bluuebunny/crossref_metadata_2025_split huggingface dataset:
Donor-derived vasculature is required to support neocortical cell grafts after stroke
Authors: Krzyspiak Joanna , Yan Jingqi , Ghosh Hiyaa , Galinski Basia , Lituma Pablo J. , Alvina Karina , Kee Samantha , Grońska-Pęski Marta , De Tai Yi , McDermott Kelsey , Zukin R. Suzanne , Weiser Daniel A. , Castillo Pablo E. , Khodakhah Kamran , Hébert Jean M. 
Published: March 2021

SummaryNeural precursor cells (NPCs) transplanted into the adult neocortex generate neurons that synaptically integrate with host neurons, supporting the possibility of achieving functional tissue repair. However, poor survival of transplanted NPCs greatly limits efficient engraftment. Here, we test the hypothesis that combining blood vessel-forming vascular cells with neuronal precursors improves engraftment. By transplanting mixed embryonic neocortical cells into adult mice with neocortical strokes, we show that transplant-derived neurons synapse with appropriate targets while donor vascular cells form vessels that fuse with the host vasculature to perfuse blood within the graft. Although all grafts became vascularized, larger grafts had greater contributions of donor-derived vessels that increased as a function of their distance from the host-graft border. Moreover, excluding vascular cells from the donor cell population strictly limited graft size. Thus, inclusion of vessel-forming vascular cells with NPCs is required for more efficient engraftment and ultimately for tissue repair.
Pathology dynamics in healthy-toxic protein interaction and the multiscale analysis of neurodegenerative diseases
Authors: Pal Swadesh , Melnik Roderick 
Published: March 2021

AbstractNeurodegenerative diseases are frequently associated with aggregation and propagation of toxic proteins. In particular, it is well known that along with amyloid-beta, the tau protein is also driving Alzheimer’s disease. Multiscale reaction-diffusion models can assist in our better understanding of the evolution of the disease. We have modified the heterodimer model in such a way that it can now capture some of critical characteristics of this evolution such as the conversion time from healthy to toxic proteins. We have analyzed the modified model theoretically and validated the theoretical findings with numerical simulations.
Drug repurposing: Hydroxyurea therapy improves the transfusion-free interval in HbE/beta-thalassemia–major patients with Xmn1 polymorphism
Authors: Ghosh Debojoyti , Panja Amrita , Saha Dipankar , Banerjee Uma , Dutta Asok Kumar , Basu Anupam 
Published: March 2021

AbstractAimsHbE/β-thalassemia is the prevalent form of severe β-thalassemia in Asian countries. Hydroxyurea (HU) is the most common drug used for the management of sickle-cell anemia but not thalassemia. Here, we aimed to assess clinical HU response among patients with HbE/β-thalassemia with respect to Xmn1 γGglobin polymorphism and elucidate the association between this polymorphism and HU response efficacy.MethodsWe enrolled 49 transfusion-dependent patients with HbE/β-thalassemia. Fetal hemoglobin level was measured using High-performance liquid chromatography (HPLC) and complete blood count was determined pre- and post-HU therapy. Polymerase chain reaction–Restriction fragment length polymorphism (PCR-RFLP) was performed for genotyping Xmn1 γGglobin polymorphism.ResultsA total of 30 (61.22%) patients were found to be responders, whereas the remaining 19 (38.78%) were non-responders. We found 33 patients with heterozygous (C/T) and three with homozygous mutant (T/T) genotype status. We obtained a statistically significant correlation (p < 0.001) between Xmn1 polymorphism and transfusion-free interval. Patients with Xmn1 polymorphism were found to be good responders for HU therapy and showed increased hemoglobin levels.ConclusionsOur findings indicate that HU is a potential drug candidate for thalassemia management, particularly HbE/β-thalassemia. The results hold implications in repurposing HU as an effective and efficient therapy for HbE/β-thalassemia.
The negative consequences of failing to communicate uncertainties during a pandemic: The case of COVID-19 vaccines
Authors: Batteux Eleonore , Bilovich Avri , Johnson Samuel G. B. , Tuckett David 
Published: March 2021

