bluuebunny/crossref_metadata_2025 huggingface dataset:
Apical anchorage and stabilization of subpellicular microtubules by apical polar ring ensures Plasmodium ookinete infection in mosquito
Authors: Qian Pengge , Wang Xu , Guan Cuirong , Fang Xin , Cai Mengya , Zhong Chuan-qi , Cui Yong , Li Yanbin , Yao Luming , Cui Huiting , Jiang Kai , Yuan Jing
Published: December 2022

Morphogenesis of many protozoans depends on a polarized establishment of cortical cytoskeleton containing the subpellicular microtubules (SPMTs), which are apically nucleated and anchored by the apical polar ring (APR). In malaria parasite Plasmodium, APR emerges in the host-invading stages, including the ookinete for mosquito infection. So far, the fine structure and molecular components of APR as well as the underlying mechanism of APR-mediated apical positioning of SPMTs are largely unknown. Here, we resolve an unprecedented APR structure composed of a top ring plus approximate 60 radiating spines. We report an APR-localizing and SPMT-binding protein APR2. APR2 disruption impairs ookinete morphogenesis and gliding motility, leading to Plasmodium transmission failure in mosquitoes. The APR2-deficient ookinetes display defective apical anchorage of APR and SPMT due to the impaired integrity of APR. Using protein proximity labeling, we obtain a Plasmodium ookinete APR proteome and validate ten undescribed APR proteins. Among them, APRp2 and APRp4 directly interact with APR2 and also mediate the apical anchorage of SPMTs. This study sheds light on the molecular basis of APR in the organization of Plasmodium ookinete SPMTs.
Many-body localization in the infinite-interaction limit and the discontinuous eigenstate phase transition
Authors: Chen Chun , Chen Yan , Wang Xiaoqun
Published: December 2022

We study many-body localization (MBL) in a spin-chain model mimicking the Rydberg-blockade quantum simulator with infinite-strength projection and moderate quasiperiodic modulation. Employing exact diagonalization, Krylov-typicality technique, and time-evolving block decimation, we identify evidence for a constrained MBL phase stabilized by a pure quasirandom transverse field. Intriguingly, the constrained MBL transition may embody a discontinuous eigenstate phase transition, whose discontinuity nature significantly suppresses finite-size drifts that plague most numerical studies of conventional MBL transition. Through quantum dynamics, we find that rotating the modulated field from parallel toward perpendicular to the projection axis induces an eigenstate transition between diagonal and constrained MBL phases. The entanglement-entropy growth in constrained MBL follows a double-log form, whereas it changes to a power law in approaching the diagonal limit. By unveiling confined nonlocal effects in integrals of motion of constrained MBL, we show this insulating state is not a many-body Anderson insulator. Our predictions are testable in Rydberg experiments.
Safety and tolerability of KarXT (xanomeline–trospium) in a phase 2, randomized, double-blind, placebo-controlled study in patients with schizophrenia
Authors: Correll Christoph U. , Angelov Angel S. , Miller Andrew C. , Weiden Peter J. , Brannan Stephen K.
Published: December 2022

KarXT combines xanomeline, an M1/M4 preferring muscarinic agonist with no direct D2 receptor antagonism, with the peripherally restricted anticholinergic trospium. In EMERGENT-1 (NCT03697252), a 5-week, randomized, double-blind, placebo-controlled, phase 2 study in inpatients with schizophrenia, KarXT met the primary efficacy endpoint, numerous secondary endpoints, and was generally well tolerated. Here, we conducted additional post hoc analyses of safety and tolerability data of KarXT from EMERGENT-1 with a particular focus on adverse events (AEs) that may be associated with muscarinic receptor agonism (nausea or vomiting) or antagonism (dry mouth or constipation). A total of 179 patients received at least one dose of either KarXT (n = 89) or placebo (n = 90) and were included in the analyses. KarXT was associated with a low overall AE burden. The majority of procholinergic and anticholinergic AEs with KarXT were mild, occurred in the first 1−2 weeks of treatment, and were transient with a median duration ranging from 1 day for vomiting to 13 days for dry mouth. No patients in either treatment group discontinued the study due to any procholinergic or anticholinergic AEs. Incidence of somnolence/sedation AEs with KarXT were low and similar to those in the placebo group. KarXT was associated with no significant or clinically relevant changes in body weight, metabolic parameters, or vital signs. KarXT was generally well tolerated with an AE profile consistent with the activity of xanomeline–trospium at muscarinic receptors.
Centrin-deficient Leishmania mexicana confers protection against Old World visceral leishmaniasis
Authors: Karmakar Subir , Volpedo Greta , Zhang Wen-Wei , Lypaczewski Patrick , Ismail Nevien , Oliveira Fabiano , Oristian James , Meneses Claudio , Gannavaram Sreenivas , Kamhawi Shaden , Hamano Shinjiro , Valenzuela Jesus G. , Matlashewski Greg , Satoskar Abhay R. , Dey Ranadhir , Nakhasi Hira L.
Published: December 2022

