bluuebunny/crossref_metadata_2025 huggingface dataset:
Investigating Attachment Insecurity and Somatosensory Amplification,	and the Mediating Role of Interpersonal Problems
Authors: Kealy David , Rice Simon M. , Chartier Gabrielle B. , Cox Daniel W.
Published: May 2021

Abstract. Background: Somatosensory amplification involves perceptual sensitivity to and cognitive-affective interpretation of bodily sensations and external stimuli, contributing to heightened experiences of somatic symptoms. However, little is known about somatosensory amplification in relation to vulnerabilities such as attachment insecurity. Aims: The present study investigated the link between attachment insecurity and somatosensory amplification, including the mediating role of dysfunctional interpersonal behaviors. Method: A sample of 245 adult community members completed the Somatosensory Amplification Scale, Generalized Anxiety Disorder Scale, and abbreviated versions of the Experiences in Close Relationships scale and Inventory of Interpersonal Problems. Correlational and regression analyses were used to examine relations among study variables, including a hypothesized parallel mediation model. Results: Somatosensory amplification was significantly associated with attachment anxiety, but not attachment avoidance. Regression analyses, controlling for general anxiety symptoms and gender, found that interpersonal sensitivity (but not aggression or ambivalence) mediated the link between attachment anxiety and somatosensory amplification. Limitations: Study limitations include the use of cross-sectional data and a non-clinical sample. Conclusion: The findings indicate that somatosensory amplification may be related to individuals’ attachment anxiety, through the mediating effect of interpersonal sensitivity problems.
Cretaceous to Miocene NW Pacific Plate Kinematic Constraints: Paleomagnetism and Ar–Ar Geochronology in the Mineoka Ophiolite Mélange (Japan)
Authors: Ganbat Ariuntsetseg , Pastor‐Galán Daniel , Hirano Naoto , Nakamura Norihiro , Sumino Hirochika , Yamaguchi Yuji , Tsujimori Tatsuki
Published: May 2021

The Mineoka Ophiolite Mélange is located at the intersection of the Pacific, Philippine Sea, Eurasian, and North American plates. The Mineoka ophiolite origin is disputed, and it has been ascribed to a fully subducted plate or part of the Pacific and Philippine Sea plates. In this paper, we present a kinematic reconstruction of the Mineoka Ophiolite Mélange and its relation with the Pacific Plate, based on new paleomagnetic data and bulk‐rock 40Ar/39Ar ages of basaltic rocks. In addition to standard analyses for paleolatitudes, we performed a Net tectonic rotation analysis on sheeted dolerite dikes to infer the paleospreading direction that formed the ophiolite. The analysis shows that 85–80 Ma MOR pillow basalts erupted at a paleolatitude of N ∼16°, whereas ∼50 Ma basalts formed at N ∼34°. Net Tectonic Rotation analysis suggests that the spreading direction was NE 60°. Ar–Ar ages yielded 53–49 Ma for MORBs and 41–35 Ma for island‐arc basalts. The formation of this ophiolite occurred in the back‐arc spreading of the Nemuro–Olyutorsky arcs of the NW Pacific. It infers that the final consumption of Izanagi below Japan instigated a subduction jump and flipped its polarity. Subduction initiated parallel to the ridge, and a piece of the original back‐arc crust got trapped near the Japan trench during the northwards motion of the Philippine Sea Plate. The contrasting motion between the Pacific and the Philippine Sea plates generated a highly unstable setting followed by a subduction zone that left a small‐sized and short‐lived plate (“Mineoka”), surrounded by subduction zones.
Ice‐Shelf Meltwater Overturning in the Bellingshausen Sea
Authors: Ruan Xiaozhou , Speer Kevin G. , Thompson Andrew F. , Schulze Chretien Lena M. , Shoosmith Deborah R.
Published: May 2021

Hydrographic data are analyzed for the broad continental shelf of the Bellingshausen Sea, which is host to a number of rapidly thinning ice shelves. The flow of warm Circumpolar Deep Water (CDW) onto the continental shelf is observed in the two major glacially carved troughs, the Belgica and Latady troughs. Using ship‐based measurements of potential temperature, salinity, and dissolved oxygen, collected across several coast‐to‐coast transects over the Bellingshausen shelf in 2007, the velocity and circulation patterns are inferred based on geostrophic balance and further constrained by the tracer and mass budgets. Meltwater was observed at the surface and at intermediate depth toward the western side of the continental shelf, collocated with inferred outflows. The maximum conversion rate from the dense CDW to lighter water masses by mixing with glacial meltwater is estimated to be 0.37 ± 0.1 Sv in both depth and potential density spaces. This diapycnal overturning is comparable to previous estimates made in the neighboring Amundsen Sea, highlighting the overlooked importance of water mass modification and meltwater production associated with glacial melting in the Bellingshausen Sea.
“An Entrainment Paradox: How Hysteretic Saltation and Secondary Transport Augment Atmospheric Uptake of Aeolian Source Materials”
Authors: Rana Santosh , Anderson William , Day Mackenzie
Published: May 2021

