bluuebunny/crossref_metadata_2025_split huggingface dataset:
Human basal-like breast cancer is represented by one of the two mammary tumor subtypes in dogs
Authors: Watson Joshua , Wang Tianfang , Ho Kun-Lin , Feng Yuan , Dobbin Kevin K , Zhao Shaying 
Published: March 2023

AbstractBackgroundAbout 20% of breast cancers in humans are basal-like, a subtype that is often triple negative and difficult to treat. An effective translational model for basal-like breast cancer (BLBC) is currently lacking and urgently needed. To determine if spontaneous mammary tumors in pet dogs could meet this need, we subtyped canine mammary tumors and evaluated the dog-human molecular homology at the subtype level.MethodsWe subtyped 236 canine mammary tumors from 3 studies by applying various subtyping strategies on their RNA-seq data. We then performed PAM50 classification with canine tumors alone, as well as with canine tumors combined with human breast tumors. We investigated differential gene expression, signature gene set enrichment, expression association, mutational landscape, and other features for dog-human subtype comparison.ResultsOur independent genome-wide subtyping consistently identified two molecularly distinct subtypes among the canine tumors. One subtype is mostly basal-like and clusters with human BLBC in cross-species PAM50 classification, while the other subtype does not cluster with any human breast cancer subtype. Furthermore, the canine basal-like subtype recaptures key molecular features (e.g., cell cycle gene upregulation, TP53 mutation) and gene expression patterns that characterize human BLBC. It is enriched histological subtypes that match human breast cancer, unlike the other canine subtype. However, about 33% of canine basal-like tumors are estrogen receptor negative (ER-) and progesterone receptor positive (PR+), which is rare in human breast cancer. Further analysis reveals that these ER-PR+ canine tumors harbor additional basal-like features, including upregulation of genes of interferon-γ response and of the Wnt-pluripotency pathway. Interestingly, we observed an association ofPGRexpression with gene silencing in all canine tumors, and with the expression of T cell exhaustion markers (e.g.,PDCD1) in ER-PR+ canine tumors.ConclusionsWe identify a canine mammary tumor subtype that molecularly resembles human BLBC overall, and thus could serve as a vital spontaneous animal model of this devastating breast cancer subtype. Our study also sheds light on the dog-human difference in the mammary tumor histology and the hormonal cycle.
The concordance of length- and sequence-based STRs used in forensic markers with guidance for practice
Authors: Sathirapatya Tikumphorn , Worrapitirungsi Wikanda , Sukawutthiya Poonyapat , Noh Hasnee , Pitiwararom Rachatipan , Vongpaisarnsin Kornkiat 
Published: March 2023

AbstractNext-generation sequencing (NGS) technology has shed light on every aspect of genetic discoveries, including forensic genetics. The Miseq® FGx Forensic Genetic System (Verogen) is one of the pioneering forensic NGS that provided a complete system from library preparation to data analysis. The system has been validated by several studies and led to a more practical aspect. Short tandem repeat (STR) is a well-established marker that was designed specifically for human individualization. Since NGS provides different data from fragment analysis, a new STR nomenclature is established to make NGS backward compatible with the previous data. In this study, Thai population were used to evaluate the Miseq® FGx Forensic genetic system (Verogen) in practical aspect, including concordance study and forensic population parameters. In summary, we purposed a practical guideline for sequence-based STRs.
Combined statistical-biophysical modeling links ion channel genes to physiology of cortical neuron types
Authors: Bernaerts Yves , Deistler Michael , Gonçalves Pedro J. , Beck Jonas , Stimberg Marcel , Scala Federico , Tolias Andreas S. , Macke Jakob , Kobak Dmitry , Berens Philipp 
Published: March 2023

