bluuebunny/crossref_metadata_2025_split huggingface dataset:
Evidence of active oviposition avoidance to systemically applied imidacloprid in the Colorado Potato Beetle (Leptinotarsa decemlineata)
Authors: Edison Alitha , Michelbach Anja , Sowade Dominique , Schmidt Luise , Schäfer Martin , Nauen Ralf , Duchen Pablo , Xu Shuqing 
Published: July 2022

AbstractAgricultural pests can develop behavioral resistance to insecticides via choosing to feed or oviposit on non-toxic hosts. As young larvae have relatively low mobility, oviposition preferences from female adults may play a critical role in shaping the evolutionary trajectory of pest populations. While oviposition avoidance of toxic hosts was found in different agriculture pests, it remains unclear whether such preferences can be learned from female adults. To address this question, we investigated feeding and oviposition preferences to imidacloprid in the Colorado Potato Beetle (CPB, Leptinotarsa decemlineata), a major potato pest. We first identified two CPB strains that have different levels of resistance to imidacloprid. Then, we performed choice assays in the two strains and found that both strains did not have an innate feeding avoidance to systemically applied imidacloprid at both larval and adult stages. Further oviposition choice assays showed that the susceptible strain preferred to lay eggs on insecticide-free plants while the resistant strain did not. Analysing moving patterns of the two strains suggested that the oviposition preference is likely due to active learning by the female adults. Together, these results indicate that CPB can have active oviposition avoidance, which might have contributed to the rapid global invasion of this agricultural pest.
Approximating Scaffold Printability Utilizing Computational Methods
Authors: Sedigh Ashkan , Ghelich Pejman , Quint Jacob , Samandari Mohamadmahdi , Tamayol Ali , Tomlinson Ryan E. 
Published: July 2022

ABSTRACTBioprinting facilitates the generation of complex, three-dimensional (3D), cell-based constructs for various applications. Although multiple bioprinting technologies have been developed, extrusion-based systems have become the dominant technology due to the diversity of materials (bioinks) that can be utilized, either individually or in combination. However, each bioink has unique material properties and extrusion characteristics that affect bioprinting utility, accuracy, and precision. Here, we have extended our previous work to achieve high precision (i.e., repeatability) across samples by optimizing bioink-specific printing parameters. Specifically, we hypothesized that an adaptive neuro-fuzzy inference system (ANFIS) could be used as a computational method to address the imprecision in 3D bioprinting test data and uncover the optimal printing parameters for a specific bioink that result in high accuracy and precision. To test this hypothesis, we have implemented an ANFIS model consisting of four inputs (bioink concentration, printing pressure, speed, and temperature) and a single output to quantify the precision (scaffold bioprinted linewidth range). We validate our use of the bioprinting precision index (BPI) with both standard and normalized printability factors. In total, our results indicate that computational methods are a cost-efficient measure to improve the precision and robustness of extrusion 3D bioprinting with gelatin-based bioinks.
Optimised DNA isolation from marine sponges for natural sampler DNA (nsDNA) metabarcoding
Authors: Harper Lynsey R. , Neave Erika F. , Sellers Graham S. , Cunnington Alice V. , Arias María Belén , Craggs Jamie , MacDonald Barry , Riesgo Ana , Mariani Stefano 
Published: July 2022

