bluuebunny/crossref_metadata_2025 huggingface dataset:
Melatonin protects mice from 5-FU hepatotoxicity and improves 5-FU antitumor effects by an apoptotic pathway dependent on cell cycle arrest in A549 human lung cancer cells
Authors: Elbanan Mona E , Amer Maggie E , El-Missiry Mohamed A , Othman Azza I , Shabana Sameh M
Published: October 2023

Objectives

This study determined if melatonin (MLT) can be used with 5-fluorouracil (5-FU), an anticancer drug as adjuvants to reduce A549 lung cancer cell proliferation and sensitise those cells to 5-FU at lower doses while protecting mice from hepatotoxicity.

Methods

In vitro, MTT assays assessed cell proliferation, and Annexin-V flow cytometry measured A549 cell apoptosis. RT-qPCR measured apoptotic markers tumour suppressor gene P53, KI-67, Bax, Bcl-2, and caspase3; and immunoblotting evaluated cell cycle parameters P21, CDK2, and cyclin E. ELISA biochemical analysis examined liver function, reactive oxygen species (ROS) and antioxidant assays, and inflammatory markers, in vivo. Masson’s trichome, haematoxylin, and eosin stains examined histopathological changes and fibrosis under a microscope.

Key findings

MLT combined with 5-FU elevated chemo-sensitization by decreasing A549 cell proliferation, lowering the IC50, increasing P21, P53, and Bax, decreasing Bcl-2, Ki-67, CDK2, and cyclin E, and inducing apoptosis and cell cycle arrest at G0/G1. After 5-FU [intraperitoneal (IP)]/MLT (oral) co-administration in vivo, all parameters improved and reversed. Liver enzymes (aspartate aminotransferase and alanine transaminase), bilirubin, albumin, total protein, albumin/globulin ratio, ROS, 4-HNE, H2O2, and pro-inflammatory cytokines; IL-6, IL-1β, and TNFα declined while antioxidant enzymes like SOD, CAT, GSH, and GPx, and IL-10 (anti-inflammatory) increased in combined MLT/5-FU treated groups compared with untreated and 5-FU alone treated groups. Histopathology confirmed these results.

Conclusions

MLT protected A549 cells from 5-FU-induced hepatotoxicity and enhanced 5-FU’s antitumor effect in vitro. These results support MLT/5-FU’s benefits, suggesting a more effective lung cancer treatment with fewer hepatotoxicity side effects. That could provide a novel therapeutic strategy for lung cancer.
Complete Genome Sequence Resource for Xanthomonas hortorum Isolated from Greek Oregano
Authors: González-Tobón Juliana , Helmann Tyler C. , Daughtrey Margery , Stodghill Paul V. , Filiatrault Melanie J.
Published: October 2023

In spring 2019, necrotic leaf spots were detected on Greek oregano (Origanum vulgare var. hirtum) plants in a commercial greenhouse operation. An isolate was recovered from the diseased plants. Partial 16S ribosomal RNA sequencing and multilocus sequence analysis revealed that the isolate was a Xanthomonas sp. but proved insufficient to identify the species with certainty. Therefore, whole-genome sequencing using both Nanopore and Illumina technologies was performed. Here, we report the complete and annotated genome sequence of Xanthomonas hortorum strain 108, which was originally isolated from Greek oregano in Long Island, NY, U.S.A.
The Validation of a Simultaneous Ocular and Cervical VEMP Recording Protocol to Unilateral AC Stimuli
Authors: Verrecchia Luca , Jansson Karl-Johan Fredén , Reinfeldt Sabine , Håkansson Bo
Published: October 2023

Introduction

A simultaneous recording of cervical and ocular vestibular evoked myogenic potential (sVEMP) to unilateral air-conducted (AC) stimulation reduces the test time and halves the sound load.

Materials and Methods

The sVEMP has been compared with the conventional sequential unilateral AC cervical and ocular VEMP in a consecutive cohort of 120 subjects attending the vestibular laboratory. The stimulus was a 500-Hz 6-ms tone burst, at 130 dB peSPL for sequential recordings but at 125 dB for the added sVEMP, for cumulative sound load containment. Amplitudes, latencies, and amplitude asymmetry ratios (ARs) were the parameters included in analysis.

Results

Relevant results were as follows: 1) significantly lower amplitudes in sVEMP versus VEMP (ocular recordings, median = 2.90 [IQR = 0–4.98] vs. 4.15 [1.73–8.98] μV, p < 0.001; cervical, 0.84 [0.30–1.69] vs. 1.36 [0.60–2.30], p < 0.001; electromyography scaled values); 2) 10% lower response rate at cervical recordings and 11% at ocular recordings in sVEMP, particularly in older subjects; 3) significant correlations between cervical amplitudes (r
s = 0.88, p < 0.001), ocular amplitudes (r
s = 0.71, p < 0.001), peak latencies (r
s = 0.36–0.67, p < 0.001), and ARs (ocular, r
s = 0.56; cervical, r
s = 68, p < 0.001); and 4) good agreement in pathological AR detection (cervical recordings, Cohen’s κ = 0.649, p < 0.001; ocular, κ = 0.589, p < 0.001).

