bluuebunny/crossref_metadata_2025_split huggingface dataset:
Induced pluripotent stem cells and cerebral organoids from the critically endangered Sumatran rhinoceros
Authors: Zywitza Vera , Frahm Silke , Krüger Norman , Weise Anja , Göritz Frank , Hermes Robert , Holtze Susanne , Colleoni Silvia , Galli Cesare , Drukker Micha , Hildebrandt Thomas B. , Diecke Sebastian 
Published: May 2022

SUMMARYLess than 80 Sumatran rhinos (SR, Dicerorhinus sumatrensis) are left on earth. Habitat loss and limited breeding possibilities are the greatest threats for the species and lead to a continuous population decline. To stop erosion of genetic diversity, reintroduction of genetic material is indispensable. However, as the propagation rate of captive breeding is far too low, innovative technologies have to be developed. Induced pluripotent stem cells (iPSCs) are a powerful tool to fight extinction. They give rise to each cell within the body including gametes, and provide a unique modality to preserve genetic material across time. Additionally, they enable studying species-specific developmental processes.Here, we generate iPSCs from the last male Malaysian SR Kertam, who died in 2019, and characterize them comprehensively. Differentiation in cells of the three germ layers and cerebral organoids demonstrate their high quality and great potential for supporting rescue of this critically endangered species.HIGHLIGHTS-Characterization of Sumatran Rhino (SR) fibroblasts-Generation of SR induced pluripotent stem cells (SR-iPSCs)-SR-iPSCs generate cells of the three germ layers-SR-iPSCs give rise to cerebral organoids
Transretinal migration of astrocytes and brain/spinal cord-like cells arising from transplanted human retinal organoids
Authors: Liu Ying V. , Santiago Clayton P. , Sogunro Akin , Konar Gregory J. , Hu Ming-wen , McNally Minda M. , Lu Yu-chen , Li Zhuo-lin , Agakishiev Dzhalal , Hadyniak Sarah E. , Hussey Katarzyna A. , Creamer Tyler J. , Orzolek Linda D. , Teng Derek , Qian Jiang , Jiang Zheng , Johnston Robert J. , Blackshaw Seth , Singh Mandeep S. 
Published: May 2022

AbstractHuman retinal organoid transplantation can potentially restore vision in patients with degenerative retinal diseases. How the recipient retina regulates the maturation, fate specification, and migration of transplanted organoid cells is unknown. We transplanted human retinal organoid-derived cells into photoreceptor-deficient mice, conducted histology and single-cell RNA sequencing analyses, and observed two main classes of graft-derived cells. The first class consisted of retinal astrocytes and brain/spinal cord-like neural precursors, absent or rare in cultured organoids, that migrated into all recipient retinal layers and traveled long distances. The second class consisted of retinal progenitor-derived cells, including rods and cones, that remained in the subretinal space and matured more rapidly than photoreceptors in culture. These data suggest that the recipient subretinal space promotes the maturation of transplanted photoreceptors while inducing or expanding migratory cell populations that are not normally derived from retinal progenitors. These findings have important implications for cell-based treatment of retinal diseases.
Insights into the genomics of clownfish adaptive radiation: the genomic substrate of the diversification
Authors: Marcionetti Anna , Salamin Nicolas 
Published: May 2022

ABSTRACTClownfishes are an iconic group of coral reef fishes that evolved a mutualistic interaction with sea anemones, which triggered the rapid diversification of the group. We investigated the genomic architecture underlying this process to determine the genomic characteristics associated with the adaptive radiation of the group and assess the mechanisms of parallel evolution in clownfishes.We took advantage of the available genomic data of five pairs of closely related but ecologically divergent clownfish species to perform comparative genomic analyses. We found that clownfish genomes show two bursts of transposable elements, overall accelerated coding evolution, and topology inconsistencies potentially resulting from hybridization events. These characteristics possibly facilitated the rapid diversification of the group. We also detected a signature of positive selection throughout the radiation in 5.4 % of the clownfish genes. Among them, five presented functions associated with social behavior and ecology. They could have potentially played a role in the evolution of size-based hierarchical social structure so particular to clownfishes. Finally, we found genes with patterns of either relaxation or intensification of purifying selection and signals of positive selection linked with clownfish ecological divergence, suggesting some level of parallel evolution during the diversification of the group.Altogether, these results provide the first insights into the genomic substrate of clownfish adaptive radiation. This work integrates the growing collection of studies investigating the genomic mechanisms governing species diversification, which brings us a step closer to understanding how biodiversity on Earth is created
Assessment of Human Renal Transporter Based Drug-Drug Interactions Using Proximal Tubule Kidney-Chip
Authors: Nookala Anantha Ram , Ronxhi Janey , Sliz Josiah , Jeanty Sauvear , Manatakis Dimitris V. , Jadalannagari Sushma , Hamilton Geraldine , Park Hyoungshin , He Yu , Lavarias Mitchell , Luo Gang , Jang Kyung-Jin , Mckenzie Donald 
Published: May 2022

