bluuebunny/crossref_metadata_2025_split huggingface dataset:
Quantum engineering of non-equilibrium efficient p-doping in ultra-wide band-gap nitrides
Authors: Jiang Ke , Sun Xiaojuan , Shi Zhiming , Zang Hang , Ben Jianwei , Deng Hui-Xiong , Li Dabing 
Published: March 2021

AbstractUltra-wide band-gap nitrides have huge potential in micro- and optoelectronics due to their tunable wide band-gap, high breakdown field and energy density, excellent chemical and thermal stability. However, their application has been severely hindered by the low p-doping efficiency, which is ascribed to the ultrahigh acceptor activation energy originated from the low valance band maximum. Here, a valance band modulation mode is proposed and a quantum engineering doping method is conducted to achieve high-efficient p-type ultra-wide band-gap nitrides, in which GaN quantum-dots are buried in nitride matrix to produce a new band edge and thus to tune the dopant activation energy. By non-equilibrium doping techniques, quantum engineering doped AlGaN:Mg with Al content of 60% is successfully fabricated. The Mg activation energy has been reduced to about 21 meV, and the hole concentration reaches higher than 1018 cm−3 at room temperature. Also, similar activation energies are obtained in AlGaN with other Al contents such as 50% and 70%, indicating the universality of the quantum engineering doping method. Moreover, deep-ultraviolet light-emission diodes are fabricated and the improved performance further demonstrates the validity and merit of the method. With the quantum material growth techniques developing, this method would be prevalently available and tremendously stimulate the promotion of ultra-wide band-gap semiconductor-based devices.
2D materials for conducting holes from grain boundaries in perovskite solar cells
Authors: You Peng , Tang Guanqi , Cao Jiupeng , Shen Dong , Ng Tsz-Wai , Hawash Zafer , Wang Naixiang , Liu Chun-Ki , Lu Wei , Tai Qidong , Qi Yabing , Lee Chun-Sing , Yan Feng 
Published: March 2021

AbstractGrain boundaries in organic–inorganic halide perovskite solar cells (PSCs) have been found to be detrimental to the photovoltaic performance of devices. Here, we develop a unique approach to overcome this problem by modifying the edges of perovskite grain boundaries with flakes of high-mobility two-dimensional (2D) materials via a convenient solution process. A synergistic effect between the 2D flakes and perovskite grain boundaries is observed for the first time, which can significantly enhance the performance of PSCs. We find that the 2D flakes can conduct holes from the grain boundaries to the hole transport layers in PSCs, thereby making hole channels in the grain boundaries of the devices. Hence, 2D flakes with high carrier mobilities and short distances to grain boundaries can induce a more pronounced performance enhancement of the devices. This work presents a cost-effective strategy for improving the performance of PSCs by using high-mobility 2D materials.
Prostate cancer prognosis after initiation of androgen deprivation therapy among statin users. A population-based cohort study
Authors: Peltomaa A. I. , Raittinen P. , Talala K. , Taari K. , Tammela T. L. J. , Auvinen A. , Murtola T. J. 
Published: March 2021

Abstract
Purpose
Statins’ cholesterol-lowering efficacy is well-known. Recent epidemiological studies have found that inhibition of cholesterol synthesis may have beneficial effects on prostate cancer (PCa) patients, especially patients treated with androgen deprivation therapy (ADT). We evaluated statins’ effect on prostate cancer prognosis among patients treated with ADT.

Materials and methods
Our study population consisted of 8253 PCa patients detected among the study population of the Finnish randomized study of screening for prostate cancer. These were limited to 4428 men who initiated ADT during the follow-up. Cox proportional regression model adjusted for tumor clinical characteristics and comorbidities was used to estimate hazard ratios for risk of PSA relapse after ADT initiation and prostate cancer death.

Results
During the median follow-up of 6.3 years after the ADT initiation, there were 834 PCa deaths and 1565 PSA relapses in a study cohort. Statin use after ADT was associated with a decreased risk of PSA relapse (HR 0.73, 95% CI 0.65–0.82) and prostate cancer death (HR 0.82; 95% CI 0.69–0.96). In contrast, statin use defined with a one-year lag (HR 0.89, 95% CI 0.76–1.04), statin use before ADT initiation (HR 1.12, 95% CI 0.96–1.31), and use in the first year on ADT (HR 1.02, 95% CI 0.85–1.24) were not associated with prostate cancer death, without dose dependency.

