bluuebunny/crossref_metadata_2025_split huggingface dataset:
Arabidopsis Apoplastic Fluid Contains sRNA- and Circular RNA-Protein Complexes that Are Located Outside Extracellular Vesicles
Authors: Zand Karimi Hana , Baldrich Patricia , Rutter Brian D. , Borniego Lucía , Zajt Kamil K. , Meyers Blake C. , Innes Roger W. 
Published: October 2021

ABSTRACTPreviously, we have shown that apoplastic wash fluid purified from Arabidopsis leaves contains small RNAs (sRNAs). To investigate whether these sRNAs are encapsulated inside extracellular vesicles (EVs), we treated EVs isolated from Arabidopsis leaves with the protease trypsin and RNase A, which should degrade RNAs located outside EVs but not those located inside. These analyses revealed that apoplastic RNAs are mostly located outside EVs and are associated with proteins. Further analyses of these extracellular RNAs (exRNAs) revealed that they comprise both sRNAs and long non-coding RNAs (lncRNAs), including circular RNAs (circRNAs). We also found that exRNAs are highly enriched in the post-transcriptional modification N6-methyladenine (m6A). Consistent with this, we identified a putative m6A-binding protein in apoplastic wash fluid, GLYCINE-RICH RNA-BINDING PROTEIN 7 (GRP7), as well as the small RNA-binding protein ARGONAUTE2 (AGO2). These two proteins co-immunoprecipitated with each other, and with lncRNAs, including circRNAs. Mutation of GRP7 or AGO2 caused changes in both the sRNA and lncRNA content of apoplastic wash fluid, suggesting that these proteins contribute to the secretion and/or stabilization of exRNAs. We propose that these extravesicular RNAs mediate host-induced gene silencing, rather than RNA inside EVs.One-sentence summaryThe apoplast of Arabidopsis leaves contains diverse small and long-noncoding RNAs, including circular RNAs, that are bound to protein complexes and are located outside extracellular vesicles.
Stress-dependent cell stiffening by tardigrade tolerance proteins through reversible formation of cytoskeleton-like filamentous network and gel-transition
Authors: Tanaka Akihiro , Nakano Tomomi , Watanabe Kento , Masuda Kazutoshi , Honda Gen , Kamata Shuichi , Yasui Reitaro , Kozuka-Hata Hiroko , Watanabe Chiho , Chinen Takumi , Kitagawa Daiju , Sawai Satoshi , Oyama Masaaki , Yanagisawa Miho , Kunieda Takekazu 
Published: October 2021

AbstractTardigrades are able to tolerate almost complete dehydration by entering a reversible ametabolic state called anhydrobiosis and resume their animation upon rehydration. Dehydrated tardigrades are exceptionally stable and withstand various physical extremes. Although trehalose and late embryogenesis abundant (LEA) proteins have been extensively studied as potent protectants against dehydration in other anhydrobiotic organisms, tardigrades produce high amounts of tardigrade-unique protective proteins. Cytoplasmic-abundant heat-soluble (CAHS) proteins are uniquely invented in the lineage of eutardigrades, a major class of the phylum Tardigrada and are essential for their anhydrobiotic survival. However, the precise mechanisms of their action in this protective role are not fully understood. In the present study, we first postulated the presence of tolerance proteins that form protective condensates via phase separation in a stress-dependent manner and searched for tardigrade proteins that reversibly form condensates upon dehydration-like stress. Through comprehensive analysis, we identified 336 such proteins, collectively dubbed “Desolvataion-induced ReversiblY condensing Proteins (DRYPs)”. Unexpectedly, we rediscovered CAHS proteins as highly enriched in DRYPs, 3 of which were major components of DRYPs. We revealed that these CAHS proteins reversibly polymerize into many cytoskeleton-like filaments depending on hyperosmotic stress in cultured cells and undergo reversible gel-transition in vitro. CAHS filamentation increases cell stiffness to resist deformation and improves resistance to dehydration-like stress. The conserved putative helical C-terminal region is necessary and sufficient for filament formation by CAHS proteins, and mutations disrupting the secondary structure of this region impaired both the filament formation and the gel transition. On the basis of these results, we propose that CAHS proteins are novel cytoskeletal proteins that form filamentous networks and undergo gel-transition in a stress-dependent manner to provide on-demand physical stabilization of cell integrity against deformative forces during dehydration and also contribute to the exceptional physical stability in a dehydrated state.
Cockroaches adjust body and appendages to traverse cluttered large obstacles
Authors: Wang Yaqing , Othayoth Ratan , Li Chen 
Published: October 2021

