bluuebunny/crossref_metadata_2025_split huggingface dataset:
Discussion-based DEI education to help create inclusive and open BME research lab environments
Authors: Naiknavare Ritika , Maisel Katharina 
Published: April 2022

AbstractDiversity in teams has been shown to enhance creativity and innovation, particularly in teams where all members felt a sense of belonging. Creating an inclusive environment in a lab setting that provides a sense of belonging to all is challenging. This is particularly true in a field like Biomedical Engineering/Bioengineering where diversity is multifaceted and includes people’s diverse personal/cultural backgrounds and also diverse scientific backgrounds. In a research lab, there is additional diversity in training, as most labs contain trainees at different levels (undergrad, grad, postdoc, high school). To aid in creating a sense of belonging in a research lab, we have devised a novel initiative based upon open group discussions on diversity, equity, and inclusion topics. The initiative included a first presentation/discussion by the PI to set the stage for defining diversity, equity, and inclusion, and provided examples of existing DEI issues within our field, such as lack of racial diversity in awards like the NIH New Innovator Award and among conference speakers. After the initial presentation, trainee-led, bi-weekly-structured discussions were maintained. First, discussions focused broadly on any DEI related topic to enhance general knowledge on DEI issues and provide discussion comfort among the group. Second, there was a period to deepen knowledge of a specific topic (in our example, microaggressions), which was followed up with a period of discussions on potential solutions (such as how to react when observing a microaggression and what to do in response to realizing one’s own microaggression). Students reported that our discussions were the only ones they have had in their training thus far, and felt that these discussions made them feel like they belonged in the lab, made the lab more inclusive, enhanced their awareness of how to create inclusive spaces, and taught them about a variety of DEI topics. Overall, our DEI discussions have fostered open conversations within our lab group about DEI-related issues and topics at the lab, department, university, and countrywide levels and has established a space where students feel safe to voice their opinions and ask questions. We hope to ultimately use these DEI discussions to create actionable steps for addressing topics, e.g., microaggressions, in different scenarios that can be applied by group members in their future careers.
Unraveling axonal mechanisms of traumatic brain injury
Authors: Pozo Devoto Victorio M. , Lacovich Valentina , Feole Monica , Bhat Pratiksha , Chovan Jaroslav , Čarna Maria , Onyango Isaac G. , Dragišic Neda , Sűsserová Martina , Barrios-Llerena Martin E. , Stokin Gorazd B. 
Published: April 2022

SUMMARYAxonal swellings (AS) are the neuropathological hallmark of axonal injury in several disorders from trauma to neurodegeneration. Current evidence proposes a role of perturbed Ca2+ homeostasis in AS formation, involving impaired axonal transport and focal distension of the axons. Mechanisms of AS formation, in particular moments following injury, however, remain unknown. Here we show that AS form independently from intra-axonal Ca2+ changes, which are required primarily for the persistence of AS in time. We further show that the majority of axonal proteins undergoing de/phosphorylation immediately following injury belong to the cytoskeleton. This correlates with an increase in the distance of the actin/spectrin periodic rings and with microtubule tracks remodeling within AS. Observed cytoskeletal rearrangements support axonal transport without major interruptions. Our results demonstrate that the earliest axonal response to injury consists in physiological adaptations of axonal structure to preserve function rather than in immediate pathological events signaling axonal destruction.
Methylene blue, Mycophenolic acid, Posaconazole, and Niclosamide inhibit SARS-CoV-2Omicron variant BA.1 infection of human airway epithelial explant cultures
Authors: Volle Romain , Murer Luca , Petkidis Anthony , Andriasyan Vardan , Savi Alessandro , Bircher Cornelia , Meili Nicole , Fischer Lucy , Sequeira Daniela Policarpo , Mark Daniela Katharina , Gomez-Gonzalez Alfonso , Greber Urs F. 
Published: April 2022