AbstractUncertainties pervade our health choices, particularly in the context of a novel pandemic. Despite this, rather little is known about when and how to effectively communicate these uncertainties. The focus in the medical literature so far has been on how patients respond to mentions of uncertainty relating to diagnosis or treatment, showing that these can have detrimental effects on trust and satisfaction. On the other hand, how patients are affected by these communications over time, particularly in the face of conflicting information, has received little attention. This is particularly important in the context a novel pandemic where uncertainty is rife and information changes over time. To fill this gap, we conducted an online study with UK participants on hypothetical communications relating to COVID-19 vaccines. Participants first read a vaccine announcement, which either communicated with certainty or uncertainty, and then received information which conflicted with the announcement. Those who were exposed to the certain announcement reported a greater loss of trust and vaccination intention than those who were exposed to the uncertain announcement. This shows that communicating with unwarranted certainty can backfire in the long-term, whereas communicating uncertainties can protect people from the negative impact of exposure to conflicting information.
DLL4 and PDGF-BB regulate migration of human iPSC-derived skeletal myogenic progenitors
Authors: Ferrari Giulia , Choi SungWoo , Moyle Louise A. , Mackinlay Kirsty , Naouar Naira , Wells Christine , Muntoni Francesco , Tedesco Francesco Saverio 
Published: March 2021

SUMMARYMuscle satellite stem cells (MuSCs) are responsible for skeletal muscle growth and regeneration. Despite their differentiation potential, human MuSCs have limitedin vitroexpansion andin vivomigration capacity, limiting their use in cell therapies for diseases affecting multiple skeletal muscle groups such as muscular dystrophies. Several protocols have been developed to derive progenitor cells similar to MuSCs from human induced pluripotent stem cells (hiPSCs), in order to establish a source of myogenic cells with controllable proliferation and differentiation capacity. However, currently available hiPSC myogenic derivatives also suffer from limitations of cell migration, ultimately delaying their clinical translation. Here we provide evidence that activation of NOTCH and PDGF pathways with DLL4 and PDGF-BB improves migration of hiPSC-derived myogenic progenitorsin vitro. Transcriptomic and functional analyses demonstrate that this property is conserved across species and multiple hiPSC lines, including genetically-corrected hiPSC derivatives from a patient with Duchenne muscular dystrophy. DLL4 and PDGF-BB treatment had no negative impact on cell proliferation; cells maintained their myogenic memory, with differentiation fully rescued by NOTCH inhibition. RNAseq analysis indicate that pathways involved in cell migration are modulated in treated myogenic progenitors, consistent with results from functional profiling of cell motility at single cell resolution. Notably, treated cells also showed enhanced trans-endothelial migration in transwell assays. Enhancing extravasation is a key translational milestone for intravascular delivery of hiPSC myogenic derivatives: our study establishes the foundations of a transgene-free, developmentally inspired strategy to achieve this goal, moving hiPSCs one step closer to future muscle gene and cell therapies.
ProxLogs: Miniaturised proximity loggers for monitoring association behaviour in small mammals
Authors: Kirkpatrick Lucinda , Hererra Olivares Ivan , Massawe Apia , Sabuni Christopher , Leirs Herwig , Berkvens Rafael , Weyn Maarten 
Published: March 2021

AbstractThe ability to monitor associations between wild animals is essential for understanding the processes governing gene transfer, information transfer, competition, predation and disease transmission.Until recently, such insights have been confined to large, visible or captive animals. However, the rapid development of miniature sensors for consumer electronics is allowing ecologists to monitor the natural world in ways previously considered impossible.Here we describe miniature (<1g) proximity loggers we have developed that use Bluetooth Low Energy transmission to register contacts between individuals. Our loggers are open source, low cost, rechargeable, able to store up to 2000 contacts, can be programmed insituand can download data remotely or through a mobile phone application, increasing their utility in remote areas or with species which are challenging to recapture.We successfully trialled our loggers in a range of field realistic conditions, demonstrating that Bluetooth Low Energy is capable of logging associations in structurally complex habitats, and that changes in received signal strength can be equated to short range changes in distance between loggers. Furthermore, we tested the system on starlings (Sturnidae vulgaris).The ability to include other sensors is retained in our prototypes, allowing for the potential integration of physiological and behavioural inference into social networks derived from our approach. Due to its open source nature, small size, flexibility of use and the active research currently being undertaken with Bluetooth Low Energy, we believe that our approach is a valuable addition to the biologging toolkit.
Gut microbial structural variations as determinants of human bile acid metabolism
Authors: Wang Daoming , Doestzada Marwah , Chen Lianmin , Andreu-Sánchez Sergio , van den Munckhof Inge C.L. , Augustijn Hannah , Koehorst Martijn , Bloks Vincent W. , Riksen Niels P. , Rutten Joost H.W. , Netea Mihai G. , Zhernakova Alexandra , Kuipers Folkert , Fu Jingyuan 
Published: March 2021

