bluuebunny/crossref_metadata_2025_split huggingface dataset:
GBS and a newly developed mRNA-GBS approach to link population genetic and transcriptome analyses reveal pattern differences between sites and treatments in red clover (Trifolium pratenseL.)
Authors: Gemeinholzer B , Rupp O , Becker A , Strickert M. , Müller C-M 
Published: December 2021

AbstractThe important worldwide forage crop red clover (Trifolium pratenseL.) is widely cultivated as cattle feed and for soil improvement. Wild populations and landraces have great natural diversity that could be used to improve cultivated red clover. However, to date, there is still insufficient knowledge about the natural genetic and phenotypic diversity of the species. Here, we developed a low-cost transcriptome analysis (mRNA-GBS) with reduced complexity and compared the results with population genetic (GBS) and previously published mRNA-Seq data, to assess whether analysis of intraspecific variation within and between populations and transcriptome responses is possible simultaneously. The mRNA-GBS approach was successful. SNP analyses from the mRNA-GBS approach revealed comparable patterns to the GBS results, but it was not possible to link transcriptome analyses with reduced complexity and sequencing depth to previously published greenhouse and field expression studies. The use of short sequences upstream of the poly(A) tail of mRNA to reduce complexity are promising approaches that combine population genetics and expression profiling to analyze many individuals with trait differences simultaneously and cost-effectively, even in non-model species. Our mRNA-GBS approach revealed too many additional short mRNA sequences, hampering sequence alignment depth and SNP recovery. Optimizations are being discussed. Nevertheless, our study design across different regions in Germany was also challenging as the use of differential expression analyses with reduced complexity, in which mRNA is fragmented at specific sites rather than randomly, is most likely counteracted under natural conditions by highly complex plant reactions at low sequencing depth.
Clinical implementation of single-cell RNA sequencing using liver fine needle aspirate tissue sampling and centralized processing captures compartment specific immuno-diversity
Authors: Genshaft Alex S. , Subudhi Sonu , Keo Arlin , Vasquez Juan D. Sanchez , Conceição-Neto Nádia , Mahamed Deeqa , Boeijen Lauke L. , Alatrakchi Nadia , Oetheimer Chris , Vilme Mike , Drake Riley , Fleming Ira , Tran Nancy , Tzouanas Constantine , Joseph-Chazan Jasmin , Villanueva Martin Arreola , van de Werken Harmen J. G. , van Oord Gertine W. , Groothuismink Zwier M.A. , Beudeker Boris J. , Osmani Zgjim , Nkongolo Shirin , Mehrotra Aman , Feld Jordan , Chung Raymond T. , de Knegt Robert J. , Janssen Harry L. A. , Aerssens Jeroen , Bollekens Jacques , Hacohen Nir , Lauer Georg M. , Boonstra Andre , Shalek Alex K. , Gehring Adam 
Published: December 2021

AbstractBlood samples are frequently collected in human studies of the immune system but poorly represent tissue-resident immunity. Understanding the immunopathogenesis of tissue-restricted diseases, such as chronic hepatitis B, necessitates direct investigation of local immune responses. We developed a workflow that enables frequent, minimally invasive collection of liver fine-needle aspirates in multi-site international studies and centralized single-cell RNA sequencing data generation using the Seq-Well S3 picowell-based technology. All immunological cell types were captured, including liver macrophages, and showed distinct compartmentalization and transcriptional profiles, providing a systematic assessment of the capabilities and limitations of peripheral blood samples when investigating tissue-restricted diseases. The ability to electively sample the liver of chronic viral hepatitis patients and generate high-resolution data will enable multi-site clinical studies to power fundamental and therapeutic discovery.
The influence of sponge-dwelling gobies (Elacatinus horsti) on feeding efficiency of Caribbean sponge hosts, Aplysina lacunosa and Aplysina archeri
Authors: Siemann Megan J. , Turco Aldo 
Published: December 2021