ABSTRACTNeural cell types have classically been characterized by their anatomy and electrophysiology. More recently, single-cell transcriptomics has enabled an increasingly fine genetically defined taxonomy of cortical cell types, but the link between the gene expression of individual cell types and their physiological and anatomical properties remains poorly understood. Here, we develop a hybrid modeling approach to bridge this gap. Our approach combines statistical and mechanistic models to predict cells’ electrophysiological activity from their gene expression pattern. To this end, we fit biophysical Hodgkin-Huxley-based models for a wide variety of cortical cell types using simulation-based inference, while overcoming the challenge posed by the mismatch between the mathematical model and the data. Using multimodal Patch-seq data, we link the estimated model parameters to gene expression using an interpretable sparse linear regression model. Our approach recovers specific ion channel gene expressions as predictive of biophysical model parameters including ion channel densities, directly implicating their mechanistic role in determining neural firing.
Identifying key features of digital elements used during online science practicals
Authors: Janštová Vanda , Novotný Petr , Chlebounová Irena , Guitart Fina , Forne Ester , Tortosa Montserrat 
Published: March 2023

AbstractAs in everyday life, we use more digital elements as part of formal and informal education. To serve their educational purpose well, systematic research is desirable on identifying and measuring their characteristics. This study focuses on science practicals, which are complex and vary in organizational settings and specific arrangements, including usage of digital elements. We describe digital resources on which teaching online science practicals during COVID-19 forced lockdowns were built. We identified their key characteristics, as part of the Erasmus+ project ‘My Home – My Science Lab’, where science teachers in Slovakia, Czechia, Slovenia, France, and Spain shared web resources they used and would recommend and why. We recorded 89 inputs representing 50 unique web resources. Teachers preferred free web resources, mostly for knowledge revision, and newly discovered half of them due to forced distant teaching. The best evaluated resources were those supporting interaction (especially among peers), focused on teaching subjects and/or ICT, ready to use, and with a clear structure. The web resource most frequently mentioned and used in all countries was PhET (Interactive Simulations for Science and Math) providing free science principles simulations. Other characteristics mentioned in the literature (eg., supporting creativity and independent solving, connecting different levels of organization, authenticity, flexibility) were not that important for the overall rating.
A paper based microfluidic platform combining LAMP-CRISPR/Cas12a for fluorometric detection of nucleic acids
Authors: Sen Anindita , Morris Calum , Priye Aashish , Broom Murray 
Published: March 2023

AbstractNucleic acid isothermal amplification methods are advantageous for point-of-care (POC) diagnostics because of their precision, sensitivity, and low power requirements. Loop-mediated isothermal amplification (LAMP) is an established method, renowned for its nucleic acid amplification efficiency and robust amplification of semi purified target nucleic acids. However, LAMP may be prone to non-specific amplification causing false positives and therefore fails to replace PCR as the gold standard method in clinical testing. We show that LAMP combined with clustered regularly interspaced short palindromic repeats (CRISPR) technology is an effective alternative for overcoming the limitations of LAMP alone. Nucleic acids are first isothermally pre-amplified to enrich for targets, then specific amplification detection signals are generated by sequences of RNA guided recognition of amplicons. We are the first to demonstrate a paper based microfluidic system for detecting pathogen nucleic acids in samples by combining the power of LAMP and CRISPR technology. We show that although LAMP may produce non-specific amplification, the possibility of detecting a false positive can be eliminated by combining LAMP with CRISPR based detection. We demonstrate that a paper based microfluidic platform has the potential to compete with the conventional Nucleic acid testing (NAT) technologies not only in terms of robustness but also in terms of cost and complexity.
Neutralizing Antibodies with Neurotropic Factor Treatment Maintain Neurodevelopmental Gene Expression Upon Exposure to Human Cytomegalovirus
Authors: O’Brien Benjamin S. , Mokry Rebekah L. , Schumacher Megan L. , Rosas Suzette , Terhune Scott S. , Ebert Allison D. 
Published: March 2023

