bluuebunny/crossref_metadata_2025 huggingface dataset:
Revisiting sour rot of grapevine through disease-associated microbiomes: a tripartite co-infection?
Authors: Sébastien Hévin , Wilhelm Matthieu , Kehrli Patrik , Buyck Bart , Gindro Katia , Wolfender Jean-Luc , Hofstetter Valérie
Published: September 2024

Sour rot in grapevines is thought to result from berry infection by yeasts, acetic acid bacteria and vinegar flies. Our results confirm previous studies having shown that sour rot supersedes grey mould when both diseases are present in a vineyard, but also indicate that the two diseases can cohabit at an advanced stage of grape decay. To better characterize the role of each of the actors involved in sour rot expression, we conducted experiments involving the isolation of 1593 fungi and bacteria to understand the composition and dynamics of the microbiomes associated with healthy berries, diseased berries and insect vectors. As some grape clusters became symptomatic for sour rot in the absence of acetic acid bacteria, the latter do not always appear necessary for disease expression. The yeast genusGeotrichum,is reported here for the first time to be able to initiate sour rot in grapes, similar to other yeast genera. By allowing or denying the access of insect vectors to intact or artificially wounded grapes, we demonstrate that vinegar flies accelerate disease expression but only when berries are previously injured. Furthermore, the yeast communities identified on native and introduced vinegar flies (Drosophila suzukii) are very similar and yeast-dominated. This confirms the key role of both introduced and endemic vinegar flies in the transmission of sour rot fungi. However, berry skin wounds, induced by heavy rainfall leading to high water uptake and rapid berry swelling, appear to be the main factor in disease expression.

IMPORTANCE

This study sheds new light on the complex interactions between microbiomes, insect vectors and physical factors favoring the development of sour rot. While previous studies suggested that acetic acid bacteria were mandatory for sour rot expression and that the introducedDrosophila suzukiiflies were the main insect vector, our results indicate that grape sour rot can also result solely from yeast infection and that endemicDrosophilaflies are equally important in yeast transportation and transmission in the vineyard. The fruit flies accelerate the infection process leading to disease expression in the weeks prior to harvest, but we demonstrate here that they can do this only on the condition that the skin of grape berries shows already injuries, for example due to excessive water uptake after heavy rain. Consequently, sour rot of grapes is suggested to depend principally on climatic conditions during the maturation of grape berries.
A ground surface rolling method for detecting environmental DNA of terrestrial animals
Authors: Kakita Manami , Furuta Yoshikazu , Tanaka Hidenori
Published: September 2024

Biological information obtained from environmental DNA has been helpful for conservation of ecosystems and biodiversity. Methods for environmental DNA of terrestrial habitats are limited such as sampling of water near terrestrial habitat and of shoveled soil, whereas those of aquatic habitats are well-established. We developed a method using a sampler for terrestrial habitat utilizing a combination of a simple rotating body and a single-use non-woven fabric collector as a sampler, enabling sample collection from wide area of various surfaces without power supply. The sampler was applied to collect 90 ground surface and 29 water samples in a secondary nature environment, resulted in the detection of 53 species of birds and mammals in total. The result covered 92% of the species detected by cameras installed in front of the sampling areas, validating the sensitivity of the method. Time course analysis also revealed that the timing of the detection of birds matched that of the birds’ actual arrival. These results suggest that our labor-saving method could provide accurate and time-resolved data for biodiversity monitoring of terrestrial areas. Combining with established aquatic environmental analysis, the sampler would enable systematic monitoring of both aquatic and terrestrial habitats, enhancing our understanding of the whole ecosystem.
Response of Various Concentrations Of Indole Acetic Acid (IAA) to Morphological Attributes in Different Plum (Prunus domesticaL.) Curltivars
Authors: Ullah Kaleem , Jan Samin , Zamir Roshan , Majeed Abdul , Ahmad Bakhtiyar , Rehman Gouhar
Published: September 2024

Abstracts

This study was conducted to evaluate the effects of indole-3-acetic acid (IAA) on budwood treated with different concentrations of indole acetic acid i.e. ((300, 600, 900 and 1200 ppm) of three plum varieties (Fazle Manani, Santa Rosa and Red Beauty) in respect of various morphological parameters e.g. days to sprouting, plant height, number of branches, percent sprouting, number of leaves, budling diameter and internode length. Results revealed that different varieties of plum had different responses to the applied concentrations in different plum cultivars. Cultivar Fazle manani showed significant decline in days to sprouting (at 300 ppm dose), plant height (at 600 dose), percent sprouting and budling diameter (at all concentrations) while increase in number of branches (1200 dose), number of leaves (all concentrations except 600 ppm), and internode length (at 300 ppm and 900 ppm concentrations). Days to sprouting in cultivar Santa rosa were non-significantly affected while plant height and internode length were significantly reduced at all concentrations particularly at 300 ppm. Number of branches, number of leaves and percent sprouting increased significantly at 300 ppm and 900 ppm concentrations. Cultivar red beauty exhibited significant decline in days to sprouting at 600 ppm and 900 ppm concentrations while elevated plant height at 900 concentrations. Number of branches, percent sprouting, number of leaves and budling diameter in Red Beauty were inhibited by all concentrations. However, internode length was increased significantly at 300 ppm, 600 ppm and 1200 ppm concentrations but decreased at 900 ppm concentrations. The study revealed that the most effective dose was 300 ppm. These findings demonstrate the differential sensitivity of plum cultivars to IAA and highlight its potential for regulating their growth and morphology.
Quantifying Data Distortion in Bar Graphs in Biological Research
Authors: Lin Teng-Jui , Landry Markita P.
Published: September 2024

