bluuebunny/crossref_metadata_2025_split huggingface dataset:
Explainable autoencoder-based representation learning for gene expression data
Authors: Yu Yang , Kossinna Pathum , Li Qing , Liao Wenyuan , Zhang Qingrun 
Published: December 2021

AbstractModern machine learning methods have been extensively utilized in gene expression data analysis. In particular, autoencoders (AE) have been employed in processing noisy and heterogenous RNA-Seq data. However, AEs usually lead to “black-box” hidden variables difficult to interpret, hindering downstream experimental validation and clinical translation. To bridge the gap between complicated models and biological interpretations, we developed a tool, XAE4Exp (eXplainable AutoEncoder for Expression data), which integrates AE and SHapley Additive exPlanations (SHAP), a flagship technique in the field of eXplainable AI (XAI). It quantitatively evaluates the contributions of each gene to the hidden structure learned by an AE, substantially improving the expandability of AE outcomes. By applying XAE4Exp to The Cancer Genome Atlas (TCGA) breast cancer gene expression data, we identified genes that are not differentially expressed, and pathways in various cancer-related classes. This tool will enable researchers and practitioners to analyze high-dimensional expression data intuitively, paving the way towards broader uses of deep learning.AvailabilityOpen source at https://github.com/QingrunZhangLab/Explainable-Deep-Autoencoder.Contactsqingrun.zhang@ucalgary.ca and wliao@ucalgary.ca.
Early exposure to UV radiation causes telomere shortening and poorer condition later in life
Authors: Lundsgaard Niclas U. , Cramp Rebecca L. , Franklin Craig E. 
Published: December 2021

ABSTRACTDetermining the contribution of elevated ultraviolet-B radiation (UVBR; 280 – 315 nm) to amphibian population declines is being hindered by a lack of knowledge about how different acute UVBR exposure regimes during early life history stages might affect post-metamorphic stages via long-term carryover effects. We acutely exposed tadpoles of the Australian green tree frog (Litoria caerulea) to a combination of different UVBR irradiances and doses in a multi-factorial experiment, and then reared them to metamorphosis in the absence of UVBR to assess carryover effects in subsequent juvenile frogs. Dose and irradiance of acute UVBR exposure influenced carryover effects into metamorphosis in somewhat opposing manners. Higher doses of UVBR exposure in larvae yielded improved rates of metamorphosis. However, exposure at a high irradiance resulted in frogs metamorphosing smaller in size and in poorer condition than frogs exposed to low and medium irradiance UVBR as larvae. We also demonstrate some of the first empirical evidence of UVBR-induced telomere shortening in vivo, which is one possible mechanism for life-history trade-offs impacting condition post-metamorphosis. These findings contribute to our understanding of how acute UVBR exposure regimes in early life affect later life-history stages, which has implications for how this stressor may shape population dynamics.SUMMARY STATEMENTWe demonstrate physiological carryover effects in amphibians that link larval UV exposure to detrimental impacts on juvenile frogs, including telomere shortening, which has implications for how UV shapes amphibian populations.
Plant growth promoting activity of bacteria isolated from Asian rice (Oryza sativa L.) are plant subspecies dependent
Authors: Balasjin Nasim Maghboli , Maki James S. , Schläppi Michael R. , Marshall Christopher W. 
Published: December 2021

AbstractAsian rice is one of the most important crops because it is a staple food for almost half of the world’s population. Rice has two subspecies, JAPONICA and INDICA. To have production of rice keep pace with a growing world population, it is anticipated that the use of fertilizers will also need to increase, which may cause environmental damage through runoff impacts. An alternative strategy to increase crop yield is the use of plant growth promoting bacteria. Thousands of microbial species can exist in association with plant roots and shoots, and some are critical to the plant’s survival. We isolated 140 bacteria from rice and investigated whether JAPONICA and INDICA rice subspecies were positively influenced by these isolates. The bacterial isolates were screened for their ability to solubilize phosphate, a known plant growth promoting characteristic, and 25 isolates were selected for further analysis. These 25 phosphate solubilizing isolates were also able to produce other potentially growth-promoting factors. Five of the most promising bacterial isolates were chosen for whole genome sequencing. Four of these bacteria, isolates related to Pseudomonas mosselii, Microvirga sp., Paenibacillus rigui and Paenibacillus graminis, improved root and shoot growth, root to shoot ratio, and increased root dry weights of JAPONICA plants but had no effect on growth and development of INDICA plants. This indicates that while bacteria have several known plant growth promoting functions, their effects on growth parameters can be plant subspecies dependent and suggest close relationships between plants and their microbial partners.
Neural correlates of perceiving and interpreting engraved prehistoric patterns as human production: effect of archaeological expertise
Authors: Salagnon M , Cremona S , Joliot M , d’Errico F , Mellet E 
Published: December 2021