AbstractSublineages of SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) Omicron variants continue to amass mutations in the spike (S) glycoprotein, which leads to immune evasion and rapid spread of the virus across the human population. Here we demonstrate the susceptibility of the Omicron variant BA.1 (B.1.1.529.1) to four repurposable drugs, Methylene blue (MB), Mycophenolic acid (MPA), Posaconazole (POS), and Niclosamide (Niclo) in post-exposure treatments of primary human airway cell cultures. MB, MPA, POS, and Niclo are known to block infection of human nasal and bronchial airway epithelial explant cultures (HAEEC) with the Wuhan strain, and four variants of concern (VoC), Alpha (B.1.1.7), Beta (B.1.351), Gamma (B.1.1.28), Delta (B.1.617.2) (1, 2). Our results not only show broad anti-coronavirus effects of MB, MPA, POS and Niclo, but also demonstrate that the Omicron variant BA.1 (B.1.1.529.1) sheds infectious virus from HAEEC over at least 15 days, and maintains both intracellular and extracellular viral genomic RNA without overt toxicity, suggesting viral persistence. The data underscore the broad effects of MB, MPA, POS, and Niclo against SARS-CoV-2 and the currently circulating VoC, and reinforce the concept of repurposing drugs in clinical trials against COVID-19.
dartR v2: an accessible genetic analysis platform for conservation, ecology, and agriculture
Authors: Mijangos Jose Luis , Gruber Bernd , Berry Oliver , Pacioni Carlo , Georges Arthur 
Published: April 2022

AbstractInnumerable approaches to analyse genetic data are now available to guide conservation, ecological and agricultural projects. However, streamlined and accessible tools are needed to bring these approaches within reach of a broader user base. dartR was released in 2018 to lessen the intrinsic complexity of analysing single nucleotide polymorphisms (SNPs) and dominant markers (presence/absence of amplified sequence tags) by providing user-friendly data quality control and marker selection functions. dartR users have grown steadily since its release and provided valuable feedback on their interaction with the package allowing us to enhance dartR capabilities.Here, we present Version 2 of dartR. In this iteration, we substantially increased the number of available functions from 45 to 144. In addition to improved functionality, we focused on enhancing the user experience by extending plot customisation, function standardisation, increasing user support and function speed. dartR provides functions for various stages in analysing genetic data, from data manipulation to reporting.dartR provides many functions for importing, exporting and linking to other packages, to provide an easy-to-navigate conduit between data generation and analysis options already available via other packages. We also implemented simulation functions whose results can be analysed seamlessly with several other dartR functions.As more methods and approaches mature to inform conservation, we envision that accessible platforms to analyse genetic data will play a crucial role in translating science into practice.
The cardiopharyngeal mesoderm contributes to lymphatic vessel development
Authors: Maruyama Kazuaki , Miyagawa-Tomita Sachiko , Haneda Yuka , Kida Mayuko , Matsuzaki Fumio , Imanaka-Yoshida Kyoko , Kurihara Hiroki 
Published: April 2022

ABSTRACTLymphatic vessels are crucial for tissue homeostasis and immune responses in vertebrates. Recent studies have demonstrated that lymphatic endothelial cells (LECs) arise from both venous sprouting (lymphangiogenesis) and de novo production from non-venous origins (lymphvasculogenesis), which is similar to blood vessel formation through angiogenesis and vasculogenesis. However, the contribution of LECs from non-venous origins to lymphatic networks is considered to be relatively small. Here, we identify the Islet1 (Isl1)-expressing cardiopharyngeal mesoderm (CPM) as a non-venous origin of craniofacial and cardiac LECs. Genetic lineage tracing with Isl1-Cre and Isl1-MerCreMer mice suggested that a subset of CPM cells gives rise to LECs. These CPM-derived LECs are distinct from venous-derived LECs in terms of their developmental processes and anatomical locations. Later, they form the craniofacial and cardiac lymphatic vascular networks in collaboration with venous-derived LECs. Collectively, our results demonstrate that there are two major sources of LECs, the cardinal vein and the CPM. As the CPM is evolutionarily conserved, these findings may improve our understanding of the evolution of lymphatic vessel development across species. Most importantly, our findings may provide clues to the pathogenesis of lymphatic malformations, which most often develop in the craniofacial and mediastinal regions.
Hierarchical architecture of dopaminergic circuits enables second-order conditioning in Drosophila
Authors: Yamada Daichi , Bushey Daniel , Feng Li , Hibbard Karen , Sammons Megan , Funke Jan , Litwin-Kumar Ashok , Hige Toshihide , Aso Yoshinori 
Published: April 2022