Over 88% of biological research articles use bar graphs, of which 29% have undocumented data distortion mistakes that over- or under-state findings. We developed a framework to quantify data distortion and analyzed bar graphs published across 3387 articles in 15 journals, finding consistent data distortions across journals and common biological data types. To reduce bar graph-induced data distortion, we propose recommendations to improve data visualization literacy and guidelines for effective data visualization.
Vascular responses of hypercapnia challenge in mice
Authors: Yang Xiuli , Li Yuguo , Wei Zhiliang
Published: September 2024

Hypercapnia challenge with a few percent of carbon dioxide is popularly used in physiological studies to investigate the dynamic vascular properties. A typical hypercapnia experiment can be divided into four phases: baseline (regular air), transition (CO2enriched), hypercapnia (CO2enriched), and recovery (regular air). Cerebrovascular reactivity (CVR), denoting the percentage of functional changes between baseline and hypercapnia phases, can be measured to assess vascular health. In this study, we focus on the transition and recovery phases to track the built-up of cerebral blood flow (CBF) increase induced by CO2-enriched gas and recovery of CBF after returning to regular air. Dynamic features were compared with those of another potent vasodilatory agent, acetazolamide. Our results reveal that 5 min is sufficiently long to ensure 95% built-up of CBF increase under 5% CO2, but it takes much longer to recover to baseline.
Covariation between metabolic and radioactive dose rates in Chornobyl rodents
Authors: Boratyński Zbyszek , Lavrinienko Anton , Lehmann Philipp , Mousseau Timothy A. , Tukalenko Eugene , Vasylenko Andrii , Watts Phillip C. , Mappes Tapio , Nowick Katja
Published: September 2024

High metabolic rate may provide fitness benefits for individuals. But high metabolic rates incur energetic costs and the need to ingest more food, increasing the risks of ingesting harmful substances from the environment. How organisms respond to elevated levels of ionizing radiation is an important question in the light of increasing pollution from nuclear accidents and waste, as well as ever-increasing reliance on radiation in medical diagnostics and therapies. We investigated how limits to metabolic rate, and aerobic metabolic scope (ceiling of energetic activity above maintenance levels), of wild rodents inhabiting a gradient of radioactive contamination from the Chernobyl accident covary with the biological burden of radionuclides in their bodies. Our results demonstrate that high biological dose rate correlates with high self-maintenance and low aerobic capacity in adults. In contrast, in subadults high dose rate correlates with high aerobic capacity. Consequently, high dose rate correlates with low aerobic scope in adults, but with high aerobic scope in subadults. Despite the uncertainty of the causal mechanisms, whether the dose rate affects the metabolic rate, the reverse or the reciprocal feedback prevail, it can be hypothesized that metabolic down-regulation could contribute to protection against radioactive exposure. Yet, metabolic down-regulation might be constrained by developmental obligations. Understanding the physiological mechanisms affecting responses to radiation exposure is key for risk assessment of environmental contamination, radiotherapies, and space exploration, and may help to rectify discordant opinions concerning the effects of radiation on the ecology of organisms living in Chornobyl.
Exploring midgut expression dynamics: longitudinal transcriptomic analysis of adult femaleAmblyomma americanummidgut and comparative insights with other hard tick species
Authors: Lu Stephen , de Sousa Paula Lucas C. , Ribeiro Jose M.C. , Tirloni Lucas
Published: September 2024

Background

Female ticks remain attached to their host for multiple days to complete a blood meal. This prolonged feeding period is accompanied by a significant increase in the tick’s size and body weight, paralleled by noteworthy changes to the tick midgut. While the midgut is recognized for its established role in blood storage and processing, its importance extends to playing a crucial role in the acquisition, survival, and proliferation of pathogens. Despite this, our overall understanding of tick midgut biology is limited.

Results

We conducted a comprehensive longitudinal transcriptome analysis of the midgut in adult femaleA. americanumticks across various feeding stages, including unfed, slow-feeding, and rapid-feeding phases. Our analysis revealed 15,599 putative DNA coding sequences (CDS) classified within 26 functional groups. Dimensional and differential expression analysis highlighted the dynamic transcriptional changes in the tick midgut as feeding progresses, particularly during the initial period of feeding and the transition from the slow-feeding to the rapid-feeding phase. Additionally, we performed an orthology analysis comparing our dataset with midgut transcriptomes from other hard ticks, such asIxodes scapularisandRhipicephalus microplus. This comparison allowed us to identify transcripts commonly expressed during different feeding phases across these three species.