AbstractIt has been suggested that engraved abstract patterns dating from the Middle and Lower Palaeolithic served as means of representation and communication. Identifying the brain regions involved in visual processing of these engravings can provide insights into their function. In this study, brain activity was measured during perception of the earliest known Palaeolithic engraved patterns and compared to natural patterns mimicking human-made engravings. Participants were asked to categorise marks as being intentionally made by humans or due to natural processes (e.g. erosion, root etching). To simulate the putative familiarity of our ancestors with the marks, the responses of expert archaeologists and control participants were compared, allowing characterisation of the effect of previous knowledge on both behaviour and brain activity in perception of the marks. Besides a set of regions common to both groups and involved in visual analysis and decision-making, the experts exhibited greater activity in the inferior part of the lateral occipital cortex, ventral occipitotemporal cortex, and medial thalamic regions. These results are consistent with those reported in visual expertise studies, and confirm the importance of the integrative visual areas in the perception of the earliest abstract engravings. The attribution of a natural rather than human origin to the marks elicited greater activity in the salience network in both groups, reflecting the uncertainty and ambiguity in the perception of, and decision-making for, natural patterns. The activation of the salience network might also be related to the process at work in the attribution of an intention to the marks. The primary visual area was not specifically involved in the visual processing of engravings, which argued against its central role in the emergence of engraving production.
Continental-scale hyperspectral tree species classification in the United States National Ecological Observatory Network
Authors: Marconi Sergio , Weinstein Ben. G. , Zou Sheng , Bohlman Stephanie A. , Zare Alina , Singh Aditya , Stewart Dylan , Harmon Ira , Steinkraus Ashley , White Ethan P. 
Published: December 2021

AbstractAdvances in remote sensing imagery and machine learning applications unlock the potential for developing algorithms for species classification at the level of individual tree crowns at unprecedented scales. However, most approaches to date focus on site-specific applications and a small number of taxonomic groups. Little is known about how well these approaches generalize across broader geographic areas and ecosystems. Leveraging field surveys and hyperspectral remote sensing data from the National Ecological Observatory Network (NEON), we developed a continental-extent model for tree species classification that can be applied to the network, including a wide range of US terrestrial ecosystems. We compared the performance of a model trained with data from 27 NEON sites to models trained with data from each individual site, evaluating advantages and challenges posed by training species classifiers at the US scale. We evaluated the effect of geographic location, topography, and ecological conditions on the accuracy and precision of species predictions (72 out of 77 species). On average, the general model resulted in good overall classification accuracy (micro-F1 score), with better accuracy than site-specific classifiers (average individual tree level accuracy of 0.77 for the general model and 0.70 for site-specific models). Aggregating species to the genus-level increased accuracy to 0.83. Regions with more species exhibited lower classification accuracy. Predicted species were more likely to be confused with congeneric and co-occurring species and confusion was highest for trees with structural damage and in complex closed-canopy forests. The model produced accurate estimates of uncertainty, correctly identifying trees where confusion was likely. Using only data from NEON, this single integrated classifier can make predictions for 20% of all tree species found in forest ecosystems across the entire US, which make up to roughly 90% of the upper canopy of the studied ecosystems. This suggests the potential for integrating information from multiple datasets and locations to develop broad scale general models for species classification from hyperspectral imaging.
Multi-Pathway DNA Double-Strand Break Repair Reporters Reveal Extensive Cross-Talk Between End-Joining, Single Strand Annealing, and Homologous Recombination
Authors: van de Kooij Bert , Kruswick Alex , van Attikum Haico , Yaffe Michael B. 
Published: December 2021