AbstractMarine sponges have recently been recognised as natural samplers of environmental DNA (eDNA) due to their effective water filtration and their ubiquitous, sessile and regenerative nature. However, laboratory workflows for metabarcoding of sponge tissue have not been optimised to ensure that these natural samplers achieve their full potential for community survey. We used a phased approach to investigate the influence of DNA isolation procedures on the biodiversity information recovered from sponges. In Phase 1, we compared three treatments of residual ethanol preservative in sponge tissue alongside five DNA extraction protocols. The results of Phase 1 informed which ethanol treatment and DNA extraction protocol should be used in Phase 2, where we assessed the effect of starting tissue mass on extraction success and whether homogenisation of sponge tissue is required. Phase 1 results indicated that ethanol preservative may contain unique and/or additional biodiversity information to that present in sponge tissue, but blotting tissue dry generally recovered more taxa and generated more sequence reads from the wild sponge species. Tissue extraction protocols performed best in terms of DNA concentration, taxon richness and proportional read counts, but the non-commercial tissue protocol was selected for Phase 2 due to cost-efficiency and greater recovery of target taxa. In Phase 2 overall, we found that homogenisation may not be required for sponge tissue and more starting material does not necessarily improve taxon detection. These results combined provide an optimised DNA isolation procedure for sponges to enhance marine biodiversity assessment using natural sampler DNA metabarcoding.
Immunodominant influenza epitope GILGFVFTL engage common and divergent TCRs when presented as a 9-mer or a 15-mer peptide
Authors: Bhojak Keshav , Kode Vasumathi , Miriam Coral M. , Lee Kayla , Ramesh Athulya , Sudheendra HV , Chakraborty Papia , Chaudhuri Amitabha 
Published: July 2022

AbstractAntigen-specific T-cells are a powerful modality for treating cancer and other life-threatening viral and bacterial diseases. Technologies to identify and expand antigen-specific T-cells rapidly can shorten the time, and lower the cost of treatment. In this regard, screening short overlapping peptides to identify antigen-specific T-cells in ex vivo T-cell activation assay is becoming routine. Screening assays typically use 15-mer peptides to stimulate patient-derived, or healthy peripheral blood mononuclear cells to activate T-cells and identify expanded TCRs by next generation sequencing. Previous studies comparing the kinetics of T-cell activation using a 9 and a 15-mer peptide versions of a CMV immunodominant epitope demonstrated that 15-mer peptides induced CD8 T-cell activation at a slower kinetics reaching a lower magnitude compared to 9-mer peptides. The fact that 9-mer peptides are an optimal fit for the MHC class-I binding groove could explain this difference, with the 15-mer peptide requiring additional proteolytic processing before binding to the deeper binding groove of class-I MHC. Alternatively, the delay in kinetics and magnitude can result from the activation of a wider diversity of TCRs engaging novel epitopes generated from the 15-mer peptide whose activation profile may be different from the profile of TCRs that normally respond to the 9-mer immunodominant epitope. We sought to address these two possibilities by comparing T-cell engagement to the HLA-2-restricted GILGFVFTL epitope presented as a 9-mer, or a 15-mer peptide and analyzing CDR3 expansion as a measure of T-cell engagement diversity. This approach also addressed an important question as to whether optimal TCRs could be missed using a 15-mer peptide used routinely in screening assays.
Insights from Incorporating Quantum Computing into Drug Design Workflows
Authors: Lau Bayo , Emani Prashant S. , Chapman Jackson , Yao Lijing , Lam Tarsus , Merrill Paul , Warrell Jonathan , Gerstein Mark B. , Lam Hugo Y.K. 
Published: July 2022

AbstractWhile many quantum computing (QC) methods promise theoretical advantages over classical counterparts, quantum hardware remains limited. Exploiting near-term QC in computer-aided drug design (CADD) thus requires judicious partitioning between classical and quantum calculations. We present HypaCADD, a hybrid classical-quantum workflow for finding ligands binding to proteins, while accounting for genetic mutations. We explicitly identify modules of our drug design workflow currently amenable to replacement by QC: non-intuitively, we identify the mutation-impact predictor as the best candidate. HypaCADD thus combines classical docking and molecular dynamics with quantum machine learning (QML) to infer the impact of mutations. We present a case study with the SARS-CoV-2 protease and associated mutants. We map a classical machine-learning module onto QC, using a neural network constructed from qubit-rotation gates. We have implemented this in simulation and on two commercial quantum computers. We find that the QML models can perform on par with, if not better than, classical baselines. In summary, HypaCADD offers a successful strategy for leveraging QC for CADD.
Mechano-epigenetic regulation of extracellular matrix homeostasis via Yap and Taz
Authors: Jones Dakota L. , Daniels Ryan N. , Jiang Xi , Locke Ryan C. , Evans Mary Kate , Bonnevie Edward D. , Srikumar Anjana , Nijsure Madhura P. , Boerckel Joel D. , Mauck Robert L. , Dyment Nathaniel A. 
Published: July 2022