AbstractStudy of renal transporters is crucial for understanding drug disposition and toxicity, and more importantly, predicting potential drug-drug interactions (DDIs). However, conventional in vitro models often fail to predict renal transporter activity and are not scalable to a predictive clinical outcome due to in vitro-in vivo discrepancy. Here, we successfully developed a human Proximal Tubule Kidney-Chip model that emulated in vivo renal physiology and function to assess renal transporter-based DDIs. Active and improved functionality of key renal transporters including p-glycoprotein (P-gp), multidrug and toxin extrusion (MATE) 1 and 2-K, organic anion transporter (OAT) 1 and 3, and organic cation transporter (OCT) 2 were demonstrated using appropriate probe substrates in Kidney-Chips compared to transwell controls. Moreover, comparative transcriptomic analysis revealed that key efflux and uptake transporters were expressed significantly higher in the Kidney-Chip compared to the transwell. Additionally, key parameters obtained from substrate-inhibitor interactions in the model were used to predict clinical DDIs as well as clearance values, which were closer to in vivo clearances. Overall, these results support that the human Proximal Tubule Kidney-Chip can reliably assess the role of human renal transporters in drug disposition and drug interactions, providing a critical tool to assess renal transport in vitro.
Longitudinal comparison of the developing gut virome in infants and their mothers
Authors: Granados Andrea C , Ley Catherine , Walters William A. , Federman Scot , Santos Yale , Haggerty Thomas , Sotomayor-Gonzalez Alicia , Servellita Venice , Ley Ruth E , Parsonnet Julie , Chiu Charles Y 
Published: May 2022

AbstractThe virome of the human gut and its development in early life are poorly understood. Here we performed viral metagenomic sequencing on stool samples from a multiethnic, socioeconomically diverse cohort of 53 infants collected longitudinally over their first 3 years of life and their mothers to investigate and compare their viromes. The asymptomatic infant virome consisted of bacteriophages, dietary/environmental viruses, and human pathogenic viruses, in contrast to the material virome, in which sequence reads from human pathogenic viruses were absent or present at extremely low levels. Picornaviruses and phages in the family Microviridae (microviruses) dominated the infant virome, while microviruses and tomato mosaic virus dominated the maternal virome. As the infants aged, the human pathogenic and dietary/environmental virus components remained distinct from the materal virome, while the phage component evolved to become more similar. However, the composition of the evolving infant virome was not determined by the mother and was still maturing to the adult virome at three years of age.ImportanceThe development of the human gut virome in early childhood is poorly understood. Here we use viral metagenomic sequencing in a cohort of 53 infants to the characterize their gut viromes and compare them to their mothers’.. This study finds that the infant virome consists of phages and human pathogenic viruses in asymptomatic individuals and is still maturing into the adult virome at three years of age.
The Drosophila attP40 docking site and derivatives are insertion mutations of MSP300
Authors: van der Graaf Kevin , Srivastav Saurabh , Singh Pratibha , McNew James A , Stern Michael 
Published: May 2022

