bluuebunny/crossref_metadata_2025 huggingface dataset:
Contemporary risk factors for a longer hospital stay following bidirectional cavopulmonary anastomosis
Authors: Almasarweh Saleem I. , Suntharos Patcharapong , Saini Ashish , Prieto Lourdes , Sasaki Jun
Published: August 2022

Background:

Despite high survival after bidirectional cavopulmonary anastomosis, a considerable number of patients suffer significant post-operative morbidities related to prolonged length of stay.

Methods:

A single-center retrospective cohort study of all consecutive patients undergoing a first-time bidirectional cavopulmonary anastomosis from 2006 to 2019.

Results:

Prolonged length of stay was defined as hospital stay greater than the 75th percentile for our cohort. Of 195 patients who met inclusion criteria, the median post-operative length of stay was 8 days (interquartile range, 4-15 days). Prolonged length of stay was defined as greater than 15 days. In multivariate analysis, greater than mild systemic atrioventricular valve regurgitation (odds ratio 3.7, 95% CI 1.05-13.068, p = 0.04), longer length of stay after the initial palliative procedure (odds ratio 1.028, 95% CI 1.004-1.05, p = 0.02), and pre-operative higher superior vena cava oxygen saturation (odds ratio 0.922, 95% CI 0.85-0.99, p = 0.04) maintained statistical significance as independent risk and protective factors for prolonged length of stay. A one-level increase in the severity of pre-operative systemic atrioventricular valve regurgitation was associated with a multiplicative change in the odds ratio of prolonged length of stay of 5.45 (p = 0.005) independent of the severity of systemic ventricular dysfunction.

Conclusion:

Pre-operative characteristics with greater than mild systemic atrioventricular valve regurgitation, longer length of stay after the initial palliative procedure, and lower superior vena cava oxygen saturation were associated with prolonged length of stay after a first-time bidirectional cavopulmonary anastomosis.
Implications of climate change for environmental niche overlap between fiveCuscutapest species and their two main Leguminosae host crop species
Authors: Cai Chaonan , Xiao Jianhua , Wan Jizhong , Ren Zichun , van Kleunen Mark , Li Junmin
Published: August 2022

Some parasitic plants are major pests in agriculture, but how this might be affected by climate change remains largely unknown. In this study, we assessed this question for five generalist holoparasiticCuscutaspecies (smoothseed alfalfa dodder [Cuscuta approximataBab.], alfalfa dodder [Cuscuta europaeaL.], soybean dodder [Cuscuta chinensisC. Wright], Peruvian dodder [Cuscuta australisR. Br.], and Japanese dodder [Cuscuta japonicaChoisy]) and two of their main Leguminosae host crop species (soybean [Glycine max(L.) Merr.] and alfalfa [Medicago sativaL.]. For each of the fiveCuscutaspecies and the two crop species, we ran MaxEnt models, using climatic and soil variables to predict their potential current distributions and potential future distributions for 2070. We ran species distribution models for all seven species for multiple climate change scenarios, and tested for changes in the overlap of suitable ranges of each crop with the five parasites. We found that annual mean temperature and isothermality are the main bioclimatic factors determining the suitable habitats of theCuscutaspecies and their hosts. For both host species, the marginally to optimally suitable area will increase by 2070 for all four representative concentration pathway scenarios. For most of theCuscutaspecies, the marginally to optimally suitable area will also increase. While the suitable areas for both the hosts and the parasites will increase overall, Schoener’sD, indicating the relative overlap in suitable area, will change only marginally. However, the absolute area of potential niche overlap may increase up to 6-fold by 2070. Overall, our results indicate that larger parts of the globe will become suitable for both host species, but that they could also suffer fromCuscutaparasitism in larger parts of their suitable ranges.
A Common Diffusional Mechanism for Creep and Grain Growth in Polymineralic Rocks: Experiments
Authors: Okamoto A. , Hiraga T.
Published: August 2022

We conducted uniaxial compression and grain growth experiments on fine‐grained forsterite (Mg2SiO4) + 10 vol% periclase (MgO) aggregates. This aggregate is a unique polymineralic system in which all of the constituent elements in the secondary phase constitute the primary mineral phase, except for Si, which is the slowest diffusing species in the primary phase. Grain growth in polymineralic aggregates, where the presence of a secondary phase results in grain boundary pinning of the primary phase, proceeds via Ostwald ripening of the secondary phase. Grain growth and diffusion creep rates were analyzed, and both rates were found to be limited by the same grain‐boundary diffusivity. For periclase ripening, forsterite grains surrounding the periclase grains must be deformed, such that diffusion of Si as well as Mg and O is necessary for periclase ripening, similarly to diffusion creep of the aggregates. Most rocks are polymineralic and usually contain a silicate mineral as their main phase, in which Si is the slowest diffusing species. This leads to the prediction that a single diffusivity, which is Si diffusivity in most cases, determines the rates of grain growth and diffusion creep in much of the Earth's interior. The grain size, which is the result of grain growth, and the time it takes to achieve that size, indicate the diffusivity. Viscosity during diffusion creep is determined by these grain size and diffusivity values. We view these findings as a unique opportunity to estimate the viscosity from the Earth's crust to the lower mantle.
Translatome proteomics identifies autophagy as a resistance mechanism to on-target FLT3 inhibitors in acute myeloid leukemia
Authors: Koschade Sebastian E. , Klann Kevin , Shaid Shabnam , Vick Binje , Stratmann Jan A. , Thölken Marlyn , Meyer Laura M. , Nguyen The Duy , Campe Julia , Moser Laura M. , Hock Susanna , Baker Fatima , Meyer Christian T. , Wempe Frank , Serve Hubert , Ullrich Evelyn , Jeremias Irmela , Münch Christian , Brandts Christian H.
Published: August 2022