Aerodynamic surface stress imposed by the atmospheric surface layer (ASL) drives aeolian sediment transport processes. When the imposed stress exceeds fluid threshold, splashing sand grains release fine (aerosol) particles. This process stops when the imposed stress falls below an impact threshold. Turbulence in the ASL is composed of elongated streaks of relatively high and low streamwise momentum (high‐momentum and low‐momentum regions, HMR and LMR, respectively), and these streaks are aligned with the prevailing winds. Streamwise‐wall‐normal turbulent stress is the concurrent product of fluctuations in streamwise and vertical velocity. These production mechanisms are categorized into quadrants: sweeps, inner interactions, ejections, and outer interactions, where the first two and last two occur within HMRs and LMRs, respectively. Under typical ASL conditions, the time‐averaged shear velocity is bound between 0.3 and 0.5 m/s, demonstrating the importance of fluctuations in mobilizing sand grains via saltation: time‐averaged shear velocity exceeding threshold does not correspond with typical ASL conditions. Given the aforementioned contributions to streamwise‐wall‐normal turbulent stresses from sweeps and ejections, it is self‐evident that under typical conditions only sweeps possess the momentum required to exceed threshold. But, any dust released is trapped by downwelling from aloft; ejections rarely exceed threshold, but they contain the positive vertical velocity needed to entrain. These attributes represent an entrainment paradox. Complementary field data are used to demonstrate the existence of an entrainment paradox. Large eddy simulation has been used to capture space‐time evolution of an idealized ASL and identify mechanistic flow physics central to entrainment.
Evaluation of Novel NASA Moderate Resolution Imaging Spectroradiometer and Visible Infrared Imaging Radiometer Suite Aerosol Products and Assessment of Smoke Height Boundary Layer Ratio During Extreme Smoke Events in the Western USA
Authors: Loría‐Salazar S. Marcela , Sayer Andrew M. , Barnes John , Huang Jingting , Flynn Connor , Lareau Neil , Lee Jaehwa , Lyapustin Alexei , Redemann Jens , Welton Ellsworth J. , Wilkins Joseph L. , Holmes Heather A.
Published: May 2021

We analyze new aerosol products from NASA satellite retrievals over the western USA during August 2013, with special attention to locally generated wildfire smoke and downwind plume structures. Aerosol optical depth (AOD) at 550 nm from MODerate Resolution Imaging Spectroradiometer (MODIS) (Terra and Aqua Collections 6 and 6.1) and Visible Infrared Imaging Radiometer Suite (VIIRS) Deep Blue (DB) and MODIS (Terra and Aqua) Multi‐Angle Implementation of Atmospheric Correction (MAIAC) retrievals are evaluated against ground‐based AErosol RObotic NETwork (AERONET) observations. We find a significant improvement in correlation with AERONET and other metrics in the latest DB AOD (MODIS C6.1 r2 = 0.75, VIIRS r2 = 0.79) compared to MODIS C6 (r2 = 0.62). In general, MAIAC (r2 = 0.84) and DB (MODIS C6.1 and VIIRS) present similar statistical evaluation metrics for the western USA and are useful tools to characterize aerosol loading associated with wildfire smoke. We also evaluate three novel NASA MODIS plume injection height (PIH) products, one from MAIAC and two from the Aerosol Single scattering albedo and layer Height Estimation (ASHE) (MODIS and VIIRS) algorithm. Both Terra and Aqua MAIAC PIHs statistically agree with ground‐based and satellite lidar observations near the fire source, as do ASHE, although the latter is sensitive to assumptions about aerosol absorption properties. We introduce a first‐order approximation Smoke Height Boundary Layer Ratio (SHBLR) to qualitatively distinguish between aerosol pollution within the planetary boundary layer and the free troposphere. We summarize the scope, limitations, and suggestions for scientific applications of surface level aerosol concentrations specific to wildfire emissions and smoke plumes using these novel NASA MODIS and VIIRS aerosol products.
Improving Convection Trigger Functions in Deep Convective Parameterization Schemes Using Machine Learning
Authors: Zhang Tao , Lin Wuyin , Vogelmann Andrew M. , Zhang Minghua , Xie Shaocheng , Qin Yi , Golaz Jean‐Christophe
Published: May 2021

Deficiencies in convection trigger functions, used in deep convection parameterizations in General Circulation Models (GCMs), have critical impacts on climate simulations. A novel convection trigger function is developed using the machine learning (ML) classification model XGBoost. The large‐scale environmental information associated with convective events is obtained from the long‐term constrained variational analysis forcing data from the Atmospheric Radiation Measurement (ARM) program at its Southern Great Plains (SGP) and Manaus (MAO) sites representing, respectively, continental mid‐latitude and tropical convection. The ML trigger is separately trained and evaluated per site, and jointly trained and evaluated at both sites as a unified trigger. The performance of the ML trigger is compared with four convective trigger functions commonly used in GCMs: dilute convective available potential energy (CAPE), undilute CAPE, dilute dynamic CAPE (dCAPE), and undilute dCAPE. The ML trigger substantially outperforms the four CAPE‐based triggers in terms of theF1 score metric, widely used to estimate the performance of ML methods. The site‐specific ML trigger functions can achieve, respectively, 91% and 93%F1 scores at SGP and MAO. The unified trigger also has a 91%F1 score, with virtually no degradation from the site‐specific training, suggesting the potential of a global ML trigger function. The ML trigger alleviates a GCM deficiency regarding the overprediction of convection occurrence, offering a promising improvement to the simulation of the diurnal cycle of precipitation. Furthermore, to overcome the black box issue of the ML methods, insights derived from the ML model are discussed, which may be leveraged to improve traditional CAPE‐based triggers.
Remediating the Adverse Effects of Treated Wastewater Irrigation by Repeated On‐Surface Surfactant Application
Authors: Ogunmokun Felix A. , Wallach Rony
Published: May 2021

