bluuebunny/crossref_metadata_2025_split huggingface dataset:
Microbial community-based bacterial protein from soybean-processing wastewater as a value-added alternative fish feed ingredient for Asian sea bass (Lates calcarifer)
Authors: Santillan Ezequiel , Yasumaru Fanny , Vethathirri Ramanujam Srinivasan , Thi Sara Swa , Hoon Hui Yi , Pek Sian Diana Chan , Wuertz Stefan 
Published: January 2023

AbstractAs the global demand for food increases, aquaculture plays a key role as the fastest growing animal protein sector. However, existing aquafeeds contain protein ingredients that are not sustainable under current production systems. We evaluated the use of microbial community-based single cell protein (SCP), produced from soybean processing wastewater, as a partial fishmeal protein substitute in juvenile Asian seabass (Lates calcarifer). A 24-day feeding trial was conducted with a control fishmeal diet and a 50% fishmeal replacement with microbial community-based SCP as an experimental group, in triplicate tanks containing 20 fish each. Both diets met the protein, essential amino acids (except for lysine), and fat requirements for juvenile Asian sea bass. The microbial composition of the SCP was dominated by the generaAcidipropionibacteriumandPropioniciclava, which have potential as probiotics and producers of valuable metabolites. The growth performance in terms of percent weight gain, feed conversion ratio (FCR), specific growth rate (SGR), and survival were not significantly different between groups after 24 days. The experimental group had less variability in terms of weight gain and FCR than the control group. Overall, microbial community-based protein produced from soybean processing wastewater has potential as a value-added feed ingredient for sustainable aquaculture feeds.
AUTOMATIC EXTRACTION OF ACTIN NETWORKS IN PLANTS
Authors: Hembrow Jordan , Deeks Michael J. , Richards David M. 
Published: January 2023

AbstractThe actin cytoskeleton is essential in eukaryotes, not least in the plant kingdom where it plays key roles in cell expansion, cell division, environmental responses and pathogen defence. Yet, the precise structure-function relationships of properties of the actin network in plants are still to be unravelled, including details of how the network configuration depends upon cell type, tissue type and developmental stage. Part of the problem lies in the difficulty of extracting high-quality, three-dimensional, quantitative measures of actin network features from microscopy data. To address this problem, we have developed DRAGoN, a novel image analysis algorithm that can automatically extract the actin network across a range of cell types, providing seventeen different quantitative measures that describe the network at a local level. Using this algorithm, we then studied a number of cases inArabidopsis thaliana, including several different tissues, a variety of actin-affected mutants, and cells responding to powdery mildew. In many cases we found statistically-significant differences in actin network properties. In addition to these results, our algorithm is designed to be easily adaptable to other tissues, mutants and plants, and so will be a valuable asset for the study and future biological engineering of the actin cytoskeleton in globally-important crops.
A robust normalized local filter to estimate compositional heterogeneity directly from cryo-EM maps
Authors: Forsberg Bjoern O. , Shah Pranav N.M. , Burt Alister 
Published: January 2023

AbstractCryo electron microscopy (cryo-EM) is used by biological research to visualize biomolecular complexes in 3D, but the heterogeneity of cryo-EM reconstructions is not easily estimated. Current processing paradigms nevertheless exert great effort to reduce flexibility and heterogeneity to improve the quality of the reconstruction. Clustering algorithms are typically employed to identify populations of data with reduced variability, but lack assessment of remaining heterogeneity. We have developed a fast and simple algorithm based on spatial filtering to estimate the heterogeneity of a reconstruction. In the absence of flexibility, this estimate approximates macromolecular component occupancy. We show that our implementation can derive reliable input parameters automatically, that the resulting estimate is accurate, and the reconstruction can be modified accordingly to emulate altered constituent occupancy, which may benefit conventionally employed maximum-likelihood classification methods. Here, we demonstrate the utility of this method for cryo-EM map interpretation, quantification, and particle-image signal subtraction.
Towards stability of dynamic FC estimates in neuroimaging and electrophysiology: solutions and limits
Authors: Alonso Sonsoles , Vidaurre Diego 
Published: January 2023