Conclusion
Statin use after initiation of ADT, but not before, was associated with improved prostate cancer prognosis.
Gut microbial taxa elevated by dietary sugar disrupt memory function
Authors: Noble Emily E. , Olson Christine A. , Davis Elizabeth , Tsan Linda , Chen Yen-Wei , Schade Ruth , Liu Clarissa , Suarez Andrea , Jones Roshonda B. , de La Serre Claire , Yang Xia , Hsiao Elaine Y. , Kanoski Scott E. 
Published: March 2021

AbstractEmerging evidence highlights a critical relationship between gut microbiota and neurocognitive development. Excessive consumption of sugar and other unhealthy dietary factors during early life developmental periods yields changes in the gut microbiome as well as neurocognitive impairments. However, it is unclear whether these two outcomes are functionally connected. Here we explore whether excessive early life consumption of added sugars negatively impacts memory function via the gut microbiome. Rats were given free access to a sugar-sweetened beverage (SSB) during the adolescent stage of development. Memory function and anxiety-like behavior were assessed during adulthood and gut bacterial and brain transcriptome analyses were conducted. Taxa-specific microbial enrichment experiments examined the functional relationship between sugar-induced microbiome changes and neurocognitive and brain transcriptome outcomes. Chronic early life sugar consumption impaired adult hippocampal-dependent memory function without affecting body weight or anxiety-like behavior. Adolescent SSB consumption during adolescence also altered the gut microbiome, including elevated abundance of two species in the genus Parabacteroides (P. distasonis and P. johnsonii) that were negatively correlated with hippocampal function. Transferred enrichment of these specific bacterial taxa in adolescent rats impaired hippocampal-dependent memory during adulthood. Hippocampus transcriptome analyses revealed that early life sugar consumption altered gene expression in intracellular kinase and synaptic neurotransmitter signaling pathways, whereas Parabacteroides microbial enrichment altered gene expression in pathways associated with metabolic function, neurodegenerative disease, and dopaminergic signaling. Collectively these results identify a role for microbiota “dysbiosis” in mediating the detrimental effects of early life unhealthy dietary factors on hippocampal-dependent memory function.
Statistics of pathogenic bacteria in the search of host cells
Authors: Otte Stefan , Ipiña Emiliano Perez , Pontier-Bres Rodolphe , Czerucka Dorota , Peruani Fernando 
Published: March 2021

AbstractA crucial phase in the infection process, which remains poorly understood, is the localization of suitable host cells by bacteria. It is often assumed that chemotaxis plays a key role during this phase. Here, we report a quantitative study on how Salmonella Typhimurium search for T84 human colonic epithelial cells. Combining time-lapse microscopy and mathematical modeling, we show that bacteria can be described as chiral active particles with strong active speed fluctuations, which are of biological, as opposed to thermal, origin. We observe that there exists a giant range of inter-individual variability of the bacterial exploring capacity. Furthermore, we find Salmonella Typhimurium does not exhibit biased motion towards the cells and show that the search time statistics is consistent with a random search strategy. Our results indicate that in vitro localization of host cells, and also cell infection, are random processes, not involving chemotaxis, that strongly depend on bacterial motility parameters.
Genome-wide binding potential and regulatory activity of the glucocorticoid receptor’s monomeric and dimeric forms
Authors: Johnson Thomas A. , Paakinaho Ville , Kim Sohyoung , Hager Gordon L. , Presman Diego M. 
Published: March 2021

AbstractA widely regarded model for glucocorticoid receptor (GR) action postulates that dimeric binding to DNA regulates unfavorable metabolic pathways while monomeric receptor binding promotes repressive gene responses related to its anti-inflammatory effects. This model has been built upon the characterization of the GRdim mutant, reported to be incapable of DNA binding and dimerization. Although quantitative live-cell imaging data shows GRdim as mostly dimeric, genomic studies based on recovery of enriched half-site response elements suggest monomeric engagement on DNA. Here, we perform genome-wide studies on GRdim and a constitutively monomeric mutant. Our results show that impairing dimerization affects binding even to open chromatin. We also find that GRdim does not exclusively bind half-response elements. Our results do not support a physiological role for monomeric GR and are consistent with a common mode of receptor binding via higher order structures that drives both the activating and repressive actions of glucocorticoids.
Single trial neuronal activity dynamics of attentional intensity in monkey visual area V4
Authors: Ghosh Supriya , Maunsell John H. R. 
Published: March 2021