SummaryBile acids (BAs) facilitate intestinal fat absorption and act as important signaling molecules in host□gut microbiota crosstalk. BA-metabolizing pathways in the microbial community have been identified, but how the highly variable genomes of gut bacteria interact with host BA metabolism remains largely unknown. We characterized 8,282 structural variants (SVs) of 55 bacterial species in the gut microbiomes of 1,437 individuals from two Dutch cohorts and performed a systematic association study with 39 plasma BA parameters. Both variations in SV-based continuous genetic makeup and discrete subspecies showed correlations with BA metabolism. Metagenome-wide association analysis identified 797 replicable associations between bacterial SVs and BAs and SV regulators that mediate the effects of lifestyle factors on BA metabolism. This is the first large-scale microbial genetic association analysis to demonstrate the impact of bacterial SVs on human BA composition, and highlights the potential of targeting gut microbiota to regulate BA metabolism through lifestyle intervention.
Kinesin-4 Motor Teams Effectively Navigate Dendritic Microtubule Arrays Through Track Switching and Regulation of Microtubule Dynamics
Authors: Masucci Erin M. , Relich Peter K. , Lakadamyali Melike , Ostap E. Michael , Holzbaur Erika L. F. 
Published: March 2021

ABSTRACTMicrotubules establish the directionality of intracellular transport by kinesins and dynein through their polarized assembly, but it remains unclear how directed transport occurs along microtubules organized with mixed polarity. We investigated the ability of the plus-end directed kinesin-4 motor KIF21B to navigate mixed polarity microtubules in mammalian dendrites. Reconstitution assays with recombinant KIF21B and engineered microtubule bundles or extracted neuronal cytoskeletons indicate that nucleotide- independent microtubule binding regions of KIF21B modulate microtubule dynamics and promote directional switching on antiparallel microtubules. Optogenetic recruitment of KIF21B to organelles in live neurons resulted in unidirectional transport in axons but bi-directional transport with a net retrograde bias in dendrites; microtubule dynamics and the secondary microtubule binding regions are required for this net directional bias. We propose a model in which cargo-bound KIF21B motors coordinate nucleotide- sensitive and insensitive microtubule binding sites to achieve net retrograde movement along the dynamic mixed polarity microtubule arrays of dendrites.
PDX1 directs a core developmentally and evolutionarily conserved gene program in the pancreatic islet
Authors: Yang Xiaodun , Raum Jeffrey C. , Kim Junil , Yu Reynold , Yang Juxiang , Rice Gabriella , Li Changhong , Won Kyoung-Jae , Stoffers Doris A. , Stanescu Diana E. 
Published: March 2021

SummaryPancreatic and duodenal homeobox 1 (PDX1)is crucial for pancreas organogenesis, yet the dynamic changes in PDX1 targets in mouse or human pancreas development have not been examined. We integrated the PDX1 cistrome with cell lineage-specific gene expression in both mouse and human developing pancreas. We identified a core set of developmentally and evolutionarily conserved PDX1 bound genes that reveal the broad multifaceted role of PDX1 in pancreas development. Despite the well-known, dramatic changes in PDX1 function and expression, we showed that PDX1 binding is largely stable from embryonic pancreas to adult islet. This may point towards a dual role of PDX1, activating or repressing the expression of its targets at different ages, dependent on other functionally-congruent or directly-interacting partners. Our work also suggests that PDX1 functions not only in initiating pancreas differentiation, but also as a potential keepsake of the progenitor program in the adult beta cells.
MetaFetcheR: An R package for complete mapping of small compound data
Authors: Yones Sara A. , Csombordi Rajmund , Komorowski Jan , Diamanti Klev 
Published: March 2021