The use of treated wastewater (TWW) has gained recognition as an alternative source for freshwater irrigation, and is steadily expanding worldwide. Despite the benefits of freshwater conservation and nutrient richness, there is mounting evidence of TWW adverse effects on soil, yield, and the environment. Irrigation using TWW has resulted in soil water repellency, in which preferential flow pathways and uneven soil water and chemical distribution occur. These increase deep water percolation and chemical leaching, which can lead to soil and groundwater pollution. This study was conducted in a commercial citrus orchard grown on sandy‐loam soil in central Israel and irrigated with TWW, with the aim of investigating the remediation of these adverse effects, by repeatedly spraying a nonionic surfactant on the soil surface. The surfactant application succeeded to turn the soil wettable, diminishing the preferential flow pathways, and rendering the soil water and dissolved chemicals uniformly distributed. The overall water content in the 0–40 cm layer increased, and deep percolation and chemical leaching substantially decreased. The grapefruit yield increase during the two‐year study period increased the water use efficiency. Electrical resistance tomography scans executed during and after irrigation events for two subsequent years revealed that a “soil memory” phenomenon has been developed for water repellent soils, where water flow takes place through previously developed preferential flow pathways in such soils. This study demonstrates that recurrent surfactant application enables a continuous use of TWW, while eliminating most of its prejudicial effects.
Disentangling the Effects of Vapor Pressure Deficit and Soil Water Availability on Canopy Conductance in a Seasonal Tropical Forest During the 2015 El Niño Drought
Authors: Fang Yilin , Leung L. Ruby , Wolfe Brett T , Detto Matteo , Knox Ryan G , McDowell Nate G , Grossiord Charlotte , Xu Chonggang , Christoffersen Bradley O , Gentine Pierre , Koven Charles D , Chambers Jeffrey Q
Published: May 2021

Water deficit in the atmosphere and soil are two key interactive factors that constrain transpiration and vegetation productivity. It is not clear which of these two factors is more important for the water and carbon flux response to drought stress in ecosystems. In this study, field data and numerical modeling were used to isolate their impact on evapotranspiration (ET) and gross primary productivity (GPP) at a tropical forest site in Barro Colorado Island (BCI), Panama, focusing on their response to the drought induced by the El Niño event of 2015–2016. Numerical simulations were performed using a plant hydrodynamic scheme (HYDRO) and a heuristic approach that ignores stomatal sensitivity to leaf water potential in the Energy Exascale Earth System Model (E3SM) Land Model (ELM). The sensitivity of canopy conductance (Gs) to vapor pressure deficit (VPD) obtained from eddy‐covariance fluxes and measured sap flux shows that, at both ecosystem and plant scale, soil water stress is more important in limiting Gs than VPD at BCI during the El Niño event. The model simulations confirmed the importance of water stress limitation on Gs, but overestimated the VPD impact on Gs compared to that estimated from the observations. We also found that the predicted soil moisture is less sensitive to the diversity of plant hydraulic traits than ET and GPP. During the dry season at BCI, seasonal ET, especially soil evaporation at VPD > 0.42 kPa, simulated using HYDRO and ELM, were too strong and will require alternative parameterizations.
Targeting autocrine amphiregulin robustly and reproducibly inhibits ovarian cancer in a syngeneic model: roles for wildtype p53
Authors: Lindzen Moshit , Ghosh Soma , Noronha Ashish , Drago Diana , Nataraj Nishanth Belugali , Leitner Orith , Carvalho Silvia , Zmora Einav , Sapoznik Stav , Shany Keren Bahar , Levanon Keren , Aderka Dan , Ramírez Belinda Sánchez , Dahlhoff Maik , McNeish Iain , Yarden Yosef
Published: May 2021

Ovarian cancer (OvCA) remains one of the most devastating malignancies, but treatment options are still limited. We report that amphiregulin (AREG) can serve as an effective and safe pharmacological target in a syngeneic murine model. AREG is highly abundant in abdominal fluids of patients with advanced OvCa. In immunocompetent animals, depletion or overexpression of AREG respectively prolonged or shortened animal survival. A new antibody we generated in AREG-knockout mice recognized murine AREG and reproducibly prolonged animal survival in the syngeneic model. The underlying mechanism likely involves binding of wildtype p53 to AREG’s promoter and autocrine activation of the epidermal growth factor receptor (EGFR), a step blocked by the antibody. Accordingly, depletion of p53 downregulated AREG secretion and conferred tolerance, whereas blocking an adaptive process involving CXCL1, which transactivates EGFR, might increase therapeutic efficacy. Consistent with these observations, analysis of OvCa patients revealed that high AREG correlates with poor prognosis of patients expressing wildtype TP53. In conclusion, clinical tests of the novel antibody are warranted; high AREG, normal TP53, and reduced CXCL1 activity might identify patients with OvCa who may derive therapeutic benefit.
Chlorine disinfection facilitates natural transformation through ROS-mediated oxidative stress
Authors: Zhang Shuai , Wang Yue , Lu Ji , Yu Zhigang , Song Hailiang , Bond Philip L , Guo Jianhua
Published: May 2021

The bacterial infection that involves antimicrobial resistance is a rising global threat to public health. Chlorine-based water disinfection processes can inactivate antibiotic resistant bacteria. However, at the same time, these processes may cause the release of antibiotic resistance genes into the water as free DNA, and consequently increase the risk to disseminate antibiotic resistance via natural transformation. Presently, little is known about the contribution of residual chlorine affecting the transformation of extracellular antibiotic resistance genes (ARGs). This study investigates whether chloramine and free chlorine promote the transformation of ARGs and how this may occur. We reveal that both chloramine and free chlorine, at practically relevant concentrations, significantly stimulated the transformation of plasmid-encoded ARGs by the recipient Acinetobacter baylyi ADP1, by up to a 10-fold increase. The underlying mechanisms underpinning the increased transformations were revealed. Disinfectant exposure induced a series of cell responses, including increased levels of reactive oxygen species (ROS), bacterial membrane damage, ROS-mediated DNA damage, and increased stress response. These effects thus culminated in the enhanced transformation of ARGs. This promoted transformation was observed when exposing disinfectant-pretreated A. baylyi to free plasmid. In contrast, after pretreating free plasmid with disinfectants, the transformation of ARGs decreased due to the damage of plasmid integrity. These findings provide important insight on the roles of disinfectants affecting the horizontal transfer of ARGs, which could be crucial in the management of antibiotic resistance in our water systems.
PP2Acα promotes macrophage accumulation and activation to exacerbate tubular cell death and kidney fibrosis through activating Rap1 and TNFα production
Authors: Liang Yan , Sun Xiaoli , Wang Mingjie , Lu Qingmiao , Gu Mengru , Zhou Lu , Hou Qing , Tan Mengzhu , Wang Sudan , Xue Xian , Dai Chunsun
Published: May 2021