Conclusion

Our findings provide a detailed temporal resolution of numerous metabolic pathways inA. americanum, emphasizing the dynamic transcriptional changes occurring in the tick midgut throughout the feeding process. Furthermore, we identified conserved transcripts across three different tick species that exhibit similar expression patterns. This knowledge has significant implications for future research aimed at deciphering the physiological pathways relevant within the tick midgut. It also offers potential avenues for developing control methods that target multiple tick species.
Constructing a Norm for Children’s Scientific Drawing: Distribution Features Based on Semantic Similarity of Large Language Models
Authors: Zhang Yi , Wei Fan , Wang Yan , Yu Yanyan , Chen Jianli , Cai Zipo , Liu Xinyu , Wang Wei , Wang Peng , Li Jingyi , Wang Zhong
Published: September 2024

Using children’s drawings to understand children’s concept learning has been proven to be an effective method, but there are still two major problems in previous research: 1. The drawings heavily relies on the task, so the ecological validity of the conclusions is low; 2. The subjective interpretation of drawings is inevitable. To address these problems, this study uses the Large Language Model (LLM) to identify the drawing contents of 1096 children’s scientific drawings (covering 6 scientific concepts), and uses the word2vec algorithm to calculate their semantic similarity. The study explores whether there are consistent drawing representations among children with the same theme, and attempts to establish a norm for children’s scientific drawings, providing a baseline reference for following children’s drawing research. The results showed that there were significant differences in the consistency of children’s representations of different concepts, and there was a possibility of consistency bias, that is, the appearance of consistency representations misled LLM. At the same time, linear regression tests were used to analyze the relevant factors that affect children’s representation. The results show that sample size and teaching strategies can affect the accuracy of LLM’s image recognition, while the degree of conceptual abstraction may affect the consistency of representation.
MolAR: memory-safe library for analysis of MD simulations written in Rust
Authors: Yesylevskyy Semen
Published: September 2024

Transition to the memory safe natively compiled programming languages is a major software development trend in recent years, which eliminates memory-related security exploits, enables a fearless concurrency and parallelization, and drastically improves ergonomics and speed of software development. Modern memory-safe programing languages, such as Rust, are currently not used for developing molecular modeling and simulation software despite such obvious benefits as faster development cycle, better performance and smaller amount of bugs. In this work we present MolAR -the first memory-safe library for analysis of MD simulations written in Rust. MolAR is intended to explore the advantages and challenges of implementing molecular analysis software in the memory-safe natively compiled language and to develop specific memory-safe abstractions for this kind of software. MolAR demonstrates an excellent performance in benchmarks outperforming popular molecular analysis libraries, which makes it attractive for implementing computationally intensive analysis tasks.

MolAR is freely available under Artistic License 2.0 athttps://github.com/yesint/molar.
Evolutionary fingerprint in rodent PD1 confers weakened activity and enhanced tumor immunity compared to human PD1
Authors: Masubuchi Takeya , Chen Lin , Marcel Nimi , Wen George A. , Caron Christine , Zhang Jibin , Zhao Yunlong , Morris Gerald P. , Chen Xu , Hedrick Stephen M. , Lu Li-Fan , Wu Chuan , Zou Zhengting , Bui Jack D. , Hui Enfu
Published: September 2024

Mechanistic understanding of the immune checkpoint receptor PD1 is largely based on mouse models, but human and mouse PD1 orthologs exhibit only 59.6% identity in amino acid sequences. Here we show that human PD1 is more inhibitory than mouse PD1 due to stronger interactions with the ligands PDL1 and PDL2 and with the effector phosphatase Shp2. A novel motif highly conserved among PD1 orthologs in vertebrates except in rodents is primarily responsible for the differential Shp2 recruitment. Evolutionary analysis suggested that rodent PD1 orthologs uniquely underwent functional relaxation, particularly during the K-Pg boundary. Humanization of the PD1 intracellular domain disrupted the anti-tumor activity of mouse T cells while increasing the magnitude of anti-PD1 response. Together, our study uncovers species-specific features of the PD1 pathway, with implications to PD1 evolution and differential anti-PD(L)1 responses in mouse models and human patients.
Observation of general and specific adverse effects of organic solvents onCaenorhabditis elegansby toxicity testing using behavioral analysis
Authors: Tomioka Masahiro
Published: September 2024

Novel chemical compounds are continuously being developed and are used in various industries as well as in our daily lives. Workers in industries estimate and avoid chemical hazardous risks based on published information on chemical toxicities. However, it is challenging to avoid hazards caused by chemicals with unknown toxicity. Therefore, it is necessary to understand the toxicities of chemicals in high-throughput and multifaceted ways. In this study, I develop a high-throughput method to assess chemical toxicities through the quantitative measurement of behavior inCaenorhabditis elegans. I determine the acute toxicity of 30 organic solvents that are widely used in industries with motility as an endpoint. The adverse effects of organic solvents on motility were proportional to the lipid solubility of chemicals, which is similar to the positive relationship between the anesthetic effects of volatile organic chemicals and their lipid solubility in organisms, including humans. In addition to the general toxicity on motility, organic solvents caused adverse effects on posture during locomotion in different ways depending on the chemical’s functional group. Alcohols and cellosolves, both of which have a hydroxyl group, reduced the amplitude of body bending, whereas ketones and acetate esters, both of which have a ketone group, increased it during undulatory locomotion. Furthermore, organic solvents caused defects in behavioral plasticity based on the association of starvation and chemical signals at concentrations lower than those that affect locomotion, which suggests that sensory processing is more susceptible to organic solvents than motor function. This study provides a high-throughput method for acute chemical toxicity testing and new insights into the behavioral toxicity of organic solvents based on comprehensive behavioral analysis.
Supplemental Dietary Nano Zinc Can Impart Higher Antioxidant Status by Modulating Cu-Zn SOD Expression
Authors: Tah Amrita , Pal Aruna , De Debasis , Chatterjee P.N.
Published: September 2024