AbstractDNA double-strand breaks (DSB) are repaired by multiple distinct pathways, with outcomes ranging from error-free repair to extensive mutagenesis and genomic loss. Repair pathway cross-talk and compensation within the DSB-repair network is incompletely understood, despite its importance for genomic stability, oncogenesis, and the outcome of genome editing by CRISPR/Cas9. To address this, we constructed and validated three fluorescent Cas9-based reporters, named DSB-Spectrum, that simultaneously quantify the contribution of multiple distinct pathways to repair of a DSB. These reporters distinguish between DSB-repair by error-free canonical non-homologous end-joining (c-NHEJ) versus homologous recombination (HR; reporter 1), mutagenic repair versus HR (reporter 2), and mutagenic end-joining versus single strand annealing (SSA) versus HR (reporter 3). Using these reporters, we show that inhibition of the essential c-NHEJ factor DNA-PKcs not only increases repair by HR, but also results in a substantial increase in mutagenic repair by SSA. We show that SSA-mediated repair of Cas9-generated DSBs can occur between Alu elements at endogenous genomic loci, and is enhanced by inhibition of DNA-PKcs. Finally, we demonstrate that the short-range end-resection factors CtIP and Mre11 promote both SSA and HR, whereas the long-range end-resection factors DNA2 and Exo1 promote SSA, but reduce HR, when both pathways compete for the same substrate. These new Cas9-based DSB-Spectrum reporters facilitate the rapid and comprehensive analysis of repair pathway crosstalk and DSB-repair outcome.
ModelRevelator: Fast phylogenetic model estimation via deep learning
Authors: Burgstaller-Muehlbacher Sebastian , Crotty Stephen M. , Schmidt Heiko A , Drucks Tamara , Haeseler Arndt von 
Published: December 2021

AbstractSelecting the best model of sequence evolution for a multiple-sequence-alignment (MSA) constitutes the first step of phylogenetic tree reconstruction. Common approaches for inferring nucleotide models typically apply maximum likelihood (ML) methods, with discrimination between models determined by one of several information criteria. This requires tree reconstruction and optimisation which can be computationally expensive. We demonstrate that neural networks can be used to perform model selection, without the need to reconstruct trees, optimise parameters, or calculate likelihoods.We introduce ModelRevelator, a model selection tool underpinned by two deep neural networks. The first neural network, NNmodelfind, recommends one of six commonly used models of sequence evolution, ranging in complexity from Jukes and Cantor to General Time Reversible. The second, NNalphafind, recommends whether or not a Γ--distributed rate heterogeneous model should be incorporated, and if so, provides an estimate of the shape parameter, α. Users can simply input an MSA into ModelRevelator, and swiftly receive output recommending the evolutionary model, inclusive of the presence or absence of rate heterogeneity, and an estimate of α.We show that ModelRevelator performs comparably with likelihood-based methods and the recently published machine learning method ModelTeller over a wide range of parameter settings, with significant potential savings in computational effort. Further, we show that this performance is not restricted to the alignments on which the networks were trained, but is maintained even on unseen empirical data. We expect that ModelRevelator will provide a valuable alternative for phylogeneticists, especially where traditional methods of model selection are computationally prohibitive.
Treated like dirt: Robust forensic and ecological inferences from soil eDNA after challenging sample storage
Authors: Frøslev Tobias Guldberg , Ejrnæs Rasmus , Hansen Anders J. , Bruun Hans Henrik , Nielsen Ida Broman , Ekelund Flemming , Vestergård Mette , Kjøller Rasmus 
Published: December 2021