AbstractThe ϕC31 integrase system is widely used in Drosophila to allow transgene targeting to specific loci. Over the years, flies bearing any of more than 100 attP docking sites have been constructed. One popular docking site, termed attP40, is located close to the Nesprin-1 orthologue MSP300 and lies upstream of certain MSP300 isoforms and within the first intron of others. Here we show that attP40 causes larval muscle nuclear clustering, which is a phenotype also conferred by MSP300 mutations. We also show that flies bearing insertions within attP40 can exhibit decreased MSP300 transcript levels in third instar larvae. Finally, chromosomes carrying certain “transgenic RNAi project” (TRiP) insertions into attP40 can confer pupal or adult inviability, or infertility. These phenotypes do not require transcription from the insertions within attP40. These results demonstrate that attP40 and insertion derivatives act as MSP300 insertional mutations. These findings should be considered when interpreting data from attP40-bearing flies.
Multifunctional flexible electro-optical arrays for simultaneous spatiotemporal cardiac mapping and modulation
Authors: Obaid Sofian N. , Chen Zhiyuan , Madrid Micah , Lin Zexu , Tian Jinbi , Humphreys Camille , Adams Jillian , Daza Nicolas , Balansag Jade , Efimov Igor R. , Lu Luyao 
Published: May 2022

AbstractBioelectronic devices that allow simultaneous accurate monitoring and control of the spatiotemporal patterns of cardiac activity provide an effective means to understand the mechanisms and optimize therapeutic strategies for heart disease. Optogenetics is a promising technology for cardiac research due to its advantages such as cell-type selectivity and high space-time resolution, but its efficacy is limited by the insufficient number of modulation channels and lack of simultaneous spatiotemporal mapping capabilities in current cardiac optogenetics tools. Here we present soft implantable electro-optical cardiac devices integrating multilayered highly uniform arrays of transparent microelectrodes and multicolor micro-light-emitting-diodes in thin, flexible platforms for mechanically compliant high-content electrical mapping and single-/multi-site optogenetics and electrical stimulation without light-induced artifacts. Systematic benchtop characterizations, together with ex vivo and in vivo evaluations on healthy and diseased small animal and human hearts demonstrate their functionalities in real-time spatiotemporal mapping and control of cardiac rhythm and function, with broad applications in basic and ultimately clinical cardiology.
Comparing Heart Rate Variability in Canadian Armed Forces Patients to Control Participants without Chronic Pain/Mental Health Issues
Authors: Kamal Latifah , Minerbi Amir , Sahar Tali , Heilman Keri J. , Besemann LCol Markus , Sreenivasan Vidya , Aggerwal Salena , Gupta Gaurav 
Published: May 2022

AbstractBackgroundThe autonomic nervous system is subserved by the sympathetic and parasympathetic which regulate vital involuntary physiological functions like heart rate. Parasympathetic activity can be measured from the high-frequency component of heart rate variability (HRV), measured via the amplitude of RSA, as a possible predictor for mental health and chronic pain disorders. Therefore, investigators looked to correlate HRV with chronic pain when compared healthy controls.MethodsAs part of a larger ongoing study, patients complete pre-defined questionnaires on their pain condition, potential risk factors, and function. For patients and controls investigators collected performance and cardiac measures (RSA, LF-HRV, heart period) while at rest, walking and lifting tests. This analysis focused on differences in heart rate variability measures between 100 patients and 48 controls.ResultsPreliminary analysis revealed demographic and anthropometric variables varied significantly between groups. When comparing HRV measures, respiratory sinus arrhythmia (RSA) during lying and sitting were significantly decreased in patients compared to controls while heart period lying and walking were significantly increased in patients. Correlation analysis revealed significant positive correlation between RSA during lying and sitting when looking at age, gender, and weight. Heart periods during lying and walking were negatively correlated with gender and weight.DiscussionTo our knowledge it is the first study to look at chronic pain and HRV in the Canadian Forces, while also collecting data on patient reported outcomes, and during various resting and activities. Many potential limitations exist for this study including challenges with respect to controlling for known confounders of heart variability.ConclusionBy establishing heart rate variability as a correlate of chronic pain, the outcome of this project could potentially improve quality of care for patients with these conditions. Further work controlling for confounders and relating HRV to pain severity, subtypes, patient reported outcomes and functional abilities will be required to determine the exact value for clinical decision making.
Pan-cancer scale screening reveals NRF2 associated immunoevasive characteristics in non-small cell lung cancer and squamous malignancies
Authors: Härkönen Jouni , Pölönen Petri , Jawahar Deen Ashik , Selvarajan Ilakya , Teppo Hanna-Riikka , Dimova Elitsa Y , Kietzmann Thomas , Ahtiainen Maarit , Eklund Tiia , Kuopio Teijo , Talvitie Eva-Maria , Taimen Pekka , Kallajoki Markku , Kaikkonen Minna U , Heinäniemi Merja , Levonen Anna-Liisa 
Published: May 2022