Zinc seems to be the most critical micronutrients dietary adequacy of which ensures optimum health and body defence. Considering its immunomodulation potency, zinc is often used for dietary fortification more particularly in face of challenges. However indiscriminate use of zinc as therapeutic agent often leads to secondary deficiencies of other critical nutrients due to the unwanted antagonism with other interacting nutrients available in gut. In the present study we targeted to devise a nano-structured zinc which will remain inert to other dietary micronutrients present in gut to ensure its high bioavailability. An environment benign colloidal chemistry route was employed for the synthesis of nano-dimensional zinc oxide. The microanalytical characterizations revealed that the apparent particle size of our nano-Zinc oxide ranged between 30-40 nm. The as-synthesized ZnO-NP was used for dietary fortification and the MTT assay confirmed the safe limit for its dietary inclusion. The antioxidant potential of the synthesized nano-zinc was evaluated in milk fish (Chanos chanos) considering it as a model organism. We have employed Cu-Zn SOD gene as molecular marker for antioxidant assessment with integral zinc binding sites. We have characterized Cu-Zn SOD gene inChanos chanosfor the first time and identified certain important zinc binding sites present in the Cu-Zn SOD. A significantly better expression profile of Cu-Zn SOD was observed among the fish fed dietary ZnO-NP and the best effect was observed when the fish feed was fortified with 20 ppm ZnO-NP. The outcome of this study ensures the higher bioavailability of the synthesized ZnO-NP to be assimilated into Cu-Zn SOD, which in turn imparts higher body antioxidant. Nano zinc being inert, may directly bind through the zinc binding sites of Cu-Zn SOD molecules thereby leads to its better expression and more antioxidant status through molecular interaction with other molecules throughlongevity regulating pathwayas explored by the String and KEGG pathway analysis carried out in the present investigation.
From Biobanking to Personalized Medicine: the journey of the Estonian Biobank
Authors: Milani Lili , Alver Maris , Laur Sven , Reisberg Sulev , Haller Toomas , Aasmets Oliver , Abner Erik , Alavere Helene , Allik Annely , Annilo Tarmo , Fischer Krista , Hudjashov Georgi , Jõeloo Maarja , Kals Mart , Karo-Astover Liis , Kasela Silva , Kolde Anastassia , Krebs Kristi , Krigul Kertu Liis , Kronberg Jaanika , Kruusmaa Karoliina , Kukuškina Viktorija , Kõiv Kadri , Lehto Kelli , Leitsalu Liis , Lind Sirje , Luitva Laura Birgit , Läll Kristi , Lüll Kreete , Metsalu Kristjan , Metspalu Mait , Mõttus René , Nelis Mari , Nikopensius Tiit , Nurm Miriam , Nõukas Margit , Oja Marek , Org Elin , Palover Marili , Palta Priit , Pankratov Vasili , Pantiukh Kateryna , Pervjakova Natalia , Pujol-Gualdo Natàlia , Reigo Anu , Reimann Ene , Smit Steven , Sokurova Diana , Taba Nele , Talvik Harry-Anton , Teder-Laving Maris , Tõnisson Neeme , Vaht Mariliis , Vainik Uku , Võsa Urmo , Esko Tõnu , Kolde Raivo , Mägi Reedik , Vilo Jaak , Laisk Triin , Metspalu Andres
Published: September 2024

Large biobanks have set a new standard for research and innovation in human genomics and implementation of personalised medicine. The Estonian Biobank was founded a quarter of a century ago, and its biological specimens, clinical, health, omics, and lifestyle data have been included in over 800 publications to date. What makes the biobank unique internationally is its translational focus, with active efforts to conduct clinical studies based on genetic findings, and to explore the effects of return of results on participants. In this review we provide an overview of the Estonian Biobank, highlight its strengths for studying the effects of genetic variation and quantitative phenotypes on health-related traits, development of methods and frameworks for bringing genomics into the clinic, and its role as a driving force for implementing personalized medicine on a national level and beyond.
Large-scale multi-omic analysis identifies noncoding somatic driver mutations and nominatesZFP36L2as a driver gene for pancreatic ductal adenocarcinoma
Authors: Zhong Jun , O’Brien Aidan , Patel Minal , Eiser Daina , Mobaraki Michael , Collins Irene , Wang Li , Guo Konnie , TruongVo ThucNhi , Jermusyk Ashley , O’Neill Maura , Dill Courtney D. , Wells Andrew D. , Leonard Michelle E. , Pippin James A. , Grant Struan F.A. , Zhang Tongwu , Andresson Thorkell , Connelly Katelyn E. , Shi Jianxin , Arda H. Efsun , Hoskins Jason W. , Amundadottir Laufey T.
Published: September 2024