Macrophage accumulation and activation play an essential role in kidney fibrosis; however, the underlying mechanisms remain to be explored. By analyzing the kidney tissues from patients and animal models with kidney fibrosis, we found a large induction of PP2Acα in macrophages. We then generated a mouse model with inducible macrophage ablation of PP2Acα. The knockouts developed less renal fibrosis, macrophage accumulation, or tubular cell death after unilateral ureter obstruction or ischemic reperfusion injury compared to control littermates. In cultured macrophages, PP2Acα deficiency resulted in decreased cell motility by inhibiting Rap1 activity. Moreover, co-culture of PP2Acα−/−macrophages with tubular cells resulted in less tubular cell death attributed to downregulated Stat6-mediated tumor necrosis factor α (TNFα) production in macrophages. Together, this study demonstrates that PP2Acα promotes macrophage accumulation and activation, hence accelerates tubular cell death and kidney fibrosis through regulating Rap1 activation and TNFα production.
Depleting long noncoding RNA HOTAIR attenuates chronic myelocytic leukemia progression by binding to DNA methyltransferase 1 and inhibiting PTEN gene promoter methylation
Authors: Song Haiping , Chen Lijuan , Liu Wei , Xu Xiaoli , Zhou Yongming , Zhu Jianhua , Chen Xuexing , Li Ziping , Zhou Hao
Published: May 2021

Long noncoding RNAs (lncRNAs) are known to play a key role in chronic myelocytic leukemia (CML) development, and we aimed to identify the involvement of the lncRNA HOX antisense intergenic RNA (HOTAIR) in CML via binding to DNA methyltransferase 1 (DNMT1) to accelerate methylation of the phosphatase and tensin homolog (PTEN) gene promoter. Bone marrow samples from CML patients and normal bone marrow samples from healthy controls were collected. HOTAIR, DNMT1, DNMT3A, DNMT3B, and PTEN expression was detected. The biological characteristics of CML cells were detected. The relationship among HOTAIR, DNMT1, and PTEN was verified. Tumor volume and weight in mice injected with CML cells were tested. We found that HOTAIR and DNMT1 expression was increased and PTEN expression was decreased in CML. We also investigated whether downregulated HOTAIR or DNMT1 reduced proliferation, colony formation, invasion, and migration and increased the apoptosis rate of CML cells. Moreover, we tested whether low expression of HOTAIR or DNMT1 reduced the volume and weight of tumors in mice with CML. Collectively, the results of this studied showed that depleted HOTAIR demonstrated reduced binding to DNMT1 to suppress CML progression, which may be related to methylation of the PTEN promoter.
Hypoxia-induced miR-210 modulates the inflammatory response and fibrosis upon acute ischemia
Authors: Zaccagnini Germana , Greco Simona , Longo Marialucia , Maimone Biagina , Voellenkle Christine , Fuschi Paola , Carrara Matteo , Creo Pasquale , Maselli Davide , Tirone Mario , Mazzone Massimiliano , Gaetano Carlo , Spinetti Gaia , Martelli Fabio
Published: May 2021

Hypoxia-induced miR-210 is a crucial component of the tissue response to ischemia, stimulating angiogenesis and improving tissue regeneration. Previous analysis of miR-210 impact on the transcriptome in a mouse model of hindlimb ischemia showed that miR-210 regulated not only vascular regeneration functions, but also inflammation. To investigate this event, doxycycline-inducible miR-210 transgenic mice (Tg-210) and anti-miR-210 LNA-oligonucleotides were used. It was found that global miR-210 expression decreased inflammatory cells density and macrophages accumulation in the ischemic tissue. To dissect the underpinning cell mechanisms, Tg-210 mice were used in bone marrow (BM) transplantation experiments and chimeric mice underwent hindlimb ischemia. MiR-210 overexpression in the ischemic tissue was sufficient to increase capillary density and tissue repair, and to reduce inflammation in the presence of Wt-BM infiltrating cells. Conversely, when Tg-210-BM cells migrated in a Wt ischemic tissue, dysfunctional angiogenesis, inflammation, and impaired tissue repair, accompanied by fibrosis were observed. The fibrotic regions were positive for α-SMA, Vimentin, and Collagen V fibrotic markers and for phospho-Smad3, highlighting the activation of TGF-β1 pathway. Identification of Tg-210 cells by in situ hybridization showed that BM-derived cells contributed directly to fibrotic areas, where macrophages co-expressing fibrotic markers were observed. Cell cultures of Tg-210 BM-derived macrophages exhibited a pro-fibrotic phenotype and were enriched with myofibroblast-like cells, which expressed canonical fibrosis markers. Interestingly, inhibitors of TGF-β type-1-receptor completely abrogated this pro-fibrotic phenotype. In conclusion, a context-dependent regulation by miR-210 of the inflammatory response was identified. miR-210 expression in infiltrating macrophages is associated to improved angiogenesis and tissue repair when the ischemic recipient tissue also expresses high levels of miR-210. Conversely, when infiltrating an ischemic tissue with mismatched miR-210 levels, macrophages expressing high miR-210 levels display a pro-fibrotic phenotype, leading to impaired tissue repair, fibrosis, and dysfunctional angiogenesis.
Histone modifications centric-regulation in osteogenic differentiation
Authors: Li Kun , Han Jinxiang , Wang Ziqiang
Published: May 2021

