bluuebunny/crossref_metadata_2025_split huggingface dataset:
Novel triplex nucleic acid lateral flow immuno-assay (NALFIA) for rapid detection of Nipah virus, Middle East respiratory syndrome coronavirus and Reston ebolavirus
Authors: Chingtham Santhalembi , Kulkarni Diwakar D , Sumi TS , Mishra Anamika , Pateriya Atul K , Singh Vijendra Pal , Raut Ashwin Ashok 
Published: October 2022

AbstractWe report the development of the first triplex Nucleic Acid Lateral Flow Assay (NALFIA) for detection of genomes of Nipah virus (NiV), Middle East respiratory syndrome coronavirus (MERS-CoV) and Reston ebolavirus (REBOV), intended for screening of bats as well as other hosts and reservoirs of these three viruses. Our triplex NALFIA is a two-step assay format wherein the target nucleic acid in sample is first amplified using tagged primers, and the tagged ds DNA amplicons are captured by immobilized antibodies on NALFIA device resulting to signal development from binding of streptavidin-colloidal gold conjugate to biotin tag on the captured amplicons. Triplex amplification of N gene of NiV, UpE gene of MERS-CoV, and Vp40 gene of REBOV was optimized using primers adapted from validated real-time RT-PCR assays of previous studies and the compatible combinations of hapten-labels and antibodies for triplex NALFIA device were identified. Digoxigenin, rhodamine red and alexa fluor 488 were identified as suitable 5’ labels on forward primers. The lowest copy number detected by the triplex NALFIA with 2 μl of triplex RT-PCR product were up to 8.21e4 for NiV N target, 7.09e1 for MERS-CoV UpE target, and 1.83e4 for REBOV Vp40 target. Using simulated samples and Taqman real-time RT-PCR as standard, the sensitivity and positive predictive values were found to be 100% for MERS-CoV UpE and REBOV Vp40 targets and 91% for NiV N target while the specificity and negative predictive values were 100% for MERS-CoV UpE targets and REBOV Vp40, and 93.3% for NiV N target.
Commitment in the PINK1/Parkin mitophagy decision circuit
Authors: Waters Christopher S. , Angenent Sigurd B. , Altschuler Steven J. , Wu Lani F. 
Published: October 2022

AbstractMechanisms that prevent accidental degradation of healthy mitochondria by the PINK1/Parkin mitophagy pathway are poorly understood. On the surface of damaged mitochondria, PINK1 accumulates and acts as the input signal to a positive feedback loop of Parkin recruitment, which in turn promotes mitochondrial degradation via mitophagy. However, PINK1 is also present on healthy mitochondria where it could errantly recruit Parkin and thereby activate this positive feedback loop. Here, we quantitatively mapped the relationship between PINK1 input levels and Parkin recruitment dynamics using live-cell microscopy and mathematical modeling. We found that Parkin is recruited to the mitochondria only if PINK1 levels exceed a threshold and only after a delay that is inversely proportional to PINK1 levels. The threshold and delay provide a “two-factor authentication” step for PINK1/Parkin activation. These properties arise from the PINK1/Parkin circuit topology and provide a mechanism for cells to assess damage signals before committing to mitophagy.
Chemoproteomics-guided development of SLC15A4 inhibitors with anti-inflammatory activity
Authors: Lazar Daniel C. , Wang Wesley W. , Chiu Tzu-Yuan , Li Weichao , Jadhav Appaso M. , Wozniak Jacob M. , Gazaniga Nathalia , Theofilopoulos Argyrios N. , Teijaro John R. , Parker Christopher G. 
Published: October 2022