AbstractMotivationSmall-compound databases contain large amount of information for metabolites and metabolic pathways. However, the plethora of such databases and the redundancy of their information lead to major issues with analysis and standardization. Lack of preventive establishment of means of data access at the infant stages of a project might lead to mislabelled compounds, reduced statistical power and large delays in delivery of results.ResultsWe developed MetaFetcheR, an open-source R package that links metabolite data from several small-compound databases, resolves inconsistencies and covers a variety of use-cases of data fetching. We showed that the performance of MetaFetcheR was superior to existing approaches and databases by benchmarking the performance of the algorithm in two independent case studies based on two published datasets.AvailabilityMetaFetcheR is available athttps://github.com/komorowskilab/MetaFetcheR/.
Collagen polarization promotes epithelial elongation by stimulating locoregional cell proliferation
Authors: Katsuno-Kambe Hiroko , Teo Jessica L. , Ju Robert J. , Hudson James E. , Stehbens Samantha J. , Yap Alpha S. 
Published: March 2021

AbstractEpithelial networks are commonly generated by processes where multicellular aggregates elongate and branch. Here we focus on understanding cellular mechanisms for elongation, using an organotypic culture system as a model of mammary epithelial anlage. Isotropic cell aggregates broke symmetry and slowly elongated when transplanted into collagen 1 gels. The elongating regions of aggregates displayed enhanced cell proliferation that was necessary for elongation to occur. Strikingly, this loco-regional increase in cell proliferation occurred where collagen 1 fibrils reorganized into bundles which were polarized with the elongating aggregates. Applying external stretch as a cell-independent way to reorganize the ECM, we found that collagen polarization stimulated regional cell proliferation to precipitate symmetry-breaking and elongation. This required β1-integrin and ERK signaling. We propose that collagen polarization supports epithelial anlagen elongation by stimulating loco-regional cell proliferation. This could provide a long-lasting structural memory of the initial axis that is generated when anlage break symmetry.
Reverse complementary matches simultaneously promote both back-splicing and exon-skipping
Authors: Cao Dong 
Published: March 2021

SummaryCircular RNAs (circRNAs) play diverse roles in different biological and physiological environments and are always expressed in a tissue-specific manner. Tissue-specific circRNA expression profile can help understand how circRNAs are regulated. Here, using large-scale neuron isolation from the first larval stage ofCaenorhabditis elegans(C. elegans) followed by whole-transcriptome RNA sequencing, I provide the first neuronal circRNA data inC. elegans. I show that circRNAs are highly expressed in the neurons ofC. elegansand are preferably derived from neuronal genes. More importantly, reverse complementary matches in circRNA-flanking introns are not only required for back-splicing but also promote the skipping of exon(s) to be circularized. Interestingly, one pair of RCM inzip-2is highly conserved across five nematode ortholog genes, which show conserved exon-skipping patterns. Finally, through one-by-one mutagenesis of all the splicing sites and branch points required for exon-skipping and back-splicing in thezip-2gene, I show that exon-skipping is not absolutely required for back-splicing, neither the other way. Instead, the coupled exon-skipping and back-splicing are happening at the same time.
Molecular diet analysis in zebra and quagga mussels (Dreissenaspp.) and an assessment of the utility of aquatic filter feeders as biological eDNA filters
Authors: Weber Sven , Brink Lukas , Wörner Manuel , Künzel Sven , Veith Michael , Teubner Diana , Klein Roland , Paulus Martin , Krehenwinkel Henrik 
Published: March 2021