AbstractCells integrate mechanical cues to direct fate specification to maintain tissue function and homeostasis. While disruption of these cues is known to lead to aberrant cell behavior and chronic diseases, such as tendinopathies, the underlying mechanisms by which mechanical signals maintain cell function is not well understood. Here, we show using a novel model of tendon de-tensioning that loss of tensile cues in vivo acutely changes nuclear morphology, positioning, and expression of catabolic gene programs. Using paired ATAC/RNAseq, we further identify that a loss of cellular tension rapidly reduces chromatin accessibility in the vicinity of Yap/Taz genomic targets while also increasing expression of genes involved in matrix catabolism. Overexpression of Yap results in a reduction of chromatin accessibility at matrix catabolic gene loci, while also reducing transcriptional levels. Concordantly, depletion of Yap/Taz elevates matrix catabolic expression. Finally, we demonstrate that overexpression of Yap not only prevents the induction of a broad catabolic program following a loss of cellular tension, but also preserves the underlying chromatin state from force-induced alterations. Taken together, these results provide novel mechanistic details by which mechanical signals regulate tendon cell function to preserve matrix homeostasis through a Yap/Taz axis.Significance StatementCells integrate mechanical signals to regulate biological outputs within tissues. These processes are required for tissue function and homeostasis. Here, we show how mechanical cues (e.g. tension) directs tendon cell function and fate at a transcriptional and epigenetic level. Furthermore, we show that disruption of these mechanical cues leads to a disease-like cell state, indicating these mechanosensitive pathways could be important for diseases driven by perturbed mechanical signaling, such as tendinopathy. Finally, we demonstrate that genetic perturbation of a single protein can preserve cell and chromatin state following a loss of tension, supporting novel avenues for the development of innovative mechano-therapeutics.
Two-year interview and match outcomes of otolaryngology preference signaling
Authors: Chang C.W. David , Thorne Marc C. , Malekzadeh Sonya , Pletcher Steven D. 
Published: July 2022

ObjectiveTo present the first year-over-year data comparison of preference signaling for residency interviews in the otolaryngology application marketplace.Study DesignCross-sectional study conducted over 2 application cyclesSettingOtolaryngology training programs in the United States.MethodsOtolaryngology residency applicants were invited to participate in preference signaling during the 2021 and 2022 application cycles. Submissions were collected using a web-based interface. The distribution of signals among programs was evaluated descriptively and in relationship to program rankings. Surveys were sent to applicants to assess general attitudes and the number of interview invitations received from signaled and non-signaled programs. Surveys were sent to programs to evaluate use of signals and the impact on Match results.ResultsPrograms received a range of signals from 0-66, with 50% of signals going to 24% of programs, which was similarly found in 2021. Programs of higher rank tended to receive more signals. Overall, greater than 87% of surveyed applicants received an interview offer from at least one program they signaled. In 2021 and 2022, applicants were 2.6 times more likely to get an interview from a signaled program than from a comparator non-signaled program. A greater positive impact on interview offer rate was seen for less competitive applicants. Signaling was viewed favorably by the vast majority surveyed applicants and programs.ConclusionsPreference signaling for otolaryngology residency interviews demonstrates a promising mechanism to improve applicant visibility to programs during the application cycle. This impact is consistent over 2 application cycles.
Causal associations of education, lifestyle behaviors, and cardiometabolic traits with epigenetic age acceleration: a Mendelian randomization study
Authors: Kong Lijie , Ye Chaojie , Wang Yiying , Zheng Jie , Wang Shuangyuan , Lin Hong , Zhao Zhiyun , Li Mian , Xu Yu , Lu Jieli , Chen Yuhong , Xu Min , Wang Weiqing , Ning Guang , Bi Yufang , Wang Tiange 
Published: July 2022

