bluuebunny/crossref_metadata_2025_split huggingface dataset:
A photopolymerizable hydrogel enhances intramyocardial vascular cell delivery and promotes post-myocardial infarction healing by polarizing pro-regenerative neutrophils
Authors: Hong Xuechong , Luo Allen Chilun , Doulamis Ilias , Oh Nicholas , Im Gwang-Bum , del Nido Pedro J. , Melero-Martin Juan M. , Lin Ruei-Zeng 
Published: July 2022

AbstractThe success of vascular progenitor cell transplantation to treat myocardial infarction (MI) is primarily limited by the low engraftment of delivered cells due to a washout effect during myocardium contraction. A clinically applicable biomaterial to improve cell retention is arguably needed to enable optimization of intramyocardial cell delivery. Here, we developed a novel therapeutic cell delivery method for MI treatment based on a photocrosslinkable gelatin methacryloyl (GelMA) hydrogel. A combination of human vascular progenitor cells (endothelial progenitors and mesenchymal stem cells) with the capacity to form functional vasculatures after transplantation, were injected with a rapid in-situ photopolymerization approach into the infarcted zone of mouse hearts. Our approach significantly improved acute cell retention and achieved a long-term beneficial post-MI cardiac healing, including stabilizing cardiac functions, preserving viable myocardium, and preventing cardiac fibrosis. Furthermore, the engrafted vascular cells polarized recruited bone marrow-derived neutrophils toward a non-inflammatory phenotype via TGFβ signaling, establishing a pro-regenerative microenvironment. Depletion of neutrophils canceled the therapeutic benefits produced by cell delivery in the ischemic hearts, indicating that the non-inflammatory, pro-regenerative neutrophils were indispensable mediators of cardiac remodeling. In summary, our novel GelMA hydrogel-based intramyocardial vascular cell delivery approach has the potential to improve the treatment of acute MI.
Discovery of two novel Torque Teno viruses in Callithrix penicillata provides insights on Anelloviridae diversification dynamics
Authors: Cosentino Matheus Augusto Calvano , D’arc Mirela , Moreira Filipe Romero Rebello , Cavalcante Liliane Tavares de Faria , Mouta Ricardo , Coimbra Amanda , Schiffler Francine Bittencourt , Miranda Thamiris dos Santos , Viana Gabriel Medeiros , Dias Cecilia A , Souza Antonizete R , Tavares Maria Clotilde Henriques , Tanuri Amilcar , Soares Marcelo Alves , dos Santos André Felipe Andrade 
Published: July 2022

1.AbstractThe development of high throughput sequencing (HTS) technologies and metagenomics protocols deeply impacted the discovery of viral diversity. Moreover, the comprehension of evolution and immunology of the Neotropical primates (NP) and their susceptibility to infectious diseases are central for the characterization of the scope of etiological agents that may impact global health, due to their evolutionary proximity to Old World primates, including humans. In the present work, novel anelloviruses were detected and characterized through HTS protocols in the NP Callithrix penicillata, the common black-tufted marmoset. De novo assembly of generated sequences was carried out and a total of 15 contigs were identified with complete Anelloviridae ORF1 gene, two of them including a flanking GC-rich region, confirming the presence of two whole novel genomes of ~3kb. The identified viruses were monophyletic within the Epsilontorquevirus genus, a lineage harboring previously reported anelloviruses infecting hosts from the Cebidae family. The genetic divergence found in the new viruses characterized two novel species, named Epsilontorquevirus callithrichensis I and II. The phylogenetic pattern inferred for the Epsilontorquevirus genus was consistent with the topology of their host species tree, echoing a virus-host diversification model observed in other viral groups. This study expands the host span of Anelloviridae and provides insights into their diversification dynamics, highlighting the importance of sampling animal viral genomes to obtain a clearer depiction of their long-term evolutionary processes.
Healthy and diseased placenta barrier on-a-chip models suitable for high-throughput studies
Authors: Rabussier Gwenaёlle , Bünter Ivan , Bouwhuis Josse , Soragni Camilla , Ng Chee Ping , Dormansky Karel , de Windt Leon J. , Vulto Paul , Murdoch Colin E. , Bircsak Kristin M. , Lanz Henriёtte L. 
Published: July 2022