AbstractTime-varying functional connectivity methods are used to map the spatiotemporal organization of brain activity. However, their estimation can be unstable, in the sense that different runs of the inference may yield different solutions. But to draw meaningful relations to behaviour, estimates must be robust and reproducible. Here, we propose two solutions using the Hidden Markov Model (HMM) as a descriptive model of time-varying FC. The first, best-ranked HMM, involves running the inference multiple times and selecting the best model based on a quantitative measure combining fitness and model complexity. The second, hierarchical clustered HMM, generates stable aggregated state timeseries by applying hierarchical clustering to the state timeseries obtained from multiple runs. Experimental results on fMRI and MEG data demonstrate that these approaches substantially improve the stability of time-varying FC estimations. Overall, hierarchical clustered HMM is preferred when the inference variability is high, while the best-ranked HMM performs better otherwise.
Validation and characterization of a viral antisense transcript with Northern blot analysis and qRT-PCR
Authors: Kara Mehmet 
Published: January 2023

AbstractThe transcription of mammalian genomes has been shown to possess an intriguing complexity and numerous novel RNA molecules have been identified in the last 10-15 years. Viruses with large DNA genomes, especially herpesviruses, are also shown to generate many different RNA species and some of them may function as long non-coding RNAs. Viral genomes harbor several genes within close proximity to each other and can generate multigenic transcripts in addition to commonly observed antisense transcription. It is essential to study the biological roles of these transcripts aside from the protein-coding counterparts. A transcriptionally complex locus can be studied with a combination of methods. Generally, quantitative PCR assays are very commonly used for expression analyses of the transcripts of interest. Here an example from a gammaherpesvirus is discussed in more detail. A recently developed method, for the resolution of complicated transcriptomes for viral genomes, elucidated multiple antisense transcripts from ORF63-64 locus in murine gammaherpesvirus 68 (MHV68). In order to identify the roles of these new transcripts, quantitative PCR assays may not be enough alone and should be supported by alternative methods such as Northern blots. A more detailed transcriptional map of the locus of interest is useful to design experimental strategies and perform functional studies.
Mechanistic Basis for Enhanced Strigolactone Sensitivity in KAI2 Triple Mutant
Authors: Sobecks Briana L. , Chen Jiming , Shukla Diwakar 
Published: January 2023

AbstractStriga hermonthicais a parasitic weed that destroys billions of dollars’ worth of staple crops every year. Its rapid proliferation stems from an enhanced ability to metabolize strigolactones (SLs), plant hormones that direct root branching and shoot growth.Striga’sSL receptor,ShHTL7, bears more similarity to the staple crop karrikin receptor KAI2 than to SL receptor D14, though KAI2 variants in plants likeArabidopsis thalianashow minimal SL sensitivity. Recently, studies have indicated that a small number of point mutations to HTL7 residues can confer SL sensitivity toAtKAI2. Here, we analyze both wild-typeAtKAI2 and SL-sensitive mutant Var64 through all-atom, long-timescale molecular dynamics simulations to determine the effects of these mutations on receptor function at a molecular level. We demonstrate that the mutations stabilize SL binding by about 2 kcal/mol. They also result in a doubling of the average pocket volume, and eliminate the dependence of binding on certain pocket conformational arrangements. While the probability of certain non-binding SL-receptor interactions increases in the mutant compared with the wild-type, the rate of binding also increases by a factor of ten. All these changes account for the increased SL sensitivity in mutant KAI2, and suggest mechanisms for increasing functionality of host crop SL receptors.
Effects of Dopamine Receptor Antagonists and Radiation on Mouse Neural Stem/Progenitor Cells
Authors: He Ling , Bhat Kruttika , Ioannidis Angeliki , Pajonk Frank 
Published: January 2023