Histone modification critically contributes to the epigenetic control of gene expression by changing the configuration of chromatin and modifying the access of transcription factors to gene promoters. Recently, we observed that histone acetylation and crotonylation mediated the expression of endocytosis-related genes and tumor-related immune checkpoint genes by regulating the enrichment of signal transducer and activator of transcription 3 on these gene promoters in Alzheimer’s disease and tumorigenesis, suggesting that histone modification plays an important role in disease development. Furthermore, studies performed in the past decade revealed that histone modifications affect osteogenic differentiation by regulating the expression of osteogenic marker genes. In this review, we summarize and discuss the histone modification-centric regulation of osteogenic gene expression. This review improves the understanding of the role of histone modifications in osteogenic differentiation and describes its potential as a therapeutic target for osteogenic differentiation-related diseases.
Estimation of coalescence probabilities and population divergence times from SNP data
Authors: Mualim Kristy , Theunert Christoph , Slatkin Montgomery
Published: May 2021

We present a method called the G(A|B) method for estimating coalescence probabilities within population lineages from genome sequences when one individual is sampled from each population. Population divergence times can be estimated from these coalescence probabilities if additional assumptions about the history of population sizes are made. Our method is based on a method presented by Rasmussen et al. (2014) to test whether an archaic genome is from a population directly ancestral to a present-day population. The G(A|B) method does not require distinguishing ancestral from derived alleles or assumptions about demographic history before population divergence. We discuss the relationship of our method to two similar methods, one introduced by Green et al. (2010) and called the F(A|B) method and the other introduced by Schlebusch et al. (2017) and called the TT method. When our method is applied to individuals from three or more populations, it provides a test of whether the population history is treelike because coalescence probabilities are additive on a tree. We illustrate the use of our method by applying it to three high-coverage archaic genomes, two Neanderthals (Vindija and Altai) and a Denisovan.
Brassinosteroids suppress ethylene-induced fruitlet abscission through LcBZR1/2-mediated transcriptional repression of LcACS1/4 and LcACO2/3 in litchi
Authors: Ma Xingshuai , Yuan Ye , Li Caiqin , Wu Qian , He Zidi , Li Jianguo , Zhao Minglei
Published: May 2021

Abscission in plants is tightly controlled by multiple phytohormones and the expression of various genes. However, whether the plant hormone brassinosteroids (BRs) are involved in this process is largely unknown. Here, we found that exogenous application of BRs reduced the ethylene-induced fruitlet abscission of litchi due to lower ethylene (ET) production and suppressed the expression of the ethylene biosynthetic genes LcACS1/4 and LcACO2/3 in the fruitlet abscission zone (FAZ). Two genes that encode the BR core signaling components brassinazole resistant (BZR) proteins, namely, LcBZR1 and LcBZR2, were characterized. LcBZR1/2 were localized to the nucleus and acted as transcription repressors. Interestingly, the LcBZR1/2 transcript levels were not changed during ET-induced fruitlet abscission, while their expression levels were significantly increased after BR application. Moreover, gel shift and transient expression assays indicated that LcBZR1/2 could suppress the transcription of LcACS1/4 and LcACO2/3 by specifically binding to their promoters. Importantly, ectopic expression of LcBZR1/2 in Arabidopsis significantly delayed floral organ abscission and suppressed ethylene biosynthesis. Collectively, our results suggest that BRs suppress ET-induced fruitlet abscission through LcBZR1/2-controlled expression of genes related to ethylene biosynthesis in litchi. In addition, similar results were observed in the Arabidopsis gain-of-function mutant bzr1-1D, which showed delayed floral organ abscission in parallel with lower expression of ACS/ACO genes and reduced ethylene production, suggesting that the mechanism of BZR-controlled organ abscission via regulation of ethylene biosynthesis might be conserved in Arabidopsis.
FKBP52 overexpression accelerates hippocampal-dependent memory impairments in a tau transgenic mouse model
Authors: Criado-Marrero Marangelie , Gebru Niat T. , Gould Lauren A. , Blazier Danielle M. , Vidal-Aguiar Yamile , Smith Taylor M. , Abdelmaboud Salma S. , Shelton Lindsey B. , Wang Xinming , Dahrendorff Jan , Beaulieu-Abdelahad David , Dickey Chad A. , Blair Laura J.
Published: May 2021

Abnormal accumulation of hyperphosphorylated tau induces pathogenesis in neurodegenerative diseases, like Alzheimer’s disease. Molecular chaperones with peptidyl-prolyl cis/trans isomerase (PPIase) activity are known to regulate these processes. Previously, in vitro studies have shown that the 52 kDa FK506-binding protein (FKBP52) interacts with tau inducing its oligomerization and fibril formation to promote toxicity. Thus, we hypothesized that increased expression of FKBP52 in the brains of tau transgenic mice would alter tau phosphorylation and neurofibrillary tangle formation ultimately leading to memory impairments. To test this, tau transgenic (rTg4510) and wild-type mice received bilateral hippocampal injections of virus overexpressing FKBP52 or GFP control. We examined hippocampal-dependent memory, synaptic plasticity, tau phosphorylation status, and neuronal health. This work revealed that rTg4510 mice overexpressing FKBP52 had impaired spatial learning, accompanied by long-term potentiation deficits and hippocampal neuronal loss, which was associated with a modest increase in total caspase 12. Together with previous studies, our findings suggest that FKBP52 may sensitize neurons to tau-mediated dysfunction via activation of a caspase-dependent pathway, contributing to memory and learning impairments.
Alternative splicing during mammalian organ development
Authors: Mazin Pavel V. , Khaitovich Philipp , Cardoso-Moreira Margarida , Kaessmann Henrik
Published: May 2021