AbstractSLC15A4 is an endolysosome-resident transporter that is intimately linked with autoinflammation and autoimmunity. Specifically, SLC15A4 is critical for Toll-like receptor (TLR) 7, 8, and 9 as well as the nucleotide-binding oligomerization domain-containing protein (NOD) 2 signaling in several immune cell subsets. Notably, SLC15A4 is essential for the development of systemic lupus erythematosus in murine models and is associated with autoimmune conditions in humans. Despite its therapeutic potential, to our knowledge no pharmacological tools have been developed that target SLC15A4. Here, we use an integrated chemical proteomics approach to develop a suite of chemical tools, including first-in-class functional inhibitors, for SLC15A4. We demonstrate SLC15A4 inhibitors suppress endosomal TLR and NOD functions in a variety of human and mouse immune cells and provide early evidence of their ability to suppress inflammation in vivo and in clinical settings. Our findings establish SLC15A4 as a druggable target for the treatment of autoimmune/autoinflammatory conditions.One-Sentence SummaryDiscovery and characterization of SLC15A4 inhibitors with anti-inflammatory activity.
Lifespan Extension in Female Mice By Early, Transient Exposure to Adult Female Olfactory Cues
Authors: Garratt Michael , Erturk Ilkim , Alonzo Roxann , Zufall Frank , Leinders-Zufall Trese , Pletcher Scott D. , Miller Richard A. 
Published: October 2022

AbstractSeveral previous lines of research have suggested, indirectly, that mouse lifespan is particularly susceptible to endocrine or nutritional signals in the first few weeks of life, as tested by manipulations of litter size, growth hormone levels, or mutations with effects specifically on early-life growth rate. The pace of early development in mice can also be influenced by exposure of nursing and weanling mice to olfactory cues. In particular, odors of same-sex adult mice can in some circumstances delay maturation. We hypothesized that olfactory information might also have a sex-specific effect on lifespan, and we show here that lifespan of female mice can be increased significantly by odors from adult females administered transiently, i.e. from 3 days until 60 days of age. Female lifespan was not modified by male odors, nor was male lifespan susceptible to odors from adults of either sex. Conditional deletion of the G protein Gαo in the olfactory system, which leads to impaired accessory olfactory system function and blunted reproductive priming responses to male odors in females, did not modify the effect of female odors on female lifespan. Our data provide support for the idea that very young mice are susceptible to influences that can have long-lasting effects on disease resistance, and provide the first example of lifespan extension by olfactory cues in mice.
Low-cost and highly efficient: A method for high-quality nucleic acid isolation from cotton fibres
Authors: Ahmed Mukhtar , Sarwar Muhammad Bilal , Ashfaq Ramla , Ahmed Adnan , Yanang X. , Fanglu M. , Salah-ud-Din  , Sajid Muhammad , Syed Quratulain , Abidi Syed Hussain , Wang Xuede 
Published: October 2022

AbstractGene expression analyses to study the development of cotton fibers require high-quality nucleic acid. The conventional methods of nucleic acid extraction results in sub-quality nucleic acids with low yields. Young fibers are rich in polyphenols and sugars that react with nucleic acid to form phenols and insoluble substances. Furthermore, mature fibers contain more than 95% cellulose, hindering the nucleic acid isolation. Cytoplasm collapse and cellulose deposition also result in a very low yield of nucleic acid. Three different methods of RNA isolation from different cotton tissues were compared in this study to determine the best and most efficient one. The integrity and quality of RNA were analyzed using UV spectrum, agarose gel electrophoresis, RIN values, PCR, and Northern blot hybridization. RNA of functional quality was observed when using the high ion and pH method, with an A260/A280 ratio up to 1.87 and an average yield of 0.68 mg g-1 from fiber cells. From leaves, we found an A260/A280 ratio of 2.02 and an average yield of 6.35 mg g-1, which is suitable for molecular biology experiments. The extraction buffer with a high ion density and pH value include Tris-HCl, LiCl, EDTA, SDS, sodium deoxycholate, Nonident P-40, mercaptoethanol, and PVP. The addition of sodium deoxycholate and Nonider-40 (NP-40) enhances the density of other salt compounds and elevates the pH value. The results depicted that the high ion and pH method is a simple and effective way to extract a copious amount of high-quality RNA from polysaccharide-rich tissues. This method is also suitable for the extraction of cotton genomic DNA with high purity. Genomic DNA extracted from cotton using this method showed an A260/A230 ratio up to 2.09 and a yield of 1.44 mg g-1. This method is useful for isolating DNA and RNA from cotton fibers and produces high yields and quality at a comparatively low cost.
Integrative Multi-Omics Approaches for Identifying Cervical Cancer Therapeutic Targets
Authors: Duppala Santosh Kumari , Yadala Rajesh , Velingkar Aayushi , Suravajhala Prashanth , Pawar Smita C , Vuree Sugunakar 
Published: October 2022