Discussion

AC sVEMP showed good correlation/agreement with sequential AC VEMP. Test time containment and halved sound load are clinical adds in sVEMP, opening to its use as laboratory standard. However, AC sVEMP presented reduced amplitudes and response rates, secondary to the reduced AC stimulation used in this study to allow checking of the null responses and the pathological ARs at AC sVEMP with conventional AC VEMP.
Causal Role of the Frontal Eye Field in Attention-induced Ocular Dominance Plasticity
Authors: Song Fangxing , Dong Xue , Zhao Jiaxu , Wang Jue , Sang Xiaohui , He Xin , Bao Min
Published: October 2023

Previous research has found that prolonged eye-based attention can bias ocular dominance. If one eye long-termly views a regular movie meanwhile the opposite eye views a backward movie of the same episode, perceptual ocular dominance will shift towards the eye previously viewing the backward movie. Yet it remains unclear whether the role of eye-based attention in this phenomenon is causal or not. To address this issue, the present study relied on both the functional magnetic resonance imaging (fMRI) and transcranial magnetic stimulation (TMS) techniques. We found robust activation of the frontal eye field (FEF) and intraparietal sulcus (IPS) when participants were watching the dichoptic movie while focusing their attention on the regular movie. Interestingly, we found a robust effect of attention-induced ocular dominance shift when the cortical function of vertex or IPS was transiently inhibited by continuous theta burst stimulation (cTBS), yet the effect was significantly attenuated to a negligible extent when cTBS was delivered to FEF. A control experiment verified that the attenuation of ocular dominance shift after inhibitory stimulation of FEF was not due to any impact of the cTBS on the binocular rivalry measurement of ocular dominance. These findings suggest that the fronto-parietal attentional network is involved in controlling eye-based attention in the “dichoptic-backward-movie” adaptation paradigm, and in this network, FEF plays a crucial causal role in generating the attention-induced ocular dominance shift.
TreePPL: A Universal Probabilistic Programming Language for Phylogenetics
Authors: Senderov Viktor , Kudlicka Jan , Lundén Daniel , Palmkvist Viktor , Braga Mariana P. , Granqvist Emma , Çaylak Gizem , Virgoulay Thimothée , Broman David , Ronquist Fredrik
Published: October 2023

We present TreePPL, a universal probabilistic programming language (PPL) designed for probabilistic modeling and inference in phylogenetics. In TreePPL, the model is expressed as a computer program, which can generate simulations from the model conditioned on some input data. Specialized inference machinery then uses this program to estimate the posterior probability distribution. The aim is to allow the user to focus on describing the model, and provide the inference machinery for free. The TreePPL modeling language is meant to be familiar to users of R or Python, and utilizes a functional programming style that facilitates the application of generic inference algorithms. The model program can be conveniently compiled and run from a Python or R environment, which can be used for pre-processing, feeding the model with the observed data, controlling and running the inference, and receiving and post-processing the output data. The inference machinery is generated by a compiler framework developed specifically for supporting domain-specific modeling and inference, the Miking CorePPL framework. It currently supports a range of inference strategies—including sequential Monte Carlo, Markov chain Monte Carlo, and combinations thereof—and is based on several recent innovations that are important for efficient PPL inference on phylogenetic models. It also allows advanced users to implement novel inference strategies for models described using TreePPL or other domain-specific modeling languages. We briefly describe the TreePPL modeling language and the Python environment, and give some examples of modeling and inference with TreePPL. The examples illustrate how TreePPL can be used to address a range of common problem types considered in statistical phylogenetics, from diversification and tree inference to complex trait evolution. A few major challenges remain to be addressed before the phylogenetic model space is adequately covered by efficient automatic inference techniques, but several of them are being addressed in ongoing work on TreePPL. We end the paper by discussing how probabilistic programming can facilitate further use of machine learning in addressing important challenges in statistical phylogenetics.
Cognitive Reserve Against Alzheimer’s Pathology Is Linked to Brain Activity During Memory Formation
Authors: Vockert Niklas , Machts Judith , Kleineidam Luca , Nemali Aditya , Schütze Hartmut , Yakupov Renat , Peters Oliver , Gref Daria , Schneider Luisa Sophie , Preis Lukas , Priller Josef , Spruth Eike Jakob , Altenstein Slawek , Schneider Anja , Fliessbach Klaus , Wiltfang Jens , Rostamzadeh Ayda , Glanz Wenzel , Incesoy Enise I. , Teipel Stefan , Kilimann Ingo , Goerss Doreen , Laske Christoph , Munk Matthias H. , Spottke Annika , Roy Nina , Heneka Michael T. , Brosseron Frederic , Wagner Michael , Wolfsgruber Steffen , Dobisch Laura , Dechent Peter , Hetzer Stefan , Scheffler Klaus , Zeidman Peter , Stern Yaakov , H.Schott Björn , Jessen Frank , Düzel Emrah , Maass Anne , Ziegler Gabriel ,   the DELCODE study group
Published: October 2023

The cognitive reserve (CR) hypothesis posits that individuals can differ in how their brain function is disrupted by pathology associated with aging and neurodegeneration. Here, we tested this hypothesis in the Alzheimer’s disease continuum using longitudinal data from 490 participants of the DELCODE multicentric observational study. Brain function was measured using task fMRI of visual memory encoding. Using a multivariate moderation analysis we identified a CR-related activity pattern underlying successful memory encoding that moderated the detrimental effect of AD pathological load on cognitive performance. CR was mainly represented by a more pronounced expression of the task-active network encompassing the default mode network (DMN), anterior cingulate cortex (ACC) and inferior temporal regions including the fusiform gyrus. We devised personalized fMRI-based CR scores that moderated the impact of AD pathology on cognitive performance and were positively associated with years of education. Furthermore, higher CR scores were associated with slower cognitive decline over time. Our findings suggest maintenance of core cognitive circuits including the DMN and ACC as the primary mechanism of CR. Individual brain activity levels of these areas during memory encoding have prognostic value for future cognitive decline.
CytoPipeline & CytoPipelineGUI: A Bioconductor R package suite for building and visualizing automated pre-processing pipelines for flow cytometry data
Authors: Hauchamps Philippe , Bayat Babak , Delandre Simon , Hamrouni Mehdi , Toussaint Marie , Temmerman Stéphane , Lin Dan , Gatto Laurent
Published: October 2023