Internal tandem duplications (ITD) in the receptor tyrosine kinase FLT3 occur in 25 % of acute myeloid leukemia (AML) patients, drive leukemia progression and confer a poor prognosis. Primary resistance to FLT3 kinase inhibitors (FLT3i) quizartinib, crenolanib and gilteritinib is a frequent clinical challenge and occurs in the absence of identifiable genetic causes. This suggests that adaptive cellular mechanisms mediate primary resistance to on-target FLT3i therapy. Here, we systematically investigated acute cellular responses to on-target therapy with multiple FLT3i in FLT3-ITD + AML using recently developed functional translatome proteomics (measuring changes in the nascent proteome) with phosphoproteomics. This pinpointed AKT-mTORC1-ULK1-dependent autophagy as a dominant resistance mechanism to on-target FLT3i therapy. FLT3i induced autophagy in a concentration- and time-dependent manner specifically in FLT3-ITD + cells in vitro and in primary human AML cells ex vivo. Pharmacological or genetic inhibition of autophagy increased the sensitivity to FLT3-targeted therapy in cell lines, patient-derived xenografts and primary AML cells ex vivo. In mice xenografted with FLT3-ITD + AML cells, co-treatment with oral FLT3 and autophagy inhibitors synergistically impaired leukemia progression and extended overall survival. Our findings identify a molecular mechanism responsible for primary FLT3i treatment resistance and demonstrate the pre-clinical efficacy of a rational combination treatment strategy targeting both FLT3 and autophagy induction.
Association between antidepressant use and ED or hospital visits in outpatients with SARS-CoV-2
Authors: Fritz Bradley A. , Hoertel Nicolas , Lenze Eric J. , Jalali Farid , Reiersen Angela M.
Published: August 2022

Antidepressants have previously been associated with better outcomes in patients hospitalized with COVID-19, but their effect on clinical deterioration among ambulatory patients has not been fully explored. The objective of this study was to assess whether antidepressant exposure was associated with reduced emergency department (ED) or hospital visits among ambulatory patients with SARS-CoV-2 infection. This retrospective cohort study included adult patients (N = 25 034) with a positive SARS-CoV-2 test performed in a non-hospital setting. Logistic regression analyses tested associations between home use of antidepressant medications and a composite outcome of ED visitation or hospital admission within 30 days. Secondary exposures included individual antidepressants and antidepressants with functional inhibition of acid sphingomyelinase (FIASMA) activity. Patients with antidepressant exposure were less likely to experience the primary composite outcome compared to patients without antidepressant exposure (adjusted odds ratio [aOR] 0.89, 95% CI 0.79–0.99, p = 0.04). This association was only observed with daily doses of at least 20 mg fluoxetine-equivalent (aOR 0.87, 95% CI 0.77–0.99, p = 0.04), but not with daily doses lower than 20 mg fluoxetine-equivalent (aOR 0.94, 95% CI 0.80–1.11, p = 0.48). In exploratory secondary analyses, the outcome incidence was also reduced with exposure to selective serotonin reuptake inhibitors (aOR 0.87, 95% CI 0.75–0.99, p = 0.04), bupropion (aOR 0.70, 95% CI 0.55–0.90, p = 0.005), and FIASMA antidepressant drugs (aOR 0.87, 95% CI 0.77–0.99, p = 0.03). Antidepressant exposure was associated with a reduced incidence of emergency department visitation or hospital admission among SARS-CoV-2 positive patients, in a dose-dependent manner. These data support the FIASMA model of antidepressants’ effects against COVID-19.
CDK5RAP3 acts as a tumour suppressor in gastric cancer through the infiltration and polarization of tumour-associated macrophages
Authors: Wang Jia-Bin , Gao You-Xin , Ye Yin-Hua , Lin Tong-Xing , Li Ping , Lin Jian-Xian , Chen Qi-Yue , Cao Long-Long , Lin Mi , Tu Ru-Hong , Lin Ju-Li , Huang Ze-Ning , Zheng Hua-Long , Xie Jian-Wei , Zheng Chao-Hui , Huang Chang-Ming
Published: August 2022

We have demonstrated that CDK5RAP3 exerts a tumour suppressor effect in gastric cancer, but its role in regulating tumour-associated macrophages (TAMs) has not yet been reported. Here, we show that CDK5RAP3 is related to the infiltration and polarization of macrophages. It inhibits the polarization of TAMs to M2 macrophages and promotes the polarization of the M1 phenotype. CDK5RAP3 reduces the recruitment of circulating monocytes to infiltrate tumour tissue by inhibiting the CCL2/CCR2 axis in gastric cancer. Blocking CCR2 reduces the growth of xenograft tumours and the infiltration of monocytes. CDK5RAP3 inhibits the nuclear transcription of NF-κB, thereby reducing the secretion of the cytokines IL4 and IL10 and blocking the polarization of M2 macrophages. In addition, the absence of CDK5RAP3 in gastric cancer cells allows macrophages to secrete more MMP2 to promote the epithelial-mesenchymal transition (EMT) process of gastric cancer cells, thereby enhancing the invasion and migration ability. Our results imply that CDK5RAP3 may be involved in the regulation of immune activity in the tumour microenvironment and is expected to become a potential immunotherapy target for gastric cancer.
Estimating effects of parents’ cognitive and non-cognitive skills on offspring education using polygenic scores
Authors: Demange Perline A. , Hottenga Jouke Jan , Abdellaoui Abdel , Eilertsen Espen Moen , Malanchini Margherita , Domingue Benjamin W. , Armstrong-Carter Emma , de Zeeuw Eveline L. , Rimfeld Kaili , Boomsma Dorret I. , van Bergen Elsje , Breen Gerome , Nivard Michel G. , Cheesman Rosa
Published: August 2022

