bluuebunny/crossref_metadata_2025 huggingface dataset:
p63, a key regulator of Ago2, links to the microRNA-144 cluster
Authors: Wang Benfan , Wu H. Helena , Abuetabh Yasser , Leng Sarah , Davidge Sandra T. , Flores Elsa R. , Eisenstat David D. , Leng Roger
Published: April 2022

As a key component of the RNA-induced silencing complex (RISC), Argonaute2 (Ago2) exhibits a dual function regulatory role in tumor progression. However, the mechanistic basis of differential regulation remains elusive. p63 is a homolog of the tumor suppressor p53. p63 isoforms play a critical role in tumorigenesis and metastasis. Herein, we show that p63 isoforms physically interact with and stabilize Ago2. Expression of p63 isoforms increases the levels of Ago2 protein, while depletion of p63 isoforms by shRNA decreases Ago2 protein levels. p63 strongly guides Ago2 dual functions in vitro and in vivo. Ectopic expression of the miR-144/451 cluster increases p63 protein levels; TAp63 transactivates the miR-144/451 cluster, forming a positive feedback loop. Notably, miR-144 activates p63 by directly targeting Itch, an E3 ligase of p63. Ectopic expression of miR-144 induces apoptosis in H1299 cells. miR-144 enhances TAp63 tumor suppressor function and inhibits cell invasion. Our findings uncover a novel function of p63 linking the miRNA-144 cluster and the Ago2 pathway.

Facts and questions

Identification of Ago2 as a p63 target.

Ago2 exhibits a dual function regulatory role in tumor progression; however, the molecular mechanism of Ago2 regulation remains unknown.

p63 strongly guides Ago2 dual functions in vitro and in vivo.

Unraveling a novel function of p63 links the miRNA-144 cluster and the Ago2 pathway.
Fragile, unfaithful and persistent Ys—on how meiosis can shape sex chromosome evolution
Authors: Ruiz-Herrera Aurora , Waters Paul D.
Published: April 2022

Sex-linked inheritance is a stark exception to Mendel’s Laws of Heredity. Here we discuss how the evolution of heteromorphic sex chromosomes (mainly the Y) has been shaped by the intricacies of the meiotic programme. We propose that persistence of Y chromosomes in distantly related mammalian phylogroups can be explained in the context of pseudoautosomal region (PAR) size, meiotic pairing strategies, and the presence of Y-borne executioner genes that regulate meiotic sex chromosome inactivation. We hypothesise that variation in PAR size can be an important driver for the evolution of recombination frequencies genome wide, imposing constraints on Y fate. If small PAR size compromises XY segregation during male meiosis, the stress of producing aneuploid gametes could drive function away from the Y (i.e., a fragile Y). The Y chromosome can avoid fragility either by acquiring an achiasmatic meiotic XY pairing strategy to reduce aneuploid gamete production, or gain meiotic executioner protection (a persistent Y). Persistent Ys will then be under strong pressure to maintain high recombination rates in the PAR (and subsequently genome wide), as improper segregation has fatal consequences for germ cells. In the event that executioner protection is lost, the Y chromosome can be maintained in the population by either PAR rejuvenation (extension by addition of autosome material) or gaining achiasmatic meiotic pairing, the alternative is Y loss. Under this dynamic cyclic evolutionary scenario, understanding the meiotic programme in vertebrate and invertebrate species will be crucial to further understand the plasticity of the rise and fall of heteromorphic sex chromosomes.
Exploring dopant effects in stannic oxide nanoparticles for CO2 electro-reduction to formate
Authors: Ko Young-Jin , Kim Jun-Yong , Lee Woong Hee , Kim Min Gyu , Seong Tae-Yeon , Park Jongkil , Jeong YeonJoo , Min Byoung Koun , Lee Wook-Seong , Lee Dong Ki , Oh Hyung-Suk
Published: April 2022

The electrosynthesis of formate from CO2 can mitigate environmental issues while providing an economically valuable product. Although stannic oxide is a good catalytic material for formate production, a metallic phase is formed under high reduction overpotentials, reducing its activity. Here, using a fluorine-doped tin oxide catalyst, a high Faradaic efficiency for formate (95% at 100 mA cm−2) and a maximum partial current density of 330 mA cm−2 (at 400 mA cm−2) is achieved for the electroreduction of CO2. Furthermore, the formate selectivity (≈90%) is nearly constant over 7 days of operation at a current density of 100 mA cm−2. In-situ/operando spectroscopies reveal that the fluorine dopant plays a critical role in maintaining the high oxidation state of Sn, leading to enhanced durability at high current densities. First-principle calculation also suggests that the fluorine-doped tin oxide surface could provide a thermodynamically stable environment to form HCOO* intermediate than tin oxide surface. These findings suggest a simple and efficient approach for designing active and durable electrocatalysts for the electrosynthesis of formate from CO2.
Enabling reactive microscopy with MicroMator
Authors: Fox Zachary R. , Fletcher Steven , Fraisse Achille , Aditya Chetan , Sosa-Carrillo Sebastián , Petit Julienne , Gilles Sébastien , Bertaux François , Ruess Jakob , Batt Gregory
Published: April 2022

Microscopy image analysis has recently made enormous progress both in terms of accuracy and speed thanks to machine learning methods and improved computational resources. This greatly facilitates the online adaptation of microscopy experimental plans using real-time information of the observed systems and their environments. Applications in which reactiveness is needed are multifarious. Here we report MicroMator, an open and flexible software for defining and driving reactive microscopy experiments. It provides a Python software environment and an extensible set of modules that greatly facilitate the definition of events with triggers and effects interacting with the experiment. We provide a pedagogic example performing dynamic adaptation of fluorescence illumination on bacteria, and demonstrate MicroMator’s potential via two challenging case studies in yeast to single-cell control and single-cell recombination, both requiring real-time tracking and light targeting at the single-cell level.
Similarities and differences between nigral and enteric dopaminergic neurons unravel distinctive involvement in Parkinson’s disease
Authors: Chalazonitis Alcmène , Rao Meenakshi , Sulzer David
Published: April 2022

