bluuebunny/crossref_metadata_2025_split huggingface dataset:
Xeno-monitoring of molecular drivers of artemisinin and partner drug resistance in P. falciparum populations in malaria vectors across Cameroon
Authors: Nkemngo Francis N. , Mugenzi Leon M.J. , Tchouakui Magellan , Nguiffo-Nguete Daniel , Wondji Murielle J. , Mbakam Bertrand , Tchoupo Micareme , Ndo Cyrille , Wanji Samuel , Wondji Charles S. 
Published: January 2022

AbstractBackgroundMonitoring of drug resistance in Plasmodium populations is crucial for malaria control. This has primarily been performed in humans and rarely in mosquitoes where parasites genetic recombination occurs. Here, we characterized the Plasmodium spp populations in wild Anopheles vectors by analyzing the genetic diversity of the P. falciparum kelch13 and mdr1 gene fragments implicated in artemisinin and partner drug resistance across Cameroon in three major malaria vectors.MethodsAnopheles mosquitoes were collected across nine localities in Cameroon and dissected into the head/thorax (H/T) and abdomen (Abd) after species identification. A TaqMan assay was performed to detect Plasmodium infection. Fragments of the Kelch 13 and mdr1 genes were amplified in P. falciparum positive samples and directly sequenced to assess their drug resistance polymorphisms and genetic diversity profile.ResultsThe study revealed a high Plasmodium infection rate in the major Anopheles vectors across Cameroon. Notably, An. funestus vector recorded the highest sporozoite (8.02%) and oocyst (14.41%) infection rates. A high P. falciparum sporozoite rate (80.08%) alongside epidemiological signatures of significant P. malariae (15.94%) circulation were recorded in these vectors. Low genetic diversity with six (A578S, R575I, G450R, L663L, G453D, N458D) and eight (H53H, V62L, V77E, N86Y, G102G, L132I, H143H, Y184F) point mutations were observed in the k13 and mdr1 backbones respectively. Remarkably, the R575I (4.44%) k13 and Y184F (64.2%) mdr1 mutations were the predominant variants in the P. falciparum populations.ConclusionThe emerging signal of the R575I polymorphism in the Pfk13 propeller backbone entails the regular surveillance of molecular markers to inform evidence-based policy decisions. Moreover, the high frequency of the 86N184F allele highlights concerns on the plausible decline in efficacy of artemisinin-combination therapies (ACTs); further implying that parasite genotyping from mosquitoes can provide a more relevant scale for quantifying resistance epidemiology in the field.
Machine learning algorithms predict soil seed bank persistence from easily available traits
Authors: Rosbakh Sergey , Pichler Maximilian , Poschlod Peter 
Published: January 2022

AbstractQuestionSoil seed banks (SSB), i.e., pools of viable seeds in the soil and its surface, play a crucial role in plant biology and ecology. Information on seed persistence in soil is of great importance for fundamental and applied research, yet compiling datasets on this trait still requires enormous efforts. We asked whether the machine learning (ML) approach could be used to infer and predict SSB properties of a regional flora based on easily available data.LocationEighteen calcareous grasslands located along an elevational gradient of almost 2000 m in the Bavarian Alps, Germany.MethodsWe compared a commonly used ML model (random forest) with a conventional model (linear regression model) as to their ability to predict SSB presence/absence and density using empirical data on SSB characteristics (environmental, seed traits and phylogenetic predictors). Further, we identified the most important determinants of seed persistence in soil for predicting qualitative and quantitative SSB characteristics using the ML approach.ResultsWe demonstrated that the ML model predicts SSB characteristics significantly better than the linear regression model. A single set of predictors (either environment, or seed traits, or phylogenetic eigenvectors) was sufficient for the ML model to achieve high performance in predicting SSB characteristics. Importantly, we established that a few widely available SSB predictors can achieve high predictive power in the ML approach, suggesting a high flexibility of the developed approach for use in various study systems.ConclusionsOur study provides a novel methodological approach that combines empirical knowledge on the determinants of SSB characteristics with a modern, flexible statistical approach based on ML. It clearly demonstrates that ML can be developed into a key tool to facilitate labor-intensive, costly and time-consuming functional trait research.
Rice Pan-genome Array (RPGA): an efficient genotyping solution for pan-genome-based accelerated crop improvement in rice
Authors: Daware Anurag , Malik Ankit , Srivastava Rishi , Das Durdam , Ellur Ranjith K. , Singh Ashok K. , Tyagi Akhilesh K. , Parida Swarup K. 
Published: January 2022