AbstractMolecular gut content analysis is a popular tool to study food web interactions and was recently also suggested as an alternative source for DNA based biomonitoring. However, the overabundant consumer’s DNA often outcompetes that of its diet during PCR. Blocking approaches are an efficient means to reduce consumer amplification while retaining broad specificity for dietary taxa. We here designed an assay to monitor the eukaryotic diet of mussels and test their utility as biological eDNA filters to monitor planktonic communities. We designed several rDNA primer sets with a broad taxonomic suitability for eukaryotes, which suppress the amplification of mussels. The primers were tested using mussel DNA extracts and the results were compared to eDNA water samples collected next to the mussel colonies. Taxonomic recovery, as well as patterns of alpha and beta diversity, were compared between mussels and water samples. In addition, we analyzed time series samples of mussel samples from different German rivers. Our primer sets efficiently block the amplification of various mussel genera. The recovered DNA reflects a broad dietary preference across the eukaryotic tree of life and considerable taxonomic overlap with filtered water samples. We also recover various taxa of possible commensals and parasites, associated with the mussels. Our protocol will enable large scale dietary analysis in mussels, facilitate aquatic food web analysis, elucidate the ecological impact of invasive bivalves and the rapid survey of mussel aquacultures for pathogens. Moreover, we show that mussels could serve as an interesting complementary DNA source for biomonitoring.
TheopenCARPSimulation Environment for Cardiac Electrophysiology
Authors: Plank Gernot , Loewe Axel , Neic Aurel , Augustin Christoph , Huang Yung-Lin , Gsell Matthias A. F. , Karabelas Elias , Nothstein Mark , Prassl Anton J. , Sánchez Jorge , Seemann Gunnar , Vigmond Edward J. 
Published: March 2021

AbstractBackground and ObjectiveCardiac electrophysiology is a medical specialty with a long and rich tradition of computational modeling. Nevertheless, no community standard for cardiac electrophysiology simulation software has evolved yet. Here, we present theopenCARPsimulation environment as one solution that could foster the needs of large parts of this community.Methods and ResultsopenCARPand the Python-basedcarputilsframework allow developing and sharing simulation pipelines which automatein silicoexperiments including all modeling and simulation steps to increase reproducibility and productivity. The continuously expandingopenCARPuser community is supported by tailored infrastructure. Documentation and training material facilitate access to this complementary research tool for new users. After a brief historic review, this paper summarizes requirements for a high-usability electrophysiology simulator and describes howopenCARPfulfills them. We introduce theopenCARPmodeling workflow in a multi-scale example of atrial fibrillation simulations on single cell, tissue, organ and body level and finally outline future development potential.ConclusionAs an open simulator,openCARPcan advance the computational cardiac electrophysiology field by making state-of-the-art simulations accessible. In combination with thecarputilsframework, it offers a tailored software solution for the scientific community and contributes towards increasing use, transparency, standardization and reproducibility ofin silicoexperiments.
Desalination and temperature increase will shift seasonal grazing patterns of invasiveGammarus tigrinuson charophytes
Authors: Berthold M. , Porsche C. , Hofmann A. , Nowak P. 
Published: March 2021

AbstractCharophytes are a refuge for zooplankton and stabilize sediments, but they are also a food source for various animal species (water birds, fishes, invertebrates). Especially the introduction of new species, likeGammarus tigrinus, into the Baltic Sea led to yet not understood changes in the food web. Furthermore, future projections point to increased water temperatures at lowered salinity levels affecting species capacity to acclimatize to changing abiotic factors. In this study we investigated the influence of temperature and salinity on the grazing pressure ofGammarus tigrinuson two charophyte species:Chara asperaandChara tomentosa. The grazing experiments were conducted in a full factorial design with the factors salinity (3 – 13 g kg-1), temperature (5 – 30 °C), and charophyte species. Grazing rates were determined as mass deviation within 48 hours considering biomass changes in the presence and absence of gammarids. Grazing rate were further used to calculate charophyte losses in two coastal lagoons with different salinity concentrations for recent and future time periods. The potential grazing peak of about 24 °C is not yet reached in these coastal waters but may be reached in the near future as shown by our future projection results. However, the temperature increase, and desalination will cause a shift in seasonal individual grazing patterns from summer to spring and autumn. Desalination and temperature increase can lead to a shift in optimal habitats forG. tigrinusin the future.