SummaryThe NRF2 pathway is frequently activated in various cancer types, yet a comprehensive analysis of its effects across different malignancies is currently lacking. We developed a robust NRF2 activity metric and utilized it to conduct a pan-cancer wide analysis of oncogenic NRF2 signaling. We identified a distinct immunoevasive phenotype where high NRF2 activity is associated with low interferon-gamma (IFNγ), HLA-I expression and T-cell infiltration spanning non-small cell lung cancer (NSCLC) and squamous malignancies of head and neck area, cervix and esophagus. In squamous cell cancers, NRF2 overactive tumors comprise a molecular phenotype with SOX2/TP63 amplification, TP53 mutation and CDKN2A loss. These immune-cold NRF2 hyperactive diseases are associated with upregulation of immunomodulatory NAMPT, WNT5A, SPP1, SLC7A11 and SLC2A1 that represent candidate NRF2 target genes, suggesting direct modulation of the tumor immune milieu. Based on single-cell mRNA data, coupled with a priori information on intercellular ligand-receptor interactions, cancer cells of this subtype exhibit decreased expression of IFNγ responsive ligands, and increased expression of immunosuppressive ligands NAMPT, SPP1 and WNT5A that mediate signaling in intercellular crosstalk. As we observed differential cytokine mRNA expression with IFNγ treatment in NSCLC adenocarcinoma subtype, we explored the cytokine secretome in vitro. We found that secreted neutrophil chemoattractants interleukin-8 (CXCL8) and ENA-78 (CXCL5) are elevated in NRF2 overactive cells, suggesting contribution of immunosuppressive neutrophils in NRF2 driven immune escape. Importantly, as overactive NRF2 is associated with immune-cold characteristics, our results highlight the utility of NRF2 pathway activation as a putative biomarker for stratifying immune-checkpoint blockade responders and non-responders across NSCLC and squamous cancers.Abstract Figure
Alignment of Single-Molecule Sequencing Reads by Enhancing the Accuracy and Efficiency of Locality-Sensitive Hashing
Authors: Nikaein Hassan , Sharifi-Zarchi Ali 
Published: May 2022

AbstractAligning single-molecule sequencing (SMS) reads to a reference genome has been computationally challenging due to the high sequencing error rates in this technology. Short distances between consecutive errors in SMS reads confront finding seeds, subsequences of the reads with exact matches to the reference, that specifically target a unique genomic position. To overcome this issue, one can look for similarities, rather than exact matches. MinHash, a locality-sensitive hashing (LSH) scheme, measures the similarity of two sequences by listing all k-mers of each one and approximating the fraction of common k-mers between them using a family of hash functions, which usually includes hundreds to thousands of different hash functions in order to increase the measurement accuracy. MinHash is used to address various bioinformatics problems, including the assembly of SMS reads. Here, we enhance both the efficiency and accuracy of the MinHash scheme by algorithmic techniques. We use a single hash function, rather than hundreds or thousands of different hash functions as used in the other MinHash-based algorithms, without losing the accuracy. We also double the size of the seed sequences by allowing one sequencing error of any form inside a pair of k-mers, which has a significant impact on the accuracy. We show algorithm, called Aryana-LoR, outperforms the accuracy of the other existing SMS aligners in both E-coli and Human genomes.AvailabilityAryana-LoR is freely available at https://gitlab.com/hnikaein/aryana-LoR
Identifying Neural Correlates of Balance Deficits in Traumatic Brain Injury Using Partial Least Squares Correlation Analysis
Authors: Handiru Vikram Shenoy , Suviseshamuthu Easter S. , Saleh Soha , Su Haiyan , Yue Guang H. , Allexandre Didier 
Published: May 2022