ABSTRACTThe advent of the pan-genome era has unraveled previously unknown genetic variation existing within diverse crop plants including rice. This untapped genetic variation is believed to account for a major portion of phenotypic variation existing in crop plants and might be responsible for missing heritability. However, the use of conventional single reference-guided genotyping often fails to capture large portion of this genetic variation leading to a reference bias. This makes it difficult to identify and utilize novel population/cultivar-specific genes for crop improvement. To overcome this challenge, we developed a rice pan-genome genotyping array (RPGA) includes 80K genome-wide SNPs which provides simple, user-friendly and cost-effective solution for rapid pan-genome-based genotyping in rice. The GWAS conducted using RPGA-SNP genotyping data of a rice diversity panel detected total of 42 loci, including previously known as well as novel genomic loci regulating grain size/weight traits in rice. Eight of the identified trait-associated loci (dispensable loci) could not be detected with conventional single reference genome-based GWAS and found to be missing from the commonly used Nipponbare reference genome. WD repeat-containing PROTEIN 12 gene underlying one of such dispensable locus on chromosome 7 (qLWR7) along with few other non-dispensable loci was subsequently detected using high-resolution QTL mapping confirming authenticity of RPGA-led GWAS. This demonstrates the potential of RPGA-based genotyping to overcome reference bias. Besides GWAS, the application of RPGA-based genotyping for natural allelic diversity and population structure analysis, seed purity and hybridity testing, ultra-high-density genetic map construction and chromosome level genome assembly, and marker-assisted foreground/background selection was successfully demonstrated. Based on these salient outcomes, a web application (http://www.rpgaweb.com) was also developed to provide easy to use platform for imputation of RPGA-based genotyping data using 3K Rice Reference Panel and subsequent GWAS in order to drive genetic improvement of rice.
Tracking the dynamics of perisaccadic visual signals with magnetoencephalography
Authors: Nasiotis Konstantinos , Neupane Sujaya , Bakhtiari Shahab , Baillet Sylvain , Pack Christopher C. 
Published: January 2022

AbstractMany brain functions are difficult to localize, as they involve distributed networks that reconfigure themselves on short timescales. One example is the integration of oculomotor and visual signals that occurs with each eye movement: The brain must combine motor signals about the eye displacement with retinal signals, to infer the structure of the surrounding environment. Our understanding of this process comes primarily from single-neuron recordings, which are limited in spatial extent, or fMRI measurements, which have poor temporal resolution. We have therefore studied visual processing during eye movements, using magnetoencephalography (MEG), which affords high spatiotemporal resolution. Human subjects performed a task in which they reported the orientation of a visual stimulus while executing a saccade. After removal of eye movement artifacts, time-frequency analysis revealed a signal that propagated in the beta-frequency band from parietal cortex to visual cortex. This signal had the characteristics of perisaccadic “remapping”, a neural signature of the integration of oculomotor and visual signals. These results reveal a novel mechanism of visual perception and demonstrate that MEG can provide a useful window into distributed brain functions.
Actin networks modulate heterogenous NF-κB dynamics in response to TNFα
Authors: Butera Francesca , Sero Julia E. , Dent Lucas G. , Bakal Chris 
Published: January 2022