AbstractBackgroundGrimAge acceleration (GrimAgeAccel) and PhenoAge acceleration (PhenoAgeAccel) are DNA methylation-based markers of accelerated biological ageing, standing out in predicting mortality and age-related cardiometabolic morbidities. Causal risk factors for GrimAgeAccel and PhenoAgeAccel are unclear.ObjectiveTo evaluate causal associations of 18 common modifiable socioeconomic, lifestyle, and cardiometabolic factors with GrimAgeAccel and PhenoAgeAccel.MethodsWe performed two-sample univariable and multivariable Mendelian randomization (MR), using summary-level data for GrimAgeAccel and PhenoAgeAccel derived from a genome-wide association study of 34,710 European participants. We used the inverse-variance weighted method as the main analysis, supplemented by three sensitivity analyses.ResultsEleven and eight factors were causally associated with GrimAgeAccel and PhenoAgeAccel, respectively. Smoking initiation was the strongest risk factor (β [SE]: 1.299 [0.107] years) for GrimAgeAccel, followed by higher alcohol intake, higher waist circumference, daytime napping, higher body fat percentage, higher BMI, higher C-reactive protein, higher triglycerides, childhood obesity, and type 2 diabetes; whereas education was the strongest protective factor (β [SE] per 1-SD increase in years of schooling: -1.143 [0.121] years). Higher waist circumference (β [SE]: 0.850 [0.269] years) and education (β [SE]: -0.718 [0.151] years) were the leading causal risk and protective factors for PhenoAgeAccel, respectively. Sensitivity analyses strengthened the robustness of these causal associations, and the multivariable MR analyses demonstrated independent direct effects of the strongest risk and protective factors on GrimAgeAccel and PhenoAgeAccel, respectively.ConclusionOur findings provide novel quantitative evidence on modifiable causal risk factors for epigenetic ageing, and hint at underlying contributors and intervention targets to the ageing process.Key PointsGenetically predicted higher educational attainment is the strongest protective factor for both GrimAgeAccel and PhenoAgeAccel, independent of causal lifestyle and cardiometabolic risk factors.Smoking is the leading causal lifestyle risk factor for GrimAgeAccel or PhenoAgeAccel, followed by alcohol intake and daytime napping. Adiposity traits are the leading causal cardiometabolic risk factors for GrimAgeAccel and PhenoAgeAccel, followed by type 2 diabetes, triglycerides, and C-reactive protein.This study provides novel quantitative evidence on modifiable causal risk factors for accelerated epigenetic ageing, indicating underlying contributors to the ageing process and promising intervention targets to promote healthy longevity.
A u-shape association of serum uric acid with gout in US adults
Authors: Xinmiao Yan , Taolan Sun , Zixuan Zhao , Yanrong Luo , Hanbing Zhao , Han Zhao , Miaojing Li 
Published: July 2022

AbstractBackgroundSerum uric acid (SUA) level is the strongest determinant of gout, and the relationship between hyperuricemia and gout has been found. However, the association between the across-full range of SUA level and gout also remains uncertain. We aimed to investigate the trend across an across-full range of SUA level and gout in the general population.Materials and MethodsThis study included 4,738 US adults from The National Health and Nutrition Examination Survey (NHANES). A generalized additive model was used to fit the non-linear trend between SUA level and gout.Results2,209 males and 2,469 females were included in our study, with the age range of 20∼80 years. The range of SUA level was from 0.8 to 15.1 mg/dL. About 5.9% of participants had gout. There was a U-shape association between SUA level and gout in univariable GAM (EDF = 3.881, p <0.001) and multivariable GAM (EDF = 3.795, p <0.001). The lowest risk of gout was observed in participants with SUA level of 5-6mg/dL. We evaluated the trend of SUA level with gout by gender. Both males and females with high SUA level have a high prevalence of gout. Male have a high prevalence of gout with low SUA level. The SUA level and prevalence of gout support a U-shape in males, while females show a linear shape.ConclusionThis study showed that low as well as high SUA are associated with gout. Hypouricemia is a candidate predictor of gout in US adults.
Hotspot residues and resistance mutations in the nirmatrelvir-binding site of SARS-CoV-2 main protease: Design, identification, and correlation with globally circulating viral genomes
Authors: Padhi Aditya K. , Tripathi Timir 
Published: July 2022