In addition to the well-known degeneration of midbrain dopaminergic neurons, enteric neurons can also be affected in neurodegenerative disorders such as Parkinson’s disease (PD). Dopaminergic neurons have recently been identified in the enteric nervous system (ENS). While ENS dopaminergic neurons have been shown to degenerate in genetic mouse models of PD, analyses of their survival in enteric biopsies of PD patients have provided inconsistent results to date. In this context, this review seeks to highlight the distinctive and shared factors and properties that control the evolution of these two sets of dopaminergic neurons from neuronal precursors to aging neurons. Although their cellular sources and developmental times of origin differ, midbrain and ENS dopaminergic neurons express many transcription factors in common and their respective environments express similar neurotrophic molecules. For example, Foxa2 and Sox6 are expressed by both populations to promote the specification, differentiation, and long-term maintenance of the dopaminergic phenotype. Both populations exhibit sustained patterns of excitability that drive intrinsic vulnerability over time. In disorders such as PD, colon biopsies have revealed aggregation of alpha-synuclein in the submucosal plexus where dopaminergic neurons reside and lack blood barrier protection. Thus, these enteric neurons may be more susceptible to neurotoxic insults and aggregation of α-synuclein that spreads from gut to midbrain. Under sustained stress, inefficient autophagy leads to neurodegeneration, GI motility dysfunction, and PD symptoms. Recent findings suggest that novel neurotrophic factors such as CDNF have the potential to be used as neuroprotective agents to prevent and treat ENS symptoms of PD.
Autonomous quantum error correction in a four-photon Kerr parametric oscillator
Authors: Kwon Sangil , Watabe Shohei , Tsai Jaw-Shen
Published: April 2022

Autonomous quantum error correction has gained considerable attention to avoid complicated measurements and feedback. Despite its simplicity compared with the conventional measurement-based quantum error correction, it is still a far from practical technique because of significant hardware overhead. We propose an autonomous quantum error correction scheme for a rotational symmetric bosonic code in a four-photon Kerr parametric oscillator. Our scheme is the simplest possible error correction scheme that can surpass the break-even point—it requires only a single continuous microwave tone. We also introduce an unconditional reset scheme that requires one more continuous microwave tone in addition to that for the error correction. The key properties underlying this simplicity are protected quasienergy states of a four-photon Kerr parametric oscillator and the degeneracy in its quasienergy level structure. These properties eliminate the need for state-by-state correction in the Fock basis. Our schemes greatly reduce the complexity of autonomous quantum error correction and thus may accelerate the use of the bosonic code for practical quantum computation.
An adjuvanted zoster vaccine elicits potent cellular immune responses in mice without QS21
Authors: Nam Hyo Jung , Hong Sung Jun , Lee Ara , Kim Jiyeon , Lee Sangho , Casper Corey , Carter Darrick , Reed Steven G. , Simeon George , Shin Eui-Cheol
Published: April 2022

Herpes zoster (HZ) is caused by reactivation of latent varicella-zoster virus (VZV) when VZV-specific cellular immunity is insufficient to control reactivation. Currently, Shingrix, which contains the VZV gE protein and GSK’s AS01Badjuvant composed of liposomes formulated with cholesterol, monophosphoryl lipid A (MPL) and QS21, is used for prevention of HZ. However, reactogenicity to Shingrix is common leading to poor patient compliance in receiving one or both shots. Here, we evaluated the immunogenicity of a newly formulated gE protein-based HZ vaccine containing Second-generation Lipid Adjuvant (SLA), a synthetic TLR4 ligand, formulated in an oil-in-water emulsion (SLA-SE) without QS21 (gE/SLA-SE). In VZV-primed mouse models, gE/SLA-SE-induced gE-specific humoral and cellular immune responses at comparable levels to those elicited by Shingrix in young mice, as both gE/SLA-SE and Shingrix induce polyfunctional CD4+T-cell responses. In aged mice, gE/SLA-SE elicited more robust gE-specific T-cell responses than Shingrix. Furthermore, gE/SLA-SE-induced T-cell responses were sustained until 5 months after immunization. Thus, QS21-free, gE/SLA-SE is a promising candidate for development of gE-based HZ vaccines with high immunogenicity—particularly when targeting an older population.
S-Nitrosylated hemoglobin predicts organ yield in neurologically-deceased human donors
Authors: Nazemian Ryan , Matta Maroun , Aldamouk Amer , Zhu Lin , Awad Mohamed , Pophal Megan , Palmer Nicole R. , Armes Tonya , Hausladen Alfred , Stamler Jonathan S. , Reynolds James D.
Published: April 2022