Alternative splicing (AS) is pervasive in mammalian genomes, yet cross-species comparisons have been largely restricted to adult tissues and the functionality of most AS events remains unclear. We assessed AS patterns across pre- and postnatal development of seven organs in six mammals and a bird. Our analyses revealed that developmentally dynamic AS events, which are especially prevalent in the brain, are substantially more conserved than nondynamic ones. Cassette exons with increasing inclusion frequencies during development show the strongest signals of conserved and regulated AS. Newly emerged cassette exons are typically incorporated late in testis development, but those retained during evolution are predominantly brain specific. Our work suggests that an intricate interplay of programs controlling gene expression levels and AS is fundamental to organ development, especially for the brain and heart. In these regulatory networks, AS affords substantial functional diversification of genes through the generation of tissue- and time-specific isoforms from broadly expressed genes.
Author Correction: Comparing the visual outcome, visual quality, and satisfaction among three types of multi-focal intraocular lenses
Authors: Paik Dong Won , Park Jun Sang , Yang Chan Min , Lim Dong Hui , Chung Tae‑Young
Published: May 2021

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
Preoperative prediction of perineural invasion with multi-modality radiomics in rectal cancer
Authors: Guo Yu , Wang Quan , Guo Yan , Zhang Yiying , Fu Yu , Zhang Huimao
Published: May 2021

Perineural invasion (PNI) as a grossly underreported independent risk predictor in rectal cancer is hard to identify preoperatively. We aim to predict PNI status in rectal cancer using multi-modality radiomics. In total, 396 radiomics features were extracted from T2-weighted images (T2WIs), diffusion-weighted images (DWIs), and portal venous phase of contrast-enhanced CT (CE-CT) respectively of 94 consecutive patients with histologically confirmed rectal cancer. T2WI score, DWI score, and CT score were calculated via the radiomics features selection and optimization. Discrimination, calibration, and clinical benefit ability were used to evaluate the performance of the radiomics scores in both training and testing datasets. CT score and T2WI score were independent risk predictors [CT score, OR (95% CI) = 4.218 (1.070–16.620); T2WI score, OR (95% CI) = 105.721 (3.091–3615.790)]. The concise score which combined CT score and T2WI score, showed the best performance [training dataset, AUC (95% CI) = 0.906 (0.833–0.979); testing dataset, AUC (95% CI) = 0.884 (0.761–1.000)] and good calibration (P > 0.05 in the Hosmer–Lemeshow test for the training and testing datasets). Decision curve analysis showed that the multi-modality radiomics nomogram had a higher clinical net benefit. The multi-modality radiomics score could be used to preoperatively assess PNI status in rectal cancer.
Cell-free synthetic biochemistry upgrading of ethanol to 1,3 butanediol
Authors: Liu Hongjiang , Bowie James U.
Published: May 2021

It is now possible to efficiently fix flue gas CO/CO2 into ethanol using acetogens, thereby making carbon negative ethanol. While the ethanol could be burned as a fuel, returning the CO2 to the atmosphere, it might also be possible to use the fixed carbon in more diverse chemicals, thereby keeping it fixed. Here we describe a simple synthetic biochemistry approach for converting carbon negative ethanol into the synthetic building block chemical 1,3 butanediol (1,3-BDO). The pathway completely conserves carbon from ethanol and can ultimately be powered electrochemically via formate oxidation. Our proof-of-principle system reached a maximum productivity of 0.16 g/L/h and, with replenishment of feedstock and enzymes, achieved a titer of 7.7 g/L. We identify a number of elements that can be addressed in future work to improve both cell-free and cell-based production of 1,3-BDO.
A novel, complex systems approach to modelling risk of psychological distress in young adolescents
Authors: Beaudequin Denise , Schwenn Paul , McLoughlin Larisa T. , Parker Marcella , Boyes Amanda , Simcock Gabrielle , Lagopoulos Jim , Hermens Daniel F.
Published: May 2021

Adolescence is a period of significant anatomical and functional brain changes, and complex interactions occur between mental health risk factors. The Longitudinal Adolescent Brain Study commenced in 2018, to monitor environmental and psychosocial factors influencing mental health in 500 adolescents, for 5 years. Participants are recruited at age 12 from the community in Australia’s Sunshine Coast region. In this baseline, cross-sectional study of N = 64 participants, we draw on the network perspective, conceptualising mental disorders as causal systems of interacting entities, to propose a Bayesian network (BN) model of lifestyle and psychosocial variables influencing chances of individuals being psychologically well or experiencing psychological distress. Sensitivity analysis of network priors revealed that psychological distress (Kessler-10) was most affected by eating behaviour. Unhealthy eating increased the chance of moderate psychological distress by 600%. Low social connectedness increased the chance of severe psychological disorder by 200%. Certainty for psychological wellness required 33% decrease in unhealthy eating behaviours, 11% decrease in low social connectedness, and 9% reduction in less physical activity. BN can augment clinician judgement in mental disorders as probabilistic decision support systems. The full potential of BN methodology in a complex systems approach to psychopathology has yet to be realised.
Author Correction: Feeding efficiency gains can increase the greenhouse gas mitigation potential of the Tanzanian dairy sector
Authors: Hawkins James , Yesuf Gabriel , Zijlstra Mink , Schoneveld George C. , Rufino Mariana C.
Published: May 2021