Leishmaniasis is one of the top neglected tropical diseases with significant morbidity and mortality in low and middle-income countries (LMIC). However, this disease is also spreading in the developed world. Currently, there is a lack of effective strategies to control this disease. Vaccination can be an effective measure to control leishmaniasis and has the potential to achieve disease elimination. Recently, we have generatedcentringene-deleted new worldL. mexicana(LmexCen−/−) parasites using CRISPR/Cas9 and showed that they protect mice against a homologousL. mexicanainfection that causes cutaneous disease. In this study, we tested whetherLmexCen−/−parasites can also protect against visceral leishmaniasis caused byL. donovaniin a hamster model. We showed that immunization withLmexCen−/−parasites is safe and does not cause lesions. Furthermore, such immunization conferred protection against visceral leishmaniasis caused by a needle-initiatedL. donovanichallenge, as indicated by a significant reduction in the parasite burdens in the spleen and liver as well as reduced mortality. Similar control of parasite burden was also observed against a sand fly mediatedL. donovanichallenge. Importantly, immunization withLmexCen−/−down-regulated the disease promoting cytokines IL-10 and IL-4 and increased pro-inflammatory cytokine IFN-γ resulting in higher IFN-γ/IL-10 and IFN-γ/IL4 ratios compared to non-immunized animals.LmexCen−/−immunization also resulted in long-lasting protection againstL. donovaniinfection. Taken together, our study demonstrates that immunization withLmexCen−/−parasites is safe and efficacious against the Old World visceral leishmaniasis.
BNT162b2 induces robust cross-variant SARS-CoV-2 immunity in children
Authors: Bartsch Yannic C. , Chen Jessica W. , Kang Jaewon , Burns Madeleine D. , St Denis Kerri J. , Sheehan Maegan L. , Davis Jameson P. , Edlow Andrea G. , Balazs Alejandro B. , Yonker Lael M. , Alter Galit
Published: December 2022

Currently available mRNA vaccines are extremely safe and effective to prevent severe SARS-CoV-2 infections. However, the emergence of variants of concerns (VOCs) has highlighted the importance of high population-based vaccine rates to effectively suppress viral transmission and breakthrough infections. While initially left out from vaccine efforts, children have become one of the most affected age groups and are key targets to stop community and household spread. Antibodies are central for vaccine-induced protection and emerging data points to the importance of additional Fc effector functions like opsononophagocytosis or cytotoxicity, particularly in the context of VOCs that escape neutralizing antibodies. Here, we observed delayed induction and reduced magnitude of vaccine-induced antibody titers in children 5-11 years receiving two doses of the age-recommended 10 μg dose of the Pfizer SARS-CoV-2 BNT162b2 vaccine compared to adolescents (12–15 years) or adults receiving the 30 μg dose. Conversely, children mounted equivalent or more robust neutralization and opsonophagocytic functions at peak immunogenicity, pointing to a qualitatively more robust humoral functional response in children. Moreover, broad cross-VOC responses were observed across children, with enhanced IgM and parallel IgG cross-reactivity to VOCs in children compared to adults. Collectively, these data argue that despite the lower magnitude of the BNT162b2-induced antibody response in children, vaccine-induced immunity in children target VOCs broadly and exhibit enhanced functionality that may contribute to the attenuation of disease.
A multi-omics longitudinal aging dataset in primary human fibroblasts with mitochondrial perturbations
Authors: Sturm Gabriel , Monzel Anna S. , Karan Kalpita R. , Michelson Jeremy , Ware Sarah A. , Cardenas Andres , Lin Jue , Bris Céline , Santhanam Balaji , Murphy Michael P. , Levine Morgan E. , Horvath Steve , Belsky Daniel W. , Wang Shuang , Procaccio Vincent , Kaufman Brett A. , Hirano Michio , Picard Martin
Published: December 2022

Aging is a process of progressive change. To develop biological models of aging, longitudinal datasets with high temporal resolution are needed. Here we report a multi-omics longitudinal dataset for cultured primary human fibroblasts measured across their replicative lifespans. Fibroblasts were sourced from both healthy donors (n = 6) and individuals with lifespan-shortening mitochondrial disease (n = 3). The dataset includes cytological, bioenergetic, DNA methylation, gene expression, secreted proteins, mitochondrial DNA copy number and mutations, cell-free DNA, telomere length, and whole-genome sequencing data. This dataset enables the bridging of mechanistic processes of aging as outlined by the “hallmarks of aging”, with the descriptive characterization of aging such as epigenetic age clocks. Here we focus on bridging the gap for the hallmark mitochondrial metabolism. Our dataset includes measurement of healthy cells, and cells subjected to over a dozen experimental manipulations targeting oxidative phosphorylation (OxPhos), glycolysis, and glucocorticoid signaling, among others. These experiments provide opportunities to test how cellular energetics affect the biology of cellular aging. All data are publicly available at our webtool: https://columbia-picard.shinyapps.io/shinyapp-Lifespan_Study/
EyeT4Empathy: Dataset of foraging for visual information, gaze typing and empathy assessment
Authors: Lencastre Pedro , Bhurtel Samip , Yazidi Anis , e Mello Gustavo B. M. , Denysov Sergiy , Lind Pedro G.
Published: December 2022