Current human donor care protocols following death by neurologic criteria (DNC) can stabilize macro-hemodynamic parameters but have minimal ability to preserve systemic blood flow and microvascular oxygen delivery. S-nitrosylated hemoglobin (SNO-Hb) within red blood cells (RBCs) is the main regulator of tissue oxygenation (StO2). Based on various pre-clinical studies, we hypothesized that brain death (BD) would decrease post-mortem SNO-Hb levels to negatively-impact StO2and reduce organ yields. We tracked SNO-Hb and tissue oxygen in 61 DNC donors. After BD, SNO-Hb levels were determined to be significantly decreased compared to healthy humans (p = 0·003) and remained reduced for the duration of the monitoring period. There was a positive correlation between SNO-Hb and StO2(p < 0.001). Furthermore, SNO-Hb levels correlated with and were prognostic for the number of organs transplanted (p < 0.001). These clinical findings provide additional support for the concept that BD induces a systemic impairment of S-nitrosylation that negatively impacts StO2and reduces organ yield from DNC human donors. Exogenous S-nitrosylating agents are in various stages of clinical development. The results presented here suggest including one or more of these agents in donor support regimens could increase the number and quality of organs available for transplant.
No evidence for disruption of reconsolidation of conditioned threat memories with a cognitively demanding intervention
Authors: Jaswetz Lars , de Voogd Lycia D. , Becker Eni S. , Roelofs Karin
Published: April 2022

Simultaneous execution of memory retrieval and cognitively demanding interventions alter the subjective experience of aversive memories. This principle can be used in treatment to target traumatic memories. An often-used interpretation is that cognitive demand interferes with memory reconsolidation. Laboratory models applying this technique often do not meet some important procedural steps thought necessary to trigger reconsolidation. It remains therefore unclear whether cognitively demanding interventions can alter the reconsolidation process of aversive memories. Here, 78 (41 included) healthy participants completed an established 3-day threat conditioning paradigm. Two conditioned stimuli were paired with a shock (CS+ s) and one was not (CS-). The next day, one CS+ (CS+ R), but not the other (CS+), was presented as a reminder. After 10 min, participants performed a 2-back working memory task. On day three, we assessed retention. We found successful acquisition of conditioned threat and retention (CS+ s > CS-). However, SCRs to the CS+ R and the CS+ during retention did not significantly differ. Although threat conditioning was successful, the well-established cognitively demanding intervention did not alter the reconsolidation process of conditioned threat memories. These findings challenge current views on how cognitively demand may enhance psychotherapy-outcome.
Latent state-trait structure of BPRS subscales in clinical high-risk state and first episode psychosis
Authors: Hochstrasser Lisa , Studerus Erich , Riecher-Rössler Anita , Schimmelmann Benno G. , Lambert Martin , Lang Undine E. , Borgwardt Stefan , Stieglitz Rolf-Dieter , Huber Christian G.
Published: April 2022

To investigate the longitudinal latent state-trait structure of the different dimensions of psychosis symptoms in clinical high-risk state (CHRS) and first episode psychosis (FEP) individuals over a one year time-span. This paper examines if the symptom clusters Positive Symptoms, Negative Symptoms, Affectivity, Resistance, Activation, and Excitement according to the Brief Psychiatric Rating Scale (BPRS) differ in their trait and state characters in 196 CHRS and 131 FEP individuals. Statistical analysis was performed using latent state-trait analysis. On average, trait differences accounted for 72.2% of Positive Symptoms, 81.1% of Negative Symptoms, 57.0% of Affectivity, and 69.2% of Activation, whereas 15.0% of the variance of Resistance and 13.2% of the variance of Excitement were explained by trait differences. Explorative analyses showed a trait components’ increase of 0.408 in Positive Symptoms from baseline up to the 9th month and an increase of 0.521 in Affectivity from baseline up to the 6th month. Negative Symptoms had the highest trait component levels of all subscales between baseline and 6 months. The finding that an increasing proportion of psychosis symptoms is persisting over time underlines the importance of early intervention programs in individuals with psychotic disorders.
Characterization of transcriptome diversity and in vitro behavior of primary human high-risk breast cells
Authors: Alothman Sahar J. , Kang Keunsoo , Liu Xuefeng , Krawczyk Ewa , Azhar Redha I. , Hu Rong , Goerlitz David , Kallakury Bhaskar V. , Furth Priscilla A.
Published: April 2022

Biology and transcriptomes of non-cancerous human mammary epithelial cells at risk for breast cancer development were explored following primary isolation utilizing conditional reprogramming cell technology from mastectomy tissue ipsilateral to invasive breast cancer. Cultures demonstrated consistent categorizable behaviors. Relative viability and mammosphere formation differed between samples but were stable across three different mammary-specific media. E2F cell cycle target genes expression levels were positively correlated with viability and advancing age was inversely associated. Estrogen growth response was associated with Tissue necrosis factor signaling and Interferon alpha response gene enrichment. Neoadjuvant chemotherapy exposure significantly altered transcriptomes, shifting them towards expression of genes linked to mammary stem cell formation. Breast cancer prognostic signature sets include genes that in normal development are limited to specific stages of pregnancy or the menstrual cycle. Sample transcriptomes were queried for stage specific gene expression patterns. All cancer samples and a portion of high-risk samples showed overlapping stages reflective of abnormal gene expression patterns, while other high-risk samples exhibited more stage specific patterns. In conclusion, at-risk cells preserve behavioral and transcriptome diversity that could reflect different risk profiles. It is possible that prognostic platforms analogous to those used for breast cancer could be developed for high-risk mammary cells.
Self-esteem depends on beliefs about the rate of change of social approval
Authors: Low Alexis An Yee , Hopper William John Telesfor , Angelescu Ilinca , Mason Liam , Will Geert-Jan , Moutoussis Michael
Published: April 2022