AbstractSince the onset of the COVID-19 pandemic, SARS-CoV-2 has acquired numerous variations in its intracellular proteins to quickly adapt, become more infectious, and ultimately develop drug resistance by mutating certain hotspot residues. To keep the emerging variants at bay, including Omicron and subvariants, FDA has approved the antiviral nirmatrelvir for mild-to-moderate and high-risk COVID-19 cases. Like other viruses, SARS-CoV-2 could acquire mutations in its main protease (Mpro) to adapt and develop resistance against nirmatrelvir. Employing a unique high-throughput protein design technique, the hotspot residues and signatures of adaptation of Mprohaving the highest probability of mutating and rendering nirmatrelvir ineffective were identified. Our results show that ∼40% of the designed mutations in Mproalready exist in the globally circulating SARS-CoV-2 lineages. The work provides a first-hand explanation of the resistance mutations in Mproand is crucial in comprehending viral adaptation, robust antiviral design, and surveillance of evolving Mprovariations.
The evolutionary constraints on angiosperm chloroplast adaptation
Authors: Robbins Elizabeth Hannah Joan , Kelly Steven 
Published: July 2022

AbstractThe chloroplast (plastid) arose via endosymbiosis of a photosynthetic cyanobacterium by a non-photosynthetic eukaryotic cell approximately 1.5 billion years ago. Although the plastid underwent rapid evolution by genome reduction, its rate of molecular evolution is low and its genome organisation is highly conserved. Here, we investigate the factors that have constrained the rate of molecular evolution of protein coding genes in the plastid genome. Through analysis of 773 angiosperm plastid genomes we show that there is substantial variation in the rate of molecular evolution between genes. We show that variation in the strength of purifying selection between genes is a major determinant of variation in the rate of molecular evolution. We further demonstrate that the distance of a gene from the likely origin of replication influences the rate at which it has evolved, consistent with time and distance dependent mutation gradients. In addition, we show that the amino acid composition of a gene product constraints its substitution tolerance, limiting its rate of molecular evolution. Finally, we demonstrate that the mRNA abundance of a gene is a key factor in determining its rate of molecular evolution, suggesting an interaction between transcription and DNA repair in the plastid. Collectively, we show that the location, composition, and expression of a plastid gene can account for ≥32% of the variation in its rate of molecular evolution. Thus, these three factors have exerted a substantial limitation on the capacity for adaptive evolution of plastid genes, and constrained the evolvability of the chloroplast.
LRP2 contributes to planar cell polarity-dependent coordination of motile cilia function
Authors: Bunatyan Lena , Margineanu Anca , Boutin Camille , Montcouquiol Mireille , Bachmann Sebastian , Christensen Erik Ilsø , Willnow Thomas E. , Christ Annabel 
Published: July 2022

ABSTRACTMotile cilia are protruding organelles on specialized epithelia that beat in a synchronous fashion to propel extracellular fluids. Coordination and orientation of cilia beating on individual cells and across tissues is a complex process dependent on planar cell polarity (PCP) signaling. Asymmetric sorting of PCP pathway components, essential to establish planar polarity, involves trafficking along the endocytic path, but the underlying regulatory processes remain incompletely understood. Here, we identified the endocytic receptor LRP2 as regulator of PCP component trafficking in ependyma, a multi-ciliated cell type that is involved in facilitating flow of the cerebrospinal fluid in the brain ventricular system. Lack of receptor expression in gene-targeted mice results in a failure to sort PCP core proteins to the anterior or posterior cell side and, consequently, in the inability to coordinate cilia arrangement and to aligned beating (loss of rotational and translational polarity). LRP2 deficiency coincides with a failure to sort NHERF1, a cytoplasmic LRP2 adaptor to the anterior cell side. As NHERF1 is essential to translocate PCP core protein Vangl2 to the plasma membrane, these data suggest a molecular mechanism whereby LRP2 interacts with PCP components through NHERF1 to control their asymmetric sorting along the endocytic path. Taken together, our findings identified the endocytic receptor LRP2 as a novel regulator of endosomal trafficking of PCP proteins, ensuring their asymmetric partition and establishment of translational and rotational planar cell polarity in the ependyma.