Understanding how parents’ cognitive and non-cognitive skills influence offspring education is essential for educational, family and economic policy. We use genetics (GWAS-by-subtraction) to assess a latent, broad non-cognitive skills dimension. To index parental effects controlling for genetic transmission, we estimate indirect parental genetic effects of polygenic scores on childhood and adulthood educational outcomes, using siblings (N = 47,459), adoptees (N = 6407), and parent-offspring trios (N = 2534) in three UK and Dutch cohorts. We find that parental cognitive and non-cognitive skills affect offspring education through their environment: on average across cohorts and designs, indirect genetic effects explain 36–40% of population polygenic score associations. However, indirect genetic effects are lower for achievement in the Dutch cohort, and for the adoption design. We identify potential causes of higher sibling- and trio-based estimates: prenatal indirect genetic effects, population stratification, and assortative mating. Our phenotype-agnostic, genetically sensitive approach has established overall environmental effects of parents’ skills, facilitating future mechanistic work.
Linear and nonlinear correlation estimators unveil undescribed taxa interactions in microbiome data
Authors: Lin Huang , Eggesbø Merete , Peddada Shyamal Das
Published: August 2022

It is well-known that human gut microbiota form an ecosystem where microbes interact with each other. Due to complex underlying interactions, some microbes may correlate nonlinearly. There are no measures in the microbiome literature we know of that quantify these nonlinear relationships. Here, we develop a methodology called Sparse Estimation of Correlations among Microbiomes (SECOM) for estimating linear and nonlinear relationships among microbes while maintaining the sparsity. SECOM accounts for both sample and taxon-specific biases in its model. Its statistical properties are evaluated analytically and by comprehensive simulation studies. We test SECOM in two real data sets, namely, forehead and palm microbiome data from college-age adults, and Norwegian infant gut microbiome data. Given that forehead and palm are related to skin, as desired, SECOM discovers each genus to be highly correlated between the two sites, but that is not the case with any of the competing methods. It is well-known that infant gut evolves as the child grows. Using SECOM, for the first time in the literature, we characterize temporal changes in correlations among bacterial families during a baby’s first year after birth.
Evolution of longitudinal division in multicellular bacteria of the Neisseriaceae family
Authors: Nyongesa Sammy , Weber Philipp M. , Bernet Ève , Pulido Francisco , Nieves Cecilia , Nieckarz Marta , Delaby Marie , Viehboeck Tobias , Krause Nicole , Rivera-Millot Alex , Nakamura Arnaldo , Vischer Norbert O. E. , vanNieuwenhze Michael , Brun Yves V. , Cava Felipe , Bulgheresi Silvia , Veyrier Frédéric J.
Published: August 2022

Rod-shaped bacteria typically elongate and divide by transverse fission. However, several bacterial species can form rod-shaped cells that divide longitudinally. Here, we study the evolution of cell shape and division mode within the familyNeisseriaceae, which includes Gram-negative coccoid and rod-shaped species. In particular, bacteria of the generaAlysiella,SimonsiellaandConchiformibius, which can be found in the oral cavity of mammals, are multicellular and divide longitudinally. We use comparative genomics and ultrastructural microscopy to infer that longitudinal division withinNeisseriaceaeevolved from a rod-shaped ancestor. In multicellular longitudinally-dividing species, neighbouring cells within multicellular filaments are attached by their lateral peptidoglycan. In these bacteria, peptidoglycan insertion does not appear concentric, i.e. from the cell periphery to its centre, but as a medial sheet guillotining each cell. Finally, we identify genes and alleles associated with multicellularity and longitudinal division, including the acquisition of amidase-encoding geneamiC2, and amino acid changes in proteins including MreB and FtsA. Introduction ofamiC2and allelic substitution ofmreBin a rod-shaped species that divides by transverse fission results in shorter cells with longer septa. Our work sheds light on the evolution of multicellularity and longitudinal division in bacteria, and suggests that members of theNeisseriaceaefamily may be good models to study these processes due to their morphological plasticity and genetic tractability.
Raptors avoid the confusion effect by targeting fixed points in dense aerial prey aggregations
Authors: Brighton Caroline H. , Kloepper Laura N. , Harding Christian D. , Larkman Lucy , McGowan Kathryn , Zusi Lillias , Taylor Graham K.
Published: August 2022

Collective behaviours are widely assumed to confuse predators, but empirical support for a confusion effect is often lacking, and its importance must depend on the predator’s targeting mechanism. Here we show that Swainson’s Hawks Buteo swainsoni and other raptors attacking swarming Mexican Free-tailed Bats Tadarida brasiliensis steer by turning towards a fixed point in space within the swarm, rather than by using closed-loop pursuit of any one individual. Any prey with which the predator is on a collision course will appear to remain on a constant bearing, so target selection emerges naturally from the geometry of a collision. Our results show how predators can simplify the demands on their sensory system by decoupling steering from target acquisition when capturing prey from a dense swarm. We anticipate that the same tactic will be used against flocks and schools across a wide range of taxa, in which case a confusion effect is paradoxically more likely to occur in attacks on sparse groups, for which steering and target acquisition cannot be decoupled.
Derivation and utility of schizophrenia polygenic risk associated multimodal MRI frontotemporal network
Authors: Qi Shile , Sui Jing , Pearlson Godfrey , Bustillo Juan , Perrone-Bizzozero Nora I. , Kochunov Peter , Turner Jessica A. , Fu Zening , Shao Wei , Jiang Rongtao , Yang Xiao , Liu Jingyu , Du Yuhui , Chen Jiayu , Zhang Daoqiang , Calhoun Vince D.
Published: August 2022