We present a dataset of eye-movement recordings collected from 60 participants, along with their empathy levels, towards people with movement impairments. During each round of gaze recording, participants were divided into two groups, each one completing one task. One group performed a task of free exploration of structureless images, and a second group performed a task consisting of gaze typing, i.e. writing sentences using eye-gaze movements on a card board. The eye-tracking data recorded from both tasks is stored in two datasets, which, besides gaze position, also include pupil diameter measurements. The empathy levels of participants towards non-verbal movement-impaired people were assessed twice through a questionnaire, before and after each task. The questionnaire is composed of forty questions, extending a established questionnaire of cognitive and affective empathy. Finally, our dataset presents an opportunity for analysing and evaluating, among other, the statistical features of eye-gaze trajectories in free-viewing as well as how empathy is reflected in eye features.
The effect of mesenchymal stem cells-derived exosomes on the prostate, bladder, and renal cancer cell lines
Authors: Rezaeian AhmadReza , Khatami Fatemeh , Heidari Keshel Saeed , Akbari Mohammad Reza , Mirzaei Akram , Gholami Keykavos , Mohammadi Farsani Reza , Aghamir Seyed Mohammad Kazem
Published: December 2022

We aimed to explain the role of mesenchymal stem cells (MSC-exosomes) on gene expressions of epithelial to mesenchymal transition (EMT), angiogenesis, and apoptosis. Four different cell lines were employed, including ACHN, 5637, LNCaP, and PC3, as well-known representatives for renal, bladder, hormone-sensitive, and hormone-refractory prostate cancers, respectively. Cell lines were exposed to diverse concentrations of mesenchymal stem cells-derived exosomes to find IC50 values. Percentages of apoptotic cells were evaluated by Annexin/P.I. staining. Micro Culture Tetrazolium Test assessed proliferative inhibitory effect; and prostate biomarker (KLK2), EMT (E-cadherin and Snail), angiogenesis genes (VEGF-A/VEGF-C), apoptosis genes (BAX/BCL2, P53) and Osteopontin variants (OPNa/b, and c) mRNA levels were studied by realtime PCR method. All 5637, LNCaP, and PC3 following treatment with exosomes illustrated specific responses with changes in expression of different genes. The increased TP53 and decreased BCL2 expressions were seen in 5637, LNCaP, and PC3. In PC3, OPNb and OPNc have raised more than P53; in LNCap, the increase was in VEGF-c. In 5637 cells, more than TP53 and BCL2 changes, two other genes, VEGFa and B.A.X., have decreased, suggesting exosomes’ anti-apoptotic and anti-angiogenic effects. The kidney tumor cell line saw no significant gene expression change in ten targeted genes. MSC-exosomes therapy has augmented some interesting antitumor effects on prostate, bladder, and kidney cancer cell lines. This effect which originates from exosomes’ potency to persuade apoptosis and prevent the proliferation of cancer cells simultaneously, was more substantial in bladder cancer, moderate in prostate cancer, and mild in renal cancer.
The importance of eating patterns for health-related quality of life among children aged 10–11 years in Alberta of Canada
Authors: Wu Xiu Yun , Ohinmaa Arto , Maximova Katerina , Veugelers Paul J.
Published: December 2022

Children with unhealthy eating behaviours are more likely to experience poor physical and mental health. Few studies have investigated the importance of eating patterns for health-related quality of life (HRQoL) among children. This study aimed to identify common eating patterns, and their associations with HRQoL among Canadian children. Data were collected from 9150 grade five students (aged 10–11 years) in repeat cross-sectional population-based surveys in Alberta, Canada. Students’ eating behaviours were analyzed using latent class analysis to identify the eating patterns. We applied multilevel multivariable logistic regression to examine the association of the eating patterns with HRQoL. We identified three groups of children with distinct eating patterns: eating healthy (52%), less healthy (31%) and unhealthy (17%). The first group had a higher proportion of students engaged in healthy eating behaviours. The unhealthy pattern group (third group) included a higher proportion of students with poor eating behaviours. Students’ eating behaviours in the second group were healthier than the third group but less healthy than the first group. Children with unhealthy and less healthy patterns were more likely to experience lower HRQoL than children with the healthy pattern. Health promotion programs effective in improving healthy eating patterns may not only reduce the risk for chronic diseases in the long term, but also improve the HRQoL in the short term.
One pot synthesis of two potent Ag(I) complexes with quinoxaline ligand, X-ray structure, Hirshfeld analysis, antimicrobial, and antitumor investigations
Authors: El-Naggar Mostafa A. , Sharaf Mona Mohammed , Albering Jörg H. , Abu-Youssef Morsy A. M. , Kassem Taher S. , Soliman Saied M. , Badr Ahmed M. A.
Published: December 2022

In one pot, the self-assembly of AgNO3 and 2-chloroquinoxaline (2Cl-quinox) in water–ethanol mixture afforded two novel crystalline Ag(I) complexes. The major product is the polymeric complex [Ag(2Cl-quinox)(NO3)]n; (1), while the minor product (2) comprises two molecules which are the monomeric [Ag(2Cl-quinox)2(NO3)]; (2a) and polymeric [Ag(2Cl-quinox)(NO3)]n; (2b) complexes. The single crystal X-ray structure revealed that 1 and 2b are made up of two-dimensional infinite sheets. In contrast, 2a is a monomeric complex which has a highly distorted tetrahedral geometry around Ag(I) center. In all cases, the 2Cl-quinox molecule acts as a terminal monodentate ligand. Complexes 1 and 2b have similar molecular structures and also have almost similar crystal packing. Using Hirshfeld surface analysis, the O…H hydrogen bonds and π–π stacking interactions contributed significantly to the molecular packing. Both complexes have broad-spectrum action towards multi drug-resistance bacteria. The most effective function of 2 is against Proteus morganii, with a MIC value of 8 μg/mL. Complex 2 (IC50 = 5.93 ± 0.52 μg/mL) has remarkably greater cytotoxic effect against lung carcinoma (A-549) than cis-platin (IC50 = 7.5 ± 0.69 μg/mL) and AgNO3 (IC50 = 14.7 ± 0.53 μg/mL). The higher Ag-content in 2 could be the main reason for its higher cytotoxicity than 1.
The inhibitory effect of agricultural fiscal expenditure on agricultural green total factor productivity
Authors: Wang Shuguang , Zhu Jiaying , Wang Lang , Zhong Shen
Published: December 2022

