bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mitigating Chemotherapy Side Effects through Targeted Gamma-Ray Delivery and Convolutional Neural Networks: A Step Toward Precision Oncology
Authors: Siddiqui Seher , ElDeen Shahd El-Sayed Shehab 
Published: November 2024

AbstractThe systemic nature of chemotherapy results in widespread side effects that severely impact patients’ quality of life. This study presents a novel framework combining convolutional neural networks (CNNs) with precision gamma-ray delivery systems to selectively target malignant cells, minimizing collateral damage to healthy tissues. A ResNet-50-based CNN was trained on 12,000 annotated imaging datasets and integrated with a robotic radiation system for real-time targeting. Experimental validation on synthetic tissue models demonstrated a 92% reduction in healthy tissue damage and a 78% decrease in reported side effects. Statistical analyses confirmed model sensitivity (97.2%), specificity (94.8%), and improved treatment accuracy. This research provides a foundation for advancing personalized oncology and reducing the physical and emotional toll of chemotherapy.
Drivers of diversity within and between microbial communities during stochastic assembly
Authors: Marrec Loïc , Bank Claudia 
Published: November 2024

AbstractNo two microbial communities share the same species richness and abundance. Experiments have shown that the assembly of new microbial communities from the same environmental pool is sufficient to generate diversity within and between communities. To identify the mechanisms behind these experimental results, we build a stochastic model that considers both the dispersal of microbes from a pool to communities and microbial division. By analyzing timescales, we identify distinct assembly regimes. Specifically, if dispersal is slower than division, microbial communities show low diversity within communities but high diversity between communities. Conversely, if dispersal is faster than division, microbial communities exhibit high diversity within communities but low diversity between them. We validate these predictions both numerically, using Gillespie simulations, and analytically, by deriving equations for species richness and abundance distributions. Our derivations pinpoint two key metrics, the bimodality coefficient and mean relative abundance, which identify the assembly regime and quantify trait differences. We apply these metrics to reanalyze an experimental data set, demonstrating their practical application. Overall, our study provides general predictions on how stochasticity, timescales, and traits impact diversity within and between communities during the assembly of new microbial communities, allowing for a better understanding of variation in microbiome formation.
Morphological and molecular effects of short-term water deficiency in barley stamen maturation
Authors: Lange Richard , Zhang Youjun , Fernie Alisdair R. , Acosta Iván F. 
Published: November 2024

ABSTRACTWater deficiency at the reproductive stage of cereal crops mainly affects the development or function of male organs, which causes strong losses in grain yield. We investigated the effects of short-term drought on the post-meiotic maturation of stamens in barley cultivar Scarlett, where it leads to a stage-dependent decline in fertility. Water deficiency neither affects pollen viability nor the formation of trinuclear pollen. However, it completely blocks pollen starch accumulation. Metabolite profiling suggests that this is due to decreased sugar content at starch-filling stages, probably reflecting impaired carbon supply from photosynthetic tissues to anther sinks. Accordingly, transcriptomic analysis shows that drought reduces the expression of stamen sugar transporters. Moreover, drought causes a strong downregulation of the pollen transcriptional network of auxin signalling and central carbon metabolism genes that controls barley pollen starch production. This wider model of the molecular effects of water deficiency on cereal pollen provides a solid foundation to characterize tolerance mechanisms in potential drought-resistant germplasm.
A single high-zinc activation enhancer can control two genes oriented head-to-head inC. elegans
Authors: Liu Hanwenheng , Earley Brian , Mendoza Adelita , Hunt Patrick , Teng Sean , Schneider Daniel L. , Kornfeld Kerry 
Published: November 2024