Schizophrenia is a highly heritable psychiatric disorder characterized by widespread functional and structural brain abnormalities. However, previous association studies between MRI and polygenic risk were mostly ROI-based single modality analyses, rather than identifying brain-based multimodal predictive biomarkers. Based on schizophrenia polygenic risk scores (PRS) from healthy white people within the UK Biobank dataset (N = 22,459), we discovered a robust PRS-associated brain pattern with smaller gray matter volume and decreased functional activation in frontotemporal cortex, which distinguished schizophrenia from controls with >83% accuracy, and predicted cognition and symptoms across 4 independent schizophrenia cohorts. Further multi-disease comparisons demonstrated that these identified frontotemporal alterations were most severe in schizophrenia and schizo-affective patients, milder in bipolar disorder, and indistinguishable from controls in autism, depression and attention-deficit hyperactivity disorder. These findings indicate the potential of the identified PRS-associated multimodal frontotemporal network to serve as a trans-diagnostic gene intermediated brain biomarker specific to schizophrenia.
Lysosomal exocytosis releases pathogenic α-synuclein species from neurons in synucleinopathy models
Authors: Xie Ying Xue , Naseri Nima N. , Fels Jasmine , Kharel Parinati , Na Yoonmi , Lane Diane , Burré Jacqueline , Sharma Manu
Published: August 2022

Considerable evidence supports the release of pathogenic aggregates of the neuronal protein α-Synuclein (αSyn) into the extracellular space. While this release is proposed to instigate the neuron-to-neuron transmission and spread of αSyn pathology in synucleinopathies including Parkinson’s disease, the molecular-cellular mechanism(s) remain unclear. To study this, we generated a new mouse model to specifically immunoisolate neuronal lysosomes, and established a long-term culture model where αSyn aggregates are produced within neurons without the addition of exogenous fibrils. We show that neuronally generated pathogenic species of αSyn accumulate within neuronal lysosomes in mouse brains and primary neurons. We then find that neurons release these pathogenic αSyn species via SNARE-dependent lysosomal exocytosis. The released aggregates are non-membrane enveloped and seeding-competent. Additionally, we find that this release is dependent on neuronal activity and cytosolic Ca2+. These results propose lysosomal exocytosis as a central mechanism for the release of aggregated and degradation-resistant proteins from neurons.
Covalent TCR-peptide-MHC interactions induce T cell activation and redirect T cell fate in the thymus
Authors: Szeto Christopher , Zareie Pirooz , Wirasinha Rushika C. , Zhang Justin B. , Nguyen Andrea T. , Riboldi-Tunnicliffe Alan , La Gruta Nicole L. , Gras Stephanie , Daley Stephen R.
Published: August 2022

Interactions between a T cell receptor (TCR) and a peptide-major histocompatibility complex (pMHC) ligand are typically mediated by noncovalent bonds. By studying T cells expressing natural or engineered TCRs, here we describe covalent TCR-pMHC interactions that involve a cysteine-cysteine disulfide bond between the TCR and the peptide. By introducing cysteines into a known TCR-pMHC combination, we demonstrate that disulfide bond formation does not require structural rearrangement of the TCR or the peptide. We further show these disulfide bonds still form even when the initial affinity of the TCR-pMHC interaction is low. Accordingly, TCR-peptide disulfide bonds facilitate T cell activation by pMHC ligands with a wide spectrum of affinities for the TCR. Physiologically, this mechanism induces strong Zap70-dependent TCR signaling, which triggers T cell deletion or agonist selection in the thymus cortex. Covalent TCR-pMHC interactions may thus underlie a physiological T cell activation mechanism that has applications in basic immunology and potentially in immunotherapy.
Unveiling Trail Making Test: visual and manual trajectories indexing multiple executive processes
Authors: Linari Ignacio , Juantorena Gustavo E. , Ibáñez Agustín , Petroni Agustín , Kamienkowski Juan E.
Published: August 2022

The Trail Making Test (TMT) is one of the most popular neuropsychological tests for executive functions (EFs) assessment. It presents several strengths: it is sensitive to executive dysfunction, it is easy to understand, and has a short administration. However, it has important limitations. First, the underlying EFs articulated during the task are not well discriminated, which makes it a test with low specificity. Second, the pen-and-paper version presents one trial per condition which introduces high variability. Third, only the total time is quantified, which does not allow for a detailed analysis. Fourth, it has a fixed spatial configuration per condition. We designed a computerised version of the TMT to overcome its main limitations and evaluated it in a group of neurotypical adults. Eye and hand positions are measured with high resolution over several trials, and spatial configuration is controlled. Our results showed a very similar performance profile compared to the traditional TMT. Moreover, it revealed differences in eye movements between parts A and B. Most importantly, based on hand and eye movements, we found an internal working memory measure that showed an association to a validated working memory task. Additionally, we proposed another internal measure as a potential marker of inhibitory control. Our results showed that EFs can be studied in more detail using traditional tests combined with powerful digital setups. The cTMT showed potential use in older adult populations and patients with EFs disorders.
Comparison of the modified Singapore myocardial infarction registry risk score with GRACE 2.0 in predicting 1-year acute myocardial infarction outcomes
Authors: Sia Ching-Hui , Zheng Huili , Ko Junsuk , Ho Andrew Fu-Wah , Foo David , Foo Ling-Li , Lim Patrick Zhan-Yun , Liew Boon Wah , Chai Ping , Yeo Tiong-Cheng , Tan Huay-Cheem , Chua Terrance , Chan Mark Yan-Yee , Tan Jack Wei Chieh , Fox Keith A. A. , Bulluck Heerajnarain , Hausenloy Derek J.
Published: August 2022