AbstractTo traverse complex natural terrain, animals often transition between locomotor modes. It is well known that locomotor transitions can be induced by switching in neural control circuits or be driven by a need to minimize metabolic energetic cost. Recent work discovered that locomotor transitions in complex 3-D terrain cluttered with large obstacles can also emerge from physical interaction with the environment controlled by the nervous system. To traverse cluttered, stiff grass-like beams, the discoid cockroach often transitions from using a strenuous pitch mode to push across to using a less strenuous roll mode to maneuver through the gaps, during which a potential energy barrier must be overcome. Although previous robotic physical modeling demonstrated that kinetic energy fluctuation from body oscillation generated by leg propulsion can help overcome the barrier and facilitate this transition, the animal was observed to transition even when the barrier still exceeds kinetic energy fluctuation. Here, we further studied whether and how the cockroach makes active adjustments to facilitate this locomotor transition to traverse cluttered beams. We observed that the animal flexed its head and abdomen, reduced hind leg sprawl, and used both hind legs differentially during the pitch-to-roll transition, which were absent when running on a flat ground. Using a refined potential energy landscape with additional degrees of freedom modeling these adjustments, we found that head flexion did not substantially reduce the transition barrier, whereas the leg sprawl reduction did so dramatically. We discussed likely functions of the observed adjustments and suggested future directions.
Hemodynamics After Fontan Procedure are Determined by Patient Characteristics and Anastomosis Placement Not Graft Selection: a Patient-Specific Multiscale Computational Study
Authors: Kung Ethan , Baker Catriona , Corsini Chiara , Baretta Alessia , Biglino Giovanni , Arbia Gregory , Pant Sanjay , Marsden Alison , Taylor Andrew , Quail Michael , Vignon-Clementel Irene , Pennati Giancarlo , Migliavacca Francesco , Schievano Silvia , Hlavacek Anthony , Dorfman Adam , Hsia Tain-Yen , Figliola Richard ,   Modeling of Congenital Hearts Alliance (MOCHA)+ Investigators
Published: October 2021

AbstractObjectivesPatient-specific multiscale modeling simulates virtual surgeries of the Fontan procedure using three different graft options. Predictive modeling details post-operative outcomes that can help inform clinical decision support.MethodsSix patients underwent preoperative cardiac magnetic resonance imaging and catheterization. Virtual surgery is carried out for each patient to test the resulting hemodynamics of three Fontan graft options: ECC, 9mm Y-graft, and 12mm Y-graft.Results1) one-way ANOVA p>0.998 in all systemic pressures and flows between graft options, 2) p=0.706 for hepatic flow distribution between graft options, 3) local power loss differences do not affect the systemic circulation, 4) anastomosis positioning modification of the same Y-graft in the same patient changed left PA hepatic distribution from 0.66 to 0.49ConclusionsSystemic pressures and blood flow after the Fontan procedure are not affected by graft selection but are well influenced by patient pulmonary vascular impedance. The hepatic distribution can be affected by anastomosis placement.Ultra-mini abstractWe present the first case series of patient-specific multiscale modeling of the Fontan procedure. Despite noticeable local power loss differences, graft selection does not affect systemic pressure and flow rates or other clinically relevant quantities. Anastomosis placement can affect hepatic distribution.
Determination of utility of 3 minute and 6 minute walk tests in assessment of progression of mild COVID-19 infection at a tertiary hospital in North India
Authors: Goel Aastha , Chowdhury Souradeep , Ghosh Tamoghna , Singh Anupam , Kumar Arvind , Wig Naveet 
Published: October 2021