Background

With the increase of the dimensionality in flow cytometry data over the past years, there is a growing need to replace or complement traditional manual analysis (i.e. iterative 2D gating) with automated data analysis pipelines. A crucial part of these pipelines consists of pre-processing and applying quality control filtering to the raw data, in order to use high quality events in the downstream analyses. This part can in turn be split into a number of elementary steps : signal compensation or unmixing, scale transformation, debris, doublets and dead cells removal, batch effect correction, etc. However, assembling and assessing the pre-processing part can be challenging for a number of reasons. First, each of the involved elementary steps can be implemented using various methods and R packages. Second, the order of the steps can have an impact on the downstream analysis results. Finally, each method typically comes with its specific, non standardized diagnostic and visualizations, making objective comparison difficult for the end user.

Results

Here, we presentCytoPipelineandCytoPipelineGUI, twoRpackages to build, compare and assess pre-processing pipelines for flow cytometry data. To exemplify these new tools, we present the steps involved in designing a pre-processing pipeline on a real life dataset and demonstrate different visual assessment use cases. We also set up a benchmarking comparing two pre-processing pipelines differing by their quality control methods, and show how the package visualization utilities can provide crucial user insight into the obtained benchmark metrics.

Conclusion

CytoPipelineandCytoPipelineGUIare two BioconductorRpackages that help building, visualizing and assessing pre-processing pipelines for flow cytometry data. They increase productivity during pipeline development and testing, and complement benchmarking tools, by providing user intuitive insight into benchmarking results.
Biological aging of two innate behaviors ofDrosophila melanogaster: escape climbing versus courtship learning and memory
Authors: Thiem Jessica , Viskadourou Maria , Gaitanidis Alexandros , Stravopodis Dimitrios J , Strauß Roland , Duch Carsten , Consoulas Christos
Published: October 2023

Motor and cognitive aging can severely affect life quality of elderly people and burden health care systems. In search for diagnostic behavioral biomarkers, it has been suggested that walking speed can predict forms of cognitive decline, but in humans, it remains challenging to separate the effects of biological aging and lifestyle. We examined a possible association of motor and cognitive decline in Drosophila, a genetic model organism of healthy aging. Long term courtship memory is present in young flies but absent already during mid life (4-8 weeks). By contrast, courtship learning index and short term memory (STM) are surprisingly robust and remain stable through mid (4-8 weeks) and healthy late life (>8 weeks), until courtship performance collapses suddenly at ∼4.5 days prior to death. By contrast, climbing speed declines gradually during late life (>8 weeks). The collapse of courtship performance and short term memory close to the end of life are not related to the gradual late life decline in climbing speed. Thus, during healthy aging in Drosophila, climbing and courtship motor behaviors decline differentially, unlikely share a common cause, and motor and cognitive performance decline are not closely associated to each other.
Programmable delivery of fluoxetine via wearable bioelectronics for wound healing in vivo
Authors: Li Houpu , Yang Hsin-ya , Asefifeyzabadi Narges , Baniya Prabhat , Lopez Andrea Medina , Gallegos Anthony , Zhu Kan , Hsieh Hao-Chieh , Nguyen Tiffany , Hernandez Cristian , Zlobina Ksenia , Recendez Cynthia , Tebyani Maryam , Carrión Héctor , Selberg John , Luo Le , Alhamo Moyasar A. , Soulika Athena M. , Levin Michael , Norouzi Narges , Gomez Marcella , Zhao Min , Teodorescu Mircea , Isseroff Roslyn Rivkah , Rolandi Marco
Published: October 2023

The ability to deliver drugs with precise dosages at specific time points can significantly improve disease treatment while reducing side effects. Drug encapsulation for gradual delivery has opened up the doors for superior treatment regimen. To expand on this ability, programming bioelectronic devices to deliver small molecules enables ad-hoc personalized therapeutic profiles that are more complex than simple gradual release. Here, we introduce a wearable bioelectronic bandage with an integrated electrophoretic ion pump that affords on-demand drug delivery with precise dose control. Delivery of fluoxetine to wounds in mice resulted in a 27.2% decrease in the macrophage ratio (M1/M2) and a 39.9% increase in re-epithelialization, indicating a shorter inflammatory phase and faster overall healing. Programmable drug delivery using wearable bioelectronics in wounds introduces a broadly applicable strategy for the long-term delivery of a prescribed treatment regimen with minimal external intervention.
Highly biased agonism for GPCR ligands via nanobody tethering
Authors: Sachdev Shivani , Creemer Brendan A. , Gardella Thomas J. , Cheloha Ross W.
Published: October 2023