AbstractDopaminergic neurons with distinct projection patterns and physiological properties compose memory subsystems in a brain. However, it is poorly understood whether or how they interact during complex learning. Here, we identify a feedforward circuit formed between dopamine subsystems and show that it is essential for second-order conditioning, an ethologically important form of higher-order associative learning. The Drosophila mushroom body comprises a series of dopaminergic compartments, each of which exhibits distinct memory dynamics. We find that a slow and stable memory compartment can serve as an effective “teacher” by instructing other faster and transient memory compartments via a single key interneuron, which we identify by connectome analysis and neurotransmitter prediction. This excitatory interneuron acquires enhanced response to reward-predicting odor after first-order conditioning and, upon activation, evokes dopamine release in the “student” compartments. These hierarchical connections between dopamine subsystems explain distinct properties of first- and second-order memory long known by behavioral psychologists.
Monitoring promoter activity by RNA editing based reporter
Authors: Wang Jing , Zhao Yu-Ting , Hu Lu-Feng , Wang Yangming 
Published: April 2022

AbstractTraditional methods monitoring the promoter activity require the insertion of reporter protein (e.g. fluorescent protein) downstream of a targeted promoter. These approaches suffer from low sensitivity and potential interference to endogenous transcripts especially when the targeted transcript is a noncoding RNA. Here, we develop a mechanistically different reporter system to monitor promoter activity based on ribozyme processed ADAR engaging RNA directed editing (REDDIT). We show that REDDIT can be used to monitor the promoter activity of protein coding, long noncoding RNA, and microRNA (miRNA) genes. Furthermore, REDDIT reporter can also be adapted to use bioluminescence imaging to monitor the promoter activity, which is more suitable for in vivo live imaging. Finally, the reporter sensitivity may be further increased by the circularization of ADAR recruiting RNA. REDDIT provides a powerful platform that is promising in a variety of applications such as monitoring the promoter activity, cell lineage tracing, and processing and manipulating genetic information for synthetic biology applications.
Screening the Pathogen Box Compounds for Activity Against Plasmodium falciparum Sporozoite Motility
Authors: Kanatani Sachie , Elahi Rubayet , Kanchanabhogin Sukanat , Vartek Natasha , Tripathi Abhai K. , Prigge Sean T. , Sinnis Photini 
Published: April 2022

AbstractAs the malaria parasite becomes resistant to every drug that we develop, identification and development of novel drug candidates is essential. Many studies have screened compounds designed to target the clinically important blood stages. However, if we are to shrink the malaria map, new drugs that block transmission of the parasite are needed. Sporozoites are the infective stage of the malaria parasite, transmitted to the mammalian host as mosquitoes probe for blood. Sporozoite motility is critical to their ability to exit the inoculation site and establish infection and drug-like compounds targeting motility are effective in blocking infection in the rodent malaria model. In this study, we established a moderate throughput motility assay for sporozoites of the human malaria parasite Plasmodium falciparum, enabling us to screen the 400 drug-like compounds from the Pathogen box provided by Medicines for Malaria Venture for their activity. Compounds exhibiting inhibitory effects on P. falciparum sporozoite motility were further assessed against transmission-blocking activity and asexual stage growth. Five compounds had a significant inhibitory effect on P. falciparum sporozoite motility at 1 μM concentration and four of these compounds also showed significant inhibition on transmission of P. falciparum gametocytes to the mosquito and of these four, three had previously been shown to have inhibitory activity on asexual blood stage parasites. Our findings provide new antimalarial drug candidates that have multi-stage activity.
Cross-talk between red blood cells and plasma influences blood flow and omics phenotypes in severe COVID-19
Authors: Recktenwald Steffen M. , Simionato Greta , Lopez Marcelle G. M. , Gamboni Fabia , Dzieciatkowska Monika , Meybohm Patrick , Zacharowski Kai , Knethen Andreas von , Wagner Christian , Kaestner Lars , D’Alessandro Angelo , Quint Stephan 
Published: April 2022