AbstractUnderstanding how activity of visual neurons represents distinct components of attention and their dynamics that account for improved visual performance remains elusive because single-unit experiments have not isolated the intensive aspect of attention from attentional selectivity. We isolated attentional intensity and its single trial dynamics as determined by spatially non-selective attentional performance in an orientation discrimination task while recording from neurons in monkey visual area V4. We found that attentional intensity is a distinct cognitive signal that can be distinguished from spatial selectivity, reward expectations and motor actions. V4 spiking on single trials encodes a combination of sensory and cognitive signals on different time scales. Attentional intensity and the detection of behaviorally relevant sensory signals are well represented, but immediate reward expectation and behavioral choices are poorly represented in V4 spiking. These results provide a detailed representation of perceptual and cognitive signals in V4 that are crucial for attentional performance.
In vivo activation of pH-responsive oxidase-like graphitic nanozymes for selective killing of Helicobacter pylori
Authors: Zhang Lufeng , Zhang Liang , Deng Hui , Li Huan , Tang Wentao , Guan Luyao , Qiu Ye , Donovan Michael J. , Chen Zhuo , Tan Weihong 
Published: March 2021

AbstractHelicobacter pylori infection is a major etiological factor in gastric diseases. However, clinical antibiotic therapy for H. pylori is limited by continuously decreased therapeutic efficacy and side effects to symbiotic bacteria. Herein, we develop an in vivo activatable pH-responsive graphitic nanozyme, PtCo@Graphene (PtCo@G), for selective treatment of H. pylori. Such nanozymes can resist gastric acid corrosion, exhibit oxidase-like activity to stably generate reactive oxygen species only in acidic gastric milieu and demonstrate superior selective bactericidal property. C18-PEGn-Benzeneboronic acid molecules are modified on PtCo@G, improving its targeting capability. Under acidic gastric pH, graphitic nanozymes show notable bactericidal activity toward H. pylori, while no bacterial killing is observed under intestinal conditions. In mouse model, high antibacterial capability toward H. pylori and negligible side effects toward normal tissues and symbiotic bacteria are achieved. Graphitic nanozyme displays the desired enzyme-like activities at corresponding physiological sites and may address critical issues in clinical treatment of H. pylori infections.
Type I interferons affect the metabolic fitness of CD8+ T cells from patients with systemic lupus erythematosus
Authors: Buang Norzawani , Tapeng Lunnathaya , Gray Victor , Sardini Alessandro , Whilding Chad , Lightstone Liz , Cairns Thomas D. , Pickering Matthew C. , Behmoaras Jacques , Ling Guang Sheng , Botto Marina 
Published: March 2021

AbstractThe majority of patients with systemic lupus erythematosus (SLE) have high expression of type I IFN-stimulated genes. Mitochondrial abnormalities have also been reported, but the contribution of type I IFN exposure to these changes is unknown. Here, we show downregulation of mitochondria-derived genes and mitochondria-associated metabolic pathways in IFN-High patients from transcriptomic analysis of CD4+ and CD8+ T cells. CD8+ T cells from these patients have enlarged mitochondria and lower spare respiratory capacity associated with increased cell death upon rechallenge with TCR stimulation. These mitochondrial abnormalities can be phenocopied by exposing CD8+ T cells from healthy volunteers to type I IFN and TCR stimulation. Mechanistically these ‘SLE-like’ conditions increase CD8+ T cell NAD+ consumption resulting in impaired mitochondrial respiration and reduced cell viability, both of which can be rectified by NAD+ supplementation. Our data suggest that type I IFN exposure contributes to SLE pathogenesis by promoting CD8+ T cell death via metabolic rewiring.
Soil moisture–atmosphere feedback dominates land carbon uptake variability
Authors: Humphrey Vincent , Berg Alexis , Ciais Philippe , Gentine Pierre , Jung Martin , Reichstein Markus , Seneviratne Sonia I. , Frankenberg Christian 
Published: March 2021