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
Publisher Correction: Simultaneous, efficient and continuous oil–water separation via antagonistically functionalized membranes prepared by atmospheric‑pressure cold plasma
Authors: Kim Dong‑hyun , Mauchauffé Rodolphe , Kim Jongwoon , Moon Se Youn
Published: May 2021

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
Computer extracted gland features from H&E predicts prostate cancer recurrence comparably to a genomic companion diagnostic test: a large multi-site study
Authors: Leo Patrick , Janowczyk Andrew , Elliott Robin , Janaki Nafiseh , Bera Kaustav , Shiradkar Rakesh , Farré Xavier , Fu Pingfu , El-Fahmawi Ayah , Shahait Mohammed , Kim Jessica , Lee David , Yamoah Kosj , Rebbeck Timothy R. , Khani Francesca , Robinson Brian D. , Eklund Lauri , Jambor Ivan , Merisaari Harri , Ettala Otto , Taimen Pekka , Aronen Hannu J. , Boström Peter J. , Tewari Ashutosh , Magi-Galluzzi Cristina , Klein Eric , Purysko Andrei , NC Shih Natalie , Feldman Michael , Gupta Sanjay , Lal Priti , Madabhushi Anant
Published: May 2021

Existing tools for post-radical prostatectomy (RP) prostate cancer biochemical recurrence (BCR) prognosis rely on human pathologist-derived parameters such as tumor grade, with the resulting inter-reviewer variability. Genomic companion diagnostic tests such as Decipher tend to be tissue destructive, expensive, and not routinely available in most centers. We present a tissue non-destructive method for automated BCR prognosis, termed "Histotyping", that employs computational image analysis of morphologic patterns of prostate tissue from a single, routinely acquired hematoxylin and eosin slide. Patients from two institutions (n = 214) were used to train Histotyping for identifying high-risk patients based on six features of glandular morphology extracted from RP specimens. Histotyping was validated for post-RP BCR prognosis on a separate set of n = 675 patients from five institutions and compared against Decipher on n = 167 patients. Histotyping was prognostic of BCR in the validation set (p < 0.001, univariable hazard ratio [HR] = 2.83, 95% confidence interval [CI]: 2.03–3.93, concordance index [c-index] = 0.68, median years-to-BCR: 1.7). Histotyping was also prognostic in clinically stratified subsets, such as patients with Gleason grade group 3 (HR = 4.09) and negative surgical margins (HR = 3.26). Histotyping was prognostic independent of grade group, margin status, pathological stage, and preoperative prostate-specific antigen (PSA) (multivariable p < 0.001, HR = 2.09, 95% CI: 1.40–3.10, n = 648). The combination of Histotyping, grade group, and preoperative PSA outperformed Decipher (c-index = 0.75 vs. 0.70, n = 167). These results suggest that a prognostic classifier for prostate cancer based on digital images could serve as an alternative or complement to molecular-based companion diagnostic tests.
Pleckstrin-2 is essential for erythropoiesis in β-thalassemic mice, reducing apoptosis and enhancing enucleation
Authors: Feola Maria , Zamperone Andrea , Moskop Daniel , Chen Huiyong , Casu Carla , Lama Dechen , Di Martino Julie , Djedaini Mansour , Papa Luena , Martinez Marc Ruiz , Choesang Tenzin , Bravo-Cordero Jose Javier , MacKay Matthew , Zumbo Paul , Brinkman Nathan , Abrams Charles S. , Rivella Stefano , Hattangadi Shilpa , Mason Christopher E. , Hoffman Ronald , Ji Peng , Follenzi Antonia , Ginzburg Yelena Z.
Published: May 2021

Erythropoiesis involves complex interrelated molecular signals influencing cell survival, differentiation, and enucleation. Diseases associated with ineffective erythropoiesis, such as β-thalassemias, exhibit erythroid expansion and defective enucleation. Clear mechanistic determinants of what make erythropoiesis effective are lacking. We previously demonstrated that exogenous transferrin ameliorates ineffective erythropoiesis in β-thalassemic mice. In the current work, we utilize transferrin treatment to elucidate a molecular signature of ineffective erythropoiesis in β-thalassemia. We hypothesize that compensatory mechanisms are required in β-thalassemic erythropoiesis to prevent apoptosis and enhance enucleation. We identify pleckstrin-2—a STAT5-dependent lipid binding protein downstream of erythropoietin—as an important regulatory node. We demonstrate that partial loss of pleckstrin-2 leads to worsening ineffective erythropoiesis and pleckstrin-2 knockout leads to embryonic lethality in β-thalassemic mice. In addition, the membrane-associated active form of pleckstrin-2 occurs at an earlier stage during β-thalassemic erythropoiesis. Furthermore, membrane-associated activated pleckstrin-2 decreases cofilin mitochondrial localization in β-thalassemic erythroblasts and pleckstrin-2 knockdown in vitro induces cofilin-mediated apoptosis in β-thalassemic erythroblasts. Lastly, pleckstrin-2 enhances enucleation by interacting with and activating RacGTPases in β-thalassemic erythroblasts. This data elucidates the important compensatory role of pleckstrin-2 in β-thalassemia and provides support for the development of targeted therapeutics in diseases of ineffective erythropoiesis.
Tuning the load of gold and magnetic nanoparticles in nanogels through their design for enhanced dual magneto-photo-thermia
Authors: Cazares-Cortes Esther , Wilhelm Claire , Perez Jose Efrain , Espinosa Ana , Casale Sandra , Michel Aude , Abou-Hassan Ali , Ménager Christine
Published: May 2021