ABSTRACTCoronavirus disease 2019 (COVID-19) is caused by the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) and can affect multiple organs, among which is the circulatory system. Inflammation and mortality risk markers were previously detected in COVID-19 plasma and red blood cells (RBCs) metabolic and proteomic profiles. Additionally, biophysical properties, such as deformability, were found to be changed during the infection. Based on such data, we aim to better characterize RBC functions in COVID-19. We evaluate the flow properties of RBCs in severe COVID-19 patients admitted to the intensive care unit by usingin vitromicrofluidic techniques and automated methods, including artificial neural networks, for an unbiased RBC analysis. We find strong flow and RBC shape impairment in COVID-19 samples and demonstrate that such changes are reversible upon suspension of COVID-19 RBCs in healthy plasma. Vice versa, healthy RBCs immediately resemble COVID-19 RBCs when suspended in COVID-19 plasma. Proteomics and metabolomics analyses allow us to detect the effect of plasma exchanges on both plasma and RBCs and demonstrate a new role of RBCs in maintaining plasma equilibria at the expense of their flow properties. Our findings provide a framework for further investigations of clinical relevance for therapies against COVID-19 and possibly other infectious diseases.
Identification of carcinogenesis and tumor progression processes in pancreatic ductal adenocarcinoma using high-throughput proteomics
Authors: Trilla-Fuertes Lucía , Gámez-Pozo Angelo , Lumbreras-Herrera María Isabel , López-Vacas Rocío , Heredia-Soto Victoria , Ghanem Ismael , López-Camacho Elena , Zapater-Moros Andrea , Miguel María , Peña-Burgos Eva M , Palacios Elena , de Uribe Marta , Guerra Laura , Dittmann Antje , Mendiola Marta , Ángel Fresno Vara Juan , Feliu Jaime 
Published: April 2022

AbstractPancreatic ductal adenocarcinoma (PDAC) is an aggressive disease with an overall 5 year-survival rate of just 5%. A better understanding of the carcinogenesis processes and the mechanisms of progression of PDAC is mandatory.Fifty-two PDAC patients treated with surgery and adjuvant therapy, with available primary tumor, normal tissue, preneoplastic lesions (PanIN), and/or lymph node metastases, were selected for the study. Proteins were extracted from small punches and analyzed by LC-MS/MS using data-independent acquisition. Proteomics data was analyzed using probabilistic graphical models, allowing functional characterization. Comparisons between groups were done using linear mixed models. Three proteomics tumor subtypes were defined. T1 (32% of patients) was related to adhesion, T2 (34%) had metabolic features, and T3 (34%) presented high splicing and nucleoplasm activity. These proteomics subtypes were validated in the PDAC TCGA cohort. Relevant biological processes related to carcinogenesis and tumor progression were studied in each subtype. Carcinogenesis in T1 subtype seems to be related to an increase of adhesion and complement activation nodes activity, whereas tumor progression seems to be related to nucleoplasm and translation nodes. Regarding T2 subtype, it seems that metabolism and, especially, mitochondria act as the motor of cancer development. T3 analyses point out that nucleoplasm, mitochondria and metabolism, and extracellular matrix nodes could be involved in T3 tumors carcinogenesis. Identified processes were different among proteomics subtypes, suggesting that the molecular motor of the disease is different in each subtype. These differences can have implications in the development of future tailored therapeutic approaches for each PDAC proteomics subtype.
Size of societal volunteering predicts COVID-19 mortality
Authors: Schiltz Fritz , Van Remoortel Hans , Scheers Hans , Vandekerckhove Philippe 
Published: April 2022