Identification of somatic driver mutations in the noncoding genome remains challenging. To comprehensively characterize noncoding driver mutations for pancreatic ductal adenocarcinoma (PDAC), we first created genome-scale maps of accessible chromatin regions (ACRs) and histone modification marks (HMMs) in pancreatic cell lines and purified pancreatic acinar and duct cells. Integration with whole-genome mutation calls from 506 PDACs revealed 314 ACRs/HMMs significantly enriched with 3,614 noncoding somatic mutations (NCSMs). Functional assessment using massively parallel reporter assays (MPRA) identified 178 NCSMs impacting reporter activity (19.45% of those tested). Focused luciferase validation confirmed negative effects on gene regulatory activity for NCSMs nearCDKN2AandZFP36L2. For the latter, CRISPR interference (CRISPRi) further identifiedZFP36L2as a target gene (16.0 – 24.0% reduced expression,P= 0.023-0.0047) with disrupted KLF9 binding likely mediating the effect. Our integrative approach provides a catalog of potentially functional noncoding driver mutations and nominatesZFP36L2as a PDAC driver gene.
Multi-organ transcriptomic atlas reveals hallmarks of labor
Authors: Ni Duan , Nanan Ralph
Published: September 2024

Pregnancy and labor are dynamic processes involving various rapid biological changes. Previous studies found that during pregnancy there are gradual alterations in immune and metabolic pathways. In contrast, changes linked to labor are less well-known, generally limited to reports on specific differentially expressed genes, lacking a more comprehensive overview of changes of the overall signalling landscapes. Moreover, most previous works were standalone, based on individual organs. Here, we aimed to present a more systematic and holistic overview of the impacts of labor on both the maternal and fetal aspects. For this purpose, we collated a multi-organ transcriptomic atlas to decipher the influences of labor on multiple maternal and fetal compartments, covering the maternal adipose tissues (subcutaneous and visceral fat), peripheral blood, myometrium and placenta and fetal cord blood mononuclear cells (CBMCs), and spanning both physiological and pathological conditions. During labor, activation of pro-inflammatory TNF signaling was found in all maternal compartments except adipose tissues, which, along with myometrium, showed upregulation in glycolysis. Myc signaling, as a critical nexus within the intracellular signaling network, was generally enhanced in labor. Contrarily, fetal CBMCs in labor upregulated the anti-inflammatory TGFβ pathway. Importantly, changes in the maternal TNF signaling were conserved across the spectrum of healthy pregnancy of different parities, and pathological conditions like preterm pregnancy and smoking-affected pregnancy. Mechanistically, it might be explained by the reduction in progestin hormonal signals during labor but not by the mechanical stress.

Collectively, we present a comprehensive multi-organ transcriptomic atlas elucidating the maternal and fetal immune and metabolic landscapes associated with labor, shedding light on the complex physiology.
Comprehensive analysis of 111 Pleuronectiformes mitochondrial genomes: insights into structure, conservation, variation and evolution
Authors: Tan Suxu , Wang Wenwen , Li Jinjiang , Sha Zhenxia
Published: September 2024

Pleuronectiformes, also known as flatfish, are important model and economic animals. However, a comprehensive genome survey of their important organelles, mitochondria, is limited. In this study, we analyzed the genomic structure, codon preference, nucleotide diversity, selective pressure and repeat sequences, as well as reconstructed the phylogenetic relationship using the mitochondrial genomes of 111 flatfish species. Our analysis revealed a conserved gene content of protein-coding genes and rRNA genes, but varying numbers of tRNA genes across species. The mitochondrial genomes of most flatfish were conservative, while obvious gene rearrangements were found in several species, especially for the whole region rearrangement ofnad5-nad6-cytbin Samaridae family and the swapping rearrangement ofnad6andcytbgene in Bothidae family, suggesting a unique evolutionary history or functional benefit. Codon usage showed obvious biases, with adenine being the most frequent nucleotide at the third codon position. Nucleotide diversity and selective pressure analysis suggested that different protein-coding genes underwent varying degrees of evolutionary pressure, withcytbandcoxgenes being the most conserved ones. Phylogenetic analysis using both whole mitogenome information and concatenated independently aligned protein-coding genes largely mirrored the taxonomic classification of the species, with Samaridae family forming a distinct outgroup when the first approach was used. The identification of simple sequence repeats and various long repetitive sequences (forward, reverse, palindromic and complementary repeats) provided additional complexity of genome organization and offered markers for evolutionary studies and breeding practices. In summary, this study represents a significant step forward in our comprehension of the flatfish mitochondrial genomes, providing valuable insights into the structure, conservation and variation within flatfish mitogenomes, with implications for understanding their evolutionary history, functional genomics and fisheries management. Future research can delve deeper into the conservation biology, evolutionary biology and functional usages of variations.
PanCNV-Explorer: A pan-cancer resource to analyze copy number variations
Authors: Kornrumpf Kevin , Dönitz Jürgen
Published: September 2024

Introduction

Copy number variations (CNVs) are structural genomic alterations that involve changes in the number of copies of specific DNA regions. These variations can include deletions, duplications, and more complex rearrangements, and play a critical role in cancer progression by amplifying oncogenes, deleting tumor suppressor genes, or altering other key genomic regions. Despite the importance of CNVs in cancer biology, there is a lack of comprehensive resources that aggregate CNV data across multiple cancer types, impeding the exploration of their role in different malignancies. The PanCNV-Explorer was developed to fill this gap by providing a pan-cancer resource that integrates CNV data for over 21 cancer types.

Methods

The PanCNV-Explorer was developed, utilizing data from repositories such as COSMIC, DepMap, DGV, and dbVAR. Amplifications and deletions can be visualized, with detailed chromosome-specific plots highlighting CNV patterns. In addition, a genome browser has been implemented to display regions of interest for searching for genes of potential relevance.