AbstractBiodiversity of soil microbiota is routinely assessed with environmental DNA-based methods, among which amplification and massive parallel sequencing of marker genes (eDNA metabarcoding) is the most common. Soil microbiota may for example be investigated in relation to biodiversity research or as a tool in forensic investigations.After sampling, the taxonomic composition of soil biotic communities may change. In order to minimize community changes after sampling, it is desirable to reduce biological activity, e.g. by freezing immediately after sampling. However, this may be impossible due to remoteness of study sites or, in forensic cases, where soil has been attached to a questioned item for protracted periods of time.Here we investigated the effect of storage duration and conditions on the assessment of the soil biota with eDNA metabarcoding. We extracted eDNA from freshly collected soil samples and again from the same samples after storage under contrasting temperature conditions.We used five different primer sets targeting bacteria, fungi, protists (cercozoans), general eukaryotes, and plants. For these groups, we quantified differences in richness, evenness and community composition. Subsequently, we tested whether we could correctly infer habitat type and original sample identity after storage using a large reference dataset.We found increased community composition differences with extended storage time and with higher storage temperature. However, for samples stored less than 28 days at a maximum of 20°C, changes were generally insignificant. Classification models could successfully assign most stored samples to their exact location of origin and correct habitat type even after weeks of storage. Even samples showing larger compositional changes generally retained the original sample as the best match (relative similarity).Our results show that for most biodiversity and forensic applications, storage of samples for days and even several weeks may not be a problem, if storage temperature does not exceed 20°C. Even after suboptimal storage conditions, significant patterns can be reproduced.
Enhanced microvasculature formation and patterning in iPSC–derived kidney organoids cultured in physiological hypoxia
Authors: Schumacher A. , Roumans N. , Rademakers T. , Joris V. , Eischen-Loges M. , van Griensven M. , LaPointe V.L.S. 
Published: December 2021

AbstractFunctional kidney organoids have the potential to be used in implantable kidney grafts for patients with end-stage kidney disease, because they have been shown to self-organize from induced pluripotent stem cells into most important renal structures. To date, however, long-term kidney organoid culture has not succeeded, as nephrons lose their phenotype after approximately 25 days. Furthermore, the renal structures remain immature with diminishing endothelial networks with low connectivity and limited organoid invasion. We hypothesized that introducing long-term culture at physiological hypoxia, rather than the normally applied non-physiological, hyperoxic 21% O2, could initiate angiogenesis, lead to enhanced growth factor expression and improve the endothelial patterning. We therefore cultured the kidney organoids at 7% O2 instead of 21% O2 for up to 25 days and evaluated nephrogenesis, VEGF-A expression and vascularization. Whole mount imaging revealed a homogenous morphology of the endothelial network with enhanced sprouting and interconnectivity when the kidney organoids were cultured in hypoxia. Three-dimensional quantification confirmed that the hypoxic culture led to an increased average vessel length, likely due to the observed upregulation of proangiogenic VEGF-A189 mRNA and downregulation of the antiangiogenic protein VEGF-A165b measured in hypoxia. This research indicates the importance of optimization of oxygen availability in organoid systems and the potential of hypoxic culture conditions in improving the vascularization of organoids.Significance statementCulturing kidney organoids in a hypoxic environment improved patterning of the endothelial network and improved vascularization. These findings may help improve the quality of kidney organoids, and could eventually improve the kidney graft for transplantation in patients with end-stage kidney disease. Furthermore, the organoids will be more suitable for drug testing and in developmental biology. The findings might also be translatable to other organoid models containing endothelial cells.Graphical abstract
Type I Interferon Signaling Drives Microglial Dysfunction and Senescence in Human iPSC Models of Down Syndrome and Alzheimer’s Disease
Authors: Jin Mengmeng , Xu Ranjie , Wang Le , Alam Mahabub Maraj , Ma Ziyuan , Zhu Sining , Martini Alessandra C. , Jadali Azadeh , Bernabucci Matteo , Xie Ping , Kwan Kelvin , Pang Zhiping P. , Head Elizabeth , Liu Ying , Hart Ronald P. , Jiang Peng 
Published: December 2021