AbstractMutualistic associations between benthic marine invertebrates and reef taxa are common. Sponge-dwelling gobies benefit from protection within sponge tubes and greater food availability. Sponge-dwelling gobies are hypothesized to increase sponge pump rates by consuming polychaete parasites, but such increases have not yet been demonstrated. We investigated the association between sponge-dwelling gobies (Elacatinus horsti) and two species of tube sponge (Aplysina lacunosa and Aplysina archeri) in Bonaire, Caribbean Netherlands. We visually assessed goby presence in sponges and used in situ methods with fluorescein dye to estimate feeding rates via pump rates. Aplysina archeri were more likely to host a goby than A. lacunosa. For both sponge species, pump rates of tubes with gobies were higher on average than those of tubes without gobies. Our observations, therefore, suggest that E. horsti associations with Aplysina are likely mutualistic relationships in which sponges benefit from higher feeding rates when gobies are present.
Emotion Dynamics as Hierarchical Bayesian Inference in Time
Authors: Majumdar Gargi , Yazin Fahd , Banerjee Arpan , Roy Dipanjan 
Published: December 2021

AbstractWhat fundamental property of our environment would be most valuable and optimal in characterizing the emotional dynamics we experience in our daily life? Empirical work has shown that an accurate estimation of uncertainty is necessary for our optimal perception, learning, and decision-making. However, the role of this uncertainty in governing our affective dynamics remains unexplored. Using Bayesian encoding, decoding and computational modelling, we show that emotional experiences naturally arise due to ongoing uncertainty estimations in a hierarchical neural architecture. This hierarchical organization involves a number of prefrontal sub-regions, with the lateral orbitofrontal cortex having the highest representational complexity of uncertainty. Crucially, this representational complexity, was sensitive to temporal fluctuations in uncertainty and was predictive of participants’ predisposition to anxiety. Furthermore, the temporal dynamics of uncertainty revealed a distinct functional double dissociation within the OFC. Specifically, the medial OFC showed higher connectivity with the DMN, while the lateral OFC with that of the FPN in response to the evolving affect. Finally, we uncovered a temporally predictive code updating individual’s beliefs swiftly in the face of fluctuating uncertainty in the lateral OFC. A biologically relevant and computationally crucial parameter in theories of brain function, we extend uncertainty to be a defining component of complex emotions.
Synthetic evolution of herbicide resistance using a T7 RNAP-based random DNA base editor
Authors: Butt Haroon , Ramirez Jose Luis Moreno , Mahfouz Magdy 
Published: December 2021

AbstractSynthetic directed evolution via localized sequence diversification and the simultaneous application of selection pressure is a promising method for producing new, beneficial alleles that affect traits of interest in diverse species; however, this technique has rarely been applied in plants. Developing systems to induce localized sequence diversification at high efficiency will expand our ability to evolve traits of interest that improve global food security. In this study, we designed, built, and tested a chimeric fusion of T7 RNA Polymerase (RNAP) and deaminase to enable the localized sequence diversification of a target sequence of interest. We tested our T7 RNAP–DNA base editor in Nicotiana benthamiana transient assays to target a transgene expressing GFP under the control of the T7 promoter. More than 7% of C nucleotides were converted to T in long segments of the GFP sequence. We then targeted the T7 promoter-driven ACETOLACTATE SYNTHASE (ALS) sequence that had been stably integrated in the rice (Oryza sativa) genome and generated C-to-T and G-to-A transitions. We used herbicide treatment as selection pressure for the evolution of the ALS sequence, resulting in the enrichment of herbicide-responsive residues. We then targeted these herbicide-responsive regions in the rice genome using a CRISPR-directed evolution platform and identified herbicide-resistant ALS variants. Thus, our system could be used for the continuous synthetic evolution of gene functions to produce variants with improved herbicide resistance, as well as for other trait engineering applications.
Acceptability of Rectal Artesunate as pre-referral treatment for severe malaria in children under 5 years by health workers and caregivers in the Democratic Republic of the Congo, Nigeria and Uganda
Authors: Awor Phyllis , Kimera Joseph , Athieno Proscovia , Tumukunde Gloria , Okitawutshu Jean , Tshefu Antoinette , Omoluabi Elizabeth , Signorell Aita , Brunner Nina , Kalenga Jean-Claude , Akano Babatunde , Ayodeji Kazeem , Okon Charles , Yusuf Ocheche , Delvento Giulia , Lee Tristan , Burri Christian , Lengeler Christian , Hetzel Manuel W. 
Published: December 2021