A major challenge in understanding the neurobiological basis of psychiatric disorders is rigorously quantifying subjective metrics that lie at the core of mental illness, such as low self-esteem. Self-esteem can be conceptualized as a ‘gauge of social approval’ that increases in response to approval and decreases in response to disapproval. Computational studies have shown that learning signals that represent the difference between received and expected social approval drive changes in self-esteem. However, it is unclear whether self-esteem based on social approval should be understood as a value updated through associative learning, or as a belief about approval, updated by new evidence depending on how strongly it is held. Our results show that belief-based models explain self-esteem dynamics in response to social evaluation better than associative learning models. Importantly, they suggest that in the short term, self-esteem signals the direction and rate of change of one’s beliefs about approval within a group, rather than one’s social position.
Carry-over effects of dry period heat stress on the mammary gland proteome and phosphoproteome in the subsequent lactation of dairy cows
Authors: Skibiel Amy L. , Koh Jin , Zhu Ning , Zhu Fanchao , Yoo Mi-Jeong , Laporta Jimena
Published: April 2022

Exposure to heat stress during a cow’s dry period disrupts mammary gland remodeling, impairing mammary function and milk production during the subsequent lactation. Yet, proteomic changes in the mammary gland underlying these effects are not yet known. We investigated alterations in the mammary proteome and phosphoproteome during lactation as a result of dry period heat stress using an isobaric tag for relative and absolute quantitation (iTRAQ)-based approach. Cows were cooled (CL;n = 12) with fans and water soakers in a free stall setting or were heat stressed through lack of access to cooling devices (HT;n = 12) during the entire dry period (approximately 46 days). All cows were cooled postpartum. Mammary biopsies were harvested from a subset of cows (n = 4 per treatment) at 14, 42, and 84 days in milk. Overall, 251 proteins and 224 phosphorylated proteins were differentially abundant in the lactating mammary gland of HT compared to CL cows. Top functions of differentially abundant proteins and phosphoproteins affected were related to immune function and inflammation, amino acid metabolism, reactive oxygen species production and metabolism, tissue remodeling, and cell stress response. Patterns of protein expression and phosphorylation are indicative of increased oxidative stress, mammary gland restructuring, and immune dysregulation due to prior exposure to dry period heat stress. This study provides insights into the molecular underpinnings of disrupted mammary function and health during lactation arising from prior exposure to dry period heat stress, which might have led to lower milk yields.
Influence of hand-arm self-avatar motion delay on the directional perception induced by an illusory sensation of being twisted
Authors: Amemiya Tomohiro
Published: April 2022

Sensory information from movements of body parts can alter their position when exposed to external physical stimuli. Visual information monitors the position and movement of body parts from an exterior perspective, whereas somatosensory information monitors them from an internal viewpoint. However, how such sensory data are integrated is unclear. In this study, a virtual reality (VR) system was used to evaluate the influence of the temporal difference between visual and somatosensory information from hand movements on the directional perception of a torque while modifying the visual appearance (human hand vs. non-human object) and visuohaptic congruency (congruent vs. incongruent) of self-avatars. Visual information was provided by the movement of the self-avatars in a VR environment, while somatosensory information was provided by vibrations with asymmetrical amplitudes that gave the participants the sensation of being continuously pushed or pulled without actually moving any body part. Delaying the movement of the avatar by 50 ms resulted in the sensitivity of the force direction perception to be lower with human hands than with non-human avatars, whereas a delay of 200 ms resulted in a higher sensitivity. This study can contribute to applications requiring multisensory integration in a VR environment.
Melanin is a plenteous bioactive phenolic compound in date fruits (Phoenix dactylifera L.)
Authors: Alam Muneeba Zubair , Ramachandran Tholkappiyan , Antony Asha , Hamed Fathalla , Ayyash Mutamed , Kamal-Eldin Afaf
Published: April 2022

Date palm fruits (Phoenix dactylifera L.) were found to contain high levels of allomelanin (1.2–5.1%). The melanin is localized in the tanniferous cells between the inner and outer mesocarp tissues of the fruit. The melanin, extracted with 2 M sodium hydroxide, consisted of amorphous graphene-like granular structures of irregular shape and variable size. The date fruit melanin mainly comprises carbon (64.6%) and oxygen (30.6) but no nitrogen, and was thermally stable. It has radical scavenging (63.6–75.1 IC50, µg/mL), antimicrobial (250–1000 µg/mL), hypoglycemic (51.8–58.2%), and angiotensin-converting-enzyme inhibitory (65.8%) effects. The high level of melanin in date fruits highlights the importance of investigating its dietary intake and its impact on nutrition. This study also suggests that date fruit melanin can be a functional ingredient in foods, food packages, pharmaceuticals, and cosmetics.
The gut fungal and bacterial microbiota in pediatric patients with inflammatory bowel disease introduced to treatment with anti-tumor necrosis factor-α
Authors: Ventin-Holmberg Rebecka , Höyhtyä Miikka , Saqib Schahzad , Korpela Katri , Nikkonen Anne , Salonen Anne , de Vos Willem M. , Kolho Kaija-Leena
Published: April 2022

Pediatric inflammatory bowel disease (PIBD) is a globally increasing chronic inflammatory disease associated with an imbalanced intestinal microbiota and treated with several treatment options, including anti-tumor necrosis factor alpha (TNF-α), such as infliximab (IFX). Up to half of the patients do not respond to the drug and there are no methods for response prediction. Our aim was to predict IFX response from the gut microbiota composition since this is largely unexplored in PIBD. The gut microbiota of 30 PIBD patients receiving IFX was studied by MiSeq sequencing targeting 16S and ITS region from fecal samples collected before IFX and two and six weeks after the start of treatment. The response to IFX induction was determined by fecal calprotectin value < 100 µg/g at week six. The bacterial microbiota differed significantly between response groups, with higher relative abundance of butyrate-producing bacteria in responders compared to non-responders at baseline, validated by high predictive power (area under curve = 0.892) for baselineRuminococcusand calprotectin. Additionally, non-responders had higher abundance ofCandida, while responders had higher abundance ofSaccharomycesat the end of the study. The gut microbiota composition in PIBD patients could predict response to IFX treatment in the future.
Transcriptome analysis of fasudil treatment in the APPswe/PSEN1dE9 transgenic (APP/PS1) mice model of Alzheimer’s disease
Authors: Yan Hailong , Yan Yuqing , Gao Ye , Zhang Nianping , Kumar Gajendra , Fang Qingli , Li Ziqing , Li Jiehui , Zhang Yuna , Song Lijuan , Wang Jiawei , Sun Jingxian , Zhang Han-Ting , Ma Cun-Gen
Published: April 2022