Ligand-induced activation of G protein-coupled receptors (GPCRs) can initiate signaling through multiple distinct pathways with differing biological and physiological outcomes. There is intense interest in understanding how variation in GPCR ligand structure can be used to promote pathway selective signaling (“biased agonism”) with the goal of promoting desirable responses and avoiding deleterious side effects. Here we present a new approach in which a conventional peptide ligand for the type 1 parathyroid hormone receptor (PTHR1) is converted from an agonist which induces signaling through all relevant pathways to a compound that is highly selective for a single pathway. This is achieved not through variation in the core structure of the agonist, but rather by linking it to a nanobody tethering agent that binds with high affinity to a separate site on the receptor not involved in signal transduction. The resulting conjugate represents the most biased agonist of PTHR1 reported to date. This approach holds promise for facile generation of pathway selective ligands for other GPCRs.
Identification of a novel SNP in the miR172 binding site ofQhomoeologAP2L-D5is associated with spike compactness and agronomic traits in wheat (Triticum aestivumL.)
Authors: Zeng Victoria , Uauy Cristobal , Chen Yi
Published: October 2023

Spike architecture is a key determinant of wheat yield, a crop which supports much of the human diet but whose yield gains are stagnating. Spike architecture mutants offer opportunities to identify genetic factors contributing to inflorescence development. Here, we investigate the locus underlying the compact spike phenotype of mutant line ANK-15 by conducting mRNA-sequencing and genetic mapping using ANK-15 and its non-compact spike near-isogenic line Novosibirskaya 67 (N67). Previous literature has placed the compact spike locus of ANK-15 to chromosome 2B. However, based on the single nucleotide polymorphisms (SNPs) identified using mRNA-seq data, we were unable to detect polymorphisms between N67 and ANK-15 in the putative chromosome 2B region. We performed differential expression analysis of developing rachis and found thatAP2L-D5, theDhomoeolog of the domesticationQgene, is upregulated in ANK-15 in comparison to N67. ANK-15 carries a SNP in the microRNA172 binding site ofAP2L-D5, which is predicted to lead to higher expression ofAP2L-D5due to decreased miRNA172-mediated degradation. Furthermore, we performed genetic mapping using an ANK-15 × N67 F2population and found a single quantitative trait locus on chromosome 5D coinciding with the position ofAP2L-D5. This result suggests thatAP2L-D5is likely the underlying causal gene for the compact spike phenotype in ANK-15. We performed a field trial to investigate the effect of theAP2L-D5allele on agronomic traits and found that theAP2L-D5allele from ANK-15 is associated with a significant reduction in height, increased thousand grain weight (TGW), and increased grain width.
Uncover spatially informed shared variations for single-cell spatial transcriptomics with STew
Authors: Guo Nanxi , Vargas Juan , Fritz Douglas , Krishna Revanth , Zhang Fan
Published: October 2023

Motivation

The recent spatial transcriptomics (ST) technologies have enabled characterization of gene expression patterns and spatial information, advancing our understanding of cell lineages within diseased tissues. Several analytical approaches have been proposed for ST data, but effectively utilizing spatial information to unveil the shared variation with gene expression remains a challenge.

Results

We introduce STew, a Spatial Transcriptomic multi-viEW representative learning method, to jointly analyze spatial information and gene expression in a scalable manner, followed by a data-driven statistical framework to measure the goodness of model fit. Through benchmarking using Human DLPFC data with true manual annotations, STew achieved superior performance in both clustering accuracy and continuity of identified spatial domains compared with other methods. STew is also robust to generate consistent results insensitive to model parameters, including sparsity constraints. We next applied STew to various ST data acquired from 10x Visium and Slide-seqV2, encompassing samples from both mouse and human brain, which revealed spatially informed cell type clusters. We further identified a pro-inflammatory fibroblast spatial niche using ST data from psoriatic skins. Hence, STew is a generalized method to identify both spatially informed clusters and disease-relevant niches in complex tissues.

Availability

Source code and the R software tool STew are available fromgithub.com/fanzhanglab/STew.

Contact

fan.3.zhang@cuanschutz.edu

Supplementary information

Supplementary data are provided.
Multiomics-assisted characterization of rice-Yellow Stem Borer interaction provides genomic and mechanistic insights into stem borer tolerance in rice
Authors: Gokulan C. G. , Bangale Umakanth , Balija Vishalakshi , Ballichatla Suneel , Potupureddi Gopi , Rao Deepti , Varma Prashanth , Magar Nakul , Karteek J. , Sravan M. , Padmakumari A. P. , Laha Gouri S , Rao LV Subba , Barbadikar Kalyani M. , Raman Meenakshi Sundaram , Patel Hitendra K. , Madhav M Sheshu , Sonti Ramesh V.
Published: October 2023

Yellow stem borer (YSB),Scirpophaga incertulas(Walker) (Lepidoptera: Crambidae), is a major pest of rice in India, that can lead to 20-60% loss in rice production. Effective management of YSB infestation is challenged by the non-availability of adequate source of resistance and poor understanding of resistance mechanisms, thus necessitating studies for generating resources to breed YSB resistant rice and to understand rice-YSB interaction. In this study, by using bulk-segregant analysis in combination with next-generation sequencing, Quantitative Trait Loci (QTL) intervals in five rice chromosomes were mapped that could be associated with YSB tolerance at vegetative phase in a highly tolerant rice line named SM92. Further, multiple SNP markers that showed significant association with YSB tolerance in rice chromosomes 1, 5, 10, and 12 were developed. RNA-sequencing of the susceptible and tolerant lines revealed multiple genes present in the candidate QTL intervals to be differentially regulated upon YSB infestation. Comparative transcriptome analysis revealed a putative candidate gene that was predicted to encode an alpha-amylase inhibitor. Analysis of the transcriptome and metabolite profiles further revealed a possible link between phenylpropanoid metabolism and YSB tolerance. Taken together, our study provides insights on rice-YSB interaction at genomic, transcriptomic and metabolomic level, thereby facilitating the understanding of tolerance mechanism. Importantly, a promising breeding line and markers for YSB tolerance have been developed that can potentially aid in marker-assisted breeding of YSB resistance among elite rice cultivars.