AbstractPreeclampsia is one of the leading causes of maternal and perinatal morbidity in the world. Its fundamental mechanisms are yet poorly understood due to a lack of good experimental models. Here we report an in vitro model of the placental barrier, based on co-culture of trophoblasts and endothelial cells against a collagen extracellular matrix in a microfluidic platform. The model yielded a functional syncytium with barrier properties, polarization, secretion of relevant extracellular membrane components, thinning of the materno-fetal space, hormone secretion, and transporter function. The model was exposed to low oxygen conditions and perfusion flow was modulated to induce preeclamptic characteristics, resulting in reduced barrier function, hormone secretion, and microvilli as well as increased nuclei count. The model was implemented in a titer plate microfluidic platform fully amenable to high-throughput screening. We thus believe this model could aid mechanistic understanding of preeclampsia as well as support future development of effective therapies through target and compound screening campaigns.
Ion-channel degeneracy and heterogeneities in the emergence of complex spike bursts in CA3 pyramidal neurons
Authors: Roy Rituparna , Narayanan Rishikesh 
Published: July 2022

ABSTRACTComplex spike bursting (CSB) is a characteristic electrophysiological signature exhibited by several neurons and has been implicated in neural plasticity, learning, perception, anesthesia, and active sensing. Here, we address the question of how pronounced intrinsic and synaptic heterogeneities affect CSB, with hippocampal CA3 pyramidal neurons (CA3PN) as a substrate where CSB emergence and heterogeneities are well-characterized. We randomly generated 12,000 unique models and found 236 valid models that satisfied 11 characteristic CA3PN measurements. These morphologically and biophysically realistic valid models accounted for gating kinetics and somato-dendritic expression profiles of 10 active ion channels. This heterogeneous population of valid models was endowed with broad distributions of underlying parameters showing weak pair-wise correlations. We found two functional subclasses of valid models, intrinsically bursting and regular spiking, with significant differences in the expression of calcium and calcium-activated potassium conductances. We triggered CSB in all 236 models through different intrinsic or synaptic protocols and observed considerable heterogeneity in CSB propensity and properties spanning models and protocols. Finally, we employed virtual knockout analyses and showed that synergistic interactions between intrinsic and synaptic mechanisms regulated CSB emergence and dynamics. Specifically, although there was a dominance of calcium and calcium-activated potassium channels in the emergence of CSB, individual deletion of none of the several ion channels or N-methyl-D-aspartate receptors resulted in the complete elimination of CSB across all models. Together, our analyses critically implicate ion-channel degeneracy in the robust emergence of CSB and other characteristic signatures of CA3PNs, despite pronounced heterogeneities in underlying intrinsic and synaptic properties.
Constitutive Activation and Oncogenicity Are Mediated by Loss of Helical Structure at the Cytosolic Boundary of the Thrombopoietin Receptor
Authors: Defour Jean-Philippe , Leroy Emilie , Dass Sharmila , Balligand Thomas , Levy Gabriel , Mouton Céline , Genet Lidvine , Pecquet Christian , Smith Steven O. , Constantinescu Stefan N. 
Published: July 2022

AbstractDimerization of the thrombopoietin receptor (TpoR) is necessary for receptor activation and downstream signaling through activated Janus kinase 2. We have shown previously that different orientations of the transmembrane (TM) helices within a receptor dimer can lead to different signaling outputs. Here we addressed the structural basis of activation for receptor mutations S505N and W515K that induce myeloproliferative neoplasms. We show using in vivo bone marrow reconstitution experiments that ligand-independent activation of TpoR by TM asparagine (Asn) substitutions is proportional to the proximity of the mutation to the intracellular membrane surface. Solid-state NMR experiments on TM peptides indicate a progressive loss of helical structure in the juxtamembrane (JM) R/KWQFP motif with either proximity of Asn substitutions to the cytosolic boundary or mutation of W515 in the motif. Mutational studies in the TpoR cytosolic JM region show that the helical loss by itself can induce activation, but is localized to a maximum of 6 amino acids downstream of W515, the rest of the region until Box 1 requiring helicity for receptor function. The constitutive activation of TpoR mutants S505N and W515K can be inhibited by rotation of TM helices within the TpoR dimer, which also restores helicity around W515. Together these data allow us to develop a general model for activation and to explain the critical role of the JM W515 residue in the regulation of receptor activity.(Total manuscript without References and Figure Legends 6507 words, main text (without methods and materials):)
Quantifying the movement, behavior, and environmental context of group-living animals using drones and computer vision
Authors: Koger Benjamin , Deshpande Adwait , Kerby Jeffrey T. , Graving Jacob M. , Costelloe Blair R. , Couzin Iain D. 
Published: July 2022