Results

The database contains over 5 million CNVs from 15,809 samples, spanning 21 primary cancer types. Pathogenic CNVs from ClinVar and DepMap were compared to benign data from DGV and dbVAR, allowing a comprehensive analysis across tissues. CNV patterns were visualized for individual cancers. We demonstrate with use cases, focusing on common oncogenes such as MYC and tumor suppressor genes such as TP53, the ability of the resource to search for cancer driver genes. For example, chromosome 12 in pancreatic cancer showed frequent amplifications in the region containing the KRAS oncogene. In another example, we show how driver gene candidates already described in certain cancer entities can also be found with high frequency in other entities.

Conclusion

The PanCNV-Explorer provides a valuable resource for pan-cancer CNV analysis, facilitating the exploration of CNV-driven tumor heterogeneity. The integrated visualization tools and genome browser enable detailed exploration of genomic regions, enhancing cancer research. As a valuable and easy-to-use platform that allows researchers to quantify and compare CNVs across cancer types, the PanCNV-Explorer is an essential tool for advancing cancer genomics research. The main page is available athttps://mtb.bioinf.med.uni-goettingen.de/pancnv-explorer/.
Exploring the role of Large Language Models in Melanoma: a Systemic Review
Authors: Zarfati Mor , Nadkarni Girish N , Glicksberg Benjamin S , Harats Moti , Greenberger Shoshana , Klang Eyal , Soffer Shelly
Published: September 2024

Background

Large language models (LLMs) are gaining recognition across various medical fields; however, their specific role in dermatology, particularly in melanoma care, is not well- defined. This systematic review evaluates the current applications, advantages, and challenges associated with the use of LLMs in melanoma care.

Methods

We conducted a systematic search of PubMed and Scopus databases for studies published up to July 23, 2024, focusing on the application of LLMs in melanoma. Identified studies were categorized into three subgroups: patient education, diagnosis and clinical management. The review process adhered to PRISMA guidelines, and the risk of bias was assessed using the modified QUADAS-2 tool.

Results

Nine studies met the inclusion criteria. Five studies compared various LLM models, while four focused on ChatGPT. Three studies specifically examined multi-modal LLMs. In the realm of patient education, ChatGPT demonstrated high accuracy, though it often surpassed the recommended readability levels for patient comprehension. In diagnosis applications, multi- modal LLMs like GPT-4V showed capabilities in distinguishing melanoma from benign lesions. However, the diagnostic accuracy varied considerably, influenced by factors such as the quality and diversity of training data, image resolution, and the models’ ability to integrate clinical context. Regarding management advice, one study found that ChatGPT provided more reliable management advice compared to other LLMs, yet all models lacked depth and specificity for individualized decision-making.

Conclusions

LLMs, particularly multimodal models, show potential in improving melanoma care through patient education, diagnosis, and management advice. However, current LLM applications require further refinement and validation to confirm their clinical utility. Future studies should explore fine-tuning these models on large dermatological databases and incorporate expert knowledge.
Peroxiredoxin 2 mediates redox-stimulated adaptations to oxidative phosphorylation induced by contractile activity in human skeletal muscle myotubes
Authors: Heaton Robert A , Ball Sam T M , Staunton Caroline A , Mouly Vincent , Jones Samantha W , McArdle Anne , Jackson Malcolm J
Published: September 2024

Skeletal muscle generates superoxide during contractions, which is converted to hydrogen peroxide (H2O2). H2O2has been proposed to activate signalling pathways and transcription factors that regulate adaptive responses to exercise, but the concentration required to oxidize and activate key redox-sensitive signalling proteinsin vitrois much higher than the typical intracellular levels seen in muscle after exercise. We hypothesized that 2-Cys-peroxiredoxins (PRDX), which rapidly oxidize in the presence of physiological concentrations of H2O2, serve as intermediary signalling molecules and play a crucial role in activating adaptive pathways following muscle contractions. This study has examined the human muscle myotube responses to contractile activity, or exposure to low extracellular concentrations (2.5-5 µM) of H2O2and whether knock down of muscle PRDX2 alters the differential gene expression (DEG) that results from these stresses. Exposure of human skeletal muscle myotubes to a 15 min period of aerobic electrically stimulated isometric contractions or 5μM H2O2induced substantial changes in DEG with modification of many genes associated with adaptations of skeletal muscle to contractile activity. Common DEG in these conditions included upregulation of genes associated with increased mitochondrial oxidative phosphorylation, includingCOX1, COX2, COX3andATP6. In myotubes with PRDX2 knock down (94% decrease in PRDX2 mRNA), the upregulation of genes associated with increased mitochondrial oxidative phosphorylation was abolished following contractile activity or exposure to H2O2. These data indicate that a common effect of contractile activity and exposure to “physiological” levels of H2O2in human myotubes is to increase the expression of multiple genes associated with increased mitochondrial oxidative phosphorylation. Furthermore, these effects were abolished in PRDX2 knock down myotubes indicating that adaptations to upregulate multiple genes related to increased mitochondrial capacity in human muscle myotubes in response to exercise is both redox regulated and requires PRDX2 as an essential mediator of the effects of H2O2.
Genome biology of long non-coding RNAs in humans: a virtual karyotype
Authors: Palma Alessandro , Buonaiuto Giulia , Ballarino Monica , Laneve Pietro
Published: September 2024

Background

Long non-coding RNAs (lncRNAs) represent a unique and groundbreaking class of RNA molecules that exert regulatory functions with remarkable tissue and cellular specificities. Although the number of identified functional lncRNAs is increasing, comprehensive profiling of lncRNA genomics remains elusive. Creating a virtual lncRNA karyotype is especially important for species whose intrinsic features enable their biosynthesis and function in context-dependent manners.