AbstractThe canonical NF-κB transcription factor RELA is a master regulator of immune and stress responses and is upregulated in PDAC tumours. Here, we characterised previously unknown endogenous RELA-GFP dynamics in PDAC cell lines by live single cell imaging, which revealed rapid, sustained and non-oscillatory nuclear RELA following TNFα stimulation. Using Bayesian analysis of single cell datasets with variation in nuclear RELA, we computationally predicted that RELA heterogeneity in PDAC cell lines is dependent on F-actin dynamics. By RNA-seq, we identified the actin regulators NUAK2 and ARHGAP31 as transcriptionally regulated by RELA. In turn,NUAK2orARHGAP31siRNA depletion downregulates TNFα-stimulated RELA nuclear localisation in PDAC cells, establishing a novel negative feedback loop regulating RELA activation by TNFα. We identify an additional actin-independent feedback loop involving RELB, which suppresses TNFα-mediated RELA nuclear localisation following RELA mediated upregulation of RELB. Taken together, we provide computational and experimental support for interdependence between the F-actin network and RELA translocation dynamics in PDAC.
Spatially Aware Dimension Reduction for Spatial Transcriptomics
Authors: Shang Lulu , Zhou Xiang 
Published: January 2022

AbstractSpatial transcriptomics are a collection of genomic technologies that have enabled transcriptomic profiling on tissues with spatial localization information. Analyzing spatial transcriptomic data is computationally challenging, as the data collected from various spatial transcriptomic technologies are often noisy and display substantial spatial correlation across tissue locations. Here, we develop a spatially-aware dimension reduction method, SpatialPCA, that can extract a low dimensional representation of the spatial transcriptomics data with enriched biological signal and preserved spatial correlation structure, thus unlocking many existing computational tools previously developed in single-cell RNAseq studies for tailored and novel analysis of spatial transcriptomics. We illustrate the benefits of SpatialPCA for spatial domain detection and explores its utility for trajectory inference on the tissue and for high-resolution spatial map construction. In the real data applications, SpatialPCA identifies key molecular and immunological signatures in a newly detected tumor surrounding microenvironment, including a tertiary lymphoid structure that shapes the gradual transcriptomic transition during tumorigenesis and metastasis. In addition, SpatialPCA detects the past neuronal developmental history that underlies the current transcriptomic landscape across tissue locations in the cortex.
Reduced feedback barely slows down proprioceptive recalibration
Authors: Ruttle Jennifer E. , Hart Bernard Marius ’t , Henriques Denise Y. P. 
Published: January 2022

AbstractIntroducing altered visual feedback of the hand results in quick adaptation of reaching movements. And while this may be partly due to explicit strategies, our lab has shown that implicit changes like reach aftereffects and shift in estimates of the unseen hand, can also emerge and even saturate within a few training trials. The goal of the current study is to determine whether these rapid changes in unseen hand position that occur during classical visuomotor adaptation are diminished or slowed when feedback during training is reduced. We reduced feedback by either providing visual feedback only at the end of the reach (terminal feedback) or constraining hand movements to reduce efferent contribution (exposure). We measured changes as participants completed reaches with a 30° rotation, a −30° rotation and clamped visual feedback, with these two “impoverished” training conditions, along with classical visuomotor adaptation training, while continuously estimating their felt hand position. Classic continuous-cursor training produced exemplary learning curves and rapid and robust shifts in felt hand position. Training with terminal feedback slightly reduced the initial rate of change in overall adaptation and but not the magnitude of shifts in felt hand position. Finally using a robot to constrain and deviate hand movement direction, called exposure training, only delayed saturation of proprioceptive changes by a single trial and these changes were slightly smaller than those during classical training. Taken together, adaptation and shifts in felt hand position are a rapid and robust responses to sensory mismatches and are only slightly modulated when feedback is reduced. This means that, given a visuo-proprioceptive mismatch, the resulting shift in sense of limb position can contribute to movements from the start of adaptation.
mRNA expression explains metabolic and thermal physiology
Authors: Drown Melissa , Crawford Douglas , Oleksiak Margie 
Published: January 2022