AbstractBackgroundDopamine receptor antagonists are psychotropic drugs that have been originally developed against psychiatric disorders. We recently identified dopamine receptor antagonists as potential anti-cancer agents and some have entered clinical trials against glioblastoma. Radiotherapy is known to cause cognitive impairment in patients receiving cranial irradiation through the elimination of neural stem/progenitor cells and subsequent loss of neurogenesis.MethodsUsing transgenic mice that report the presence of neural stem/progenitor cells through Nestin promoter-driven expression of enhanced green fluorescent protein, the effects of dopamine receptor antagonists alone or in combination with radiation on murine neural stem/progenitor cells were assessed in sphere-formation assays, flow cytometry and immunofluorescencein vitroandin vivo.ResultsWe report that several dopamine receptor antagonists show sex-dependent effects on neural stem/progenitor cells bothin vitroandin vivo. Hydroxyzine, trifluoperazine, amisulpride, nemonapride or quetiapine alone or in combination with radiation significantly increased the number of neural stem/progenitor cells in female neurospheres but not in male mice. Dopamine receptor antagonists either protected neural stem/progenitor cells from radiation or expanded the stem cell pool, thus indicating that this combination therapy against glioblastoma will not increase radiation-induced cognitive decline through increasing elimination of neural stem/progenitor cells and subsequent loss of neurogenesis.ConclusionsWe conclude that a therapeutic window for dopamine receptor antagonists in combination with radiation potentially exist, making it a novel combination therapy against glioblastoma. Normal tissue toxicity of this combination potentially differs depending on age and sex and should be taken into consideration when designing clinical trials.Key Points- Neural stem/progenitor cells show sex-dependent sensitivity to dopamine receptor antagonists- Dopamine receptor antagonists active against GBM increase Neural stem/progenitor cells countsImportance of the StudyCombination therapy of dopamine receptor antagonists with radiation have entered clinical trials against glioblastoma but the normal tissue toxicity of this combination has not been fully explored yet. Here we present evidence that some dopamine receptor antagonists show sex-dependent effects on neural stem/progenitor cells either by protecting neural stem/progenitor cells from radiation or inducing an expansion of the stem cell pool, suggesting that this combination therapy against glioblastoma will not increase radiation-induced cognitive decline through increasing elimination of neural stem/progenitor cells and subsequent loss of neurogenesis. Normal tissue toxicity of this combination potentially differs depending on age and sex and should be further explored in clinical trials.
Phantom controllers: Misspecified models create the false appearance of adaptive control during value-based choice
Authors: Ritz H. , Frömer R. , Shenhav A. 
Published: January 2023

AbstractDecision scientists have grown increasingly interested in how people adaptively control their decision making. Researchers have demonstrated that parameters governing the accumulation of evidence towards a choice, such as the decision threshold, are shaped by information available prior to or in parallel with one’s evaluation of an option set (e.g., recent outcomes or choice conflict). A recent account has taken a bold leap forward in this approach, suggesting that adjustments in decision parameters can be motivated by the value of the options under consideration. This motivated control account predicts that when faced with difficult choices (similarly valued options) under time pressure, people will adaptively lower their decision threshold to ensure that they make a choice in time. This account was supported by drift diffusion modeling of a deadlined choice task, demonstrating that decision thresholds decrease for difficult relative to easy choices. Here, we reanalyze the data from this experiment, and show that evidence for this novel account does not hold up to further scrutiny. Using a more systematic and comprehensive modeling approach, we show that this previously observed threshold adjustment disappears (or even reverses) under a more complete model of the data. Importantly, we further show how this and other apparent evidence for motivated control arises as an artifact of model (mis)specification, where one model’s putatively controlled decision process (e.g., value-driven threshold adjustments) can mimic another model’s stimulus-driven decision processes (e.g., accumulator competition or collapsing bounds). Collectively, this work reveals crucial insights and constraints in the pursuit of understanding how control guides decision-making, and when it doesn’t.
Microstructural and cellular characterisation of the subchondral trabecular bone in human knee and hip osteoarthritis using synchrotron tomography
Authors: Muratovic Dzenita , Findlay David M. , Quinn Micaela J. , Quarrington Ryan D. , Solomon Lucian B. , Atkins Gerald J. 
Published: January 2023