Alzheimer's disease (AD) is the most common cause of progressive dementia. In the present study, we showed hippocampal tissue transcriptome analysis in APPswe/PSEN1dE9 (APP/PS1, AD model) mice treated with fasudil (ADF) and compared with AD mice treated with saline (ADNS) and wild type mice (WT). The competing endogenous RNA (ceRNA) network was constructed and validated the differential expression of mRNA, lncRNA, miRNA, and circRNA. Our study showed differentially expressed mRNAs (DEMs) between WT and ADNS, while enriched in cell growth and death and nervous system pathways. DEMs between ADNS-ADF were enriched in the nervous system, glycosaminoglycan biosynthesis-keratan sulfate (KS) and Quorum sensing pathways. We validated four genes with RT-PCR, whereas enrichment of Acyl-CoA Synthetase Long Chain Family Member 4 (Acsl4, ENSMUST00000112903) in Quorum sensing pathways, and BTG anti-proliferation factor 1 (Btg1, ENSMUST00000038377) in RNA degradation pathways were conducted. Expression of these two genes were higher in ADNS, but were significantly reduced in ADF. Histone H4 transcription factor (Hinfp, ENSMUST00000216508) orchestrate G1/S transition of mitotic cell cycle and co-expressed with mmu-miR-26a-2-3p-mediated ceRNA and mmu-miR-3065-5p-mediated ceRNA; Wnt family member 4 (Wnt4, ENSMUST00000045747) was enriched in mTOR, Hippo and Wnt signaling pathway. Expression of these two genes were significantly lower in ADNS, and fasudil treatment reverse it. The present studies demonstrated four genes: Acsl4, Btg1, Hinfp, Wnt4 could be potential biomarkers of AD and the targets of fasudil treatment. These results will pave a novel direction for future clinic studies for AD and fasudil treatment.
Evaluation of efficiency and sensitivity of 1D and 2D sample pooling strategies for SARS-CoV-2 RT-qPCR screening purposes
Authors: Verwilt Jasper , Hellemans Jan , Sante Tom , Mestdagh Pieter , Vandesompele Jo
Published: April 2022

To increase the throughput, lower the cost, and save scarce test reagents, laboratories can pool patient samples before SARS-CoV-2 RT-qPCR testing. While different sample pooling methods have been proposed and effectively implemented in some laboratories, no systematic and large-scale evaluations exist using real-life quantitative data gathered throughout the different epidemiological stages. Here, we use anonymous data from 9673 positive cases to model, simulate and compare 1D and 2D pooling strategies. We show that the optimal choice of pooling method and pool size is an intricate decision with a testing population-dependent efficiency-sensitivity trade-off and present an online tool to provide the reader with custom real-time 1D pooling strategy recommendations.
The probabilistic pool punishment proportional to the difference of payoff outperforms previous pool and peer punishment
Authors: Ohdaira Tetsushi
Published: April 2022

The public goods game is a multiplayer version of the prisoner’s dilemma game. In the public goods game, punishment on defectors is necessary to encourage cooperation. There are two types of punishment: peer punishment and pool punishment. Comparing pool punishment with peer punishment, pool punishment is disadvantageous in comparison with peer punishment because pool punishment incurs fixed costs especially if second-order free riders (those who invest in public goods but do not punish defectors) are not punished. In order to eliminate such a flaw of pool punishment, this study proposes the probabilistic pool punishment proportional to the difference of payoff. In the proposed pool punishment, each punisher pays the cost to the punishment pool with the probability proportional to the difference of payoff between his/her payoff and the average payoff of his/her opponents. Comparing the proposed pool punishment with previous pool and peer punishment, in pool punishment of previous studies, cooperators who do not punish defectors become dominant instead of pool punishers with fixed costs. However, in the proposed pool punishment, more punishers and less cooperators coexist, and such state is more robust against the invasion of defectors due to mutation than those of previous pool and peer punishment. The average payoff is also comparable to peer punishment of previous studies.
Automated quantitative high-throughput multiplex immunofluorescence pipeline to evaluate OXPHOS defects in formalin-fixed human prostate tissue
Authors: Sachdeva Ashwin , Hart Claire A. , Carey Christopher D. , Vincent Amy E. , Greaves Laura C. , Heer Rakesh , Oliveira Pedro , Brown Michael D. , Clarke Noel W. , Turnbull Doug M.
Published: April 2022