SIGNIFICANCE STATEMENT

Global rice production is threatened by various pests, among which stem borers pose serious challenges. Hence, understanding the molecular intricacies of rice-stem borer interaction is necessary for effective pest management. Here, we used a multi-omics approach to unravel the mechanisms that might help rice combat yellow stem borer infestation, thus providing insights and scope for developing YSB tolerant rice varieties. To facilitate the latter, we developed markers that co-segregate with tolerance.
MurSS: Multi-resolution Selective Segmentation Model for Breast Cancer
Authors: Lee Joonho , Lee Geongyu , Kwak Tae-Young , Kim Sunwoo , Jin Min-Sun , Kim Chungyeul , Chang Hyeyoon
Published: October 2023

We propose the Multi-resolution Selective Segmentation model (MurSS) for segmenting benign, Ductal Carcinoma In Situ, and Invasive Ductal Carcinoma in breast resection Hematoxylin and Eosin stained Whole Slide Images. MurSS simultaneously trains on context information from a wide area at low resolution and content information from a local area at high resolution, aiming for a more accurate diagnosis. Additionally, through the selection stage, it provides solutions for ambiguous tissue regions. Our proposed MurSS achieves a mean Intersection of Union performance of 91.1%, which is at least 16.8% and at most 19.0% higher than well-known image segmentation models.
ViCEKb: Vitiligo-linked Chemical Exposome Knowledgebase
Authors: Chivukula Nikhil , Ramesh Kundhanathan , Subbaroyan Ajay , Sahoo Ajaya Kumar , Dhanakoti Gokul Balaji , Ravichandran Janani , Samal Areejit
Published: October 2023

Vitiligo is a complex disease wherein the environmental factors, in conjuction with the underlying genetic predispositions, trigger the autoimmune destruction of melanocytes, ultimately leading to depigmented patches on the skin. Apart from being susceptible to other autoimmune disorders, the affected patients may face social stigmatization leading to a decreased quality in life. While genetic factors have been extensively studied, the knowledge on environmental triggers remains sparse and less understood. Therefore, a comprehensive understanding of the environemental triggers will not only explain the complex etiology of the disease, it will also enable the prioritization of potential toxic chemicals in human chemcical exposome. Towards this, we present the first comprehensive knowledgbase of vitiligo triggering chemicals compiled from published literature namely, Vitiligo-linked Chemical Exposome Knowledgbase (ViCEKb). ViCEKb involved an extensive and systematic manual effort in curation of published literature and subsequent compilation of 113 unique chemical triggers of vitiligo. ViCEKb standardises various chemical information, and categorizes the chemicals based on their evidences and sources of exposure. Importantly, ViCEKb contains a wide range of metrics necessary for different toxicological evaluations. Moreover, our extensive cheminformatics-based analysis of the ViCEKb chemical space highlighted its diversity and uniqueness in comparison to other skin specific chemical regulatory lists. We also observed that ViCEKb chemicals are present in various consumer products and are not regulated. Additionally, a transcriptomics based analysis of ViCEKb chemical perturbations in skin cell samples highlighted the commonality in their linked biological processes. Overall, we present the first comprehensive effort in compilation and exploration of various chemical triggers of vitiligo. We believe such a resource will enable in deciphering the complex etiology of vitiligo and aid in the characterization of human chemical exposome. ViCEKb is freely available for academic research at:https://cb.imsc.res.in/vicekb.
Effects of habitat and fruit scent on the interactions between short-tailed fruit bats andPiperplants
Authors: Sil Sneha , Visconti Flo , Chaverri Gloriana , Santana Sharlene E.
Published: October 2023

Piperis a mega-diverse genus of pioneer plants that contributes to the maintenance and regeneration of tropical forests. With deforestation and climate change threatening forest ecosystems, understanding the mutualism betweenPiperand its seed dispersers becomes especially important. In the Neotropics,Carolliabats use olfaction to forage forPiperfruit and are a main disperser ofPiperseeds via consumption and subsequent defecation during flight. In return,Piperfruits provide essential nutrients forCarolliayear-round. There is evidence that the types and diversity ofPiperfrugivores are influenced by the primary habitat of differentPiperspecies (forest, gap), with forestPiperdepending more on bats for seed dispersal; however, this pattern has not been tested broadly. We aimed to characterize and compare the interactions betweenCarolliaandPiperacross forested and gap habitats, and further investigate whether differences in fruit traits relevant to bat foraging (i.e., scent) could underlie differences inCarollia-Piperinteractions. We collected nightly acoustic ultrasonic recordings and 24h camera trap data in La Selva, Costa Rica across 12 species ofPiper(6 forest, 6 gap) and integrated this information with data onCarolliadiet andPiperfruit scent. Merging biomonitoring modalities allowed us to characterize ecological interactions in a hierarchical manner: from general activity and presence of bats, to visitations and inspections of plants, to acquisition and consumption of fruits. We found significant differences inCarollia-Piperinteractions between forested and gap habitats; however, the type of biomonitoring modality (camera trap, acoustics, diet) influenced our ability to detect these differences. ForestPiperwere exclusively visited by bats, whereas gapPiperhad a more diverse suite of frugivores; the annual diet ofCarollia, however, is dominated by gapPipersince these plants produce fruit year-round. We found evidence that fruit scent composition significantly differs between forest and gapPiper, which highlights the possibility that bats could be using chemical cues to differentially forage for gap versus forestPiper. By integrating studies ofPiperfruit scent, plant visitation patterns, andCarolliadiet composition, we paint a clearer picture of the ecological interactions betweenPiperandCarollia, and plant-animal mutualisms more generally.
vcfpp: a C++ API for rapid processing of the Variant Call Format
Authors: Li Zilong
Published: October 2023