AbstractMethods for collecting animal behavior data in natural environments, such as direct observation and bio-logging, are typically limited in spatiotemporal resolution, the number of animals that can be observed, and information about animals’ social and physical environments.Video imagery can capture rich information about animals and their environments, but image-based approaches are often impractical due to the challenges of processing large and complex multi-image datasets and transforming resulting data, such as animals’ locations, into geographic coordinates.We demonstrate a new system for studying behavior in the wild that uses drone-recorded videos and computer vision approaches to automatically track the location and body posture of free-roaming animals in georeferenced coordinates with high spatiotemporal resolution embedded in contemporaneous 3D landscape models of the surrounding area.We provide two worked examples in which we apply this approach to videos of gelada monkeys and multiple species of group-living African ungulates. We demonstrate how to track multiple animals simultaneously, classify individuals by species and age-sex class, estimate individuals’ body postures (poses), and extract environmental features, including topography of the landscape and animal trails.By quantifying animal movement and posture, while simultaneously reconstructing a detailed 3D model of the landscape, our approach opens the door to studying the sensory ecology and decision-making of animals within their natural physical and social environments.
CircRNA-regulated immune response of Asian honey bee workers to microsporidian infection
Authors: Zhu Zhiwei , Wang Jie , Fan Xiaoxue , Long Qi , Chen Huazhi , Ye Yaping , Zhang Kaiyao , Ren Zhongmin , Zhang Yang , Niu Qingsheng , Chen Dafu , Guo Rui 
Published: July 2022

AbstractNosema ceranae is a widespread fungal parasite for honey bees, causing bee nosemosis. Based on deep sequencing and bioinformatics, identification of circular RNAs (circRNAs) in Apis cerana cerana workers’ midguts and circRNA-regulated immune response of host to N. ceranae invasion were conducted in this current work, followed by molecular verification of back-splicing sites and expression trends of circRNAs. Here, 10185 and 7405 circRNAs were identified in the midguts of workers at 7 d (AcT1) and 10 d (AcT2) post inoculation (dpi) with N. ceranae. PCR amplification result verified the back-splicing sites in three specific circRNAs (novel_circ_005123, novel_circ_007177, and novel_circ_015140) expressed in N. ceranae-inoculated midgut. In combination with transcriptome data from corresponding un-inoculated midguts (AcCK1 and AcCK2), 2266 circRNAs were found to be shared by the aforementioned four groups, whereas the numbers of specific ones were 2618, 1917, 5691 and 3723 respectively. Further, 83 (52) differentially expressed circRNAs (DEcircRNAs) were identified in AcCK1 vs AcT1 (AcCK2 vs AcT2) comparison group. Source genes of DEcircRNAs in workers’ midgut at 7 dpi were involved in two cellular immune-related pathways such as endocytosis and ubiquitin mediated proteolysis. Additionally, competing endogenous RNA network analysis showed that 23 (13) DEcircRNAs in AcCK1 vs AcT1 (AcCK2 vs AcT2) can target 18 (14) miRNAs and further link to 1111 (1093) mRNAs. These target mRNAs were annotated to six cellular immunity pathways including endocytosis, lysosome, phagosome, ubiquitin mediated proteolysis, metabolism of xenobiotics by cytochrome P450, and insect hormone biosynthesis. Moreover, 284 (164) IRES and 54 (26) ORF were identified from DEcircRNAs in AcCK1 vs AcT1 (AcCK2 vs AcT2) comparison group; additionally, ORFs in DEcircRNAs in midgut at 7 dpi with N. ceranae were associated with several crucial pathways including endocytosis and ubiquitin-mediated proteolysis. Finally, RT-qPCR results showed that the expression trends of six DEcircRNAs were consistent with those in transcriptome data. These results demonstrated that N. ceranae altered the expression pattern of circRNAs in A. c. cerana workers’ midguts, and DEcircRNAs were likely to regulate host cellular and humoral immune response to microsporidian infection. Our findings lay a foundation for clarifying the mechanism underlying host immune response to N. ceranae infection and provide a new insight into interaction between Asian honey bee and microsporidian.
Tyrosine kinase inhibitor independent gene expression signature in CML offers new targets for LSPC eradication therapy
Authors: Gómez-Castañeda Eduardo , Rogers Simon , Munje Chinmay , Bittencourt-Silvestre Joana , Copland Mhairi , Vetrie David , Holyoake Tessa , Hopcroft Lisa , Jørgensen Heather 
Published: July 2022