AbstractIntroductionThere have been 214 million confirmed cases of COVID-19 worldwide with a total death tally of 4.4 million. The current study aims to determine the predictive value of 3 minute and 6-minute walk tests in assessment of progression of mild COVID-19 infection at a tertiary care hospital in North India.MethodsThe study population consisted of adults (age more than 18 years) with a confirmed diagnosis of Covid-19 by RT-PCR on nasopharyngeal specimens. Patients with only mild illness were enrolled. After the patients were admitted to the isolation ward, the presenting history, comorbidity status, vital signs and laboratory parameters were recorded. The 3 and 6 minute walk test was performed daily from admission till discharge or progression of severity of COVID-19 and it was used to calculate BDS and NEWS2 scores.ResultsOur study consisted of 50 patients with 34 (68%) males and the mean (SD) age of the patient population being 28.1 (6.4) years. The most common symptoms were fever, sore throat, and cough. All laboratory parameters were within normal ranges for all the patients. 96% recovered without progression, while only 4% of them progressed to moderate illness. Results of the 3 and 6 minutes walk tests, BDS and NEWS2 scores showed improvement over the course of hospital stay.ConclusionsAlthough the walk tests and the scores improved over time, they failed to predict the disease progression.
Actin capping protein regulates actomyosin contractility to maintain germline architecture in C. elegans
Authors: Ray Shinjini , Agarwal Priti , Zaidel-Bar Ronen 
Published: October 2021

AbstractActin dynamics play an important role in the morphogenesis of cells and tissues, yet the control of actin filament growth takes place at the molecular level. A challenge in the field is to link the molecular function of actin regulators with their physiological function. Here, we report the in vivo role of the actin capping protein CAP-1 in the C. elegans germline. We show that CAP-1 is associated with actomyosin structures in the cortex and rachis, where it keeps the level of contractility in check. A 60% reduction in the level of CAP-1 leads to a 2-fold increase in F-actin and non-muscle myosin II and only a 30% increase in Arp2/3. CAP-1 depletion leads to severe structural defects in the syncytial germline and oocytes, which can be rescued by reducing myosin activity. Thus, we uncover a physiological role for actin capping protein in maintaining C. elegans fertility by regulating the level of actomyosin contractility.
Multimodal Imaging Mass Spectrometry of Murine Gastrointestinal Tract with Retained Luminal Content Shows Molecular Localization Patterns
Authors: Guiberson Emma R. , Wexler Aaron G. , Good Christopher J. , Skaar Eric P. , Spraggins Jeffrey M. , Caprioli Richard M. 
Published: October 2021

ABSTRACTDigestive diseases impact 62 million people a year in the United States. Despite the central role of the gut to human health, past imaging mass spectrometry (IMS) investigations into the gastrointestinal tract are incomplete. The gastrointestinal tract, including luminal content, harbors a complex mixture of microorganisms, host dietary content, and immune factors. Existing imaging approaches remove luminal content, and images focus on small regions of tissue. Here, we demonstrate the use of a workflow to collect multimodal imaging data for both intestinal tissue and luminal content. This workflow for matrix-assisted laser desorption/ionization imaging mass spectrometry retains luminal content and expands the amount of tissue imaged on one slide. Results comparing tissue and luminal content show unique molecular distributions using multimodal imaging modalities including protein, lipid, and elemental imaging. Leveraging this method to investigate intestinal tissue infected with Clostridioides difficile compared to control tissue shows clear differences in lipid abundance of various lipid classes in luminal content during infection. These data highlight the potential for this approach to detect unique biological and markers of infection in the gut.
Drug screening at single-organoid resolution via bioprinting and interferometry
Authors: Tebon Peyton J. , Wang Bowen , Markowitz Alexander L. , Davarifar Ardalan , Krawczuk Patrycja , Murray Graeme , Nguyen Huyen Thi Lam , Tavanaie Nasrin , Nguyen Thang L. , Boutros Paul C. , Teitell Michael A. , Soragni Alice 
Published: October 2021