Given the widespread use of the variant call format (VCF/BCF) coupled with continuous surge in big data, there remains a perpetual demand for fast and flexible methods to manipulate these comprehensive formats across various programming languages. Many bioinformatic tools were developed in C++ to ensure high performance and modern C++ standards offer an ever expanding libraries to ease program development. This work presents vcfpp, a C++ API of HTSlib in a single file, providing an intuitive interface to manipulate VCF/BCF files rapidly and safely, in addition to being portable. Moreover, this work introduces the vcfppR package to demonstrate the development of a high performance R package with vcfpp, allowing for rapid and straightforward variants analyses. In the benchmarking, with the compressed VCF of 3202 samples and one million variants as input, the dynamic script using vcfppR is only 1.3×slower than its compiled C++ counterpart vcfpp, whereas the Python API cyvcf2 is 1.9×slower when streaming a variant analysis with little memory. Lastly, in a two-step setting where the whole VCF content is loaded first, vcfppR demonstrates a 101×speed improvement over vcfR and even more folds than data.table in processing genotypes.
Pan-cancer evolution signatures link clonal expansion to dynamic changes in the tumour immune microenvironment
Authors: Yang Xinyu , Liu Wei , Macintyre Geoff , Van Loo Peter , Markowetz Florian , Bailey Peter , Yuan Ke
Published: October 2023

Cancer is an evolutionary process characterised by profound intra-tumour heterogeneity. Intra-tumour heterogeneity can be quantified using in silico estimates of cancer cell fractions of tumour-specific somatic mutations. Here we demonstrate a data-driven approach that uses cancer cell fraction distributions to identify 4 robust pan-cancer evolutionary signatures from an analysis of 4,146 individual tumour samples (TCGA) representing 17 distinct cancer types. Evolutionary signatures defined a continuum of cancer cell fractions representing neutral evolution, clonal expansion and fixation. Correlation of evolutionary signatures with programs representing distinct mutational and biological processes demonstrated that individual tumours enriched for clonal expansions and fixations were associated with immune evasion and distinct changes in the tumour immune microenvironment. We observed a dynamic switch between adaptive and innate immune processes as tumours undergo clonal fixation and escape immune surveillance. We also identify mutational processes underpinning different modes of tumour evolution and demonstrate that switching between adaptive and innate immune cell populations is accompanied by the clonal expansion of driver genes that modulate tumour-stroma interactions1.
Manganese homeostasis modulates fungal virulence and stress tolerance inCandida albicans
Authors: Henry Manon , Khemiri Inès , Tebbji Faiza , Abu-Helu Rasmi , Vincent Antony T , Sellam Adnane
Published: October 2023

Due to the scarcity of transition metals within the human host, fungal pathogens have evolved sophisticated mechanisms to uptake and utilize these micronutrients at the infection interface. While considerable attention was turned to iron and copper acquisition mechanisms and their importance in fungal fitness, less was done regarding either the role of manganese (Mn) in infectious processes or the cellular mechanism by which fungal cells achieve their Mn- homeostasis. Here, we undertook transcriptional profiling in the pathogenic fungusCandida albicansexperiencing both Mn starvation and excess to capture biological processes that are modulated by this metal. We uncovered that Mn scarcity influences diverse processes associated with fungal fitness including invasion of host cells and antifungal sensitivity. We show that Mn levels influence the abundance of iron and zinc emphasizing the complex crosstalk between metals. Deletion ofSMF12, a member of Mn Nramp transporters confirmed its contribution to Mn uptake.smf12was unable to form hyphae and damage host cells and exhibited sensitivity to azoles. We found that the unfolded protein response (UPR), likely activated by decreased glycosylation under Mn limitation, was required to restore growth when cells were shifted from a Mn-starved to a Mn-repleted medium. RNA-seq profiling of cells exposed to Mn excess revealed that UPR was also activated. Furthermore, the UPR signaling axis Ire1-Hac1 was required to bypass Mn toxicity. Collectively, this study underscores the importance of Mn homeostasis in fungal virulence, and comprehensively provides a portrait of biological functions that are modulated by Mn in a fungal pathogen.
Epigenetic differences between wild and cultivated grapevines highlight the contribution of DNA methylation during crop domestication
Authors: Rodriguez-Izquierdo Alberto , Carrasco David , Anand Lakshay , Magnani Roberta , Catarecha Pablo , Arroyo-Garcia Rosa , Rodriguez Lopez Carlos M.
Published: October 2023