ABSTRACTHuman cytomegalovirus (HCMV) is a beta herpesvirus that causes severe congenital birth defects including microcephaly, vision loss, and hearing loss. Infection of cerebral organoids with HCMV causes significant downregulation of genes involved in critical neurodevelopmental pathways. The precise features of the infection causing this dysregulation remain unknown. Entry of HCMV into human cells is determined by the composition of glycoproteins in viral particles, which is influenced by the source of the virus. This includes a trimer complex and a pentamer complex with the latter enriched from replication in epithelial cells. To begin dissecting which features contribute to neuronal pathogenesis, we evaluated infection using virus from different sources along with the distribution of cellular entry receptors on cells in cerebral organoids. We observed significant increases in the number of viral genomes, viral spread and penetrance, and multinucleated syncytia in neural tissues infected with HCMV propagated in epithelial cells compared to fibroblasts. To determine if this was related to entry receptor distribution, we measured expressions of cellular entry receptors and observed similar distributions of all receptors on cells obtained from organoids indicating that source of virus is likely the key determinant. Next, we asked whether we could limit pathogenesis using neutralization antibodies. We found that pre-treatment with antibodies against viral glycoprotein B (gB) and gH successfully decreased viral genome levels, viral gene expression, and virus-induced syncytia. In contrast, targeting specific cellular entry receptors failed to limit infection. Using an antibody against gB, we also observed partial protection of developmental gene expression that was further improved by the addition of brain derived neurotropic factor (BDNF). These studies indicate that source of HCMV is a key determinant of neuronal pathogenesis that can be limited by neutralization antibodies and neurotropic factors.
Detrimental Impact of a Type VI Secretion System on Direct Interspecies Electron Transfer
Authors: Smith Jessica A. , Holmes Dawn E. , Woodard Trevor L. , Li Yang , Liu Xinying , Wang Li-Ying , Meier David , Schwarz Ingrid A. , Lovley Derek R. 
Published: March 2023

ABSTRACTDirect interspecies electron transfer (DIET) is important in anaerobic communities of environmental and practical significance. Other than the need for close physical contact for electrical connections, the interactions of DIET partners are poorly understood. Type VI secretion systems (T6SSs) typically kill competitive microbes. Surprisingly,Geobacter metallireducenshighly expressed T6SS genes when DIET-based co-cultures were initiated withGeobacter sulfurreducens. T6SS gene expression was lower when the electron shuttle anthraquinone-2,6-disulfonate was added to alleviate the need for interspecies contact. Disruption ofhcp, theG. metallireducensgene for the main T6SS needle-tube protein subunit, and the most highly upregulated gene in DIET-grown cells, eliminated the long lag periods required for the initiation of DIET. The mutation did not aid DIET in the presence of granular activated carbon, consistent with the fact that DIET partners do not make physical contact when electrically connected through conductive materials. Thehcp-deficient mutant also established DIET quicker withMethanosarcina barkeri. However, the mutant also reduced Fe(III) oxide faster than the wild-type strain, a phenotype not expected from the loss of the T6SS. Quantitative PCR revealed greater gene transcript abundance for key components of extracellular electron transfer in thehcp-deficient mutant versus the wild-type strain, potentially accounting for the faster Fe(III) oxide reduction and impact on DIET. The results highlight that interspecies interactions beyond electrical connections may influence DIET effectiveness. The unexpected increase in the expression of genes for extracellular electron transport components whenhcpwas deleted emphasize the complexities in evaluating the electromicrobiology of highly adaptableGeobacterspecies.IMPORTANCEDirect interspecies electron transfer (DIET) is an alternative to the much more intensively studied process of interspecies H2transfer as a mechanism for microbes to share electrons during the cooperative metabolism of energy sources. DIET is an important process in anaerobic soils and sediments generating methane, a significant greenhouse gas. Facilitating DIET can accelerate and stabilize the conversion of organic wastes to methane biofuel in anaerobic digesters. Therefore, a better understanding of the factors controlling how fast DIET partnerships are established is expected to lead to new strategies for promoting this bioenergy process. The finding that when co-cultured withG. sulfurreducens, G. metallireducensinitially expressed a type VI secretion system, a behavior not conducive to interspecies cooperation, illustrates the complexity in establishing syntrophic relationships.
ERF1 inhibits lateral root emergence by promoting local auxin accumulation with altered distribution and repressingARF7expression
Authors: Zhao Pingxia , Zhang Jing , Chen Siyan , Zhang Zisheng , Wan Guangyu , Mao Jieli , Wang Zhen , Tan Shutang , Xiang Chengbin 
Published: March 2023