A thiol-epoxy click chemistry reaction is used to introduce thiol groups on magnetic nanogels for the attachment of Au nanorods.
Chemistry self-efficacy in lower-division chemistry courses: changes after a semester of instruction and gaps still remain between student groups
Authors: Moreno Candido , Pham Duyen , Ye Li
Published: May 2021

Chemistry self-efficacy (CSE) was identified as a critical affective construct to predict student success in chemistry classrooms. We surveyed students at the beginning and toward the end of a semester to measure students’ CSE beliefs in introductory and general chemistry courses at a Hispanic-serving institution in the United States. First, the relationships between CSE (initial and toward the end) and student achievement measured by course GPA were examined. Second, trends of changes in student CSE beliefs over a semester in relation to several aspects of student characteristics including course level, gender, underrepresented minority (URM) status were investigated. Lastly, the gaps in specific areas of CSE still remain between student groups after a semester of instruction were revealed. The results showed that CSE toward the end of the semester significantly predicted students’ course GPA in lower-division chemistry courses. Even though the CSE of different student groups all increased to some extent after a semester of instruction, the levels of changes were influenced significantly by certain factors such as course level and URM status but not gender. While URM students' CSE beliefs increased more than non-URM students after a semester of instruction, there were still gaps in certain areas between the two student groups. The remaining gaps in CSE beliefs between URM and non-URM students were found to be in the areas of interpreting chemical equations and choosing appropriate formulas to solve chemistry problems. Meanwhile, students who completed introductory chemistry still lagged behind in interpreting chemical equations as compared to students who completed general chemistry. Research literature related to these two specific areas in CSE with gaps between student groups was reviewed, instructional strategies and research directions along with theoretical perspectives for closing those equity gaps in college lower-division chemistry classrooms are discussed.
Amine-functionalized carbon-fiber microelectrodes for enhanced ATP detection with fast-scan cyclic voltammetry
Authors: Li Yuxin , Weese Moriah E. , Cryan Michael T. , Ross Ashley E.
Published: May 2021

Amine functionalized carbon-fiber microelectrodes significantly improve direct adenosine triphosphate (ATP) detection with fast-scan cyclic voltammetry (FSCV).
Confocal Raman microspectral analysis and imaging of the drug response of osteosarcoma to cisplatin
Authors: Wang Haifeng , Li Jing , Qin Jie , Li Jie , Chen Yishen , Song Dongliang , Zeng Haishan , Wang Shuang
Published: May 2021

Confocal Raman microspectral analysis and imaging were used to elucidate the drug response of osteosarcoma (OS) to cisplatin.
Chemical fuel-driven transient polymeric micelle nanoreactors toward reversible trapping and reaction acceleration
Authors: Lang Xianhua , Thumu Udayabhaskararao , Yuan Ling , Zheng Chengrui , Zhang Huajun , He Lirong , Zhao Hui , Zhao Changsheng
Published: May 2021

Chemical fuels tune the assembly and dissipative processes of polymeric micelle nanoreactors to overcome product inhibition issues.
A high-nuclearity CuI/CuII nanocluster catalyst for phenol degradation
Authors: Liu Li-Juan , Zhang Jiang-Wei , Asad Muhammad , Wang Zhao-Yang , Zang Shuang-Quan , Mak Thomas C. W.
Published: May 2021

A high-nuclearity CuI/CuII nanocluster catalyst for phenol degradation.
Direct and selective metal-free N6-arylation of adenosine residues for simple fluorescence labeling of DNA and RNA
Authors: Ravi Kumara Guralamatta Siddappa , Pandith Anup , Seo Young Jun
Published: May 2021

We have developed an unprecedented transition metal–free approach for the direct fluorescence turn-on labeling of natural oligonucleotides through selective N6-arylation of adenosine moieties.
A new series of 3D lanthanide phenoxycarboxylates: synthesis, crystal structure, magnetism and photoluminescence studies
Authors: Sen Rupam , Paul Sanchayeeta , Sarkar Alolika , Botas Alexandre M. P. , Carneiro Neto Albano N. , Brandão Paula , Lopes Armandina M. L. , Ferreira Rute A. S. , Araújo João P. , Lin Zhi
Published: May 2021

A new series of 3D Ln-carboxylates was synthesized, where the Tb one shows antiferromagnetic coupling and the Dy one shows ferromagnetic interaction, and with emission spectra combining the intra-4f emission of the Ln ions and that of the ligand.
Facile and green synthesis of decatungstate-based nickel(ii) complex coated onto modified Fe3O4 nanoparticles with enhanced antimicrobial activity against antibiotic-resistant bacteria
Authors: Xing Cuili , Ma Pengtao , Zhao Meng , Chang Jiangnan , Guo Xiaoyuan , Sun Lin , Li Mingxue
Published: May 2021

A nanostructured Fe3O4@PDA@Ni-DT composite was successfully prepared with high-efficiency antibacterial properties and excellent recyclable performance.
A novel shift in the glass transition temperature of polymer nanocomposites: a molecular dynamics simulation study
Authors: Khan Raja Azhar Ashraaf , Chen Xian , Qi Hang-Kai , Huang Jian-Hua , Luo Meng-Bo
Published: May 2021

A novel shift in the glass transition temperature of polymer nanocomposites with the loading of nanoparticles. The attraction of nanoparticles increases, whereas the fast diffusion of nanoparticles decreases, the glass transition temperature.
On the association of frustrated Lewis pairs in ionic liquids: a molecular dynamics simulation study
Authors: Liu Xiaoqing , Wang Xiaojing , Li Yao , Yu Tianhao , Zhao Weizhen , Liu Lei
Published: May 2021

MD simulations reveal that the population of effective FLP structures has been increased by taking ionic liquids as solvents.