AbstractBackgroundIn children below 6 years with suspected severe malaria who are several hours from facilities providing parenteral treatment, pre-referral rectal artesunate (RAS) is recommended by the World Health Organization to prevent death and disability. A number of African countries are in the process of rolling out quality-assured RAS for pre-referral treatment of severe malaria at community-level. The success of RAS depends, among other factors, on the acceptability of RAS in the communities where it is being rolled-out. Yet to date, there is limited literature on RAS acceptability. This study aimed to determine the acceptability of RAS by health care providers and child caregivers in communities where quality assured RAS was rolled out.MethodsThis study was nested within the comprehensive multi-country observational research project Community Access to Rectal Artesunate for Malaria (CARAMAL). The CARAMAL project was implemented in the Democratic Republic of the Congo (DRC), Nigeria, and Uganda between 2018 and 2020. Data from three different sources were analysed to understand RAS acceptability: Interviews with health workers during three healthcare provider surveys, with caregivers of children under 5 years of age during three household surveys, and with caregivers of children who were recently treated with RAS and enrolled in the CARAMAL Patient Surveillance System.ResultsRAS acceptability was high among all interviewed stakeholders in the three countries. After the roll-out of RAS, 97-100% heath care providers in DRC considered RAS medication as very good or good, as well as 98-100% in Nigeria and 93-100% in Uganda. Majority of caregivers whose children had received rectal artesunate for pre-referral management of severe malaria indicated that they would want to get the medication again, if their child had the same illness (99.8% of caregivers in DRC, 100% in Nigeria and 99.9% in Uganda). Further, using data from three household surveys, 67-80% of caregivers whose children had not received RAS considered the medication as useful.ConclusionRAS was well accepted by health workers and child caregivers in DRC, Nigeria and Uganda. Acceptability is unlikely to be an obstacle to the large-scale roll-out of RAS in the studied settings.
Longitudinal prediction of motor dysfunction after stroke: a disconnectome study
Authors: Dulyan Lilit , Talozzi Lia , Pacella Valentina , Corbetta Maurizio , Forkel Stephanie J , Thiebaut de Schotten Michel 
Published: December 2021

AbstractMotricity is the most commonly affected ability after a stroke. While many clinical studies attempt to predict motor symptoms at different chronic time points after a stroke, longitudinal acute-to-chronic studies remain scarce. Taking advantage of recent advances in mapping brain disconnections, we predict motor outcomes in 62 patients assessed longitudinally two weeks, three months, and one year after their stroke. Results indicate that brain disconnection patterns accurately predict motor impairments. However, disconnection patterns leading to impairment differ between the three time points and between left and right motor impairments. These results were cross-validated using resampling techniques. In sum, we demonstrated that while some neuroplasticity mechanisms exist changing the structure-function relationship, disconnection patterns prevail when predicting motor impairment at different time points after stroke.
Stomata Detector: High-throughput automation of stomata counting in a population of African rice (Oryza glaberrima) using transfer learning
Authors: Cowling Sophie B. , Soltani Hamidreza , Mayes Sean , Murchie Erik H. 
Published: December 2021

AbstractStomata are dynamic structures that control the gaseous exchange of CO2 from the external to internal environment and water loss through transpiration. The density and morphology of stomata have important consequences in crop productivity and water use efficiency, both are integral considerations when breeding climate change resilient crops. The phenotyping of stomata is a slow manual process and provides a substantial bottleneck when characterising phenotypic and genetic variation for crop improvement. There are currently no open-source methods to automate stomatal counting. We used 380 human annotated micrographs of O. glaberrima and O. sativa at x20 and x40 objectives for testing and training. Training was completed using the transfer learning for deep neural networks method and R-CNN object detection model. At a x40 objective our method was able to accurately detect stomata (n = 540, r = 0.94, p<0.0001), with an overall similarity of 99% between human and automated counting methods. Our method can batch process large files of images. As proof of concept, characterised the stomatal density in a population of 155 O. glaberrima accessions, using 13,100 micrographs. Here, we present developed Stomata Detector; an open source, sophisticated piece of software for the plant science community that can accurately identify stomata in Oryza spp., and potentially other monocot species.
Possible Interference in Protein – Protein interaction as a new approach in microinhibition of respiratory pathogens on nasal– oral epithelium: An early on-screen study with reference toSARS-Cov-2–ACE2 binding interference
Authors: Datta Debatosh , Pant Suyash , Dhaked Devendra Kumar , Arumugam Somasundaram , Velayutham Ravichandiran , Datta Pallab 
Published: December 2021

