective
The objective was to describe the social, environmental, and cultural adaptations to an existing falls program and assess acceptability and preliminary effectiveness of the program in reducing fear, reducing falls, and improving function among individuals poststroke in Guyana.

Methods
A quasi-experimental pilot study with a pretest/posttest in-group design was developed through a collaboration of researchers in Guyana and the US. Participants took part in the falls prevention program for 8 weeks. Outcome measures included a 10-m walk test, the Five Times Sit to Stand Test, and subjective questionnaires for falls incidence and balance confidence at the beginning and end.

Results
Twenty participants completed the study. One participant experienced medical complications, and their data were excluded from analysis. Fifteen participants (78.9%) demonstrated improvements in comfortable and fast walking speed. Twelve participants completed the Five Times Sit to Stand Test. Eleven (91.67%) improved their time at the posttest, with 9 (81.8%) demonstrating a clinically important improvement. Nineteen participants had sustained at least 1 fall prior to the study. Only 1 participant reported a fall during the program. Initially, the majority of participants (11/19) were very concerned about falling. At the end, only 1 was very concerned about falling, and the majority (15/19) were not concerned at all. Posttest surveys of participants indicated acceptability of the program.

Conclusions
This pilot program helped reduce fall risk and improve confidence, gait speed, and community mobility of the study participants. Future research at other rehabilitation departments in Guyana would help increase the generalizability of the program.

Impact
The program can be used clinically by physical therapists in Guyana, both in departments and as a home program. Shared knowledge and experience of researchers considering research evidence and the environmental, social, and economic conditions of people living in Guyana were important in developing an effective program.
Exploring the association between circulating endothelial protein C receptor and disease activity of rheumatoid arthritis in a pilot study
Authors: Xue Meilang , Lin Haiyan , Lynch Tom , Bereza-Malcolm Lara , Sinnathurai Premarani , Thomas Ranjeny , Keen Helen , Hill Catherine , Lester Susan , Wechalekar Mihir , March Lyn 
Published: August 2024

Abstract

Objectives
To investigate whether circulating endothelial protein C receptor (EPCR) is associated with disease activity and inflammatory markers in rheumatoid arthritis.

Methods
Thirty-eight RA patients and 21 healthy controls (HC) were recruited via the A3BC biobank. Peripheral blood mononuclear cells and plasma were isolated from the blood of these participants. Plasma soluble (s)EPCR, IL-6, IL-17 and sCD14 were measured by enzyme-linked immunosorbent assay, cell membrane-associated (m)EPCR by flow cytometry; EPCR gene H3 single nucleotide polymorphism (SNP), which contributes to high plasma sEPCR levels, by PCR and DNA sequencing. Data were analysed using FlowJo10 and GraphPad Prism 10.

Results
RA patients had higher levels of mEPCR on T cells and plasma sEPCR compared with HC. No difference in the EPCR gene H3 SNP G genotype frequency was found between RA and HC. This SNP was significantly correlated with higher sEPCR levels in HC but not in RA patients. In RA, plasma sEPCR levels were positively correlated with IL-6, IL-17, sCD14, anti-CCP and rheumatoid factor. In contrast, mEPCR levels on T cells and natural killer cells (NK) were inversely associated with disease activity measures including 28/66 swollen joint count, 28/68 tender joint count and/or DAS28-CRP/ESR scores, and positively correlated with EPCR gene H3 SNP, which was also correlated with lower disease activity measures in RA.

Conclusion
Our findings suggest that EPCR may play an important role in RA, with plasma sEPCR being potentially associated with inflammatory markers and mEPCR and the EPCR gene H3 SNP possibly related to disease activity measures.
Rutin mitigates acetic acid-induced ulcerative colitis: novel coloprotective mechanism
Authors: Sherif Iman O , Al-Shaalan Nora H , Awadin Walaa F 
Published: August 2024

Abstract

Background
Ulcerative colitis, an inflammatory bowel disease, is characterized by a status of oxidative stress and inflammation. Rutin is a natural flavonoid with many pharmacological activities and its role in acetic acid-induced ulcerative colitis through the high mobility group B1 (HMGB1)/ toll-like receptor-4 (TLR4)/ myeloid differentiation primary response protein 88 (MYD88)/ nuclear factor-kB (NF-kB) signaling pathway needs to be explored.

Methods
Four experimental groups were divided into control group, rutin group: treated with 100 mg/kg/day rutin orally for 10 days, acetic acid (AA) group: given intracolonic instillation of AA to induce ulcerative colitis, and acetic acid with rutin treatment (AA/Rutin) group.