Risk stratification plays a key role in identifying acute myocardial infarction (AMI) patients at higher risk of mortality. However, current AMI risk scores such as the Global Registry of Acute Coronary Events (GRACE) score were derived from predominantly Caucasian populations and may not be applicable to Asian populations. We previously developed an AMI risk score from the national-level Singapore Myocardial Infarction Registry (SMIR) confined to ST-segment elevation myocardial infarction (STEMI) patients and did not include non-STEMI (NSTEMI) patients. Here, we derived a modified SMIR risk score for both STEMI and NSTEMI patients and compared its performance to the GRACE 2.0 score for predicting 1-year all-cause mortality in our multi-ethnic population. The most significant predictor of 1-year all-cause mortality in our population using the GRACE 2.0 score was cardiopulmonary resuscitation on admission (adjusted hazards ratio [HR] 6.50), while the most significant predictor using the SMIR score was age 80–89 years (adjusted HR 7.78). Although the variables used in the GRACE 2.0 score and SMIR score were not exactly the same, the c-statistics for 1-year all-cause mortality were similar between the two scores (GRACE 2.0 0.841 and SMIR 0.865). In conclusion, we have shown that in a multi-ethnic Asian AMI population undergoing PCI, the SMIR score performed as well as the GRACE 2.0 score.
Roundup and glyphosate’s impact on GABA to elicit extended proconvulsant behavior in Caenorhabditis elegans
Authors: Naraine Akshay S. , Aker Rebecca , Sweeney Isis , Kalvey Meghan , Surtel Alexis , Shanbhag Venkatesh , Dawson-Scully Ken
Published: August 2022

As 3 billion pounds of herbicides are sprayed over farmlands every year, it is essential to advance our understanding how pesticides may influence neurological health and physiology of both humans and other animals. Studies are often one-dimensional as the majority examine glyphosate by itself. Farmers and the public use commercial products, like Roundup, containing a myriad of chemicals in addition to glyphosate. Currently, there are no neurological targets proposed for glyphosate and little comparison to Roundup. To investigate this, we compared how glyphosate and Roundup affect convulsant behavior in C.elegans and found that glyphosate and Roundup increased seizure-like behavior. Key to our initial hypothesis, we found that treatment with an antiepileptic drug rescued the prolonged convulsions. We also discovered over a third of nematodes exposed to Roundup did not recover from their convulsions, but drug treatment resulted in full recovery. Notably, these effects were found at concentrations that are 1,000-fold dilutions of previous findings of neurotoxicity, using over 300-fold less herbicide than the lowest concentration recommended for consumer use. Exploring mechanisms behind our observations, we found significant evidence that glyphosate targets GABA-A receptors. Pharmacological experiments which paired subeffective dosages of glyphosate and a GABA-A antagonist yielded a 24% increase in non-recovery compared to the antagonist alone. GABA mutant strain experiments showed no effect in a GABA-A depleted strain, but a significant, increased effect in a glutamic acid decarboxylase depleted strain. Our findings characterize glyphosate’s exacerbation of convulsions and propose the GABA-A receptor as a neurological target for the observed physiological changes. It also highlights glyphosate’s potential to dysregulate inhibitory neurological circuits.
Spatial and temporal variation in New Hampshire bat diets
Authors: O’Rourke Devon , Rouillard Nicholas P. , Parise Katy L. , Foster Jeffrey T.
Published: August 2022

Insectivorous bats consume a diverse array of arthropod prey, with diets varying by bat species, sampling location, and season. North American bat diets remain incompletely described, which is concerning at a time when many bat and insect populations appear to be declining. Understanding the variability in foraging is thus an essential component for effective bat conservation. To comprehensively evaluate local foraging, we assessed the spatial and temporal variability in prey consumed by the little brown bat,Myotis lucifugus, in New Hampshire, USA. We collected bat guano samples from 20 sites over 2 years and analyzed sequence data for 899 of these samples using a molecular metabarcoding approach targeting the cytochrome oxidase I subunit (COI) gene. Some prey items were broadly shared across locations and sampling dates, with the most frequently detected arthropod orders broadly similar to previous morphological and molecular analyses; at least one representative sequence variant was assigned to Coleoptera in 92% of samples, with other frequently detected orders including Diptera (73%), Lepidoptera (65%), Trichoptera (38%), and Ephemeroptera (32%). More specifically, two turf and forest pests were routinely detected: white grubs in the genusPhyllophaga(50%), and the Asiatic Garden beetle,Maladera castanea(36%). Despite the prevalence of a few taxa shared among many samples and distinct seasonal peaks in consumption of specific arthropods, diet composition varied both temporally and spatially. However, species richness did not strongly vary indicating consumption of a broad diversity of taxa throughout the summer. These data characterize little brown bats as flexible foragers adept at consuming a broad array of locally available prey resources.
Fluid mixing optimization with reinforcement learning
Authors: Konishi Mikito , Inubushi Masanobu , Goto Susumu
Published: August 2022