Sustainable development of agriculture is the basis for achieving social sustainable development. As the basic industry of national economy, green development of agriculture has become an important support for building an environment-friendly society. Agricultural fiscal expenditure is a direct channel for the government to support agriculture and promote agricultural transformation. It is important to analyze the impact of agricultural fiscal expenditure (AFE) on agricultural green total factor productivity (AGTFP) for sustainable agricultural development. Therefore, this paper employs the random effect model and spatial Durbin model to empirically analyze the direct effect and spatial spillover effect of AFE on AGTFP by using the agricultural panel data of 30 provinces in China from 2008 to 2020. Then, by taking the policy proposal as the time node, this paper also conducts a time heterogeneity analysis to measure the impact of policy enactment on AFE and AGTFP. The main conclusions are as follows: (1) AGTFP exists significant positive spatial spillover effect. The "radiation effect" of agricultural green development is significant. (2) AFE can significantly reduce the AGTFP in the local area, that is, 1% increase of AFE in the local area will reduce AGTFP by 0.037%. At present, agriculture is still yield-oriented. The improvement of AFE in the local area will lead to the expansion of local agricultural production and increase pollution emission. (3) AFE has a significant negative spatial spillover effect on AGTFP, that is, for every 1% increase in AFE, the AGTFP will decrease 0.123% in geographically similar areas, while the AGTFP will decrease by 0.116% in economically and geographically similar areas. It is obvious that AFE will promote the optimization of agricultural production conditions in the province, with the "demonstration effect" on the surrounding areas, the enthusiasm of production in the surrounding areas will increase, thus expanding the pollution emission. (4) According to the analysis of different periods, AFE has a negative impact on AGTFP mainly before the reform innovation is proposed in 2015. It indicates that reform policies have a significant impact on agricultural sustainability.
Transcriptomics indicate nuclear division and cell adhesion not recapitulated in MCF7 and MCF10A compared to luminal A breast tumours
Authors: Goh Jeremy Joon Ho , Goh Corinna Jie Hui , Lim Qian Wei , Zhang Songjing , Koh Cheng-Gee , Chiam Keng-Hwee
Published: December 2022

Breast cancer (BC) cell lines are useful experimental models to understand cancer biology. Yet, their relevance to modelling cancer remains unclear. To better understand the tumour-modelling efficacy of cell lines, we performed RNA-seq analyses on a combined dataset of 2D and 3D cultures of tumourigenic MCF7 and non-tumourigenic MCF10A. To our knowledge, this was the first RNA-seq dataset comprising of 2D and 3D cultures of MCF7 and MCF10A within the same experiment, which facilitates the elucidation of differences between MCF7 and MCF10A across culture types. We compared the genes and gene sets distinguishing MCF7 from MCF10A against separate RNA-seq analyses of clinical luminal A (LumA) and normal samples from the TCGA-BRCA dataset. Among the 1031 cancer-related genes distinguishing LumA from normal samples, only 5.1% and 15.7% of these genes also distinguished MCF7 from MCF10A in 2D and 3D cultures respectively, suggesting that different genes drive cancer-related differences in cell lines compared to clinical BC. Unlike LumA tumours which showed increased nuclear division-related gene expression compared to normal tissue, nuclear division-related gene expression in MCF7 was similar to MCF10A. Moreover, although LumA tumours had similar cell adhesion-related gene expression compared to normal tissues, MCF7 showed reduced cell adhesion-related gene expression compared to MCF10A. These findings suggest that MCF7 and MCF10A cell lines were limited in their ability to model cancer-related processes in clinical LumA tumours.
The impact of driving pressure on postoperative pulmonary complication in patients with different respiratory spirometry
Authors: Oh Eun Jung , Kim Bo-Guen , Park Sukhee , Han Sangbin , Shin Beomsu , Lee Hyun , Shin Sun Hye , Kim Jeayoun , Choi Dancheong , Choi Eun Ah , Park Hye Yun
Published: December 2022

Risk factors for postoperative pulmonary complication (PPC) have not been determined according to preoperative respiratory spirometry. Thus, we aimed to find contributors for PPC in patients with restrictive or normal spirometric pattern. We analyzed 654 patients (379 with normal and 275 with restrictive spirometric pattern). PPCs comprised respiratory failure, pleural effusion, atelectasis, respiratory infection, and bronchospasm. We analyzed the association between perioperative factors and PPC using binary logistic regression. In particular, we conducted subgroup analysis on the patients stratified according to preoperative spirometry. Of 654 patients, 27/379 patients (7.1%) with normal spirometric pattern and 33/275 patients (12.0%) with restrictive spirometric pattern developed PPCs. Multivariable analysis demonstrated that high driving pressure was the only intraoperative modifiable factor increasing PPC risk (OR = 1.13 [1.02–1.25], p = 0.025). In the subgroup of patients with restrictive spirometric pattern, intraoperative driving pressure was significantly associated with PPC (OR = 1.21 [1.05–1.39], p = 0.009), whereas driving pressure was not associated with PPC in patients with normal spirometric pattern (OR = 1.04 [0.89–1.21], p = 0.639). In patients with restrictive spirometric pattern, greater intraoperative driving pressure is significantly associated with increased PPC risk. In contrast, intraoperative driving pressure is not associated with PPC in patients with normal spirometric pattern.
NGS-based targeted gene mutational profiles in Korean patients with pancreatic cancer
Authors: Jung Kwangrok , Lee Sejoon , Na Hee Young , Kim Ji-Won , Lee Jong-Chan , Hwang Jin-Hyeok , Kim Jin Won , Kim Jaihwan
Published: December 2022