AbstractQuantifying mRNA expression, which is heritable and physiologically inducible, reveals biologically important networks and pathways underlying complex traits. Here, we quantify mRNA expression in Fundulus heteroclitus, a small teleost fish, among three populations acclimated to 12°C and 28°C and relate it to variation in six, complex, physiological traits (whole animal metabolism (WAM), critical thermal maximum (CTmax), and four substrate specific cardiac metabolic rates (CaM)). Although 366 heart mRNAs and 528 brain mRNAs had significant differential expression between the two acclimation temperatures, none of the mRNA acclimation responses were shared across all three populations in any tissue. Yet, within an acclimation temperature across all three populations, weighted gene co-expression network analyses show that mRNA expression patterns explained WAM, CTmax, and CaM trait variation. These analyses revealed 9 significant heart MEs (first principal component of module expression) and 4 significant brain MEs. Heart MEs explained variation in WAM, CTmax, and two of the four substrate specific cardiac metabolic rates at 12°C, and CTmax at 28C. In contrast, brain MEs explained CTmax and WAM at 28°C but not at 12°C. Combining MEs as multiple correlations, 82% of variation in WAM at 12°C was explained by four heart MEs, 80% of variation in fatty-acid CaM at 12°C was explained by three heart MEs, and 72% of variation in CTmax at 28°C was explained by three brain MEs. These MEs were enriched for Kyoto Encyclopedia of Genes and Genomes (KEGG) terms related to specific metabolic pathways, suggesting that they represent biologically relevant pathways. Together these data suggest that mRNA co-expression explains complex traits; moreover, physiological traits are more reliant on heart expression at 12°C and brain expression at 28°C.Author SummaryDespite an abundance of genomic data, the molecular and genetic underpinnings of complex traits remain poorly understood. To better understand the molecular basis of complex traits, we used heart and brain mRNA expression to explain complex traits- physiological responses to temperature- in individuals collected from three saltmarsh fish (Fundulus heteroclitus) populations acclimated to 12°C and 28°C. We found that while physiological traits did not differ among populations, the mRNAs important for acclimation responses were >88% unique to a single population and differed between heart and brain tissues. We also found tissue specific co-expressed mRNAs that explain up to 82% of complex traits including whole animal metabolism, upper thermal tolerance, and substrate specific cardiac metabolism measured at 12°C or 28°C acclimation conditions. Notably, sets of co-expressed mRNAs related to these traits are enriched for molecular pathways affecting metabolism, giving insight into the molecular underpinnings of these traits.
Corneal cisterns as drainage aqueducts
Authors: Gupta Shikha , Joshi Shivani , Mahalingam Karthikeyan , Singh Abhishek , Arora Monika , Gupta Viney 
Published: January 2022

AbstractImportanceAnterior chamber paracentesis (ACP) is a known method of rapid reduction of IOP. The mechanism of how corneal fluid clears after ACP is not well described.ObjectiveTo determine the mechanism of instantaneous corneal clearing of edema after ACP.Design, setting, and participantsThis case series includes consecutive patients with high IOP and associated corneal edema, who presented to the Glaucoma Services of our tertiary care center. Pre- and post-intervention (ACP) ASOCTs were analyzed.Main outcome measuresResolution of corneal edema (clinical picture) and imaging of peripheral cornea and iridocorneal angle area.ResultsTen consecutive patients who underwent an ACP were included in this study. The mean IOP pre-intervention was 48.4 ± 8.2 mmHg. ASOCT showed ill-defined conventional pathways of aqueous outflow, which were blocked by peripheral anterior synechiae in 4 eyes. Immediately post ACP, the IOP was 16.3 ± 5.6 mmHg (p < 0.001) and corneal edema resolved immediately. We found on ASOCT, that the intrastromal hypolucency of the peripheral cornea, (corneal cistern) which was limited in extent and U shaped, showed a posterior extension into the corneo-limbal junction to form well-defined anastomoses with the conventional aqueous drainage channels demonstrating a direct conduit for intracorneal fluid to egress. In 2/10 eyes, Schlemm’s canal opened intracamerally as well, suggesting direct reflux of intra-corneal fluid into the anterior chamber.Conclusion and RelevanceAfter an ACP, in eyes with corneal edema to relieve IOP, we observed that the intracorneal cisterns undergo peripheral extension to drain corneal fluid through the conventional distal outflow channels.
Extreme γ’ fibrinogen levels in COVID-19 patients
Authors: Farrell David H. , Hudkins Matthew , Hamilton Heather , Underwood Samantha J. , Dewey Elizabeth N. , Kazmierczak Diana E. , Kazmierczak Steven C. , Messer William B. , Khan Akram , Schreiber Martin A. 
Published: January 2022