Fluid mixing is crucial in various industrial processes. In this study, focusing on the characteristics that reinforcement learning (RL) is suitable for global-in-time optimization, we propose utilizing RL for fluid mixing optimization of passive scalar fields. For the two-dimensional fluid mixing problem described by the advection–diffusion equations, a trained mixer realizes an exponentially fast mixing without any prior knowledge. The stretching and folding by the trained mixer around stagnation points are essential in the optimal mixing process. Furthermore, this study introduces a physically reasonable transfer learning method of the trained mixer: reusing a mixer trained at a certain Péclet number to the mixing problem at another Péclet number. Based on the optimization results of the laminar mixing, we discuss applications of the proposed method to industrial mixing problems, including turbulent mixing.
Numerical methodology to evaluate unipolar saturation current limit of DC corona discharge in complex geometries
Authors: Kim Sangwoo , Hwang Jungho
Published: August 2022

The unipolar saturation current limit ($${I}_{sat}$$

I

sat

) gives an upper limit to the corona current that can be obtained from a unipolar corona discharge. Therefore, it implies a theoretical limit to the performance of unipolar corona discharge devices. However, it has not been widely used in practice because it is difficult to deal with complex discharge configurations in an analytical way. This study aims to establish and validate a numerical methodology to evaluate the maximum current, which numerically imitates the unipolar saturation current limit. It was shown that the maximum current has the same mathematical definition as the unipolar saturation current. For validation, the maximum current was compared with an analytical solution of the Poisson equation for the coaxial cylinders configuration. The differences between the maximum current and unipolar saturation current limit for the coaxial cylinders, pin-to-plane, and single wire-to-plane configurations were discussed in terms of the assumptions used in the semi-analytical derivation of the unipolar saturation current limit. The validated methodology was applied to a multiple wire-to-plane configuration, for which a semi-analytical expression of the unipolar saturation current limit has not yet been developed. The effects of geometric and operation parameters on the maximum currents of the multiple wire-to-plane configuration were analyzed. The results were regressed into a single formula.
Lysyl hydroxylase 2 mediated collagen post-translational modifications and functional outcomes
Authors: Terajima Masahiko , Taga Yuki , Nakamura Tomoyuki , Guo Hou-Fu , Kayashima Yukako , Maeda-Smithies Nobuyo , Parag-Sharma Kshitij , Kim Jeong Seon , Amelio Antonio L. , Mizuno Kazunori , Kurie Jonathan M. , Yamauchi Mitsuo
Published: August 2022

Lysyl hydroxylase 2 (LH2) is a member of LH family that catalyzes the hydroxylation of lysine (Lys) residues on collagen, and this particular isozyme has been implicated in various diseases. While its function as a telopeptidyl LH is generally accepted, several fundamental questions remain unanswered: 1. Does LH2 catalyze the hydroxylation of all telopeptidyl Lys residues of collagen? 2. Is LH2 involved in the helical Lys hydroxylation? 3. What are the functional consequences when LH2 is completely absent? To answer these questions, we generated LH2-null MC3T3 cells (LH2KO), and extensively characterized the type I collagen phenotypes in comparison with controls. Cross-link analysis demonstrated that the hydroxylysine-aldehyde (Hylald)-derived cross-links were completely absent from LH2KO collagen with concomitant increases in the Lysald-derived cross-links. Mass spectrometric analysis revealed that, in LH2KO type I collagen, telopeptidyl Lys hydroxylation was completely abolished at all sites while helical Lys hydroxylation was slightly diminished in a site-specific manner. Moreover, di-glycosylated Hyl was diminished at the expense of mono-glycosylated Hyl. LH2KO collagen was highly soluble and digestible, fibril diameters were diminished, and mineralization impaired when compared to controls. Together, these data underscore the critical role of LH2-catalyzed collagen modifications in collagen stability, organization and mineralization in MC3T3 cells.
Farasan Island of Saudi Arabia confronts the measurable impacts of global warming in 45 years
Authors: Khedher Khaled Mohamed , Abu-Taweel Gasem Mohammad , Al-Fifi Zarraq , Qoradi Mofareh D. , Al-khafaji Zainab , Halder Bijay , Bandyopadhyay Jatisankar , Shahid Shamsuddin , Essaied LAATAR , Yaseen Zaher Mundher
Published: August 2022

Coastal vulnerability assessment is the key to coastal management and sustainable development. Sea level rise (SLR) and anthropogenic activities have triggered more extreme climatic events and made the coastal region vulnerable in recent decades. Many parts of the world also noticed increased sediment deposition, tidal effects, and changes in the shoreline. Farasan Island, located in the south-eastern part of Saudi Arabia, experienced changes in sediment deposition from the Red Sea in recent years. This study used Digital Shoreline Analysis System (DSAS) to delineate the shoreline changes of Farasan Island during 1975–2020. Multi-temporal Landsat data and DSAS were used for shoreline calculation based on endpoint rate (EPR) and linear regression. Results revealed an increase in vegetation area on the island by 17.18 km2 during 1975–1989 and then a decrease by 69.85 km2 during 1990–2020. The built-up land increased by 5.69 km2 over the study period to accommodate the population growth. The annual temperature showed an increase at a rate of 0.196 °C/year. The sea-level rise caused a shift in the island's shoreline and caused a reduction of land by 80.86 km2 during 1975–2020. The highly influenced areas by the environmental changes were the north, central, northwest, southwest, and northeast parts of the island. Urban expansion and sea-level rise gradually influence the island ecosystem, which needs proper attention, management, policies, and awareness planning to protect the environment of Farasan Island. Also, the study’s findings could help develop new strategies and plan climate change adaptation.
Personality similarity predicts synchronous neural responses in fMRI and EEG data
Authors: Matz Sandra C. , Hyon Ryan , Baek Elisa C. , Parkinson Carolyn , Cerf Moran
Published: August 2022