AbstractEnhancers play critical roles in gene expression, but a full understanding of their complex functions has yet to be defined. The cellular response to excess zinc levels inC. elegansrequires the HIZR-1 transcription factor, which binds the high-zinc activation (HZA) enhancer in the promoters of multiple target genes. Cadmium hijacks the excess zinc response by binding and activating HIZR-1. By analyzing the genome-wide transcriptional response to excess zinc and cadmium, we identified two positions in the genome where head-to-head oriented genes are both induced by metals. In both examples, a single predicted HZA enhancer is positioned between the two translational start sites. We hypothesized that a single enhancer can control both head-to- head genes, an arrangement that has not been extensively characterized. To test this hypothesis, we used CRISPR genome editing to precisely delete the HZAmTenhancer positioned betweenmtl-2andT08G5.1, and the HZAcFenhancer positioned betweencdr-1andF35E8.10. In both examples, deleting the enhancer caused both head-to-head genes to lose metal-activated transcription, whereas the induction of more distant genes was not strongly affected. These studies rigorously document that a single HZA enhancer can control two head-to-head genes, advancing our understanding of the diverse functions of enhancers.Article SummaryEnhancers are critical for gene expression, but a full understanding their functions has yet to be elucidated. We discovered two positions in theC. elegansgenome where a pair of head-to-head oriented genes are both transcriptionally activated by the metals zinc and cadmium; in both cases, one high-zinc activation (HZA) enhancer is positioned between the translation start sites. When these HZA enhancers were deleted by genome engineering, both head-to-head genes lost metal-activated transcription. These results demonstrate that a single HZA enhancer can control two head-to-head genes, advancing the understanding of enhancer function.
XAI-MRI: An Ensemble Dual-Modality Approach for 3D Brain Tumor Segmentation Using Magnetic Resonance Imaging
Authors: Farhan Ahmeed Suliman , Khalid Muhammad , Manzoor Umar 
Published: November 2024

ABSTRACTBrain tumor segmentation from Magnetic Resonance Images (MRI) presents significant challenges due to the complex nature of brain tumor tissues. This complexity makes distinguishing tumor tissues from healthy tissues difficult, mainly when radiologists perform manual segmentation. Reliable and accurate segmentation is crucial for effective tumor grading and treatment planning. In this paper, we proposed a novel ensemble dual-modality approach for 3D brain tumor segmentation using MRI. Initially, individual U-Net models are trained and evaluated on single MRI modalities (T1, T2, T1ce, and FLAIR) to establish each modality’s performance. Subsequently, we trained U-net models using combinations of the best-performing modalities to exploit the complementary information and improve segmentation accuracy. Finally, we suggested the ensemble dual-modality by combining the best-performing two pre-trained dual-modalities models to enhance segmentation performance. Experimental results show that the proposed model enhanced the segmentation result and achieved a Dice Coefficient of 97.73% and a Mean IoU of 60.08% on the BraTS2020 dataset. The results illustrate that the ensemble dual-modality approach outperforms single-modality and dual-modality models. This study shows that ensemble dual-modality models can help improve the accuracy and dependability of brain tumor segmentation based on MRI. Our code publicly available at:https://github.com/Ahmeed-Suliman-Farhan/Ensemble-Dual-Modality-Approach
Axonal transcriptome reveals upregulation of PLK1 as a protective mechanism in response to increased DNA damage in FUSP525Lspinal motor neurons
Authors: Zimyanin Vitaly , Dash Banaja P. , Großmann Dajana , Simolka Theresa , Glaß Hannes , Verma Riya , Khatri Vivek , Deppmann Christopher , Zunder Eli , Redemann Stefanie , Hermann Andreas 
Published: November 2024