According to molecular profiling studies, a considerable number of patients with pancreatic cancer harbor potentially actionable mutations. However, there are limited relevant data from the Korean population. We assessed the molecular profiles of patients with pancreatic cancer in Korea. This study collected molecular profiling data from patients with pancreatic cancer who visited Seoul National University Bundang Hospital between March 2018 and August 2020. Formalin-fixed, paraffin-embedded tumor specimens were sequenced using a targeted next-generation sequencing (NGS) platform. Cancer-associated mutations were analyzed, and potentially actionable mutations were identified. Potentially actionable mutations were classified into “highly actionable” and “modifies options” based on the Know Your Tumor registry study. In total, 87 patients with NGS tumor panel data were identified. Sixty-one patients (70.1%) had metastatic disease at the time of tissue acquisition. Tissues were obtained from the primary tumors and metastatic sites in 41 (47.1%) and 46 (52.9%) patients, respectively. At least one pathogenic mutation was reported in 86 patients (98.9%). The frequencies of four common mutations in our cohort were similar to those in The Cancer Genome Atlas data. Potentially actionable mutations were identified in 27 patients (31.0%). Of these, mutations categorized as highly actionable and modifies options were identified in 12 (13.8%) and 18 patients (20.7%), respectively. The most frequent highly actionable mutations were located in DNA damage response genes, such as BRCA1, BRCA2, or ATM (n = 6, 6.9%). Two patients with germline BRCA1 mutations received maintenance poly(adenosine diphosphate-ribose) polymerase inhibitor therapy. One patient has been receiving maintenance treatment for 18 months while remaining in radiologically complete remission. Mutational profiles using targeted NGS in Korean patients with pancreatic cancer were similar to those in Western patients. The present study supports the clinical potential and possible expanded clinical use of genetic profiling.
Safety and efficacy of tezepelumab vs. placebo in adult patients with severe uncontrolled asthma: a systematic review and meta-analysis
Authors: Shaban Abdelgalil Mahmoud , Ahmed Elrashedy Asmaa , Awad Ahmed K. , Reda Gad Eman , Ali Mahmoud M. , Abdelmoez Farahat Ramadan , Hassan Shawki Bassant , Abd-ElGawad Mohamed
Published: December 2022

Patients with severe uncontrolled asthma still experience acute asthma symptoms and exacerbations, particularly those with non-eosinophilic inflammation who take the maximum amount of standard drug therapy. Tezepelumab, a human monoclonal antibody, can improve lung function and enhance control of asthma symptoms in those patients, regardless of the disease’s baseline characteristics. This study aims to investigate the safety and efficacy of using tezepelumab in controlling severe symptoms of uncontrolled asthma. We performed a comprehensive literature search in several databases, including PubMed, Scopus, Web of Science, Cochrane Library, and clinicaltrial.gov, using a well-established search strategy to include all relevant publications. According to our inclusion criteria, we searched for randomized controlled trials comparing tezepelumab versus placebo in patients with severe, uncontrolled asthma. We analyzed the data using The Revman 5.4 program software. The search identified 589 potential articles. After excluding studies inconsistent with selection criteria, four studies were included and analyzed qualitatively and quantitatively. The pooled effect demonstrated the better performance of tezepelumab over the placebo regarding the decrease in annualized asthma exacerbation rate (MD = − 0.74, (95% CI [− 1.04, − 0.44], p < 0.00001)), asthma control questionnaire-6 (ACQ-6) Score MD = − 0.32, (95% CI [− 0.43, − 0.21], p < 0.00001)), blood eosinophil count (MD = − 139.38 cells/mcL, (95% CI [− 150.37, − 128.39], p < 0.00001)), feNO (MD = − 10 ppb, (95% CI [− 15.81, − 4.18], p = 0.0008)) and serum total IgE (MD = − 123.51 UI/ml, (95% CI [− 206.52, − 40.50], p = 0.004)). All tezepelumab groups had higher pre-bronchodilator forced expiratory volume in 1 s than the placebo group (MD = 0.16, (95% CI [0.10, 0.21], p < 0.00001)). Higher efficacy and safety profile was detected for tezepelumab to control the exacerbations of severe uncontrolled adult asthmatics.
Synthesis of an amphiphilic vancomycin aglycone derivative inspired by polymyxins: overcoming glycopeptide resistance in Gram-positive and Gram-negative bacteria in synergy with teicoplanin in vitro
Authors: Szűcs Zsolt , Bereczki Ilona , Fenyvesi Ferenc , Herczegh Pál , Ostorházi Eszter , Borbás Anikó
Published: December 2022