IntroductionDifferent countries responded differently to the COVID-19 pandemic in terms of timing and stringency of measures, and in types of policies adopted. Typically, policy makers tried to balance the capacity of healthcare systems to take care of the ill (as determined by ICU capacity, availability of nurses, etc.), with safeguarding economic output (preventing total lockdown of the labor force, etc.). Later on, also a broader array of considerations such as impact on schooling or the need for social contact were taken into account to varying degrees.The broad and relatively fast availability of data on healthcare and economic capacity, together with the political estimate that these were the most critical determinants for maintaining societal structure and compliance with the measures taken, in many countries prioritized decision-making. What received far less attention, in part due to the difficulty of obtaining reliable data in a timely manner, was the opposite question: to what extent do societal structures – besides healthcare and economic systems - contribute to a country’s resilience during catastrophes such as the pandemic? While it is commonly understood that the impact of a pandemic goes beyond its death count, perhaps the death count itself is impacted by the way societies are structured.One example of such societal structure is the contribution of volunteers during the COVID-19 response. Volunteers may contribute to well-functioning societies in different ways, both through practical actions (e.g. knitting face masks) as by strengthening societal cohesion (e.g. encouraging fellow citizens to comply with measures). This paper quantifies the association between COVID-19 mortality and the size of societal volunteering, using the unique context of the COVID-19 crisis with its intensity, sudden onset and global spread.
The genetic architecture of multiple mutualisms and mating system in Turnera ulmifolia
Authors: Laurich Jason R. , Reid Christopher G. , Biel Caroline , Wu Tianbu , Knox Christopher , Frederickson Megan E. 
Published: April 2022

AbstractPlants often associate with multiple arthropod mutualists. These partners provide important services to their hosts, but multiple interactions can constrain a plant’s ability to respond to complex, multivariate selection. Here, we quantified patterns of genetic variance and covariance among rewards for pollination, biotic defence, and seed dispersal mutualisms in multiple populations of Turnera ulmifolia to better understand how the genetic architecture of multiple mutualisms might influence their evolution. We phenotyped plants cultivated from 17 Jamaican populations for several mutualism and mating system-related traits. We then fit genetic variance-covariance (G) matrices for the island metapopulation and the 5 largest individual populations. At the metapopulation level, we observed significant positive genetic correlations among stigma-anther separation, floral nectar production, and extrafloral nectar production. These correlations have the potential to significantly constrain or facilitate the evolution of multiple mutualisms in T. ulmifolia and suggest that pollination, seed dispersal, and dispersal mutualisms do not evolve independently. In particular, we found that positive genetic correlations between floral and extrafloral nectar production may help explain their stable co-existence in the face of physiological trade-offs and negative interactions between pollinators and ant bodyguards. Locally, we found only small differences in G among our T. ulmifolia populations, suggesting that geographic variation in G may not shape the evolution of multiple mutualisms.
Predicting brain functions from structural connectome using graph neural network
Authors: Hui Edward S. , Sun Yuxiang , Ko Ho , Chan Chetwyn C.H. , Cao Peng 
Published: April 2022

AbstractThe relationship between brain structure and function remains elusive, amidst the tremendous advances in brain mapping techniques. In this work, we attempt to partially disentangle this relationship by connecting task–evoked functional MRI (fMRI) responses with the underlying structural connectome using graph neural network (GNN). MRI data (n = 1,063) were collected from the Human Connectome Project. We demonstrate that our GNN–based model predicts task–evoked fMRI responses with high fidelity. Using a graph attention mechanism, it is possible to infer the subsets of neighboring cortical regions whose structural connections are important for the prediction of the functional responses of individual cortical regions. Notably, for each cortical region, such subset of neighboring cortical regions is predominantly localized to the ipsilateral hemisphere and much smaller than that with direct structural connections. We found that the higher cognitive functions subserved by the cingulo–opercular, dorsal attention, frontoparietal and default mode clusters may depend on neighboring cortical regions across a wide range of functional brain clusters in the ipsilateral hemisphere, whilst the sensory functions subserved by the visual1 and auditory clusters on neighboring cortical regions across much fewer functional brain clusters.