AbstractObjectiveIt is unclear if different factors influence osteoarthritis (OA) progression and the changes characterising OA disease in hip and knee. We investigated the difference between hip OA and knee OA at the subchondral bone tissue and cellular level, relative to the degree of cartilage degeneration.DesignBone samples were collected from 11 patients (aged 70±8 years) undergoing knee arthroplasty and 8 patients (aged 64±12 years) undergoing hip arthroplasty surgery. Bone microstructure, osteocyte-lacunar network and bone matrix vascularity were evaluated using synchrotron micro-CT imaging. Samples were additionally examined histologically to determine osteocyte density, viability, and connectivity.ResultsAfter adjustment for donor gender and age, associations between the extent of cartilage degeneration, bone volume fraction [8.7, 95% CI (3.4, 14.1)], trabecular number [1.5, 95% CI (0.8, 2.3)], osteocyte lacunar density [4714.9; 95% CI (2079.1, 7350.6)] and trabecular separation [-0.06, 95% CI (0.01, 0.1)] were found in both knee and hip OA.When compared to knee OA, hip OA was characterised by higher trabecular thickness [0.006, 95% CI (-4, 0.01)], larger but less spheric osteocyte lacunae [47.3; 95% CI (11.2, 83.4), -0.04; 95% CI (-0.6, -0.01), respectively], lower vascular canal density [-22.8; 95% CI (-35.4, -10.3)] lower osteocyte density [-84.9; 95% CI (-102.4, -67.4)], and less senescent but more apoptotic osteocytes [-2.4; 95% CI (-3.6, -1.2), 24.9; 95% CI (17.7, 32.1)], respectively.ConclusionSubchondral bone from hip OA and knee OA exhibits different characteristics at the tissue and cellular levels, suggesting different mechanisms of OA progression between the hip and knee joints.
Control of Center of Mass Motion during Walking Predicts Gait and Balance in People with Incomplete Spinal Cord Injury
Authors: Dusane Shamali , Shafer Anna , Ochs Wendy L. , Cornwell Tara , Henderson Heather , Kim Kwang-Youn A. , Gordon Keith E. 
Published: January 2023

AbstractBackgroundThere is evidence that ambulatory people with incomplete spinal cord injury (iSCI) have an impaired ability to control lateral motion of their whole-body center of mass (COM) during walking. This impairment is believed to contribute to functional deficits in gait and balance, however that relationship is unclear. Thus, this cross-sectional study examines the relationship between the ability to control lateral COM motion during walking and functional measures of gait and balance in people with iSCI.MethodsWe assessed the ability to control lateral COM motion during walking and conducted clinical gait and balance outcome measures on twenty ambulatory adults with chronic iSCI (C1-T10 injury, American Spinal Injury Association Impairment Scale C or D). To assess their ability to control lateral COM motion, participants performed three treadmill walking trials. During each trial, real-time lateral COM position and a target lane were projected on the treadmill. Participants were instructed to keep their lateral COM position within the lane. If successful, an automated control algorithm progressively reduced the lane width, making the task more challenging. If unsuccessful, the lane width increased. The adaptive lane width was designed to challenge each participant’s maximum capacity to control lateral COM motion during walking. To quantify control of lateral COM motion, we calculated lateral COM excursion during each gait cycle and then identified the minimum lateral COM excursion occurring during five consecutive gait cycles. Our clinical outcome measures were Berg Balance Scale (BBS), Timed Up and Go test (TUG), 10-Meter Walk Test (10MWT) and Functional Gait Assessment (FGA). We used a Spearman correlation analysis (ρ) to examine the relationship between minimum lateral COM excursion and clinical measures.ResultsMinimum lateral COM excursion had significant moderate correlations with BBS (ρ=−0.54, p=0.014), TUG (ρ=0.59, p=0.007), 10MWT-preferred (ρ=−0.59, p=0.006), and FGA (ρ=−0.59, p=0.007) and a significant strong correlation with 10MWT-fast (ρ=−0.68, p=0.001).ConclusionControl of lateral COM motion during walking predicts a wide range of clinical gait and balance measures in people with iSCI. This finding suggests the ability to control lateral COM motion during walking could be a contributing factor to gait and balance in people with iSCI.
Nuclear genetic control of mtDNA copy number and heteroplasmy in humans
Authors: Gupta Rahul , Kanai Masahiro , Durham Timothy J. , Tsuo Kristin , McCoy Jason G. , Chinnery Patrick F. , Karczewski Konrad J. , Calvo Sarah E. , Neale Benjamin M. , Mootha Vamsi K. 
Published: January 2023