AbstractHigh-throughput drug screening is an established approach to investigate tumor biology and identify therapeutic leads. Traditional platforms for high-throughput screening use two-dimensional cultures of immortalized cell lines which do not accurately reflect the biology of human tumors. More clinically relevant model systems, such as three-dimensional tumor organoids, can be difficult to screen and scale. For example, manually seeded organoids coupled to destructive endpoint assays allow for the characterization of response to treatment, but do not capture the transitory changes and intra-sample heterogeneity underlying clinically observed resistance to therapy. We therefore developed a pipeline to generate bioprinted tumor organoids linked to label-free, real-time imaging via high-speed live cell interferometry (HSLCI) and machine learning-based quantitation of individual organoids. Bioprinting cells gives rise to 3D organoid structures that preserve tumor histology and gene expression. HSLCI imaging in tandem with machine learning-based image segmentation and organoid classification tools enables accurate, label-free parallel mass measurements for thousands of bioprinted organoids. We demonstrate that our method quantitatively identifies individual organoids as insensitive, transiently sensitive, or persistently sensitive to specific treatments. This opens new avenues for rapid, actionable therapeutic selection using automated tumor organoid screening.
Mechanistic Model of Replication Fork Progression in Yeast
Authors: Singh Ghanendra 
Published: October 2021

AbstractReplication fork progression complex plays an essential role during DNA replication. It travels along with the DNA with a particular speed called replication fork speed. Faithful duplication of the genome requires strict control over replication fork speed. Both acceleration and pausing mechanisms of the replication fork complex are regulated at the molecular level. Based on the experimental evidence, DNA replicates faster in normal cells than cancer cells, whereas cancer cells duplicate themselves more quickly than normal cells. Then in principle, accelerating the replication fork complex in cancer cells beyond a specific threshold speed limit can cause DNA damage and plausibly kill them. A modular mathematical model is proposed to explain the dynamics of replication fork control during DNA replication using the underlying molecular mechanisms in yeast which can extend to the mammalian system in the future.
Quantifying Cellular Pluripotency and Pathway Robustness through Forman-Ricci Curvature
Authors: Murgas Kevin A. , Saucan Emil , Sandhu Romeil 
Published: October 2021

AbstractIn stem cell biology, cellular pluripotency describes the capacity of a given cell to differentiate into multiple cell types. From a statistical physics perspective, entropy provides a statistical measure of randomness and has been demonstrated as a way to quantitate pluripotency when considering biological gene networks. Furthermore, recent theoretical work has established a relationship between Ricci curvature (a geometric measure of “flatness”) and entropy (also related to robustness), which one can exploit to link the geometric quantity of curvature to the statistical quantity of entropy. Therefore, this study seeks to explore Ricci curvature in biological gene networks as a descriptor of pluripotency and robustness among gene pathways. Here, we investigate Forman-Ricci curvature, a combinatorial discretization of Ricci curvature, along with network entropy, to explore the relationship of the two quantities as they occur in gene networks. First, we demonstrate our approach on an experiment of stem cell gene expression data. As expected, we find Ricci curvature directly correlates with network entropy, suggesting Ricci curvature could serve as an indicator for cellular pluripotency much like entropy. Second, we measure Forman-Ricci curvature in a dataset of cancer and non-cancer cells from melanoma patients. We again find Ricci curvature is increased in the cancer state, reflecting increased pluripotency or “stemness”. Further, we locally examine curvature on the gene level to identify several genes and gene pathways with known relevance to melanoma. In turn, we conclude Forman-Ricci curvature provides valuable biological information related to pluripotency and pathway functionality. In particular, the advantages of this geometric approach are promising for extension to higher-order topological structures in order to represent more complex features of biological systems.
A critical assessment of the detailedAedes aegyptisimulation model Skeeter Buster 2 using field experiments of indoor insecticidal control in Iquitos, Peru
Authors: Gunning C.E. , Morrison A.C. , Okamoto K.W. , Scott T.W. , Astete H. , Vasquez G.M. , Gould F. , Lloyd A.L. 
Published: October 2021