AbstractMicroglia are critical for brain development and play a central role in Alzheimer’s disease (AD) etiology. Down syndrome (DS), also known as trisomy 21, is the most common genetic origin of intellectual disability and the most common risk factor for AD. Surprisingly, little information is available on the impact of trisomy of human chromosome 21 (Hsa21) on microglia in DS brain development and AD in DS (DSAD). Using our new induced pluripotent stem cell (iPSC)-based human microglia-containing cerebral organoid and chimeric mouse brain models, here we report that DS microglia exhibit enhanced synaptic pruning function during brain development. Consequently, electrophysiological recordings demonstrate that DS microglial mouse chimeras show impaired synaptic functions, as compared to control microglial chimeras. Upon being exposed to human brain tissue-derived soluble pathological tau, DS microglia display dystrophic phenotypes in chimeric mouse brains, recapitulating microglial responses seen in human AD and DSAD brain tissues. Further flow cytometry, single-cell RNA- sequencing, and immunohistological analyses of chimeric mouse brains demonstrate that DS microglia undergo cellular senescence and exhibit elevated type I interferon signaling after being challenged by pathological tau. Mechanistically, we find that shRNA-mediated knockdown of Hsa21encoded type I interferon receptor genes,IFNARs, rescues the defective DS microglial phenotypes both during brain development and in response to pathological tau. Our findings provide firstin vivoevidence supporting a paradigm shifting theory that human microglia respond to pathological tau by exhibiting accelerated senescence and dystrophic phenotypes. Our results further suggest that targeting IFNARs may improve microglial functions during DS brain development and prevent human microglial senescence in DS individuals with AD.
Profiling subcellular localization of nuclear-encoded mitochondrial gene products in zebrafish
Authors: Uszczynska-Ratajczak Barbara , Sugunan Sreedevi , Kwiatkowska Monika , Migdal Maciej , Carbonell-Sala Silvia , Sokol Anna , Winata Cecilia L. , Chacinska Agnieszka 
Published: December 2021

AbstractMost mitochondrial proteins are encoded by nuclear genes, synthetized in the cytosol and targeted into the organelle. The import of some, but not all, nuclear-encoded mitochondrial proteins begins with translation of messenger RNAs (mRNAs) on the surface of mitochondria. To characterize the spatial organization of mitochondrial gene products in zebrafish (Danio rerio), we sequenced RNA from different cellular fractions. Our results confirmed the presence of nuclear-encoded mRNAs in the mitochondrial fraction, which in unperturbed conditions, are mainly transcripts encoding large proteins with specific properties, like transmembrane domains. To further explore the principles of mitochondrial protein compartmentalization in zebrafish, we quantified the transcriptomic changes for each subcellular fraction triggered by the chchd4a-/- mutation, causing the disorders in the mitochondrial protein import. Our results indicate that the proteostatic stress further restricts the population of transcripts on the mitochondrial surface, allowing only the largest and the most evolutionary conserved proteins to be synthetized there. We also show that many nuclear-encoded mitochondrial transcripts translated by the cytosolic ribosomes stay resistant to the global translation shutdown. Thus, vertebrates, in contrast to yeast, are not likely to employ localized translation to facilitate synthesis of mitochondrial proteins under proteostatic stress conditions.
Study of anFBXO7patient mutation reveals Fbxo7 and PI31 co-regulate proteasomes and mitochondria
Authors: Al Rawi Sara , Simpson Lorna , McDonald Neil Q. , Chernuha Veronika , Elpeleg Orly , Zeviani Massimo , Barker Roger A. , Spiegel Ronen , Laman Heike 
Published: December 2021

AbstractMutations inFBXO7have been discovered associated with an atypical parkinsonism. We report here a new homozygous missense mutation in a paediatric patient that causes an L250P substitution in the dimerization domain of Fbxo7. This alteration selectively ablates the Fbxo7-PI31 interaction and causes a significant reduction in Fbxo7 and PI31 levels in patient cells. Consistent with their association with proteasomes, L250P patient fibroblasts have reduced proteasome activity and proteasome subunits. We also show PI31 interacts directly with the MiD49/51 fission adaptor proteins, and unexpectedly, PI31 acts as an adaptor enabling SCFFbxo7ligase to ubiquitinate MiD49. Thus, the L250P mutation changes the function of Fbxo7 by altering its substrate repertoire. Although MiD49/51 expression was reduced in L250P patient cells, there was no effect on the mitochondrial network. However, patient cells had higher levels of ROS and reduced viability under stress. Our study shows that Fbxo7 and PI31 affect each other’s functions in regulating both proteasomal and mitochondrial function and demonstrate a new function for PI31, as an adaptor for the SCFFbxo7E3 ubiquitin ligase.