AbstractBackgroundCOVID-19 progression can be accompanied by a “cytokine storm” that leads to secondary sequelae such as thrombosis and acute respiratory distress syndrome. Several inflammatory cytokines have been associated with COVID-19 progression, but have far too much daily intra-individual variability to be useful in tracking the course of the disease. In contrast, we have shown that the inflammatory biomarker γ’ fibrinogen (γ’ Fbg) has a 6-fold lower coefficient of variability compared to other inflammatory markers such as hs-CRP. Objectives: The aims of the study were to measure γ’ Fbg in serial blood samples from COVID-19 patients at a tertiary care medical center in order to investigate its association with clinical measures of disease progression.MethodsCOVID-19 patients at a tertiary care medical center were retrospectively enrolled between 3/16/2020 and 8/1/2020. γ’ Fbg was measured using a commercial ELISA. Results: Our results showed that nine out of the seventeen patients with COVID-19 had extremely high levels of γ’ Fbg. γ’ Fbg levels were significantly associated with the need for ECMO and with mortality.ConclusionsWe found that COVID-19 patients can develop extraordinarily high levels of γ’ Fbg. The previous highest γ’ Fbg level that we are aware of was 80.3 mg/dL found in a study of 10,601 participants in the ARIC study. These results have several important clinical implications. γ’ Fbg contains a high affinity binding site for thrombin that binds to anion-binding exosite II on thrombin and protects it from inactivation by heparin. High levels of γ’ Fbg therefore provide a reservoir of heparin-resistant clot-bound thrombin when the γ’ Fbg is clotted. These findings have potential implications regarding prophylactic anticoagulation of COVID-19 patients and suggest that heparin prophylaxis may be less effective than using other anticoagulants, particularly direct thrombin inhibitors.
Clinically relevant combined effect of polygenic background, rare pathogenic germline variants, and family history on colorectal cancer incidence
Authors: Hassanin Emadeldin , Spier Isabel , Bobbili Dheeraj R. , Aldisi Rana , Klinkhammer Hannah , David Friederike , Dueñas Nuria , Hüneburg Robert , Perne Claudia , Brunet Joan , Capella Gabriel , Nöthen Markus M. , Forstner Andreas J. , Mayr Andreas , Krawitz Peter , May Patrick , Aretz Stefan , Maj Carlo 
Published: January 2022

AbstractBackground and aimsSummarised in polygenic risk scores (PRS), the effect of common, low penetrant genetic variants associated with colorectal cancer (CRC), can be used for risk stratification.MethodsTo assess the combined impact of the PRS and other main factors on CRC risk, 163,516 individuals from the UK Biobank were stratified as follows: 1. carriers status for germline pathogenic variants (PV) in CRC susceptibility genes (APC, MLH1, MSH2, MSH6, PMS2), 2. low (<20%), intermediate (20-80%), or high PRS (>80%), and 3. family history (FH) of CRC. Multivariable logistic regression and Cox proportional hazards models were applied to compare odds ratios (OR) and to compute the lifetime incidence, respectively.ResultsDepending on the PRS, the CRC lifetime incidence for non-carriers ranges between 6% and 22%, compared to 40% and 74% for carriers. A suspicious FH is associated with a further increase of the cumulative incidence reaching 26% for non-carriers and 98% for carriers. In non-carriers without FH, but high PRS, the CRC risk is doubled, whereas a low PRS even in the context of a FH results in a decreased risk. The full model including PRS, carrier status, and FH improved the area under the curve (AUC) in risk prediction (0.704).ConclusionThe findings demonstrate that CRC risks are strongly influenced by the PRS for both a sporadic and monogenic background. FH, PV, and common variants complementary contribute to CRC risk. The implementation of PRS in routine care will likely improve personalized risk stratification, which will in turn guide tailored preventive surveillance strategies in high, intermediate, and low risk groups.