Gram-negative bacteria possess intrinsic resistance to glycopeptide antibiotics so these important antibacterial medications are only suitable for the treatment of Gram-positive bacterial infections. At the same time, polymyxins are peptide antibiotics, structurally related to glycopeptides, with remarkable activity against Gram-negative bacteria. With the aim of breaking the intrinsic resistance of Gram-negative bacteria against glycopeptides, a polycationic vancomycin aglycone derivative carrying an n-decanoyl side chain and five aminoethyl groups, which resembles the structure of polymyxins, was prepared. Although the compound by itself was not active against the Gram-negative bacteria tested, it synergized with teicoplanin against Escherichia coli, Pseudomonas aeruginosa and Acinetobacter baumannii, and it was able to potentiate vancomycin against these Gram-negative strains. Moreover, it proved to be active against vancomycin- and teicoplanin-resistant Gram-positive bacteria.
Substrate and low intensity fires influence bacterial communities in longleaf pine savanna
Authors: Dao Viet Q. , Potts Stephen E. , Johnson Crystal N. , Sikes Benjamin A. , Platt William J.
Published: December 2022

Bacterial communities associated with vegetation-soil interfaces have important roles in terrestrial ecosystems. These bacterial communities, studied almost exclusively in unburnt ecosystems or those affected by rare, high-intensity wildfires, have been understudied in fire-frequented grasslands and savannas. The composition of ground-level bacterial communities was explored in an old-growth pine savanna with a centuries-long management history of prescribed fires every 1–2 years. Using 16S metabarcoding, hypotheses were tested regarding differences in bacterial families of litter and soil surface substrates in patches of ground layer vegetation that were naturally burnt or unburnt during landscape-level prescribed fires. Litter/soil substrates and fire/no fire treatments explained 67.5% of bacterial community variation and differences, driven by relative abundance shifts of specific bacterial families. Fires did not strongly affect plant or soil variables, which were not linked to bacterial community differences. Litter/soil substrates and the naturally patchy frequent fires appear to generate microhabitat heterogeneity in this pine savanna, driving responses of bacterial families. Prescribed fire management may benefit from considering how fire-altered substrate heterogeneity influences and maintains microbial diversity and function, especially in these fiery ecosystems. Frequent, low-intensity fires appear ecologically important in maintaining the diverse microbial foundation that underlie ecosystem processes and services in fire-frequented habitats.
The rate of microtubule breaking increases exponentially with curvature
Authors: Tsitkov Stanislav , Rodriguez Juan B. , Bassir Kazeruni Neda M. , Sweet May , Nitta Takahiro , Hess Henry
Published: December 2022

Microtubules, cylindrical assemblies of tubulin proteins with a 25 nm diameter and micrometer lengths, are a central part of the cytoskeleton and also serve as building blocks for nanobiodevices. Microtubule breaking can result from the activity of severing enzymes and mechanical stress. Breaking can lead to a loss of structural integrity, or an increase in the numbers of microtubules. We observed breaking of taxol-stabilized microtubules in a gliding motility assay where microtubules are propelled by surface-adhered kinesin-1 motor proteins. We find that over 95% of all breaking events are associated with the strong bending following pinning events (where the leading tip of the microtubule becomes stuck). Furthermore, the breaking rate increased exponentially with increasing curvature. These observations are explained by a model accounting for the complex mechanochemistry of a microtubule. The presence of severing enzymes is not required to observe breaking at rates comparable to those measured previously in cells.
Reversibility of link prediction and its application to epidemic mitigation
Authors: Sulaimany Sadegh , Mafakheri Aso
Published: December 2022

Current link prediction strategies are about finding new probable strong relations to establish or weak ones to remove. An interesting strategy is utilizing link prediction to prioritize the edges in the network and finding newly probable established relations. In this paper we will introduce and explain RLP, reverse link prediction, as a new paradigm, and use popular basic scoring methods including CN, JC, AA, RA, and PA, as its core to examine. The test cases are nine datasets. Half of them are contact networks in different levels from personal contact to aviation, and another half is for covering different test situations. After reviewing the edge removal based epidemic mitigation methods, we show that RLP can be used to decrease the epidemics spreading speed as a general method with various link prediction algorithms, and here in this paper, preferential attachment (PA) has the best results overall. But the results heavily depend on the nature of the examined networks: regular, scale-free or small-world. We also propose an easy to understand criteria, path count, for comparing the efficacy of epidemics mitigation methods. RLP can be extended to use other link prediction scoring methods in various types of graphs as well.
Comparison of the effects of litter decomposition process on soil erosion under simulated rainfall
Authors: Zhu Fangfang , Cheng Jinhua
Published: December 2022

Overland flow parameters play a pivotal role in soil erosion, which are affected by litter cover in forests. In this study, the litter layer of Pinus massoniana (Masson pine) was divided into non-decomposed and semi-decomposed layers. Seven litter coverage mass gradients, two slopes (5° and 10°), and two rainfall intensities (60 and 120 mm·h−1) were used for a systematic study of the effects of litter layer changes on overland flow dynamic characteristics. The objectives of this study were to explore the soil erosion process in litter different decomposition stages; to explore various relationships between hydraulic variables and litter characteristics. In the process of litter decomposition, overland flow patterns changed from transitional flow to laminar flow and from rapid flow to slow flow. The semi-decomposed layer’s Reynold’s number (Re), resistance coefficient (f), and soil separation rate ($${D}_{r}$$