AbstractAfter breast cancer, cervical cancer (CC) is one of the most common malignancies in women globally. Over 90% of chronic infections are caused by human papillomavirus (HPV) and its subtypes. Extensive research efforts are required to identify the treatment targets and prognostic indicators for recurring and metastatic cancers. It may be possible because of omics methods, including genomes, epigenomics, transcriptomics, proteomics, and metabolomics. High throughput (HT) data on the differential mRNA and miRNA expression and their crucial interrelationships enable promising integration and interpretation of the results. Clinical data and multi-omics have risen to the top of the heap in delivering molecular and cellular activities. They aid in comparing data from different omics approaches and bridging the gap between genotype and phenotype. Therefore, multi-omic techniques may improve the knowledge of the molecular basis of the physiology and primary cause of disease, revealing a new route for the prognosis, diagnosis, prevention, and therapy of human diseases.
BioDiscViz : a visualization support and consensus signature selector for BioDiscML results
Authors: Bouirdene Sophiane , Leclercq Mickael , Quitté Léopold , Bilodeau Steve , Droit Arnaud 
Published: October 2022

AbstractMachine learning (ML) algorithms are powerful tools to find complex patterns and biomarker signatures where conventional statistical methods may fail to identify them. While the ML field made significant progress, state of the art methodologies to build efficient and non-overfitting models are not always applied in the litterature. To this purpose, automatic programs, such as BioDiscML, have been designed to identify biomarker signatures and correlated features while escaping overfitting using multiple evaluation strategies, such as cross validation, bootstrapping and repeated holdout. To further improve BioDiscML and reach a broader audience, better visualization support and flexibility in choosing the best models and signatures are needed. Thus, to provide researchers with an easily accessible and usable tool for in depth investigation of the results from BioDiscML outputs, we developed a visual interaction tool called BioDiscViz. This tool provides summaries, tables and graphics, in the form of Principal Component Analysis (PCA) plots, heatmaps and boxplots for the best model and the correlated features. Furthermore, this tool also provides visual support to extract a consensus signature from BioDiscML models using a combination of filters. BioDiscViz will be a great visual support for research implying machine learning, hence new opportunities in this field by opening it to a broader community.
Communication between the nucleus and the mitochondria via NDUFS4 alternative splicing in gastric cancer cells
Authors: Papadaki V. , Erpapazoglou Z. , Kokkori M. , Rogalska M. , Tsakiri E. , Akhtorab H. , Smoot D. T. , Papanikolopoulou K. , Samiotaki M. , Kafasla P. 
Published: October 2022

AbstractA constant communication between the nucleus and the mitochondria allows both organelles to ensure cellular homeostasis and adaptation to mitochondrial stress. Mitochondrial biogenesis and function are controlled by anterograde regulatory pathways involving a large number of nuclear-encoded proteins. Transcriptional networks controlling the nuclear-encoded mitochondrial genes are known, however alternative splicing (AS) regulation has not been implicated in this communication. Here, we show that IQGAP1, a scaffold protein that regulates AS of distinct subsets of genes in gastric cancer cells, participates in AS regulation that strongly affects mitochondrial respiration. Combined proteomic analyses and RNA-seq profiles of IQGAP1KO and parental cells show that IQGAP1KO alters a specific AS event of the mitochondrial respiratory chain complex I subunit NDUFS4 and downregulates a subset of complex I subunits. In IQGAP1KO cells, respiratory complex I intermediates accumulate resembling assembly deficiencies observed in patients with Leigh syndrome bearing NDUFS4 mutations. Mitochondrial complex I activity is significantly lower in KO compared to parental cells, while exogenous expression of IQGAP1 partially restores NDUFS4 AS pattern and expression and reverses mitochondrial defects of IQGAP1KO cells. Our work sheds light to a novel facet of IQGAP1 in mitochondrial quality control that involves fine-tuning of complex I activity through AS regulation.
Rattractor - Instant guidance of a rat into a virtual cage using a deep brain stimulation
Authors: Sudo Naoki , Fujiwara Sei-etsu , Isoyama Takashi , Fukayama Osamu 
Published: October 2022