Successful communication and cooperation among different members of society depends, in part, on a consistent understanding of the physical and social world. What drives this alignment in perspectives? We present evidence from two neuroimaging studies using functional magnetic resonance imaging (fMRI;N = 66 with 2145 dyadic comparisons) and electroencephalography (EEG;N = 225 with 25,200 dyadic comparisons) to show that: (1) the extent to which people’s neural responses are synchronized when viewing naturalistic stimuli is related to their personality profiles, and (2) that this effect is stronger than that of similarity in gender, ethnicity and political affiliation. The localization of the fMRI results in combination with the additional eye tracking analyses suggest that the relationship between personality similarity and neural synchrony likely reflects alignment in the interpretation of stimuli and not alignment in overt visual attention. Together, the findings suggest that similarity in psychological dispositions aligns people’s reality via shared interpretations of the external world.
Experimental and modeling investigation of organic modified montmorillonite with octyl quaternary ammonium salt
Authors: Liu Hongyan , Guo Chengxin , Cui Yingna , Yin Jingmei , Li Shenmin
Published: August 2022

The sodium montmorillonite was organic modified with three kinds of quaternary ammonium salts containing 1 to 3 octyl chains, and then the organic montmorillonite was studied by FT-IR, XRD, and TG characterization as well as Monte Carlo simulations, to explore the influence of the number of octyl chains and the loading of intercalated cations on the basal spacing (d001) of the modified montmorillonite complexes. According to the distribution of intercalated quaternary ammonium cations and the energy change of the montmorillonite complexes, a reasonable explanation was given for the enlargement of the interlayer space. The results of experimental characterization and Monte Carlo simulations show that all the three intercalation agents can enlarge the interlayer space of montmorillonite complexes. The more the number of octyl chains in the salt, the more significant expanding effect on the interlayer space. The three intercalation cations exhibited a distribution arranged from mono-layered to multi-layered structure as the loading of intercalated cations increases.
New putative phenol oxidase in ascidian blood cells
Authors: Daugavet M. A. , Dobrynina M. I. , Shaposhnikova T. G. , Solovyeva A. I. , Mittenberg A. G. , Shabelnikov S. V. , Babkina I. Yu. , Grinchenko A. V. , Ilyaskina D. V. , Podgornaya O. I.
Published: August 2022

The phenol oxidase system is ancient and ubiquitously distributed in all living organisms. In various groups it serves for the biosynthesis of pigments and neurotransmitters (dopamine), defence reactions and tissue hardening. Ascidians belong to subphylum Tunicata, which is considered the closest living relative to Vertebrates. Two phenol oxidases previously described for ascidians are vertebrate-like and arthropod-like phenol oxidases. In our present study, we described a new ascidian protein, Tuphoxin, with putative phenol oxidase function, which bears no sequence similarity with two enzymes described previously. The closest related proteins to Tuphoxin are mollusc haemocyanins. Unlike haemocyanins, which are oxygen transporting plasma proteins, Tuphoxin is synthesised in ascidian blood cells and secreted in the extracellular matrix of the tunic—ascidian outer coverings. Single mature transcript coding for this phenol oxidase can give several protein products of different sizes. Thus limited proteolysis of the initial protein is suggested. A unique feature of Tuphoxins and their homologues among Tunicata is the presence of thrombospondin first type repeats (TSP1) domain in their sequence which is supposed to provide interaction with extracellular matrix. The finding of TSP1 in the structure of phenol oxidases is new and we consider this to be an innovation of Tunicata evolutionary lineage.
Loureirin B downregulates osteoclast differentiation of bone marrow macrophages by targeting the MAPK signaling pathway
Authors: Zhang Jiahao , Mo Liang , Huang Haoran , Xu Jiake , Fan Yinuo , Li Weifeng , Wang Haibin , Zhou Chi , Fang Hanjun , He Wei , Chen Zhenqiu , Liu Yuhao
Published: August 2022

Excessive absorption of osteoclasts will break the balance between osteoclasts and osteoblasts, leading to bone loss, decreased bone density, and increased bone fragility. We have shown that Loureirin B (LrB) can inhibit osteoclasts. In this study, we demonstrated the targeting-inhibitory mechanism of LrB acting on osteoclast precursor. Using SPR, HPLC and MALDI-TOF-MS to capture and analyze the target protein of Loureirin B in bone marrow macrophages (BMMs), we used this method to detect all target proteins that LrB acts on BMMs, and analyzed the distribution and enrichment rate of the target protein by DAVID enrichment analysis. Ledock molecular docking was used to detect the binding of LrB. We used Western Blot for verification. The target proteins of LrB acting on BMMs were Serpine1, Atp6ap1, Dvl1, Rhd, Fzd2, MAPK1, MAP2K2, MAPK3 and so on. MAPK1, MAP2K2 and MAPK3 were the most relevant. LrB treatment attenuated the expression of phosphorylated JNK and p38 kinases of the MAPK signaling pathway. Our research further confirmed that LrB affects the MAPK signaling pathway in BMMs, thereby inhibiting the differentiation of BMMs into osteoclasts. This discovery can confirm the mechanism by which LrB acts on BMMs.
A study on synergistic effect of chloride and sulfate ions on copper corrosion by using electrochemical noise in asymmetric cells
Authors: Sajadi Ghazal Sadat , Saheb Vahid , Shahidi-Zandi Mehdi , Hosseini Seyed Mohammad Ali
Published: August 2022