2AbstractTyrosine kinase inhibitors (TKI) have revolutionised the treatment of CML. However, TKI do not eliminate the leukaemia stem cells (LSC), which can reinitiate the disease. Thus, finding new therapeutic targets in CML LSC is key to finding a curative treatment. Using microarray datasets, we defined a list of 227 genes which were differentially expressed in CML LSC compared to healthy controls but were not affected by TKIin vitro. Two of them,CD33andPPIF, are targeted by gemtuzumab-ozogamicin and cyclosporin A, respectively. We treated CML and control CD34+cells with either drug with or without imatinib to investigate the therapeutic potential of the TKI-independent gene expression programme. Cyclosporine A in combination with imatinib reduced the number of CML CFC compared with non-CML controls, but only at supra-therapeutic concentrations. Gemtuzumab-ozogamicin showed a EC50of 146ng/mL, below the plasma peak concentration of 630ng/mL observed in AML patients and below the EC50of 3247ng/mL observed in non-CML cells. Interestingly, gemtuzumab-ozogamicin seems to promote cell cycle progression in CML CD34+cells and demonstrated activation of the RUNX1 pathway in a RNAseq experiment. This suggests that targeting the TKI-independent genes in CML LSC could be exploited for the development of new therapies in CML.1Simple summaryChronic myeloid leukaemia (CML) is initiated by a group of cancer cells called leukaemia stem cells (LSC). These LSC can survive current tyrosine kinase inhibitor (TKI) treatments and upon treatment withdrawal, are able to re-initiate the disease. Thus, eradicating the LSC would likely cure CML. In this study, we have identified a number of genes which expression is different between LSC and their healthy counterparts (haematopoietic stem cells) but are not affected by TKI treatment. We hypothesised that these genes may be potential therapeutic targets against LSC and used two different drugs, gemtuzumab-ozogamicin and cyclosporine A, to treat CMLin vitro. We found that both drugs have a stronger effect on CML cells than in healthy cells. Therefore, we propose that the list of genes we identified could represent a novel source of therapeutic targets against CML.
Virulence, Aggressiveness, and Fungicide Sensitivity ofPhytophthora spp. Associated with Soybean in Illinois
Authors: Cerritos-Garcia Daniel G. , Huang Shun-Yuan , Kleczewski Nathan M. , Mideros Santiago X. 
Published: July 2022

AbstractPhytophthora root and stem rot (PRR), caused byPhytophthora sojae, is one of the most devastating oomycete diseases of soybean in Illinois. Single resistant genes (Rps) are used to manage this pathogen, butP. sojaehas adapted toRpscausing failure of resistance in many regions. In addition toP. sojae, recent reports indicate thatPhytophthora sansomeanacould also cause root rot in soybean. Soil samples and symptomatic plants were collected across 40 Illinois counties between 2016 and 2018.Phytophthora sojae(77%) was more abundant thanP. sansomeana(23%) across Illinois fields. Both species were characterized by virulence, aggressiveness, and fungicide sensitivity. Virulence of all isolates was evaluated using the hypocotyl inoculation technique in 13 soybean differentials. Aggressiveness was evaluated in the greenhouse by inoculating a susceptible cultivar and measuring root and shoot dry weight. On average,P. sojaeisolates were able to cause disease on six soybean differentials.P. sojaewas more aggressive thanP. sansomeana. All isolates were sensitive to azoxystrobin, ethaboxam, mefenoxam, and metalaxyl. The characterization of the population of species associated with PRR will inform management decisions for this disease in Illinois.
Human cartilage progenitor cells from ear, nose, rib, and joint have a robust, stable phenotype for cartilage repair
Authors: Ghavimi Soheila Ali Akbari , Gehret Paul M , Giordano Terri , Smith Kyra W Y , Gottardi Riccardo 
Published: July 2022