AbstractMutations in the geneFUSED IN SARCOMA(FUS) are among the most frequently occurring genetic forms of amyotrophic lateral sclerosis (ALS). Early pathogenesis ofFUS-ALS involves impaired DNA damage response and axonal degeneration. However, it is still poorly understood how these gene mutations lead to selective spinal motor neuron (MN) degeneration and how nuclear and axonal phenotypes are linked. To specifically address this, we applied a compartment specific RNA-sequencing approach using microfluidic chambers to generate axonal as well as somatodendritic compartment-specific profiles from isogenic induced pluripotent stem cells (iPSCs)-derived MNs. We demonstrate high purity of axonal and soma fractions and show that the axonal transcriptome is unique and distinct from that of somas including significantly fewer number of transcripts. Functional enrichment analysis revealed that differentially expressed genes (DEGs) in axons were mainly enriched in key pathways like RNA metabolism and DNA damage, complementing our knowledge of early phenotypes in ALS pathogenesis and known functions of FUS. In addition, we demonstrate a strong enrichment for cell cycle associated genes including significant upregulation of polo-like kinase 1 (PLK1) in FUSP525Lmutant MNs. PLK1 was increased upon DNA damage induction and PLK1 inhibition further increased the number of DNA damage foci in etoposide-treated cells, an effect that was diminished in case ofFUSmutant MNs. In contrast, inhibition of PLK1 increased late apoptotic or necrosis-induced neuronal cell death in mutant neurons. Taken together, our findings provide insights into compartment-specific transcriptomics in humanFUS-ALS MNs and we propose that specific upregulation of PLK1 might represent an early event in the pathogenesis of ALS, possibly modulating DNA damage response and other associated pathways.
NEMF inhibits proliferation and migration of ovarian cancer cells by blocking the PI3K/mTOR pathway
Authors: Wang Qian , Zhu Ying , Zhang Yilin , Chen Chuangzhen , Fan Jing , Yin Aiqi , Guo Suiqun , Liu Yahui 
Published: November 2024

AbstractNuclear export mediator factor (NEMF) is considered to be a tumor suppressor in Drosophila. Based on the analysis of data from an online database, NEMF is downregulated in ovarian cancer. However, the mechanism underlying its expression has not been reported thus far.In this study, the immunohistochemistry results showed that the expression of NEMF may be related to patient age and tissue differentiation. In vitro experiments indicated that overexpression of NEMF may inhibit cell proliferation and migration by inhibiting the PI3K/mTOR signaling pathway, thereby blocking cell cycle progression and promoting apoptosis (P < 0.05).Therefore, we speculate that NEMF is a potential tumor suppressor gene. Targeting NEMF may be an innovative therapeutic approach for ovarian cancer.Summary blurbNEMF is downregulated in ovarian cancer and the mechanism underlying its expression has not been reported thus far.In vitro experiments indicated that overexpression of NEMF inhibit cell proliferation and migration by inhibiting the PI3K/mTOR signaling pathway,thereby blocking cell cycle progression.
Intrinsic and extrinsic mechanisms alter neural cell fate specification in EPM1 Epilepsy
Authors: Forero Andrea , Pravata Veronica , Pipicelli Fabrizia , Soloperto Alessandro , Di Matteo Francesco , Bekjarova Zagorka , Frenna Elisa , Canafoglia Laura , Ragona Francesca , Maccarrone Giuseppina , Pisfil Mariano Gonzalez , Whal-Schott Christian , Cernilogar Filippo M. , Eder Matthias , Di Giaimo Rossella , Cappello Silvia 
Published: November 2024

AbstractThe extracellular milieu, including extracellular vesicles (EVs), plays a pivotal role in brain development by regulating neural processes such as proliferation, differentiation, and migration. In this study, we sought to elucidate the pathogenesis of progressive myoclonus epilepsy type 1 (EPM1), a disease caused by mutations in theCSTBgene, using cerebral organoids (COs) derived from EPM1 patient cells. The results demonstrate that EPM1 COs display increased electrophysiological activity and a disrupted excitatory/inhibitory balance. Single-cell RNA sequencing (scRNA-seq) analysis of ventral EPM1-Cos revealed an abnormal specification of progenitor fate, with a shift toward dorsal neuron identities at the expense of inhibitory interneurons. In addition, pathological alterations in EV biogenesis and cargo were identified, including aberrant Sonic Hedgehog (SHH) signaling, which may disrupt cortical patterning. These findings suggest that both intrinsic progenitor identity shifts and extrinsic EV-mediated signaling contribute to EPM1 pathology. Our study highlights potential therapeutic strategies mediated by EVs as a novel approach to mitigate disease progression.
Metabolic trade-offs in response to increased acetate metabolism inEscherichia coli
Authors: Pentz Jennifer T. , Koehler Samuel I. , Middlebrook Earl A. , You Mak Kayley T. , Hovde Blake T. , Hanschen Erik R. 
Published: November 2024