Results and conclusions

To address this challenge, we employed existing annotation files to create a statistical genomics portrait of lncRNA genes for comparison with protein-coding genes. We provide a foundational reference for exploring the non-coding genome, offering insights into the genomic characteristics of lncRNAs that may enhance understanding of their biological significance and impact.
Elavl1 is dispensable for appendicular skeletal development
Authors: Parsha Rohini , Kota Satya K.
Published: September 2024

Elavl1/HuR is a RNA binding protein implicated in multiple developmental processes with pleiotropic roles in RNA life cycle. Loss of Elavl1 is incompatible with life with early embryonic loss of Elavl1 in epiblast cells being lethal with defects in placental branching and embryonic tissue growth. Postnatal global deletion of Elavl1/HuR results in lethality with atrophy in multiple tissues mainly due to loss of progenitor cells. However, roles of Elavl1 specifically during embryonic limb development is not well understood. Here we report that deletion of Elavl1 in limb bud mesenchyme in mouse did not reveal any abnormalities during embryonic development with normal development in pre- and postnatal limb skeleton. Analyses of skeletal patterning, morphogenesis and skeletal maturation including skeletal elements in stylopod, zeugopod and autopod during development did not reveal any significant differences between long bones from control and Elavl1 conditional knockout animals. Our study indicates differential dependency and susceptibility to loss of Elavl1 in different stem cell lineages with its functions being dispensable during limb development.
Metabolic mapping of the human solute carrier superfamily
Authors: Wiedmer Tabea , Teoh Shao Thing , Christodoulaki Eirini , Wolf Gernot , Tian Chengzhe , Sedlyarov Vitaly , Jarret Abigail , Leippe Philipp , Frommelt Fabian , Ingles-Prieto Alvaro , Lindinger Sabrina , Barbosa Barbara M. G. , Onstein Svenja , Klimek Christoph , Garcia Julio , Serrano Iciar , Reil Daniela , Santacruz Diana , Piotrowski Mary , Noell Stephen , Bueschl Christoph , Li Huanyu , Chi Gamma , Mereiter Stefan , Oliveira Tiago , Penninger Josef M. , Sauer David B. , Steppan Claire M. , Viollet Coralie , Klavins Kristaps , Hannich J. Thomas , Goldmann Ulrich , Superti-Furga Giulio
Published: September 2024

Solute carrier (SLC) transporters govern most of the chemical exchange across cellular membranes and are integral to metabolic regulation, which in turn is linked to cellular function and identity. Despite their key role, individual functions of the members of the SLC superfamily were not evaluated systematically. We determined the metabolic and transcriptional profiles upon SLC overexpression in knock-out or wild-type isogenic cell backgrounds. Targeted metabolomics provided a fingerprint of 189 intracellular metabolites, while transcriptomics offered insights into cellular programs modulated by SLC expression. Beyond the metabolic profiles of 102 SLCs directly related to their known substrates, we also identified putative substrates or metabolic pathway connections for 71 SLCs without previously annotatedbona fidesubstrates, including SLC45A4 as a new polyamine transporter. By comparing the molecular profiles, we identified functionally related SLC groups, including some with distinct impacts on osmolyte balancing and glycosylation. The assessment of functionally related human genes presented here may serve as a blueprint for other systematic studies of human gene function and supports future investigations into the functional roles of SLCs.
Single-cell multi-omic analysis reveals principles of transcription-chromatin interaction during embryogenesis
Authors: Bhardwaj Vivek , Griffa Alberto , Gaza Helena Viñas , Zeller Peter , van Oudenaarden Alexander
Published: September 2024

Establishing a cell-type-specific chromatin landscape is critical for the maintenance of cell identity during embryonic development. However, our knowledge of how this landscape is set during vertebrate embryogenesis has been limited, due to the lack of methods to jointly detect chromatin modifications and gene expression in the same cell. Here we present a multimodal measurement of full-length transcriptome and chromatin modifications in individual cells during early embryonic development in zebrafish. We show that before the formation of germ layers, the chromatin and transcription states of cells are uncoupled, and become progressively connected during gastrulation and somitogenesis. Silencing of key developmental genes is achieved by local spreading of repressive chromatin as development proceeds. We use a joint analysis of transcription factor (TF) expression and chromatin states to predict lineage-specific activators and repressors and identify a subset of TFs that are themselves epigenetically regulated. Altogether, our data resolves the dynamic relationship between chromatin and transcription during early embryonic development and clarifies how these two layers interact to establish cell identity.
A stolen future – aberrant hippocampal neurogenesis produces glial cells in epilepsy
Authors: Toby Segasby , Roozbeh Sanaei , Natalija Aleksejenko , Omar Mamad , David Henshall , Achilleas Floudas , Janosch Heller
Published: September 2024