AbstractBackgroundCartilage progenitor cells (CPCs) are a small but highly proliferative cell population that resides within cartilage. Joint cartilage CPCs have a high chondrogenic potential and superior cartilage formation characteristics; however, CPCs from other cartilage sources more accessible for translation such as ear, nose, and rib are broadly unexplored. Our study illuminates the differences between CPCs from these four cartilages, their corresponding tissue chondrocyte (CC), and bone marrow-derived mesenchymal stem cell (MSC).MethodsCPCs subtypes were isolated from pediatric cartilage via fibronectin selection, immunophenotyped by flow cytometry and compared to MSCs. Trilineage differentiation capacity was assessed via histology and qRT-PCR. Next, triiodothyronine was used to hypertrophically challenge each CPC subset and their corresponding chondrocyte population. After 28 days cartilage pellets were assessed via histology, immunohistochemistry, and qRT-PCR.FindingsEach CPC subset possessed a specific immunophenotypic signature with CD56 as a potential common marker. All CPC subsets proliferated 2-fold faster than MSCs and 4-fold faster than CCs. Additionally, CPCs had a substantially reduced propensity for osteogenic differentiation and very limited adipogenic capacity by histology and gene expression. Finally, all CPC subsets resisted the hypertrophic challenge more than the corresponding chondrocyte population marked by less collagen X secretion and downregulation of hypertrophy associated genes.InterpretationCPCs represent a promising cell type for cartilage regeneration. The ease of accessibility of the ear and nose CPCs present opportunities for new translational approaches and reduced clinical timelines.FundingCHOP Research Institute, Frontier Program in Airway Disorders of CHOP, NIH (R21HL159521), NSF-GRFP (DGE-1845298)
Rhythmic information sampling in the brain during visual recognition
Authors: Caplette Laurent , Jerbi Karim , Gosselin Frédéric 
Published: July 2022

AbstractWhen we fixate an object, visual information is continuously received on the retina. Several studies observed behavioral oscillations in perceptual sensitivity across such stimulus time, and these fluctuations have been linked to brain oscillations. However, whether specific brain areas show oscillations across stimulus presentation time (i.e., different time points of the stimulus being more or less processed, in a rhythmic fashion) has not been investigated. Here, we revealed random areas of face images at random moments across time and recorded the brain activity of human participants (both male and female) using magnetoencephalography (MEG) while they performed two recognition tasks. This allowed us to quantify how each snapshot of visual information coming from the stimulus is processed across time and across the brain. Oscillations across stimulus time (rhythmic sampling) were mostly visible in early visual areas, at theta, alpha and low beta frequencies. We also found that they contributed to brain activity more than previously investigated rhythmic processing (oscillations in the processing of a single snapshot of visual information). Non-rhythmic sampling was also visible at later latencies across the visual cortex, either in the form of a transient processing of early stimulus time points or of a sustained processing of the whole stimulus. Our results suggest that successive cycles of ongoing brain oscillations process stimulus information incoming at successive moments. Together, these results advance our understanding of the oscillatory neural dynamics associated with visual processing and show the importance of considering the temporal dimension of stimuli when studying visual recognition.Significance StatementSeveral behavioral studies have observed oscillations in perceptual sensitivity over the duration of stimulus presentation, and these fluctuations have been linked to brain oscillations. However, oscillations across stimulus time in the brain have not been studied. Here, we developed a MEG paradigm to quantify how visual information received at each moment during fixation is processed through time and across the brain. We showed that different snapshots of a stimulus are distinctly processed in many brain areas and that these fluctuations are oscillatory in early visual areas. Oscillations across stimulus time were more prevalent than previously studied oscillations across processing time. These results increase our understanding of how neural oscillations interact with the visual processing of temporal stimuli.
Reconstructing the genetic history of Kra-Dai speakers from Thailand
Authors: Changmai Piya , Kočí Jan , Flegontov Pavel 
Published: July 2022

AbstractGenetic history of the Thai people and, more generally, speakers of the Kra-Dai languages (also known as Tai-Kadai languages) in Thailand remains a topic of debate. Recently, Kutanan et al.1 analyzed genome-wide genetic data for dozens of present-day human populations from Thailand and surrounding countries and concluded that the Central Thai, Southern Thai, and Malay from Southern Thailand are genetically continuous with Austroasiatic speakers such as Mon, and thus the advent of Kra-Dai and Austronesian languages to Central and Southern Thailand was overwhelmingly a result of cultural rather than genetic diffusion. We re-analyzed the genetic data reported by Kutanan et al.1 using an advanced technique for inferring admixture graph models, using autosomal haplotypes, and other methods. We did not reproduce the results by Kutanan et al.1, and our analyses revealed a more complex picture of the genetic history of Kra-Dai speakers and other populations of Thailand.