Results
Acetic acid caused a marked increase in the colon weight/length ratio and induced colonic histopathological changes, leading to a marked rise in the colonic histopathological scores. Acetic acid exhibited a significant rise in LDH and CRP serum levels as well as TOS colonic levels, accompanied by a marked decline in TAS colonic contents compared to the control group. Moreover, AA-induced activation of the HMGB1/TLR4/MYD88/NF-kB signaling pathway. Rutin demonstrated a significant decrease in the colon weight/length ratio, ameliorated the colonic histopathological changes induced by AA, and exhibited a marked decline in the colonic histopathological scores. Rutin showed a significant decrease in serum LDH, and CRP levels as well as colonic TOS contents when compared with the AA group. Rutin suppressed the colonic activation of the HMGB1/TLR4/MYD88/NF-kB signaling pathway.

Conclusion
Rutin could be a promising coloprotective agent against AA-induced ulcerative colitis by targeting the HMGB1/TLR4/MYD88/NF-kB signaling pathway.
Comparative in silico and in vitro evaluation of possible toxic effects of bisphenol derivatives in HepG2 cells
Authors: Balci-Ozyurt Aylin , Yirun Anıl , Cakır Deniz Arca , Ozcelik İbrahim , Bacanli Merve , Ozkemahli Gizem , Sabuncuoglu Suna , Basaran Nursen , Erkekoglu Pınar 
Published: August 2024

Abstract

Introduction
Bisphenols are widely used in the production of polycarbonate plastics and resin coatings. Bisphenol A (BPA) is suggested to cause a wide range of unwanted effects and “low dose toxicity”. With the search for alternative substances to BPA, the use of other bisphenol derivatives namely bisphenol F (BPF) and bisphenol S (BPS) has increased.

Methods
In the current study, we aimed to evaluate the in silico predicted inhibitory concentration 50s (pIC50s) of bisphenol derivatives on immune and apoptotic markers and DNA damage on HepG2 cells. Moreover, apoptotic, genotoxic and immunotoxic effects of BPA, BPF and BPS were determined comparatively. Effects of bisphenols on apoptosis were evaluated by detecting different caspase activities. The genotoxic effects of bisphenols were evaluated by measuring the levels of 8-hydroxy-2′-deoxyguanosine (8-OHdG) and 8-oxoguanine glycosylase (OGG1). To determine the immunotoxic effect of bisphenol derivatives, the levels of interleukin 4 (IL-4) and interleukin 10 (IL-10), transforming growth factor beta (TGF-β) and tumor necrosis factor-alpha (TNF-α), which are known to be expressed by HepG2 cells, were measured. Results: In silico data indicate that all of the bisphenols may cause alterations in immune and apoptotic markers as well as DNA damage at low doses. İn vitro data revealed that all bisphenol derivatives could affect immune markers at inhibitory concentration 30s (IC30s). In addition, BPF and BPS may also have apoptotic immunotoxic effects.

Conclusion
Both in silico and in vivo research are needed further to examine the toxic effects of alternative bisphenol derivatives.
Phosphorus-induced restructuring of the ascorbate–glutathione cycle and lignin biosynthesis alleviates manganese toxicity in peach roots
Authors: Noor Iqra , Sohail Hamza , Wentao Cao , Zhu Kaijie , Hasanuzzaman Mirza , Li Guohuai , Liu Junwei 
Published: August 2024

Abstract
Manganese (Mn) is indispensable for plant growth, but its excessive uptake in acidic soils leads to toxicity, hampering food safety. Phosphorus (P) application is known to mitigate Mn toxicity, yet the underlying molecular mechanism remains elusive. Here, we conducted physiological and transcriptomic analyses of peach roots response to P supply under Mn toxicity. Manganese treatment disrupted root architecture and caused ultrastructural damage due to oxidative injury. Notably, P application ameliorated the detrimental effects and improved the damaged roots by preventing the shrinkage of cortical cells, epidermis and endodermis, as well as reducing the accumulation of reactive oxygen species (ROS). Transcriptomic analysis revealed the differentially expressed genes enriched in phenylpropanoid biosynthesis, cysteine, methionine and glutathione metabolism under Mn and P treatments. Phosphorus application upregulated the transcripts and activities of core enzymes crucial for lignin biosynthesis, enhancing cell wall integrity. Furthermore, P treatment activated ascorbate–glutathione cycle, augmenting ROS detoxification. Additionally, under Mn toxicity, P application downregulated Mn uptake transporter while enhancing vacuolar sequestration transporter transcripts, reducing Mn uptake and facilitating vacuolar storage. Collectively, P application prevents Mn accumulation in roots by modulating Mn transporters, bolstering lignin biosynthesis and attenuating oxidative stress, thereby improving root growth under Mn toxicity. Our findings provide novel insights into the mechanism of P-mediated alleviation of Mn stress and strategies for managing metal toxicity in peach orchards.