Adult hippocampal neurogenesis is disturbed in epilepsy. The increased neuronal activity in the epileptic brain leads to an increased production of newborn cells, increased mossy fibre sprouting and altered integration of new neurons within the hippocampus. Here, we set out to investigate increased astrocyte numbers following status epilepticus. We used immunolabelling of brain sections from the mouse intra-amygdala kainic acid model of epilepsy and publicly available single cell RNA sequencing datasets to assess newborn cells in the dentate gyrus. Similar to published series we found on increased number of reactive astrocytes present in the epileptic hippocampus. Additionally, we identified a cell population that expressed neurogenesis (doublecortin) and astrocyte (glial fibrillary acidic protein) markers in the epileptic brain, both in mouse and in human tissue. We further evaluated the expression profile of these cells. Immunolabelling showed expression of mature astrocyte markers aquaporin 4 and glutamate transporter-1. The single cell RNA sequencing data highlighted expression of neurogenesis and astrocyte markers in the doublecortin/glial fibrillary acidic protein-expressing cells. In conclusion, epilepsy pushes early neuroblasts to fate-switch to an astrocyte lineage as seen in the kainic acid-induced mouse model and in human resected brain tissue. Further understanding how neurogenesis is altered in epilepsy and whether the neuroblast fate-switch can be reverted will help in finding novel therapy strategies for epilepsy and other neurological diseases associated with aberrant adult hippocampal neurogenesis.

Key Messages

Following kainic acid-induced status epilepticus early neuroblasts appear to undergo a fate-switch to an astrocyte lineage. We were able to confirm the presence of cells positive for early neurogenesis and astrocyte markers in human epileptic tissue using scRNAseq data.
From Genes to Pathways: A Curated Gene Approach to Accurate Pathway Reconstruction in Teleost Fish Transcriptomics
Authors: Herrera Marcela , Vianello Stefano , Mitchell Laurie , Chamot Zoé , Lorin-Nebel Catherine , Roux Natacha , Besseau Laurence , Gibert Yann , Laudet Vincent
Published: September 2024

Interpreting the vast amounts of data generated by high-throughput sequencing technologies can often present a significant challenge, particularly for non-model organism. While automated approaches like GO (Gene Ontology) and KEGG (Kyoto Encyclopedia of Genes and Genomes) enrichment analyses are widely used, they often lack specificity for non-model organisms. To bridge this gap, we present a manually curated gene list tailored for teleost fish transcriptomics. This resource focuses on key biological processes crucial for understanding teleost fish physiology, development, and adaptation, including hormone signaling, various metabolic pathways, appetite regulation, digestion, gastrointestinal function, vision, ossification, osmoregulation, and pigmentation. Developed through collaborative efforts of specialists in diverse fields, the list prioritizes genes with established roles in teleost physiology, experimental evidence, and conservation across species. This curated list aims to provide researchers with a reliable starting point for transcriptomic analyses, offering a carefully evaluated set of genes relevant to current research priorities. By streamlining the process of gene selection and interpretation, this resource supports the broader teleost fish research community in designing and analyzing studies that investigate molecular responses to developmental and environmental changes. We encourage the scientific community to collaboratively expand and refine this list, ensuring its continued relevance and utility for teleost fish research.
Ancient biomolecules suggest learned foraging strategy in extinct cave bears
Authors: Meleg Ioana N. , Alberti Federica , Drucker Dorothée G. , Năpăruş-Aljancic Magdalena , Feurdean Angelica , Robu Marius , Vlaicu Marius , Naito Yuichi I. , Boroneanț Adina , Cârciumaru Marin , Nițu Elena C. , Hofreiter Michael , Bocherens Hervé , Barlow Axel
Published: September 2024

Studying the behavioural ecology of long-extinct species is challenging due to the difficulty in measuring the behavioural phenotype and correlating this with genetic and environmental factors. However, a multidisciplinary approach integrating isotope analysis of diet and ancient DNA analysis of genetic relationships offers a potential framework to test the proximate causes of dietary preferences. Our study focuses on Late Pleistocene cave bears from the Romanian Carpathians. Stable isotope analysis of bone collagen reveals substantial lifetime variation in food plant preferences among individuals. We find that bears with similar diets do not cluster according to their population structure, sex, time period, climatic conditions, or location. This disconnect suggests that diet preference in cave bears is not genetically inherited, and instead that individuals adapted their diets based on foraging experience. This integrative approach opens new avenues for understanding Pleistocene animal behaviour, leveraging ancient biomolecules synergistically to reveal insights otherwise inaccessible.
Design of an intracellular aptamer-based fluorescent biosensor to track burden in E. coli
Authors: Grob Alice , Copeman Tom , Chen Sifeng , Elani Yuval , Franco Elisa , Ceroni Francesca
Published: September 2024

Cell burden impacts the performance of engineered synthetic systems. For this reason, there is great interest toward the development of tools to track burden and improve biotechnology applications. Fluorogenic RNA aptamers are excellent candidates for live monitoring of burden because their production is expected to impose a negligible load on transcription resources. Here we characterise the performance of a library of aptamers when expressed from different promoters inE. coli. We find that aptamer relative performance is dependent on the promoter and the strain, and that, contrary to expectation, aptamer expression impacts host fitness. By selecting two of the aptamers with brighter output and lower impact, we then design an intracellular biosensor able to report on the activation of the burden response in engineered cells. The sensor developed here adds to the collection of tools available for burden mitigation and may support bioprocessing applications where improved host performance is sought.