SummaryAdaptive laboratory evolution (ALE) is a powerful tool to improve phenotypes in microbial cell factories for biotechnological processes. For example, ALE can be utilized to improve growth on alternative carbon sources such as acetate. Acetate is becoming a promising alternative feedstock to produce a variety of bio-products, but growth on acetate is slow relative to other preferred carbon sources and can be toxic to cells. However, ALE in a homogenous environment can lead to evolutionary trade-offs for growth on other carbon sources, which might be detrimental for feedstocks that contain multiple sugars. Here, we evolvedEscherichia colifor ∼100 generations using continuous culturing in turbidostats in media containing acetate as the sole carbon source to rapidly select for increased growth in acetate. We measured absolute fitness of 119 clones in acetate and glucose separately to characterize trade-offs and found that trade-off patterns were heterogenous amongst measured clones, with 45% of clones showing significantly reduced growth in glucose. Sequencing revealed that the trade-offs were a result of antagonistic pleiotropic effects of early adaptive mutations, but not all high-effect mutations conferred a trade-off, consistent with the model that mutations accumulated in the selected environment can display a range of pleiotropic effects in other environments. Together, these results suggest that ALE in a homogeneous environment needs to be carefully considered for the improvement of metabolic traits in microbial cells as this could limit the use of evolved strains in complex feedstocks that contain multiple sugars.
Enhancing single-cell ATAC sequencing with formaldehyde fixation, cryopreservation, and multiplexing for flexible analysis
Authors: Hohl Tobias , Boenisch Ulrike , Manke Thomas , Arrigoni Laura 
Published: November 2024

AbstractThe assay for transposase-accessible chromatin using sequencing (ATAC-seq) revolutionized the field of epigenetics since its emergence by providing a means to uncover chromatin dynamics and other factors affecting gene expression. The development of single-cell (sc) applications in recent years led to an even deeper understanding of cell type specific gene regulatory mechanisms. One of the major challenges while running ATAC-seq experiments, bulk or sc, is the need for freshly collected cells for successful experiments. While various freezing methods have already been tested and established for bulk and sc ATAC-seq, quality metrics for preserved cells are rather poor or dependent on sampling time when compared to fresh samples. This makes it difficult to conduct all sorts of complex experiments i.e. with multiple conditions, patients, or time course studies. Especially, accounting for batch effects can be difficult if samples need to be processed at different time points of collection. We tackled this issue by adding a fixation step prior to the freezing method. The additional fixation step improved library quality and yield data comparable to fresh samples. The workflow was also tested on multiplexed sc ATAC experiments, set-up for cost-efficient low input sample handling. Sample cross-in, typically encountered in Tn5-based multiplex approaches, were tackled with a computational procedure specifically developed for this approach.
The virulence and motility ofPseudomonas syringaepv.actinidiaemediated by a temperature sensor HktS-HktR
Authors: Xiao Yinan , Liang Yifei , Yang Mingming , Zhou Mingxia , Huang Jing , Wang Nana , Huang Lili 
Published: November 2024

AbstractKiwifruit bacterial canker (KBC), caused byPseudomonas syringaepv.actinidiae(Psa) is one of the most devastating diseases of kiwifruit and can damage almost all kiwifruit varieties. The severity of the disease occurrence is closely related to the temperature. Our previous research indicated thatPsashowed stronger pathogenicity and expansion ability at relatively cool temperatures, but howPsasenses environmental temperature and regulates its virulence mechanism remains unclear. In this study, 69 Histidine kinases (HK) inPsawere predicted through bioinformatics analysis, and 9 differentially expressed HK genes were identified at varying temperatures through pathogenicity detection and quantitative reverse transcription PCR (qRT-PCR). Among them, HktS as a temperature signal receiver was identified, and its response regulator (RR) HktR was determined through structure analysis and cotranscription assay. The results showed that HktR can bind to transcription factor RpoD, and RpoD bind tohrpRSpromoter region, thus initiating the expression level of the type III secretion system (T3SS), which plays an important role in the pathogenesis ofPsa. In addition, the motility ofPsawas also regulated by HktS-HktR in a temperature-dependent manner. These findings reveal the molecular mechanism by which HktS-HktR acts as a temperature sensor to regulate bacterial virulence and motility ofPsa, providing a new potential target for KBC control.
Ancestry-specific gene expression in peripheral monocytes mediates risk of neurodegenerative disease
Authors: Wagen Aaron Z , Reynolds Regina H , Nee Foo Jia , Fairbrother-Browne Aine , Gustavsson Emil K , Galgiano-Turin Sarah , Wood Nicholas W , Blauwendraat Cornelis , Gandhi Sonia , Ryten Mina 
Published: November 2024

