bluuebunny/crossref_metadata_2025 huggingface dataset:
Effects of the mGlu2/3 receptor agonist LY379268 on two models of disturbed auditory evoked brain oscillations in mice
Authors: Dormann Oana-Daniela , Schuelert Niklas , Rosenbrock Holger
Published: May 2023

Cognitive impairment is a core feature of schizophrenia and is poorly addressed by currently available medication. This is partly because the underlying circuits are insufficiently understood, and available animal models for brain dysfunction do not adequately mimic human pathology. To improve the translatability of animal studies and complement behavioral data, EEG measurements are being increasingly used in preclinical research. Brain oscillations are similar across species and can be impaired via several means. In this study, we used two approaches to impair early sensory processing and cortical oscillations in mice: a pharmacological model targeting NMDA receptor function in the whole brain via systemic MK-801 application and an optogenetic model targeting parvalbumin-positive (PV+) interneurons locally in the medial prefrontal cortex (mPFC). We evoked brain activity using auditory stimulation, a tool with high translatability from mouse to human. We then investigated the effect of LY379268, an agonist of mGlu2/3 receptors, a potential therapeutic target for schizophrenia, on single neuron and EEG responses. LY379268 was able to rescue MK-801-induced deficits for a variety of clinically relevant early sensory EEG biomarkers. Single neuron recordings revealed a strong effect of LY379268 on the signal-to-noise ratio during auditory stimulation and optogenetic inhibition of PV+ interneurons. Our results contribute to a better understanding of how group II metabotropic glutamate receptors modulate neuronal population and network activity under sensory stimulation while challenged pharmacologically or optogenetically.
Overexpression of EphB6 and EphrinB2 controls soma spacing of cortical neurons in a mutual inhibitory way
Authors: He Chun-Hui , Song Ning-Ning , Xie Pin-Xi , Wang Yu-Bing , Chen Jia-Yin , Huang Ying , Hu Ling , Li Zhao , Su Jun-Hui , Zhang Xiao-Qing , Zhang Lei , Ding Yu-Qiang
Published: May 2023

To establish functional circuitry, neurons settle down in a particular spatial domain by spacing their cell bodies, which requires proper positioning of the soma and establishing of a zone with unique connections. Deficits in this process are implicated in neurodevelopmental diseases. In this study, we examined the function of EphB6 in the development of cerebral cortex. Overexpression of EphB6 via in utero electroporation results in clumping of cortical neurons, while reducing its expression has no effect. In addition, overexpression of EphrinB2, a ligand of EphB6, also induces soma clumping in the cortex. Unexpectedly, the soma clumping phenotypes disappear when both of them are overexpressed in cortical neurons. The mutual inhibitory effect of EphB6/ EphrinB2 on preventing soma clumping is likely to be achieved via interaction of their specific domains. Thus, our results reveal a combinational role of EphrinB2/EphB6 overexpression in controlling soma spacing in cortical development.
Silencing Notch4 promotes tumorigenesis and inhibits metastasis of triple-negative breast cancer via Nanog and Cdc42
Authors: Tian Yuan , Zhang Peipei , Mou Yajun , Yang Wenxiu , Zhang Junhong , Li Qing , Dou Xiaowei
Published: May 2023

Elucidation of individual Notch protein biology in specific cancer is crucial to develop safe, effective, and tumor-selective Notch-targeting therapeutic reagents for clinical use [1]. Here, we explored the Notch4 function in triple-negative breast cancer (TNBC). We found that silencing Notch4 enhanced tumorigenic ability in TNBC cells via upregulating Nanog expression, a pluripotency factor of embryonic stem cells. Intriguingly, silencing Notch4 in TNBC cells suppressed metastasis via downregulating Cdc42 expression, a key molecular for cell polarity formation. Notably, downregulation of Cdc42 expression affected Vimentin distribution, but not Vimentin expression to inhibit EMT shift. Collectively, our results show that silencing Notch4 enhances tumorigenesis and inhibits metastasis in TNBC, indicating that targeting Notch4 may not be a potential strategy for drug discovery in TNBC.
Type I interferon response in astrocytes promotes brain metastasis by enhancing monocytic myeloid cell recruitment
Authors: Ma Weili , Oliveira-Nunes Maria Cecília , Xu Ke , Kossenkov Andrew , Reiner Benjamin C. , Crist Richard C. , Hayden James , Chen Qing
Published: May 2023