AbstractYear-to-year changes in carbon uptake by terrestrial ecosystems have an essential role in determining atmospheric carbon dioxide concentrations1. It remains uncertain to what extent temperature and water availability can explain these variations at the global scale2–5. Here we use factorial climate model simulations6 and show that variability in soil moisture drives 90 per cent of the inter-annual variability in global land carbon uptake, mainly through its impact on photosynthesis. We find that most of this ecosystem response occurs indirectly as soil moisture–atmosphere feedback amplifies temperature and humidity anomalies and enhances the direct effects of soil water stress. The strength of this feedback mechanism explains why coupled climate models indicate that soil moisture has a dominant role4, which is not readily apparent from land surface model simulations and observational analyses2,5. These findings highlight the need to account for feedback between soil and atmospheric dryness when estimating the response of the carbon cycle to climatic change globally5,7, as well as when conducting field-scale investigations of the response of the ecosystem to droughts8,9. Our results show that most of the global variability in modelled land carbon uptake is driven by temperature and vapour pressure deficit effects that are controlled by soil moisture.
Dietary glutamic acid and aspartic acid as biomarkers for predicting diabetic retinopathy
Authors: Park So Young , Kim Jieun , Son Jung Il , Rhee Sang Youl , Kim Do-Yeon , Chon Suk , Lim Hyunjung , Woo Jeong-Taek 
Published: March 2021

AbstractThe screening rate of diabetic retinopathy (DR) is low despite the importance of early diagnosis. We investigated the predictive value of dietary glutamic acid and aspartic acid for diagnosis of DR using the Korea National Diabetes Program cohort study. The 2067 patients with type 2 diabetes without DR were included. The baseline intakes of energy, glutamic acid and aspartic acid were assessed using a 3-day food records. The risk of DR incidence based on intake of glutamic acid and aspartic acid was analyzed. The DR group was older, and had higher HbA1c, longer DM duration, lower education level and income than non-DR group (all p < 0.05). The intake of total energy, glutamic acid and aspartic acid were lower in DR group than non-DR group (p = 0.010, p = 0.025 and p = 0.042, respectively). There was no difference in the risk of developing DR according to the intake of glutamic acid and ascorbic acid. But, aspartic acid intake had a negative correlation with PDR. Hence, the intake of glutamic acid and aspartic acid did not affect in DR incidence. However, lower aspartic acid intake affected the PDR incidence.
Third generation cephalosporins and piperacillin/tazobactam have distinct impacts on the microbiota of critically ill patients
Authors: Gamage Hasinika K. A. H. , Venturini Carola , Tetu Sasha G. , Kabir Masrura , Nayyar Vineet , Ginn Andrew N. , Roychoudhry Belinda , Thomas Lee , Brown Mitchell , Holmes Andrew , Partridge Sally R. , Seppelt Ian , Paulsen Ian T. , Iredell Jonathan R. 
Published: March 2021

AbstractEffective implementation of antibiotic stewardship, especially in critical care, is limited by a lack of direct comparative investigations on how different antibiotics impact the microbiota and antibiotic resistance rates. We investigated the impact of two commonly used antibiotics, third-generation cephalosporins (3GC) and piperacillin/tazobactam (TZP) on the endotracheal, perineal and faecal microbiota of intensive care patients in Australia. Patients exposed to either 3GC, TZP, or no β-lactams (control group) were sampled over time and 16S rRNA amplicon sequencing was performed to examine microbiota diversity and composition. While neither treatment significantly affected diversity, numerous changes to microbiota composition were associated with each treatment. The shifts in microbiota composition associated with 3GC exposure differed from those observed with TZP, consistent with previous reports in animal models. This included a significant increase in Enterobacteriaceae and Enterococcaceae abundance in endotracheal and perineal microbiota for those administered 3GC compared to the control group. Culture-based analyses did not identify any significant changes in the prevalence of specific pathogenic or antibiotic-resistant bacteria. Exposure to clinical antibiotics has previously been linked to reduced microbiota diversity and increased antimicrobial resistance, but our results indicate that these effects may not be immediately apparent after short-term real-world exposures.
A Strepsipteran parasite extends the lifespan of workers in a social wasp
Authors: Beani Laura , Dallai Romano , Cappa Federico , Manfredini Fabio , Zaccaroni Marco , Lorenzi Maria Cristina , Mercati David 
Published: March 2021