The domestication process in grapevine facilitated the fixation of desired traits. The vegetative propagation of grapevines through cuttings has allowed for easier preservation of these genotypes compared to sexual reproduction. Nonetheless, even with vegetative propagation, different phenotypes often emerge within the same vineyard due to potential genetic somatic mutations in the genome. These mutations, however, are not the sole factors influencing phenotype. Alongside somatic variations, epigenetic variation has been proposed as pivotal player in regulating phenotypic variability acquired during domestication. The emergence of these epialleles might have significantly influenced grapevine domestication over time. This study aims to investigate the impact of the domestication process on the methylation patterns in cultivated grapevines. Reduced-representation bisulphite sequencing was conducted on 18 cultivated and wild accessions. Results revealed that cultivated grapevines exhibited higher methylation levels than their wild counterparts. Differential Methylation Analysis between wild and cultivated grapevines identified a total of 9955 differentially methylated cytosines, of which 78% where hypermethylated in cultivated grapevines. Functional analysis shows that core methylated genes (those consistently methylated in wild and cultivated accessions) are associated to stress response and terpenoid/isoprenoid metabolic processes. While genes presenting differential methylation are associated with proteins targeting to the peroxisome, ethylene regulation, histone modifications, and defense response. Additionally, our findings reveal that environmentally induced DNA methylation patterns are, at least partially, guided by the region of origin of wild grapevine accessions. Collectively, our results shed light on the pivotal roles that epialleles might have played throughout the domestication history of grapevines.
Engineered dsRNA-protein nanoparticles for effective long-distance transport, delivery and gene silencing in plants
Authors: Sun Huayu , Kalluri Ankarao , Tang Dan , Ding Jingwen , Zhai Longmei , Gu Xianbin , Li Yanjun , Yer Huseyin , Yang Xiaohan , Tuskan Gerald A. , Deng Zhanao , Gmitter Frederick G. , Duan Hui , Kumar Challa , Li Yi
Published: October 2023

Long-distance transport of exogenous biologically active RNA molecules in higher plants has not been reported. Here, we report that cationized bovine serum albumin (cBSA) avidly binds double-stranded beta-glucuronidase RNA (dsGUS RNA) to form nucleic acid-protein nanocomplexes. Using tobacco and poplar plants, we have shown effective uptake and long-distance transport of cBSA/dsGUS RNA nanocomplexes from basal ends of leaf petioles to leaf blades as well as from basal ends of shoots to their apexes and apical leaves. We have further demonstrated that the cBSA/dsGUS RNA nanocomplexes are highly effective in silencing both conditionally inducibleDR5-GUSgene and constitutively active35S-GUSgene in leaf, shoot and shoot meristem tissues. This cBSA/dsRNA delivery technology may provide a convenient, fast, and inexpensive tool for characterizing gene functions in plants, and potentially forin plantagene-editing.
EWA-DB, Slovak Database of Speech Affected by Neurodegenerative Diseases
Authors: Rusko Milan , Sabo Róbert , Trnka Marián , Zimmermann Alfréd , Malaschitz Richard , Ružický Eugen , Brandoburová Petra , Kevická Viktória , Škorvánek Matej
Published: October 2023

A new Slovak speech database EWA-DB was created for research purposes aimed at early detection of neurodegenerative diseases from speech. It contains 1649 speakers performing various speech and language tasks, such as sustained vowel phonation, diadochokinesis, naming and picture description. The sample of speakers consists of individuals with Alzheimer’s disease, mild cognitive impairment, Parkinson’s disease, and healthy controls. In this article we describe the EWA-DB development process, the language and speech task selection, patient and healthy control recruitment, as well as the testing and recording protocol. The structure and content of the database and file formats are described in detail. We assume that the presented database could be suitable for the development of automatic systems predicting the diagnoses of Alzheimer’s disease, mild cognitive impairment, and Parkinson’s disease from language and speech features.
Connectivity changes following transcranial alternating current stimulation at 5-Hz: an EEG study
Authors: Lee Tien-Wen , Li Chiang-Shan R. , Tramontano Gerald
Published: October 2023

Introduction

Transcranial alternating current stimulation (tACS) at 5-Hz to the right hemisphere can alleviate anxiety symptoms. This study aimed to explore the connectivity changes following the treatment.

Methods

We collected electroencephalography (EEG) data from 24 participants with anxiety disorders before and after the tACS treatment during a single session. Electric stimulation was applied over the right hemisphere, with 1.0 mA at F4, 1.0 mA at P4, and 2.0 mA at T8, following the 10-10 EEG convention. With eLORETA, the scalp signals were transformed into the cortex’s current source density. We assessed the connectivity changes at theta frequency between the centers of Brodmann area (BA) 6/8 (frontal), BA 39/40 (parietal), and BA 21 (middle temporal). Functional connectivity was indicated by lagged coherences and lagged phase synchronization. Paired t-tests were used to quantify the differences statistically.

Results

We observed enhanced lagged phase synchronization at theta frequency between the frontal and parietal regions and between the parietal and temporal regions.