The current study includes a systematic examination of copper corrosion initially in each of NaCl and Na2SO4solutions separately and then in the mixture solution of Cl−and SO42−ions as aggressive ions. Electrochemical current noise (ECN) signals resulting from asymmetric (Asy) as well as symmetric (Sym) cells have been interpreted using wavelet transform (WT) along with statistical procedures. The signals have been detrended and the decomposition of every signal has been carried out into 8 crystals. Then the standard deviation of every crystal has been illustrated with the standard deviation of partial signal (SDPS) plots. The Asy electrodes increased the pitting detection on copper compared with the Sym ones, indicating higher efficiency of the Asy electrodes. Asymmetric-copper electrodes have been studied using SDPS plots at different temperatures (40, 60, as well as 80 °C). Finally, in order to partly understand the effect of Cl−and SO42−ions on the corrosion of copper, the stabilization of Cu2+cations by Cl−and SO42−ions in aqueous solutions have been modeled by DFT calculations. The derived results are in accordance with the experimental data.
Correlations between APOE4 allele and regional amyloid and tau burdens in cognitively normal older individuals
Authors: Hong Yun Jeong , Kim Chan-Mi , Lee Jae Hong , Sepulcre Jorge
Published: August 2022

The correlations between apolipoprotein epsilon 4 (APOE4) status and regional amyloid, tau, and cortical thickness in cognitively normal elderly are not fully understood. Our cross-sectional study aimed to compare regional amyloid/tau burden, and cortical thickness according to APOE4 carrier status and assess correlations between APOE4 and Alzheimer’s disease (AD)-related biomarker burdens. We analyzed 185 cognitively normal participants from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) cohort. Participants aged 55–90 with normal cognitive function were divided into amyloid ß-positive (Aß+) APOE4 carriers (group 1, n = 27), Aß+ APOE4 non-carriers (group 2, n = 29), and Aß− normal controls (group 0, n = 129). We compared amyloid depositions, tau depositions, and cortical thickness among the three groups and assessed correlations between APOE4 existence and imaging biomarkers adjusted for age and sex. The participants in group 2 were older than those in the other groups. The regional amyloid/tau standardized uptake value ratios (SUVRs) did not differ between groups 1 and 2, but the amyloid/tau SUVRs in most regions were numerically higher after adjusting for age difference. APOE4 allele had robust correlations with increased amyloid burden in the fronto-temporo-parietal cortical areas after adjustment for age and sex, but it had weaker and mixed correlations with the regional tau burden and did not have significant correlation with cortical thickness. We identified that the presence of APOE4 allele might be more highly associated with amyloid deposition than with other AD-related biomarkers such as tau or cortical thickness in cognitively normal elderly.
Monitoring non-parametric profiles using adaptive EWMA control chart
Authors: Abbasi Saddam Akber , Yeganeh Ali , Shongwe Sandile C.
Published: August 2022

To monitor the quality of a process in statistical process control (SPC), considering a functional relationship between a dependent variable and one or more independent variables (which is denoted as profile monitoring) is becoming an increasingly common approach. Most of the studies in the SPC literature considered parametric approaches in which the functional relationship has the same form in the in-control (IC) and out-of-control (OC) situations. Non-parametric profiles, which have a different functional relationship in the OC conditions are very common. This paper designs a novel control chart to monitor not only the regression parameters but also the variation of the profiles in Phase II applications using an adaptive approach. Adaptive control charts adjust the final statistic with regard to information of the previous samples. The proposed method considers the relative distance of the chart statistic to the control limits as a tendency index and provides some outcomes about the process condition. The results of Monte Carlo simulations show the superiority of the proposed monitoring scheme in comparison with the common non-parametric control charts.
Dicationic styryl dyes for colorimetric and fluorescent detection of nucleic acids
Authors: Supabowornsathit Kotchakorn , Faikhruea Kriangsak , Ditmangklo Boonsong , Jaroenchuensiri Theeranuch , Wongsuwan Sutthida , Junpra-ob Sirikarn , Choopara Ilada , Palaga Tanapat , Aonbangkhen Chanat , Somboonna Naraporn , Taechalertpaisarn Jaru , Vilaivan Tirayut
Published: August 2022

Nucleic acid staining dyes are important tools for the analysis and visualizing of DNA/RNA in vitro and in the cells. Nevertheless, the range of commercially accessible dyes is still rather limited, and they are often very costly. As a result, finding nontoxic, easily accessible dyes, with desirable optical characteristics remains important. Styryl dyes have recently gained popularity as potential biological staining agents with many appealing properties, including a straightforward synthesis procedure, excellent photostability, tunable fluorescence, and high fluorescence quantum yield in the presence of nucleic acid targets with low background fluorescence signals. In addition to fluorescence, styryl dyes are strongly colored and exhibit solvatochromic properties which make them useful as colorimetric stains for low-cost and rapid testing of nucleic acids. In this work, novel dicationic styryl dyes bearing quaternary ammonium groups are designed to improve binding strength and optical response with target nucleic acids which contain a negatively charged phosphate backbone. Optical properties of the newly synthesized styryl dyes have been studied in the presence and absence of nucleic acid targets with the aim to find new dyes that can sensitively and specifically change fluorescence and/or color in the presence of nucleic acid targets. The binding interaction and optical response of the dicationic styryl dyes with nucleic acid were superior to the corresponding monocationic styryl dyes. Applications of the developed dyes for colorimetric detection of DNA in vitro and imaging of cellular nucleic acids are also demonstrated.