Advances in multiplex immunofluorescence (mIF) and digital image analysis has enabled simultaneous assessment of protein defects in electron transport chain components. However, current manual methodology is time consuming and labour intensive. Therefore, we developed an automated high-throughput mIF workflow for quantitative single-cell level assessment of formalin fixed paraffin embedded tissue (FFPE), leveraging tyramide signal amplification on a Ventana Ultra platform coupled with automated multispectral imaging on a Vectra 3 platform. Utilising this protocol, we assessed the mitochondrial oxidative phosphorylation (OXPHOS) protein alterations in a cohort of benign and malignant prostate samples. Mitochondrial OXPHOS plays a critical role in cell metabolism, and OXPHOS perturbation is implicated in carcinogenesis. Marked inter-patient, intra-patient and spatial cellular heterogeneity in OXPHOS protein abundance was observed. We noted frequent Complex IV loss in benign prostate tissue and Complex I loss in age matched prostate cancer tissues. Malignant regions within prostate cancer samples more frequently contained cells with low Complex I & IV and high mitochondrial mass in comparison to benign–adjacent regions. This methodology can now be applied more widely to study the frequency and distribution of OXPHOS alterations in formalin-fixed tissues, and their impact on long-term clinical outcomes.
Mortality and readmission rates of patients discharged in-hours and out-of-hours from a British ICU over a 3-year period
Authors: Cumberworth Julian , Chequers Mandy , Bremner Stephen , Boyd Owen , Philips Barbara
Published: April 2022

Excess in-hospital mortality following out-of-hours ICU discharge has been reported worldwide. From preliminary data, we observed that magnitude of difference may be reduced when patients discharged for end-of-life care or organ donation are excluded. We speculated that these patients may be disproportionately discharged out-of-hours, biasing results. We now compare in-hospital mortality and ICU readmission rates following discharge in-hours and out-of-hours over 3 years, excluding discharges for organ donation or end-of-life care. This single-centre retrospective study includes patients discharged alive following ICU admission between 01/07/2015–31/07/2018, excluding readmissions and discharges for end-of-life care/organ donation. A multiple logistic regression model was fitted to estimate adjusted odds ratio of death following out-of-hours versus in-hours discharge. Characteristics and outcomes for both groups were compared. 4678 patients were included. Patients discharged out-of-hours were older (62 vs 59 years, p < 0.001), with greater APACHE II scores (15.7 vs 14.4, p < 0.001), length of ICU stay (3.25 vs 3.00 days, p = 0.01) and delays to ICU discharge (736 vs 489 min, p < 0.001). No difference was observed in mortality (4.6% vs 3.7%, p = 0.25) or readmission rate (4.1% vs 4.2%, p = 0.85). In the multiple logistic regression model out-of-hours discharge was not associated with in-hospital mortality (OR = 1.017, 95% CI 0.682–1.518, p = 0.93). Our findings present a possible explanation for reported excess mortality following out-of-hours ICU discharge, related to inclusion of organ donation and end-of-life care patients in data sets rather than standards of care delivered out-of-hours. We are not aware of any other studies investigating the influence of this group on reported post-ICU mortality rates.
Silicon mitigates nutritional stress of nitrogen, phosphorus, and calcium deficiency in two forages plants
Authors: Araújo William Bruno Silva , Teixeira Gelza Carliane Marques , de Mello Prado Renato , Rocha Antonio Márcio Souza
Published: April 2022

Forages are one of the most cultivated crops in the world. However, nutritional deficiency is common, specifically in N, P, and Ca in many forage-growing regions. Silicon (Si) can attenuate the stress caused by nutritional deficiency, but studies on Si supply’s effects on forage plants are still scarce. This research was carried out to evaluate whether the Si supply can mitigate the effects of N, P, and Ca deficiencies of two forages and the physiological and nutritional mechanisms involved. Two experiments were carried out with two forage species (Urochloa brizanthacv. Marandu andMegathyrsus maximumcv. Massai). We used nutrient solution under balanced nutrition conditions and nutritional stress due to the lack of N, P, and Ca combined with the −Si and +Si. The deficiencies of N, P, and Ca in both forages’ cultivation caused damage to physiological and nutritional variables, decreasing the plant dry matter. However, in both forage species, the Si addition to the nutrient solution decreased the extravasation of cellular electrolytes and increased the content of phenolic compounds, the green colour index, the quantum efficiency of photosystem II, the efficiencies of use of N, P and Ca and the production of shoot dry matter. The beneficial effects of Si were evidenced in stressed and non-stressed plants. The research emphasised the advantage of using Si to growU. brizanthaandM. maximumunder N, P, and Ca deficiency, contributing to their sustainable cultivation.
Numerical learning of deep features from drug-exposed cell images to calculate IC50 without staining
Authors: Cho Kookrae , Choi Eun-Sook , Kim Jung-Hee , Son Jong-Wuk , Kim Eunjoo
Published: April 2022

To facilitate rapid determination of cellular viability caused by the inhibitory effect of drugs, numerical deep learning algorithms was used for unlabeled cell culture images captured by a light microscope as input. In this study, A549, HEK293, and NCI-H1975 cells were cultured, each of which have different molecular shapes and levels of drug responsiveness to doxorubicin (DOX). The microscopic images of these cells following exposure to various concentrations of DOX were trained with the measured value of cell viability using a colorimetric cell proliferation assay. Convolutional neural network (CNN) models for the study cells were constructed using augmented image data; the predicted cell viability using CNN models was compared to the cell viability measured by colorimetric assay. The linear relationship coefficient (r2) between measured and predicted cell viability was determined as 0.94–0.95 for the three cell types. In addition, the measured and predicted IC50 values were not statistically different. When drug responsiveness was estimated using allogenic models that were trained with a different cell type, the correlation coefficient decreased to 0.004085–0.8643. Our models could be applied to label-free cells to conduct rapid and large-scale tests while minimizing cost and labor, such as high-throughput screening for drug responsiveness.
Surgical Apgar Score and Controlling Nutritional Status Score are significant predictors of major complications after cervical spine surgery
Authors: Miura Kousei , Koda Masao , Funayama Toru , Takahashi Hiroshi , Noguchi Hiroshi , Mataki Kentaro , Shibao Yosuke , Sato Kosuke , Eto Fumihiko , Kono Mamoru , Asada Tomoyuki , Yamazaki Masashi
Published: April 2022