AbstractHuman mitochondria contain a high copy number, maternally transmitted genome (mtDNA) that encodes 13 proteins required for oxidative phosphorylation. Heteroplasmy arises when multiple mtDNA variants co-exist in an individual and can exhibit complex dynamics in disease and in aging. As all proteins involved in mtDNA replication and maintenance are nuclear-encoded, heteroplasmy levels can, in principle, be under nuclear genetic control, however this has never been shown in humans. Here, we develop algorithms to quantify mtDNA copy number (mtCN) and heteroplasmy levels using blood-derived whole genome sequences from 274,832 individuals of diverse ancestry and perform GWAS to identify nuclear loci controlling these traits. After careful correction for blood cell composition, we observe that mtCN declines linearly with age and is associated with 92 independent nuclear genetic loci. We find that nearly every individual carries heteroplasmic variants that obey two key patterns: (1) heteroplasmic single nucleotide variants are somatic mutations that accumulate sharply after age 70, while (2) heteroplasmic indels are maternally transmitted as mtDNA mixtures with resulting levels influenced by 42 independent nuclear loci involved in mtDNA replication, maintenance, and novel pathways. These nuclear loci do not appear to act by mtDNA mutagenesis, but rather, likely act by conferring a replicative advantage to specific mtDNA molecules. As an illustrative example, the most common heteroplasmy we identify is a length variant carried by >50% of humans at position m.302 within a G-quadruplex known to serve as a replication switch. We find that this heteroplasmic variant exertscis-acting genetic control over mtDNA abundance and is itself undertrans-acting genetic control of nuclear loci encoding protein components of this regulatory switch. Our study showcases how nuclear haplotype can privilege the replication of specific mtDNA molecules to shape mtCN and heteroplasmy dynamics in the human population.
A computable phenotype for patients with SARS-CoV2 testing that occurred outside the hospital
Authors: Wang Lijing , Zipursky Amy , Geva Alon , McMurry Andrew J. , Mandl Kenneth D. , Miller Timothy A. 
Published: January 2023

AbstractObjectiveTo identify a cohort of COVID-19 cases, including when evidence of virus positivity was only mentioned in the clinical text, not in structured laboratory data in the electronic health record (EHR).Materials and MethodsStatistical classifiers were trained on feature representations derived from unstructured text in patient electronic health records (EHRs). We used a proxy dataset of patientswithCOVID-19 polymerase chain reaction (PCR) tests for training. We selected a model based on performance on our proxy dataset and applied it to instances without COVID-19 PCR tests. A physician reviewed a sample of these instances to validate the classifier.ResultsOn the test split of the proxy dataset, our best classifier obtained 0.56 F1, 0.6 precision, and 0.52 recall scores for SARS-CoV2 positive cases. In an expert validation, the classifier correctly identified 90.8% (79/87) as COVID-19 positive and 97.8% (91/93) as not SARS-CoV2 positive. The classifier identified an additional 960 positive cases that did not have SARS-CoV2 lab tests in hospital, and only 177 of those cases had the ICD-10 code for COVID-19.DiscussionProxy dataset performance may be worse because these instances sometimes include discussion of pending lab tests. The most predictive features are meaningful and interpretable. The type of external test that was performed is rarely mentioned.ConclusionCOVID-19 cases that had testing done outside of the hospital can be reliably detected from the text in EHRs. Training on a proxy dataset was a suitable method for developing a highly performant classifier without labor intensive labeling efforts.