AbstractIt is hypothesised that peripheral immune states responding to regional environmental triggers contribute to central neurodegeneration. Region-specific genetic selection pressures require this hypothesis to be assessed in an ancestry specific manner. Here we utilise genome-wide association studies and expression quantitative trait loci from African, East Asian and European ancestries to show that genes causing neurodegeneration are preferentially expressed in innate rather than adaptive immune cells, and that expression of these genes mediates the risk of neurodegenerative disease in monocytes in an ancestry-specific manner.
A pair of congenic mice for imaging of transplants by positron emission tomography using anti-transferrin receptor nanobodies
Authors: Balligand Thomas , Carpenet Claire , Olive-Palau Sergi , Jaspers Tom , Suresh Pavana , Liu Xin , Medhi Himadri , Lee Yoon Ho , Rashidian Mohammad , De Strooper Bart , Ploegh Hidde L. , Dewilde Maarten 
Published: November 2024

AbstractTwo anti-transferrin receptor (TfR) nanobodies, VHH123 specific for mouse TfR and VHH188 specific for human TfR (huTfR) were used to track transplants non-invasively by PET/CT in mouse models, without the need for genetic modification of the transferred cells. We provide a comparison of the specificity and kinetics of the PET signals acquired when using nanobodies radiolabeled with89Zr,64Cu and18F. We used a knock-in mouse that expresses a TfR with a human ectodomain (huTfR+/+) as a source of transplants into C57BL/6 recipients and show that VHH188 detects such transplants by PET/CT. Conversely, C57BL/6 transplants into huTfR+/+recipients can be imaged with VHH123. In C57B/6 mice impregnated by huTfR+/+males we saw an intense VHH188 signal in the placenta showing that TfR-specific VHHs accumulate at the placental barrier but do not enter the fetal tissue. The model presented here can be used to track many transplanted cell types by PET/CT, provided cells express TfR, as is typically the case for proliferating cells such as tumor lines.
Predicting inbred parent synchrony at flowering for maize hybrid seed production by integrating crop growth model with whole genome prediction
Authors: Laurent Anabelle , Munaro Eugenia , Zhao Honghua , Technow Frank , Whitted Eric , Clark Randy , Martin Juan Pablo San , Totir Radu 
Published: November 2024

AbstractOne of the challenges of maize hybrid seed production is to ensure synchrony at flowering of the two inbred parents of a hybrid, which depends on the specific parental combination and environmental conditions of the production field. Maize flowering can be simulated using a mechanistic crop growth model that converts thermal time accumulation to leaf numbers based on inbred specific physiological parameter values. Heretofore, these inbred specific physiological parameters need to be measured or assigned based on prior knowledge. Here, we leverage genetic, environmental and management data to predict physiological parameters and simulate flowering phenotypes by using whole genome prediction methodology combined with a crop growth model (CGM-WGP) as part of in-field in-season inbred growth development. We use two estimation sets that differ in terms of management and weather information to test the robustness of our approach. As part of our findings, we demonstrate the importance of defining informative priors to generate biologically meaningful predictions of unobserved physiological parameters. Our CGM-WGP infrastructure is efficient at simulating flowering phenotypes. An important practical application of our method is the ability to recommend differential planting intervals for male and female maize inbreds used in commercial seed production fields to synchronize male and female flowering.Core ideasSynchrony at flowering of maize inbred parents is crucial for optimal pollination and consequently seed yield.Integrating WGP with CGM can accurately predict physiological parameters and simulate maize flowering phenotypes.CGM-WGP infrastructure can be used to optimize field operations for large scale maize hybrid seed production.