SummaryLateral roots (LRs) are crucial for plants to sense environmental signals in addition to water and nutrient absorption. Auxin is key for LR formation, but the underlying mechanisms are not fully understood. Here we report thatArabidopsisERF1 inhibits LR emergence by promoting local auxin accumulation with altered distribution and regulating auxin signaling. Loss ofERF1increases LR density compared with the wild type, whereasERF1overexpression causes the opposite phenotype. ERF1 enhances auxin transport by upregulatingPIN1andAUX1, resulting in excessive auxin accumulation in the endodermal, cortical, and epidermal cells surrounding LR primordia. Furthermore, ERF1 repressesARF7transcription, consequently affecting the expression of cell wall remodeling genes that facilitate LR emergence. Together, our study reveals that ERF1 integrates environmental signals to promote local auxin accumulation with altered distribution and repressARF7, consequently inhibiting LR emergence in adaptation to fluctuating environments.HighlightsERF1 functions as a negative regulator of lateral root emergenceERF1 enhances rootward and shootward auxin transport by directly upregulating the expression ofPIN1andAUX1, resulting in high local auxin accumulation and abnormal auxin distribution in the endodermal, cortical, and epidermal cells overlying lateral root primordiaERF1 represses the transcription ofARF7and cell wall remodeling genes in lateral root emergence
The best plant-guarding ants in extrafloral nectaried plants and myrmecophytes according to baiting tests
Authors: Souza Leticia Silva , Calixto Eduardo Soares , Domingos Saulo Santos , Bächtold Alexandra , Silva Estevao Alves 
Published: March 2023

ABSTRACTExtrafloral nectaried plants and myrmecophytes offer resources to ants that may engage in protective mutualisms. The role of different ant species in herbivore deterrence has long been analyzed by using herbivore baits, and ants are regarded as effective plant guards if they attack and/or remove the baits (mostly termites) from plants. Here, we conducted a comparative investigation on which ants display aggression toward baits, which ants are better plant guards, and which plants (extrafloral nectaried plants or myrmecophytes) are better defended by ants. Data from the literature revealed that baiting studies have been performed on 37 extrafloral nectaried plant species and 19 myrmecophytes, and have involved over 30 genera of ants. Extrafloral nectaried plants and myrmecophytes rely on specific ant fauna to defend them from herbivores. In extrafloral nectaried plants,CamponotusandCrematogasterwere regarded as the best plant protectors, as they attacked baits in nearly all plants. In myrmecophytes,Azteca, PheidoleandPseudomyrmexwere the most important bait attackers. Myrmecophytes were better protected by ants, as all baits were attacked; in extrafloral nectaried plants, some ants failed to attack the baits. Plants can be patrolled by several different ants, but there is a core of ants that excel in protection, and this varies according to plant type (extrafloral nectaried plants and myrmecophytes). With this knowledge, it may be possible to label different ants as effective plant guards, to anticipate their effects on plant performance and even to understand their potential role as biological control agents.
Simulations suggest walking with reduced propulsive force would not mitigate the energetic consequences of lower tendon stiffness
Authors: Pimentel Richard E. , Sawicki Gregory S. , Franz Jason R. 
Published: March 2023

AbstractAging elicits numerous effects that impact both musculoskeletal structure and walking function. Tendon stiffness (kT) and push-off propulsive force (FP) both impact the metabolic cost of walking and are diminished by age, yet their interaction has not been studied. We combined experimental and computational approaches to investigate whether age-related changes in function (adopting smaller FP) may be adopted to mitigate the metabolic consequences arising from changes in structure (reduced kT). We recruited 12 young adults and asked them to walk on a force-sensing treadmill while prompting them to change FP(±20% & ±40% of typical) using targeted biofeedback. In models driven by experimental data from each of those conditions, we altered the kTof personalized musculoskeletal models across a physiological range (2-8% strain) and simulated individual-muscle metabolic costs for each kTand FPcombination. We found that kTand FPindependently affect walking metabolic cost, increasing with higher kTor as participants deviated from their typical FP. Our results show no evidence for an interaction between kTand FPin younger adults walking at fixed speeds. Individual lower body muscles showed unique effects across the kTand FPlandscape. Our simulations suggest that reducing FPduring walking would not mitigate the metabolic consequences of lower kT. Wearable devices and rehabilitative strategies can focus on either kTor FPto reduce age-related increases in walking metabolic cost.Author SummaryOur muscles and tendons are affected by aging. Tendon stiffness and push-off forces both impact the energy cost of walking, which in turn increases with age. We investigated whether age-related changes in function (less push-off force) may be adopted to mitigate the metabolic consequences arising from structural changes (lower tendon stiffness). Reducing push-off force during walking would not mitigate the metabolic consequences of lower tendon stiffness. Wearable devices and rehabilitative strategies can focus on either tendon stiffness or push off intensity to reduce age-related increases in walking metabolic cost.
A large-scale retrospective study in metastatic breast cancer patients using circulating tumor DNA and machine learning to predict treatment outcome and progression-free survival
Authors: Beddowes Emma J , Ortega-Duran Mario , Karapanagiotis Solon , Martin Alistair , Gao Meiling , Masina Riccardo , Woitek Ramona , Tanner James , Tippin Fleur , Kane Justine , Lay Jonathan , Brouwer Anja , Sammut Stephen-John , Chin Suet-Feung , Gale Davina , Tsui Dana , Dawson Sarah Jane , Rosenfeld Nitzan , Callari Maurizio , Rueda Oscar M , Caldas Carlos 
Published: March 2023