AbstractWe developed “Rattractor” (rat attractor), a system to apply electrical stimuli to the deep brain of a rat as it stays in a specified region or a virtual cage to demonstrate an instant electrophysiological feedback controller for animals.Two wire electrodes were implanted in the brains of nine rats. The electrodes targeted the medial forebrain bundle (MFB), which is a part of the reward system in the deep brain. Following the recovery period, the rats were placed in a plain field where they could move freely, but wired to a stimulation circuit. An image sensor installed over the field detected the subject’s position, which triggered the stimulator such that the rat remained within the virtual cage. We conducted a behavioral experiment to evaluate the sojourn ratio of rats residing in the region. Thereafter, a histological analysis of the rat brain was performed to confirm the position of the stimulation sites in the brain.Seven rats survived the surgery and the recovery period without technical failures such as connector breaks. We observed that three of them tended to stay in the virtual cage during stimulation, and this effect was maintained for two weeks. Histological analysis revealed that the electrode tips were correctly placed in the MFB region of the rats. The other four subjects showed no apparent preference for the virtual cage. In these rats, we did not find electrode tips in the MFB, or could not determine their positions.Almost half of the rats tended to remain inside the virtual cage when position-related reward stimuli were triggered in the MFB region. Notably, our system did not require previous training or sequential interventions to affect the behavioral preferences of subjects. This process is similar to the situation in which sheep are chased by a shepherd dog in the desired direction.
In vivocalcium imaging shows that satellite glial cells have increased activity in painful states
Authors: Jager Sara E. , Goodwin George , Chisholm Kim I. , Denk Franziska 
Published: October 2022

AbstractSatellite glial cells (SGCs) are important for proper neuronal function of primary sensory neurons to whom they provide homeostatic support. Most research of SGC function has been performed within vitrostudies, but recent advances in calcium imaging and transgenic mouse models have enabled this firstin vivostudy of single cell SGC function in mouse models of inflammation and neuropathic pain.We found that in naïve condition SGCs do not respond in a time-locked fashion to neuronal firing. In painful inflammatory and neuropathic states we detected time-locked signals in a subset of SGCs, but only with suprathreshold stimulation of the sciatic nerve. Surprisingly therefore, we conclude that most calcium signals in SGCs seem to develop at arbitrary intervals not directly linked to neuronal activity patterns.More in line with expectations, our experiments also revealed that the number of active SGCs was increased under conditions of inflammation or nerve injury. This could reflect the increased requirement for homeostatic support across dorsal root ganglion neuron populations, which are more active during such painful states.
Spatiotemporal orchestration of multicellular transcriptional programs and communications in the early stage of spinal cord injury
Authors: Wang Zeqing , Li Zhuxia , Luan Tianle , Cui Guizhong , Shu Shunpan , Liang Yiyao , Xiao Jingshu , Zhang Kai , Yu Wei , Cui Jihong , Li Ang , Peng Guangdun , Fang Yanshan 
Published: October 2022

ABSTRACTWhile spinal cord injury (SCI) involves a complex cascade of cellular and pathological changes that last for months to years, the most dramatic and comprehensive molecular rewiring and multicellular re-organization occur in the first few days, which determine the overall progression and prognosis of SCI, yet remain poorly understood. Here, we resolved the spatiotemporal architecture of multicellular gene expression in a mouse model of acute SCI, and revealed the coordinated gene co-expression networks, the upstream regulatory programs, andin situcell-cell interactions that underlay the anatomic disorganization as well as the immune and inflammatory responses conferring the secondary injury. The spatial transcriptomic analysis highlights that the genes and cell types in the white matter (WM) play a more active and predominant role in the early stage of SCI. In particular, we identified a distinct population of WM-originated,Igfbp2-expressing reactive astrocytes, which migrated to the grey matter and expressed multiple axon/synapse-supporting molecules that may foster neuron survival and spinal cord recovery in the acute phase. Together, our dataset and analyses not only showcase the spatially-defined molecular features endowing the cell (sub)types with new biological significance but also provide a molecular atlas for disentangling the spatiotemporal organization of the mammalian SCI and advancing the injury management.
Development of serum substitute medium for bone tissue engineering
Authors: Ansari Sana , Ito Keita , Hofmann Sandra 
Published: October 2022