AbstractThe importance of mosquitoes in human pathogen transmission has motivated major research efforts into mosquito biology in pursuit of more effective vector control measures.Aedes aegyptiis a particular concern in tropical urban areas, where it is the primary vector of numerous flaviviruses, including the yellow fever, Zika, and dengue viruses. With an anthropophilic habit,Ae. aegyptiprefers houses, human blood meals, and ovipositioning in water-filled containers. We hypothesized that this relatively simple ecological niche should allow us to predict the impacts of insecticidal control measures on mosquito populations. To do this, we use Skeeter Buster 2 (SB2), a stochastic, spatially explicit, mechanistic model ofAe. aegyptipopulation biology. SB2 builds on Skeeter Buster, which reproduced equilibrium dynamics ofAe. aegyptiin Iquitos, Peru. Our goal was to predict the response of mosquito populations to perturbations by indoor insecticidal spraying and widespread destructive insect surveys.To evaluate SB2, we conducted two field experiments in Iquitos, Peru: a smaller pilot study in 2013 (S-2013) followed by a larger experiment in 2014 (L-2014). Here, we compare model predictions with (pre-viously reported) empirical results from these experiments. In both simulated and empirical populations, repeated spraying yielded substantial yet temporary reductions in adult densities. The proportional effects of spraying were broadly comparable between simulated and empirical results, but we found noteworthy differences. In particular, SB2 consistently over-estimated the proportion of nulliparous females and the proportion of containers holding immature mosquitoes. We also observed less temporal variation in simulated surveys of adult abundance relative to corresponding empirical observations. Our results indicate the presence of ecological heterogeneities or sampling processes not effectively represented by SB2. Although additional empirical research could further improve the accuracy and precision of SB2, our results under-score the importance of non-linear dynamics in the response ofAe. aegyptipopulations to perturbations, and suggest general limits to the fine-grained predictability of its population dynamics over space and time.
Role of the Topoisomerase IIα Chromatin Tether domain in Nucleosome Binding & Chromosome Segregation
Authors: Sundararajan Sanjana , Park Hyewon , Kawano Shinji , Johansson Marnie , Saito-Fujita Tomoko , Saitoh Noriko , Arnaoutov Alexei , Dasso Mary , Clarke Duncan J. , Azuma Yoshiaki 
Published: October 2021

AbstractDue to the intrinsic nature of DNA replication, replicated genomes retain catenated genomic loci that must be resolved to ensure faithful segregation of sister chromatids in mitosis. Type II DNA Topoisomerase (TopoII) decatenates the catenated genomic DNA through its unique Strand Passage Reaction (SPR). Loss of SPR activity results in anaphase chromosome bridges and formation of Polo-like Kinase Interacting Checkpoint Helicase (PICH)-coated ultra-fine DNA bridges (UFBs) whose timely resolution is required to prevent micronuclei formation. Vertebrates have two TopoII isoforms– TopoIIα and TopoIIβ, that share a conserved catalytic core. However, the essential mitotic function of TopoIIα cannot be compensated by TopoIIβ, due to differences in their catalytically inert C-terminal domains (CTDs). Using genome-edited human cells, we show that specific binding of TopoIIα to methylated histone, tri-methylated H3K27 (H3K27me3), via its Chromatin Tether (ChT) domain within the CTD contributes critically to avoid anaphase UFB formation. Reducing H3K27 methylation prior to mitosis increases UFBs, revealing a requirement for proper establishment of H3K27me3 after DNA replication to facilitate TopoIIα-ChT dependent UFB prevention. We propose that interaction of the TopoIIα-ChT with H3K27me3 is a key factor that ensures the complete resolution of catenated loci to permit faithful chromosome segregation in human cells.Summary StatementGenomic catenations originating from the DNA replication process must be resolved by DNA Topoisomerase II (TopoII) to permit sister chromatid disjunction. The results show that specific recognition of methylated histone containing chromatin by TopoII is critical for complete resolution of the genome.