Conclusion

Applying tACS 5-Hz over the right hemisphere enhanced inter-regional interaction, which was spectrum-specific and mainly mediated by phase, rather than power, synchrony. The potential neural mechanisms are discussed.
N6-methyladenosine modification is not a general trait of viral RNA genomes
Authors: Baquero-Perez Belinda , Yonchev Ivaylo D , Delgado-Tejedor Anna , Medina Rebeca , Puig-Torrents Mireia , Sudbery Ian , Begik Oguzhan , Wilson Stuart A , Maria Novoa Eva , Díez Juana
Published: October 2023

Despite the nuclear localization of the m6A machinery, the genomes of multiple exclusively-cytoplasmic RNA viruses, such as chikungunya (CHIKV) and dengue (DENV), are reported to be extensively m6A-modified. However, these findings are mostly based on m6A-seq, an antibody-dependent technique with a high rate of false positives. Here, we addressed the presence of m6A in CHIKV and DENV RNAs. For this, we combined m6A-seq and the antibody-independent SELECT and nanopore direct RNA sequencing techniques with functional, molecular, and mutagenesis studies. Following this comprehensive analysis, we found no evidence of m6A modification in CHIKV or DENV transcripts. Furthermore, depletion of key components of the host m6A machinery did not affect CHIKV or DENV infection. Moreover, CHIKV or DENV infection had no effect on the m6A machinery’s localization. Our results challenge the prevailing notion that m6A modification is a general feature of cytoplasmic RNA viruses and underscore the importance of validating RNA modifications with orthogonal approaches.
MDMD: a computational model for predicting drug-related microbes based on the aggregated metapaths from a heterogeneous network
Authors: Xing Jiajie , Zhang Xianguo , Wang Juan
Published: October 2023

Clinical studies have shown that microbes are closely related to the occurrence of diseases in the human body. It is beneficial for treating diseases by means of microbes to modulate the activity and toxicity of drugs. Therefore, it is significant in predicting associations between drugs and microbes. Recently, there are several computational models for addressing the issue. However, most of them only focus on drug-related microbes and neglect related diseases, which can lead to insufficient training. Here we introduce a new model (called MDMD) is proposed to predict drug-related microbes based on the Metapaths from a heterogeneous network constructed by using the data of Diseases, Microbes, Drugs, the associations of microbe-disease and disease-drug. The MDMD uses an aggregation of the metapath features that can effectively abundance the embedding of the features for different types of nodes and edges in the heterogeneous networks. Then, the MDMD uses the attention mechanism to mark the importance of the metapath vector for each node type which can improve the quality of feature embedding. Experimental results demonstrate that the MDMD improves accuracy by 1.9% compared with other models. The MDMD is also used to predict the microbes of two drugs Lamivudine and Tenofovir which are the antiretroviral drugs used to treat the Acquired Immune Deficiency Syndrome(AIDS). The results show that 90-95% of microbes are reported in the PubMed. Mycobacterium tuberculosis(Mtb) is a specific microbe only predicted by the MDMD. An online platform of the MDMD is available inhttps://mdmd2023.bit1024.top/, in which the source code of the MDMD and the data in the work can be downloaded.

Author summary

Microbes inhabit multiple organs of the human body that consist of bacteria, fungi, and viruses. Extensive research shows that the microbes can adjust the efficacy and toxicity of drugs to treat the disease. The efficient and accurate selection of drug-related microbes is important for drug research and disease treatment. However, screening of drug-related microbes relies on traditional lab experiments that are labor-intensive and costly. With the growth of high-throughput data, the research of drug-related microbes urgently needs a computational method in bioinformatics. However, most of them only focus on drug-related microbes and neglect related diseases, which can lead to insufficient training. Therefore, we propose a new method (called MDMD) based on the aggregation of the metapath to efficiently and accurately predict potential drug-related microbes within the microbes-disease-drug network.
Antiviral and Antibacterial Efficacy of Nanocomposite Amorphous Carbon Films with Copper Nanoparticles
Authors: Bakhet Shahd , Tamulevičienė Asta , Vasiliauskas Andrius , Andrulevičius Mindaugas , Meškinis Šarūnas , Tamulevičius Sigitas , Kašėtienė Neringa , Malakauskas Mindaugas , Lelešius Raimundas , Zienius Dainius , Šalomskas Algirdas , Šmits Krišjānis , Tamulevičius Tomas
Published: October 2023

Copper compound-rich films and coatings are effective against widespread viruses and bacteria. Even though the killing mechanisms are still debated it is agreed that the metal ion, nanoparticle release, and surface effects are of paramount importance in the antiviral and antibacterial efficacy of the surfaces. In this work we have investigated the behaviour of the reactive magnetron sputtered nanocomposite diamond-like carbon thin films with copper nanoparticles (DLC:Cu). The films were etched employing oxygen plasma and/or exposed to ultra-pure water aiming to investigate the differences of the Cu release in the medium and changes in film morphology. The presence of metallic copper and Cu2O phases were confirmed by multiple analytical methods. Pristine films were more effective in the Cu release reaching up to 1.3 mg/L/cm2concentration. Plasma processing resulted in the oxidation of the films which released less Cu but after exposure to water, their average roughness increased more, up to 5.5 nm. Pristine and O2plasma processed DLC:Cu films were effective against both model coronavirus and herpesvirus after 1-hour contact time and reached virus reduction up to 2.23 and 1.63 log10, respectively. Pristine DLC:Cu films were more effective than plasma-processed ones against herpesvirus, while less expressed difference was found for coronavirus. The virucidal efficacy over up to 24 h exposures in the aqueous medium was validated. A bactericidal study confirmed that pristine DLC:Cu films were effective against gram-negativeE. coliand gram-positiveE. faecalisbacteria. After 3 hours 100% antibacterial efficiency (ABE) was obtained forE. coliand 99.97% forE. faecalis. After 8 hours and longer exposures, 100% ABE was reached. The half-life inactivation of viruses was 8.10 – 11.08 minutes and forE. faecalis15.1 – 72.2 minutes.