AbstractIn tissue engineering, cells are grown often on scaffolds and subjected to chemical/mechanical stimuli. Most such cultures still use fetal bovine serum (FBS) despite its known disadvantages including ethical concerns, safety issues, and variability in composition, which greatly influences the experimental outcomes. To overcome the disadvantages of using FBS, chemically defined serum substitute medium needs to be developed. Development of such medium depends on cell type and application - which makes it impossible to define one universal serum substitute medium for all cells in any application. Here, we developed a serum substitute medium for bone tissue engineering (BTE) in a step-by-step process. Essential components were added to the medium while human bone marrow mesenchymal stromal cells (hBMSCs, osteoblast progenitor cells) were cultured in two-dimensional (2D) and three-dimensional (3D) substrates. In a 3-week culture, the developed serum substitute medium worked equally well as FBS containing medium in term of cell attachment to the substrate, cell survival, osteoblast differentiation, and deposition of extracellular matrix. In the next step, the use of serum substitute medium was evaluated when culturing cells under mechanical loading in the form of shear stress. The outcomes showed that the application of shear stress is essential to improve extracellular matrix formation while using serum substitute medium. The developed serum substitute medium could pave the way in replacing FBS for BTE studies eliminating the use of controversial FBS and providing a better-defined chemical environment for BTE studies.Graphical abstract
Characterizing the Morphology of Costa Rican Stingless Bees to Parameterize the InVEST Crop Pollination Model
Authors: Sun Christopher , Chaplin-Kramer Rebecca 
Published: October 2022

AbstractThe InVEST Crop Pollination model operates on land use and land cover (LULC) characteristics, using available nesting sites and floral resources within a specified flight range to gauge the abundance and yield of bees species. In this study, we parameterize the InVEST Crop Pollination model to validate predictions of relative pollinator abundance in Costa Rica. Flight ranges of bee species are required as model inputs, yet are not readily available in literature compared to morphological attributes such as body length. To harness the availability of morphological data, we express the flight range of any given species as a function of its morphological attributes through a series of regressions, allowing for the estimation of flight ranges of species for which this metric is unknown. After proper parameterization, the model-predicted relative pollinator abundances of three species—Tetragonisca angustula, Partamona orizabaensis, and Trigona corvina—are compared against field data. A single proto-pollinator is then constructed as a representative species for analysis at a broader level, with model predictions validated against the total pollinator abundance across the entire spatial distribution represented by the field data. The model performs with a higher accuracy on the proto-pollinator compared to the individual species, revealing that there is surprisingly minimal added value from estimating individual flight ranges for each species. Rather, generalizing the biodiverse assortment of Costa Rican bees may yield better approximations for relative pollinator abundance.
Circadian modulation by time-restricted feeding restores brain transcription and slows amyloid deposition in a mouse model of Alzheimer’s disease
Authors: Whittaker Daniel S. , Akhmetova Laila , Romero Haylie , Welsh David K. , Colwell Christopher S. , Desplats Paula 
Published: October 2022

ABSTRACTAlzheimer’s disease (AD) is a tragic neurodegenerative disease affecting more than 5 million Americans. Circadian disruptions impact nearly all AD patients, with reversal of sleep/wake cycles and agitation in the evening being common disturbances that manifest early in disease. These alterations support a role for circadian dysfunction as a driver of AD, emphasizing a critical need to investigate the therapeutic potential of circadian-modulating interventions. One of the most powerful regulators of the circadian system is the daily feed/fast cycle. Here we show that time-restricted feeding (TRF) without caloric restriction, improved key disease components including behavior, disease pathology and transcription in the APP23 mouse model of Alzheimer’s disease. We found that TRF had the remarkable capability of simultaneously reducing amyloid deposition, increasing Aβ42 clearance, improving sleep and hyperactivity, and normalizing transcription of circadian, AD and neuroinflammation-associated genes in APP23 mice. Thus, our study unveils for the first time that circadian modulation through timed feeding has far-reaching effects beyond metabolism and affects the brain as the substrate for neurodegeneration. Since the pleiotropic effects of TRF can substantially modify disease trajectory, this intervention has immediate translational value, addressing the crucial need for accessible approaches to reduce or halt AD progression.