ABSTRACTPurposeMonitoring levels of circulating tumor-derived DNA (ctDNA) represents a non-invasive snapshot of tumor burden and potentially clonal evolution. Here we describe how a novel statistical model that uses serial ctDNA measurements from shallow whole genome sequencing (sWGS) in metastatic breast cancer patients produces a rapid and inexpensive assessment that is predictive of treatment response and progression-free survival.Patients and MethodsA cohort of 188 metastatic breast cancer patients had DNA extracted from serial plasma samples (total 1098, median=4, mean=5.87). Plasma DNA was assessed using sWGS and the tumor fraction in total cell free DNA estimated using ichorCNA. This approach was compared with ctDNA targeted sequencing and serial CA 15-3 measurements. The longitudinal ichorCNA values were used to develop a Bayesian learning model to predict subsequent treatment response.ResultsWe identified a transition point of 7% estimated tumor fraction to stratify patients into different categories of progression risk using ichorCNA estimates and a time-dependent Cox model, validated across different breast cancer subtypes and treatments, outperforming the alternative methods. We then developed a Bayesian learning model to predict subsequent treatment response with a sensitivity of 0.75 and a specificity of 0.66.ConclusionIn patients with metastatic breast cancer, sWGS of ctDNA and ichorCNA provide prognostic and predictive real-time valuable information on treatment response across subtypes and therapies. A prospective large-scale clinical trial to evaluate clinical benefit of early treatment changes based on ctDNA levels is now warranted.
Modulations of right hemisphere connectivity in young children relates to the perception of spoken words
Authors: Iyer Kartik K. , Bell Nicola , Copland David A. , Arnott Wendy L. , Wilson Wayne J. , Angwin Anthony J. 
Published: March 2023

AbstractThe early school years shape a young brain’s capability to comprehend and contextualize words within milliseconds of exposure. Parsing word sounds (phonologicalinterpretation) and word recognition (enablingsemanticinterpretation) are integral to this process. Yet little is known about the causal mechanisms of cortical activity during these early developmental stages. In this study, we aimed to explore these causal mechanisms via dynamic causal modelling of event-related potentials (ERPs) acquired from 30 typically developing children (ages 6 to 8 years) as they completed a spoken word-picture matching task. Source reconstruction of high-density electroencephalography (128 channels) was used to ascertain differences in whole-brain cortical activity during semantically “congruent” and “incongruent” conditions. Source activations analyzed during the N400 ERP window identified significant regions-of-interest (pFWE<.05) localized primarily in the right hemisphere when contrasting congruent and incongruent word-picture stimuli. Dynamic causal models (DCMs) were tested on source activations in the fusiform gyrus (rFusi), inferior parietal lobule (rIPL), inferior temporal gyrus (rITG) and superior frontal gyrus (rSFG). DCM results indicated that a fully connected bidirectional model with self-(inhibiting) connections over rFusi, rIPL and rSFG provided the highest model evidence, based on exceedance probabilities derived from Bayesian statistical inferences. Connectivity parameters of rITG and rSFG regions from the winning DCM were negatively correlated with behavioural measures of receptive vocabulary and phonological memory (pFDR<.05), such that lower scores on these assessments corresponded with increased connectivity between temporal pole and anterior frontal regions. The findings suggest that children with lower language processing skills required increased recruitment of right hemisphere frontal/temporal areas during task performance.