AbstractBackgroundBalance impairment is one of the most debilitating consequences of Traumatic Brain Injury (TBI). To study the neurophysiological underpinnings of balance impairment, the brain functional connectivity during perturbation tasks can provide new insights. To better characterize the association between the task-relevant functional connectivity and the degree of balance deficits in TBI, the analysis needs to be performed on the data stratified based on the balance impairment. However, such stratification is not straightforward, and it warrants a data-driven approach.ApproachWe conducted a study to assess the balance control using a computerized posturography platform in 17 individuals with TBI and 15 age-matched healthy controls. We stratified the TBI participants into balance-impaired and non-impaired TBI usingk-means clustering of either center of pressure (COP) displacement during a balance perturbation task or Berg Balance Scale (BBS) score as a functional outcome measure. We analyzed brain functional connectivity using the imaginary part of coherence across different cortical regions in various frequency bands. These connectivity features are then studied using the mean-centered partial least squares correlation (MC-PLSC) analysis, which is a multivariate statistical framework with the advantage of handling more features than the number of samples, thus making it suitable for a small-sample study.Main ResultsBased on the nonparametric significance testing using permutation and bootstrap procedure, we noticed that the theta-band connectivity strength in the following regions of interest significantly contributed to distinguishing balance impaired from non-impaired population, regardless of the type of strat-ification:left middle frontal gyrus, right paracentral lobule, precuneus, andbilateral middle occipital gyri.SignificanceIdentifying neural regions linked to balance impairment enhances our understanding of TBI-related balance dysfunction and could inform new treatment strategies. Future work will explore the impact of balance platform training on sensorimotor and visuomotor connectivity.
Variation in the ACE2 receptor has limited utility for SARS-CoV-2 host prediction
Authors: Mollentze Nardus , Keen Deborah , Munkhbayar Uuriintuya , Biek Roman , Streicker Daniel G. 
Published: May 2022

AbstractTransmission of SARS-CoV-2 from humans to other species threatens wildlife conservation and may create novel sources of viral diversity for future zoonotic transmission. A variety of computational heuristics have been developed to pre-emptively identify susceptible host species based on variation in the ACE2 receptor used for viral entry. However, the predictive performance of these heuristics remains unknown. Using a newly-compiled database of 96 species we show that, while variation in ACE2 can be used by machine learning models to accurately predict animal susceptibility to sarbecoviruses (accuracy = 80.2%, binomial confidence interval [CI]: 70.8 – 87.6%), the sites informing predictions have no known involvement in virus binding and instead recapitulate host phylogeny. Models trained on host phylogeny alone performed equally well (accuracy = 84.4%, CI: 75.5 – 91.0%) and at a level equivalent to retrospective assessments of accuracy for previously published models. These results suggest that the predictive power of ACE2-based models derives from strong correlations with host phylogeny rather than processes which can be mechanistically linked to infection biology. Further, biased availability of ACE2 sequences misleads projections of the number and geographic distribution of at-risk species. Models based on host phylogeny reduce this bias, but identify a very large number of susceptible species, implying that model predictions must be combined with local knowledge of exposure risk to practically guide surveillance. Identifying barriers to viral infection or onward transmission beyond receptor binding and incorporating data which are independent of host phylogeny will be necessary to manage the ongoing risk of establishment of novel animal reservoirs of SARS-CoV-2.
Choice of 3D morphometric method leads to diverging interpretations of form–function relationships in the carnivoran calcaneus
Authors: Wimberly Alexa N. , Natale Rossy , Higgins Robert , Slater Graham J. 
Published: May 2022

AbstractThree dimensional morphometric methods are a powerful tool for comparative analysis of shape. However, morphological shape is often represented using landmarks selected by the user to describe features of perceived importance, and this may lead to over confident prediction of form-function relationships in subsequent analyses. We used Generalized Procrustes Analysis (GPA) of 13 homologous 3D landmarks and spherical harmonics (SPHARM) analysis, a homology-free method that describes the entire shape of a closed surface, to quantify the shape of the calcaneus, a landmark poor structure that is important in hind-limb mechanics, for 111 carnivoran species spanning 12 of 13 terrestrial families. Both approaches document qualitatively similar patterns of shape variation, including a dominant continuum from short/stout to long/narrow calcanea. However, while phylogenetic generalized linear models indicate that locomotor mode best explains shape from the GPA, the same analyses find that shape described by SPHARM is best predicted by foot posture and body mass without a role for locomotor mode, though effect sizes for all are small. User choices regarding morphometric methods can dramatically impact macroevolutionary interpretations of shape change in a single structure, an outcome that is likely exacerbated when readily landmarkable features are few.