Nutritional screening scores, including Controlling Nutritional Status (CONUT) Score and Surgical Apgar Score (SAS), which reflect intraoperative hemodynamics, have been reported to be useful for predicting major postoperative complications in various kinds of surgery. We assessed independent risk factors for major complications after cervical spine surgery using those scoring measurements. We retrospectively reviewed medical records of patients who underwent cervical spine surgery at our institution from 2014 to 2019. Baseline clinical information, including the CONUT Score, and surgical factors, including the SAS, were assessed as risk factors for major postoperative complications. We analyzed 261 patients. Major postoperative complications occurred in 40 cases (15.3%). In the multivariate analysis, SAS (odds ratio [OR], 0.42; P < 0.01), CONUT (OR, 1.39; P < 0.01), and operative time (OR, 1.42; P < 0.01) were significant independent risk factors of major complications. The area under the SAS curve was 0.852 in the receiver operating characteristic curve analysis. Postoperative hospitalization duration was significantly longer in major complications group. Evaluating preoperative nutritional condition and intraoperative hemodynamics with CONUT score and SAS was useful for predicting major postoperative complications of cervical spine surgery. In addition, both scoring measurements are easily calculated, objective evaluations. Perioperative management utilizing those scoring measurements may help prevent them.
Allelopathic effects of sesame extracts on seed germination of moso bamboo and identification of potential allelochemicals
Authors: Zhao Jiancheng , Yang Zhenya , Zou Jingquan , Li Qin
Published: April 2022

The objectives of this study were to investigate the allelopathic effects of sesame extracts of on seed germination of moso bamboo, and to isolate and identify the potential allelochemicals. A factorial design with three organs (root, stem and leaf) and five concentrations (0, 25, 50, 75 and 100 mg mL−1) was carried out. Seeds of moso bamboo were soaked in sesame extracts to investigate their germination and growth. The allelochemicals were isolated and identified using the high performance liquid chromatograph (HPLC) system. The germination indices of the same organ decreased with the increase of extract concentrations, while the mean germination time increased, picking at the concentration of 100 mg mL−1. The radicle length and plumule length decreased, while the ratio of radicle length to plumule length increased. The allelopathy inhibition effect increased with the increase of extract concentrations, and it was significantly higher at the concentration of 100 mg mL−1 than that of 25 mg mL−1. The synthesis effect increased with the increase of extract concentrations, and it was significantly higher in leaf than root and stem. Chemical analyses identified 9 allelochemicals species (mostly phenolics and alkaloids) in the aqueous extracts. These results indicated that aqueous extracts of sesame caused the delay in seed germination and growth of moso bamboo, and phenolics and alkaloids in the aqueous extracts maybe the major reasons for the observed inhibition effects of sesame.
Transport evidence for decoupled nematic and magnetic criticality in iron chalcogenides
Authors: Ayres Jake , Čulo Matija , Buhot Jonathan , Bernáth Bence , Kasahara Shigeru , Matsuda Yuji , Shibauchi Takasada , Carrington Antony , Friedemann Sven , Hussey Nigel E.
Published: April 2022

Electronic nematicity in correlated metals often occurs alongside another instability such as magnetism. The question thus remains whether nematicity alone can drive unconventional superconductivity or anomalous (quantum critical) transport in such systems. In FeSe, nematicity emerges in isolation, providing a unique opportunity to address this question. Studies to date, however, have proved inconclusive; while signatures of nematic criticality are observed upon sulfur substitution, they appear to be quenched by the emergent magnetism under the application of pressure. Here, we study the temperature and pressure dependence of the low-temperature resistivity of FeSe1-xSx crystals at x values beyond the nematic quantum critical point. Two distinct components to the resistivity are revealed; one that is suppressed with increasing pressure and one that grows upon approaching the magnetic state at higher pressures. These findings hint that nematic and magnetic critical fluctuations in FeSe1-xSx are completely decoupled, in marked contrast to other Fe-based superconductors.
Shear band formation during nanoindentation of EuB6 rare-earth hexaboride
Authors: Karre Rajamallu , Shen Yidi , Song Shuangxi , Hu Yixuan , Lahkar Simanta , Wang Xiaodong , An Qi , Reddy Kolan Madhav
Published: April 2022

Research on rare-earth hexaborides mainly focuses on tuning their electronic structure from insulating-to-metallic states during high pressure experiments. However, the structural evolution that contributes to their mechanical failure is not well understood. Here, we examine the pressure-induced structural evolution of a model rare-earth hexaboride, EuB6, during nanoindentation. Transmission electron microscopy reveals that nanoscale amorphous shear bands, mediated by dislocations, play a decisive role in deformation failure. Density functional theory calculations confirm that amorphous bands evolve by breaking boron-boron bonds within B6 octahedra during shear deformation. Our results underscore an important damage mechanism in hard and fragile hexaborides at high shear pressures.
The potential of nanomaterials for sustainable modern agriculture: present findings and future perspectives
Authors: Farooq Muhammad Ahsan , Hannan Fakhir , Islam Faisal , Ayyaz Ahsan , Zhang Na , Chen Weiqi , Zhang Kangni , Huang Qian , Xu Ling , Zhou Weijun
Published: April 2022

Nanotechnology has received attention in the recent decade due to a plethora of advantages over conventional agriculture techniques, in terms of improved effectiveness, decreased input needs, and lesser environmental toxicity.
Real-time monitoring of epithelial barrier function by impedance spectroscopy in a microfluidic platform
Authors: Fernandes João , Karra Nikita , Bowring Joel , Reale Riccardo , James Jonathan , Blume Cornelia , Pell Theresa J. , Rowan Wendy C. , Davies Donna E. , Swindle Emily J. , Morgan Hywel
Published: April 2022