AbstractUpper and lower respiratory pathogens – both microbes and viruses –are responsible for very high morbidity, man-hour loss, residual long term clinical conditions and even mortality. In india only, high incidence of annual respiratory infections – both UT and LT – demands prophylactic intervention in addition to all therapeutic interventions available.The issue of respiratory infections is more pronounced now in the backdrop of nearly uncontrolled high incidences of SARS-Cov-2 affection resulting in death and damage of human lives to the extent of hundreds of millions spreading over entire world, with incidence variations from country to country. After the initial unanswered phase of spread of SARS-Cov-2 virus with attendant unseen mortalities, quickest invention of a series of unusual vaccines have stemmed the lethal progress to a very significant extent, although vaccinating each and every human subject – nearly 8 to 9 bn in supremely divided world –economically-- is an unthinkable proposition where economic disparity dictates vaccine availability and implementation.Moreover, being of highly unstable nucleic acid composition, the original virus, by now has a thick set of variants around the globe with variable clinical outcome. Given this complex background of scanty availability and inefficient implementation, there always is a need of a preventive approach which can possibly micro-fix the pathogens, including SARS-2 on nasal epithelium so as to interfere with viral [or any pathogen] entry through specified receptor gate[s] or any other ways. The present formulation is under study -- as a candidate of interference on nasal / oral mucosa for all respiratory pathogens. This brief report describes dry on-screen studies of protein – protein interaction as well as its possible interference by an amino acid Lysine. Phospholipid bilayerresponses in presence of added loads of the same essential amino acid –Lysine – showed unusual and unexplained behavior both in structural integrity as well in spatial orientation.
Dopaminergic challenge dissociates learning from primary versus secondary sources of information
Authors: Rybicki A. J. , Sowden S. L. , Schuster B. A. , Cook J. L 
Published: December 2021

SummarySome theories of human cultural evolution posit that humans have social-specific learning mechanisms that are adaptive specialisations moulded by natural selection to cope with the pressures of group living. However, the existence of neurochemical pathways that are specialised for learning from social information and from individual experience is widely debated. Cognitive neuroscientific studies present mixed evidence for social-specific learning mechanisms: some studies find dissociable neural correlates for social and individual learning whereas others find the same brain areas and, dopamine-mediated, computations involved in both. Here we demonstrate that, like individual learning, social learning is modulated by the dopamine D2 receptor antagonist haloperidol when social information is the primary learning source, but not when it comprises a secondary, additional element. Two groups (total N = 43) completed a decision-making task which required primary learning, from own experience, and secondary learning from an additional source. For one group the primary source was social, and secondary was individual; for the other group this was reversed. Haloperidol affected primary learning irrespective of social/individual nature, with no effect on learning from the secondary source. Thus, we illustrate that neurochemical mechanisms underpinning learning can be dissociated along a primary-secondary but not a social-individual axis. These results resolve conflict in the literature and support an expanding field showing that, rather than being specialised for particular inputs, neurochemical pathways in the human brain can process both social and non-social cues and arbitrate between the two depending upon which cue is primarily relevant for the task at hand.
Anin vitro, in uteroandin silicoframework of oxygen diffusion in intricate vascular networks of the placenta
Authors: Bappoo Nikhilesh , Kelsey Lachlan J. , Tongpob Yutthapong , Feindel Kirk W. , Caddy Harrison , Wyrwoll Caitlin S. , Doyle Barry J. 
Published: December 2021