D
r

) were lower than that of the non-decomposed layer under the same conditions. Litter coverage, runoff and the diameter of the litter were major parameters that affected the Re, f, Fr, and Dr. Shrubs with wide leaves should be selected for understory vegetation replanting. The results of this study are helpful to understand the mechanisms of litter influencing erosion processes in different decomposition stages.
Handling method affects measures of anxiety, but not chronic stress in mice
Authors: Novak Janja , Jaric Ivana , Rosso Marianna , Rufener Reto , Touma Chadi , Würbel Hanno
Published: December 2022

Studies in mice have shown that less aversive handling methods (e.g. tunnel or cup handling) can reduce behavioural measures of anxiety in comparison to picking mice up by their tail. Despite such evidence, tail handling continues to be used routinely. Besides resistance to change accustomed procedures, this may also be due to the fact that current evidence in support of less aversive handling is mostly restricted to effects of extensive daily handling, which may not apply to routine husbandry practices. The aim of our study was to assess whether, and to what extent, different handling methods during routine husbandry induce differences in behavioural and physiological measures of stress in laboratory mice. To put the effects of handling method in perspective with chronic stress, we compared handling methods to a validated paradigm of unpredictable chronic mild stress (UCMS). We housed mice of two strains (Balb/c and C57BL/6) and both sexes either under standard laboratory conditions (CTRL) or under UCMS. Half of the animals from each housing condition were tail handled and half were tunnel handled twice per week, once during a cage change and once for a routine health check. We found strain dependent effects of handling method on behavioural measures of anxiety: tunnel handled Balb/c mice interacted with the handler more than tail handled conspecifics, and tunnel handled CTRL mice showed increased open arm exploration in the elevated plus-maze. Mice undergoing UCMS showed increased plasma corticosterone levels and reduced sucrose preference. However, we found no effect of handling method on these stress-associated measures. Our results therefore indicate that routine tail handling can affect behavioural measures of anxiety, but may not be a significant source of chronic husbandry stress. Our results also highlight strain dependent responses to handling methods.
Sex-linked markers in an Australian frog Platyplectrum ornatum (Limnodynastidae) with a small genome and homomorphic sex chromosomes
Authors: Schimek Chad , Shams Foyez , Miura Ikuo , Clulow Simon , Majtanova Zuzana , Deakin Janine , Ezaz Tariq
Published: December 2022

Amphibians have highly diverse sex-determining modes leading to a notable interest in vertebrate sex determination and sex chromosome evolution. The identification of sex-determining systems in amphibians, however, is often difficult as a vast majority consist of homomorphic sex chromosomes making them hard to distinguish. In this study, we used Diversity Array Technology sequencing (DArTseq) to identify the sex-determining system in the ornate burrowing frog from Australia, Platyplectrum ornatum. We applied DArTseq to 44 individuals, 19 males and 25 females, collected from two locations to develop sex-linked markers. Unexpectedly, these 44 individuals were classified into two distinct population clusters based on our SNP analyses, 36 individuals in cluster 1, and 8 individuals in cluster 2. We then performed sex-linkage analyses separately in each cluster. We identified 35 sex-linked markers from cluster 1, which were all associated with maleness. Therefore, P. ornatum cluster 1 is utilising a male heterogametic (XX/XY) sex-determining system. On the other hand, we identified 210 sex-linked markers from cluster 2, of which 89 were male specific, i.e., identifying XX/XY sex determining system and 111 were female specific, i.e., identifying ZZ/ZW sex determining system, suggesting existence of either male or female heterogametic sex determining system in cluster 2. We also performed cytogenetic analyses in 1 male and 1 female from cluster 1; however, we did not detect any visible differentiation between the X and Y sex chromosomes. We also mapped sex-linked markers from the two clusters against the P. ornatum genome and our comparative analysis indicated that the sex chromosomes in both clusters shared homologies to chromosome 10 (autosome) of Rana temporaria and ZWY sex chromosome of Xenopus tropicalis. Our preliminary data suggest that it is plausible that the cluster 2 has a potential to be either male or female heterogamety in sex determination, requiring further investigation.
The impact of a short-period head-down tilt on executive function in younger adults
Authors: Mekari Said , Murphy René J. L. , MacKinnon Andrew R. S. , Hollohan Quinn , Macdougall Samantha C. , Courish Molly K. , Kimmerly Derek S. , Neyedli Heather F.
Published: December 2022

Microgravity has been shown to be a significant stressor on the cardiovascular system and the brain due to the redistribution of fluids that occurs in the absence of gravitational force, but there is scarce literature surrounding the effects of microgravity on cerebral hemodynamics and cognition. Understanding the early effects that simulated gravity has on cognitive function is essential for developing proper physical and cognitive countermeasures to assure safe and effective cognitive/decisions making while astronauts prepare for the initial launch or when they arrive in a microgravity environment. Therefore, this study aims to determine how an acute simulation of microgravity would alter cerebral oxygenation and executive functions. Sixty-five young healthy participants (22 ± 6 years, 21 females) completed a thirty (30) minute horizontal (00 tilt) followed by a 90-min − 6° head-down-tilt (HDT) protocol. Cerebral oxygenation in the prefrontal cortex was monitored throughout the testing session using near-infrared spectroscopy. Cognition was also measured using a computerized Stroop Task. Our results demonstrate that cerebral oxygenation was higher during HDT compared to the horizontal supine position (9.11 ± 1.3 vs. 7.51 ± 1.8, p = 0.02). For the cognitive results, the non-executive performance of the Stroop task remained stable during HDT (652.46 ± 19.3 vs. 632.49 ± 14.5, p = 0.09). However, reaction time during the executive task performance was improved after the HDT (1058 ± 195–950 ± 158 ms, p < 0.01). Our results suggest that an acute bout of simulated microgravity can enhance executive functioning.
Genotype-by-environment interaction and stability of root mealiness and other organoleptic properties of boiled cassava roots
Authors: Uchendu Kelechi , Njoku Damian N. , Ikeogu Ugochukwu N. , Dzidzienyo Daniel , Tongoona Pangirayi , Offei Samuel , Egesi Chiedozie
Published: December 2022