AbstractIn social wasps, female lifespan depends on caste and colony tasks: workers usually live a few weeks while queens as long as 1 year.Polistes dominulapaper wasps infected by the strepsipteran parasiteXenos vesparumavoid all colony tasks, cluster on vegetation where parasite dispersal and mating occur, hibernate and infect the next generation of wasp larvae. Here, we compared the survival rate of infected and uninfected wasp workers. Workers’ survival was significantly affected by parasite sex: two-third of workers parasitized by aX. vesparumfemale survived and overwintered like future queens did, while all workers infected by aX. vesparummale died during the summer, like uninfected workers that we used as controls. We measured a set of host and parasite traits possibly associated with the observed lifespan extension. Infected overwintering workers had larger fat bodies than infected workers that died in the summer, but they had similar body size and ovary development. Furthermore, we recorded a positive correlation between parasite and host body sizes. We hypothesize that the manipulation of worker’s longevity operated byX. vesparumenhances parasite’s fitness: if workers infected by a female overwinter, they can spread infective parasite larvae in the spring like parasitized gynes do, thus contributing to parasite transmission.
Hypoxia and oxidative stress induce sterile placental inflammation in vitro
Authors: Baker Bernadette C. , Heazell Alexander E. P. , Sibley Colin , Wright Rachael , Bischof Helen , Beards Frances , Guevara Tatiana , Girard Sylvie , Jones Rebecca L. 
Published: March 2021

AbstractFetal growth restriction (FGR) and stillbirth are associated with placental dysfunction and inflammation and hypoxia, oxidative and nitrative stress are implicated in placental damage. Damage-associated molecular patterns (DAMPs) are elevated in pregnancies at increased risk of FGR and stillbirth and are associated with increase in pro-inflammatory placental cytokines. We hypothesised that placental insults lead to release of DAMPs, promoting placental inflammation. Placental tissue from uncomplicated pregnancies was exposed in vitro to hypoxia, oxidative or nitrative stress. Tissue production and release of DAMPs and cytokines was determined. Oxidative stress and hypoxia caused differential release of DAMPs including uric acid, HMGB1, S100A8, cell-free fetal DNA, S100A12 and HSP70. After oxidative stress pro-inflammatory cytokines (IL-1α, IL-1β, IL-6, IL-8, TNFα, CCL2) were increased both within explants and in conditioned culture medium. Hypoxia increased tissue IL-1α/β, IL-6, IL-8 and TNFα levels, and release of IL-1α, IL-6 and IL-8, whereas CCL2 and IL-10 were reduced. IL1 receptor antagonist (IL1Ra) treatment prevented hypoxia- and oxidative stress-induced IL-6 and IL-8 release. These findings provide evidence that relevant stressors induce a sterile inflammatory profile in placental tissue which can be partially blocked by IL1Ra suggesting this agent has translational potential to prevent placental inflammation evident in FGR and stillbirth.
Age-dependent ataxia and neurodegeneration caused by an αII spectrin mutation with impaired regulation of its calpain sensitivity
Authors: Miazek Arkadiusz , Zalas Michał , Skrzymowska Joanna , Bogin Bryan A. , Grzymajło Krzysztof , Goszczynski Tomasz M. , Levine Zachary A. , Morrow Jon S. , Stankewich Michael C. 
Published: March 2021

AbstractThe neuronal membrane-associated periodic spectrin skeleton (MPS) contributes to neuronal development, remodeling, and organization. Post-translational modifications impinge on spectrin, the major component of the MPS, but their role remains poorly understood. One modification targeting spectrin is cleavage by calpains, a family of calcium-activated proteases. Spectrin cleavage is regulated by activated calpain, but also by the calcium-dependent binding of calmodulin (CaM) to spectrin. The physiologic significance of this balance between calpain activation and substrate-level regulation of spectrin cleavage is unknown. We report a strain of C57BL/6J mice harboring a single αII spectrin point mutation (Sptan1 c.3293G > A:p.R1098Q) with reduced CaM affinity and intrinsically enhanced sensitivity to calpain proteolysis. Homozygotes are embryonic lethal. Newborn heterozygotes of either gender appear normal, but soon develop a progressive ataxia characterized biochemically by accelerated calpain-mediated spectrin cleavage and morphologically by disruption of axonal and dendritic integrity and global neurodegeneration. Molecular modeling predicts unconstrained exposure of the mutant spectrin’s calpain-cleavage site. These results reveal the critical importance of substrate-level regulation of spectrin cleavage for the maintenance of neuronal integrity. Given that excessive activation of calpain proteases is a common feature of neurodegenerative disease and traumatic encephalopathy, we propose that damage to the spectrin MPS may contribute to the neuropathology of many disorders.