AbstractThe placenta is a temporary and complex organ critical for fetal development through its subtle but convoluted harmonization of endocrine, vascular, haemodynamic and exchange adaptations. Yet, due to experimental, technological and ethical constraints, this unique organ remains poorly understood.In silicotools are emerging as a powerful means to overcome these challenges and have the potential to actualize novel breakthroughs. Here, we present an interdisciplinary framework combiningin vitroexperiments used to develop an elegant and scalablein silicomodel of oxygen diffusion. We then usein uteroimaging of placental perfusion and oxygenation in both control and growth-restricted rodent placentas for validation of ourin silicomodel. Our framework revealed the structure-function relationship in the feto-placental vasculature; oxygen diffusion is impaired in growth-restricted placentas, due to the diminished arborization of growth-restricted feto-placental vasculature and the lack of decelerated flow for adequate oxygen diffusion and exchange. We highlight the mechanisms of impairment in a rat model of growth restriction, underpinned by placental vascular impairment. Our framework reports and validates the prediction of blood flow deceleration impairment in growth restricted placentas with the placenta’s oxygen transfer capability being significantly impaired, both globally and locally.
A new protocol for speed vernalisation of winter cereals
Authors: Cha Jin-Kyung , O’Connor Kathryn , Alahmad Samir , Lee Jong-Hee , Dinglasan Eric , Park Hyeonjin , Lee So-Myeong , Hirsz Dominique , Kwon Soon-Wook , Kwon Youngho , Kim Kyeong-Min , Ko Jong-Min , Hickey Lee T. , Shin Dongjin , Dixon Laura E. 
Published: December 2021

AbstractThere are many challenges facing the development of high-yielding, nutritious crops for future environments. One limiting factor is generation time, which prolongs research and plant breeding timelines. Recent advances in speed breeding protocols have dramatically reduced generation time for many short-day and long-day species by optimising light and temperature conditions during plant growth. However, winter crops with a vernalisation requirement still require up to 6–10 weeks in low-temperature conditions before transition to reproductive development. Here, we tested a suite of environmental conditions and protocols to investigate if vernalisation can be satisfied more efficiently. We identified a vernalisation method consisting of exposing seeds at the soil surface to an extended photoperiod of 22 h day:2 h night at 10°C with transfer to speed breeding conditions that dramatically reduces generation time in both winter wheat (Triticum aestivum) and winter barley (Hordeum vulgare). Implementation of this protocol achieved up to five generations per year for winter wheat or barley, instead of the two typically obtained under standard vernalisation and plant growth conditions. The protocol has great potential to enhance training and to accelerate research, pre-breeding, and breeding outcomes focussed on winter crop improvement.
Interleukin-13 and its receptor are synaptic proteins involved in plasticity and neuroprotection
Authors: Li Shun , olde Heuvel Florian , Rehman Rida , Li Zhenghui , Aousji Oumayma , Froehlich Albrecht , Zhang Wanhong , Conquest Alison , Woelfle Sarah , Schoen Michael , O’Meara Caitlin , Reinhardt Richard Lee , Voehringer David , Kassubek Jan , Ludolph Albert , Huber-Lang Markus , Knöll Bernd , Morganti-Kossmann Maria Cristina , Boeckers Tobias , Roselli Francesco 
Published: December 2021

AbstractImmune system molecules are expressed by neurons, often for unknown functions. We have identified IL-13 and its receptor IL-13Ra1 as neuronal, synaptic proteins in mouse, rat, and human brains, whose engagement upregulates the phosphorylation of NMDAR and AMPAR subunits and, in turn, increases synaptic activity and CREB-mediated transcription. We demonstrate that increased IL-13 is a hallmark of traumatic brain injury (TBI) in mice as well as in two distinct cohorts of human patients. We also provide evidence that IL-13 upregulation protects neurons from excitotoxic death. We show IL-13 upregulation occurring in several cohorts of human brain samples and in CSF. Thus, IL-13 is a previously unrecognized physiological modulator of synaptic physiology of neuronal origin, with implications for the establishment of synaptic plasticity and the survival of neurons under injury conditions. Furthermore, we suggest that the neuroprotection afforded through the upregulation of IL-13 represents a new entry point for interventions in the pathophysiology of TBI.