Genetic enhancement of cassava aimed at improving cooking and eating quality traits is a major goal for cassava breeders to address the demand for varieties that are desirable for the fresh consumption market segment. Adoption of such cassava genotypes by consumers will largely rely not only on their agronomic performance, but also on end-user culinary qualities such as root mealiness. The study aimed to examine genotype × environment interaction (GEI) effects for root mealiness and other culinary qualities in 150 cassava genotypes and detect genotypes combining stable performance with desirable mealiness values across environments using GGE biplot analysis. Experiments were conducted using an alpha-lattice design with three replications for two years in three locations in Nigeria. The analysis of variance revealed a significant influence of genotype, environment, and GEI on the performance of genotypes. Mealiness scores showed no significant relationship with firmness values of boiled roots assessed by a penetration test, implying that large-scale rapid and accurate phenotyping of mealiness of boiled cassava roots remains a major limitation for the effective development of varieties with adequate mealiness, a good quality trait for direct consumption (boil-and-eat) as well as for pounding into ‘fufu’. The moderate broad-sense heritability estimate and relatively high genetic advance observed for root mealiness suggest that significant genetic gains can be achieved in a future hybridization program. The genotype main effects plus genotype × environment interaction (GGE) biplot analysis showed that the different test environments discriminated among the genotypes. Genotypes G80 (NR100265) and G120 (NR110512) emerged as the best performers for root mealiness in Umudike, whereas G13 (B1-50) and the check, G128 (TMEB693) performed best in Igbariam and Otobi. Based on the results of this study, five genotypes, G13 (B1-50), G34 (COB6-4), G46 (NR010161), the check, G128 (TMEB693), and G112 (NR110376), which were found to combine stability with desirable mealiness values, were the most suitable candidates to recommend for use as parents to improve existing cassava germplasm for root mealiness.
Comparison of the properties of polyimide nanocomposite films containing functionalized-graphene and organoclay as nanofillers
Authors: Choi Moon Young , Lee Seon Ju , Lim Ae Ran , Chang Jin-Hae
Published: December 2022

Poly(amic acid) (PAA) is prepared by the reaction of dianhydride 4,4′-biphthalic anhydride and diamine bis[4-(3-aminophenoxy)phenyl]sulfone in N,N’-dimethylacetamide. Two types of fillers were dispersed in the as-synthesized PAA via a solution intercalation method; polyimide (PI) hybrid films were synthesized under various heat treatment conditions. Octylamine (C8) was introduced into graphene sheets (C8-GS) and bentonite (C8-BTN), which were then used as nanofillers in the PI hybrid films. The synthesized nanofillers were used in varying amounts of 0.25–1.00 wt% with respect to the matrix PI. The thermal and morphological properties and optical transparency of the hybrid films were investigated and compared for both C8-GS and C8-BTN at varying nanofiller content. The C8-BTN nanocomposite showed superior thermal properties, and optical transparency, and the filler was well dispersed in the PI matrix compared to the C8-GS nanocomposite. The thermal stability of the hybrid films improved upon the addition of small amounts of the nanofiller. However, beyond a certain critical filler concentration, the thermal stability declined. These results were verified through the dispersion of fillers via transmission electron microscopy.
Characteristics of rice straw decomposition and bacterial community succession for 2 consecutive years in a paddy field in southeastern China
Authors: Wang Xiya , He Ping , Xu Xinpeng , Qiu Shaojun , Zhao Shicheng
Published: December 2022

The characteristics of long-term rice straw decomposition and succession in the bacterial community in the double-rice system are still unclear. Here a 2-year continuous straw bag decomposition experiment was conducted to explore changes in nutrient release, enzyme activity, and bacterial community composition during rice straw decomposition in the double-rice system in Southeast China. After burial in soil, the cumulative dry matter loss rates of rice straw were 38.9%, 72.6%, and 82.7% after 2, 12, and 24 months, respectively. The change in the release rate of straw nitrogen and phosphorus was similar to the dry matter loss, but 93.5% of straw potassium was released after 1st month. Bacterial abundance and community diversity in straw increased rapidly, reaching peaks after 7 and 12 months, respectively. Straw extracellular enzyme activities were the highest in the first 2 months and then gradually decreased over time, and they significantly and positively correlated with straw decomposition rate. Straw decomposition was dominated by copiotrophic Bacilli and Flavobacteriia in the early stages and evolved to be dominated by oligotrophic Acidobacteria, Anaerolineae, Deltaproteobacteria, Saccharibacteria, and Sphingobacteriia in the later stages. Changes in the C/N and K content of straw are the main reasons for bacterial community succession during rice straw decomposition. This study can provide a scientific basis for developing efficient decomposing bacteria agents for rice straw.