Real-time monitoring of epithelial barrier function by electrical impedance spectroscopy using a scalable and easy to use microfluidic platform.
Tuning the enzyme-like activities of cerium oxide nanoparticles using a triethyl phosphite ligand
Authors: Yadav Nisha , Patel Vaishwik , McCourt Luke , Ruppert Michael , Miller Michael , Inerbaev Talgat , Mahasivam Sanje , Bansal Vipul , Vinu Ajayan , Singh Sanjay , Karakoti Ajay
Published: April 2022

Tuning the enzyme mimetic activity of cerium oxide nanoparticles using triethylphosphine modifies its enzyme mimetic activities and improves the antimicrobial activity.
Sustained-release nanocapsule based on a 3D COF for long-term enzyme prodrug therapy of cancer
Authors: Wan Xiuyan , Yin Jiaqi , Yan Qianqian , Hu Hui , Zheng Teng , Chai Yuying , Pan Wei , Gao Yanan , Li Na , Tang Bo
Published: April 2022

An enzyme nanocapsule was constructed from a three-dimensional covalent organic framework to realize long-term enzyme prodrug therapy based on a sustained-release effect.
Expanding the toolbox of the coinage bond: adducts involving new gold(iii) derivatives and bioactive molecules
Authors: Pizzi Andrea , Calabrese Miriam , Daolio Andrea , Ursini Maurizio , Frontera Antonio , Resnati Giuseppe
Published: April 2022

X-ray analyses of some adducts between AuX3 (X = Cl, Br) and several pyridine derivatives show short π-hole CiBs; computational studies reveal the attractive nature of these short contacts, confirming their key role in driving their crystal packing.
A sobering examination of the feasibility of aqueous aluminum batteries
Authors: Pastel Glenn R. , Chen Ying , Pollard Travis P. , Schroeder Marshall A. , Bowden Mark E. , Zheng Allen , Hahn Nathan T. , Ma Lin , Murugesan Vijayakumar , Ho Janet , Garaga Mounesha , Borodin Oleg , Mueller Karl , Greenbaum Steven , Xu Kang
Published: April 2022

An in-depth investigation of the solvation structure of the trivalent aluminum cation in Al(OTf)3 solutions reveals major concerns regarding the feasibility of rechargeable aqueous aluminum batteries.
Evaluating atmospheric mercury (Hg) uptake by vegetation in a chemistry-transport model
Authors: Feinberg Aryeh , Dlamini Thandolwethu , Jiskra Martin , Shah Viral , Selin Noelle E.
Published: April 2022

We study the uptake of atmospheric mercury by vegetation in a chemical transport model and available observations. Due to the importance of this sink in the global mercury cycle, perturbations to forested areas can elevate mercury risks.
Metabolic perturbations and health impact from exposure to a combination of multiple harmful Maillard reaction products on Sprague-Dawley rats
Authors: Quan Wei , Lin Yong , Xue Chaoyi , Cheng Yong , Luo Jie , Lou Aihua , Zeng Maomao , He Zhiyong , Shen Qingwu , Chen Jie
Published: April 2022

The metabolic perturbations and health impact of the co-accumulation of acrylamide, harmane, and Nε-(carboxymethyl)lysine was investigated via serum biochemical and histopathological examinations as well as metabolomic analysis.
Silicon carbide (SiC) derived from agricultural waste potentially competitive with silicon anodes
Authors: Yu Mengjie , Temeche Eleni , Indris Sylvio , Lai Wei , Laine Richard M.
Published: April 2022

Silicon carbide derived from rice hull ash reveals, on long-term cycling, capacity increases to >900 mA h g−1 without significant volume changes. Lithiation mechanisms and the extraordinary capacity increment origins were assessed in detail.
Micro-/nano-fluidic devices and in vivo fluorescence imaging based on quantum dots for cytologic diagnosis
Authors: Luo Minchuan , Yukawa Hiroshi , Baba Yoshinobu
Published: April 2022

A review for quantum dots (QDs) as fluorescent nanoprobes for biosensing of biomolecules and cells based on microfluidic chips and for in vivo imaging of transplanted cells via an in vivo imaging system.
Impact of secondary salts, temperature, and pH on the colloidal stability of graphene oxide in water
Authors: Mancillas-Salas Sergio , Reynosa-Martinez Ana C. , Barroso-Flores J. , Lopez-Honorato Eddie
Published: April 2022

Water conditions in arid and semi-arid regions would agglomerate graphene oxide regardless of the particle size and oxidation degree.
A CdxZn1−xS/TiO2 nanotube array electrode for a highly sensitive and selective nonenzymatic photoelectrochemical glucose sensor
Authors: Esmaeili Fatemeh Ostad , Tasviri Mahboubeh , Mohaghegh Neda
Published: April 2022

A highly sensitive nonenzymatic photoelectrochemical glucose sensor based on a CdxZn1−xS/TiO2 Nanotube Array Electrode.
A cyclic thioketone as biradical heterocyclopentane-1,3-diyl: synthesis, structure and activation chemistry
Authors: Beer Henrik , Linke Alexander , Bresien Jonas , Villinger Alexander , Schulz Axel
Published: April 2022

Reaction of [(μ-NR)P˙]2 with CSCl2 and Mg gives a deep blue, highly labile cyclic thioketone with singlet biradical character. It can be converted to a housane-type isomer by light and to bicyclic cage compounds by addition of CS2 and benzaldehyde.