Cancer metastasis to the brain is a significant clinical problem. Metastasis is the consequence of favorable interactions between invaded cancer cells and the microenvironment. Here, we demonstrate that cancer-activated astrocytes create a sustained low-level activated type I interferon (IFN) microenvironment in brain metastatic lesions. We further confirm that the IFN response in astrocytes facilitates brain metastasis. Mechanistically, IFN signaling in astrocytes activates C-C Motif Chemokine Ligand 2 (CCL2) production, which further increases the recruitment of monocytic myeloid cells. The correlation between CCL2 and monocytic myeloid cells is confirmed in clinical brain metastasis samples. Lastly, genetically or pharmacologically inhibiting C-C Motif Chemokine Receptor 2 (CCR2) reduces brain metastases. Our study clarifies a pro-metastatic effect of type I IFN in the brain even though IFN response has been considered to have anti-tumor effects. Moreover, this work expands our understandings on the interactions between cancer-activated astrocytes and immune cells in brain metastasis.
Mapping PTBP2 binding in human brain identifies SYNGAP1 as a target for therapeutic splice switching
Authors: Dawicki-McKenna Jennine M. , Felix Alex J. , Waxman Elisa A. , Cheng Congsheng , Amado Defne A. , Ranum Paul T. , Bogush Alexey , Dungan Lea V. , Maguire Jean Ann , Gagne Alyssa L. , Heller Elizabeth A. , French Deborah L. , Davidson Beverly L. , Prosser Benjamin L.
Published: May 2023

Alternative splicing of neuronal genes is controlled partly by the coordinated action of polypyrimidine tract binding proteins (PTBPs). While PTBP1 is ubiquitously expressed, PTBP2 is predominantly neuronal. Here, we define the PTBP2 footprint in the human transcriptome using brain tissue and human induced pluripotent stem cell-derived neurons (iPSC-neurons). We map PTBP2 binding sites, characterize PTBP2-dependent alternative splicing events, and identify novel PTBP2 targets including SYNGAP1, a synaptic gene whose loss-of-function leads to a complex neurodevelopmental disorder. We find that PTBP2 binding to SYNGAP1 mRNA promotes alternative splicing and nonsense-mediated decay, and that antisense oligonucleotides (ASOs) that disrupt PTBP binding redirect splicing and increase SYNGAP1 mRNA and protein expression. In SYNGAP1 haploinsufficient iPSC-neurons generated from two patients, we show that PTBP2-targeting ASOs partially restore SYNGAP1 expression. Our data comprehensively map PTBP2-dependent alternative splicing in human neurons and cerebral cortex, guiding development of novel therapeutic tools to benefit neurodevelopmental disorders.
Exploring spatial feedbacks between adaptation policies and internal migration patterns due to sea-level rise
Authors: Reimann Lena , Jones Bryan , Bieker Nora , Wolff Claudia , Aerts Jeroen C.J.H. , Vafeidis Athanasios T.
Published: May 2023

Climate change-induced sea-level rise will lead to an increase in internal migration, whose intensity and spatial patterns will depend on the amount of sea-level rise; future socioeconomic development; and adaptation strategies pursued to reduce exposure and vulnerability to sea-level rise. To explore spatial feedbacks between these drivers, we combine sea-level rise projections, socioeconomic projections, and assumptions on adaptation policies in a spatially-explicit model (‘CONCLUDE’). Using the Mediterranean region as a case study, we find up to 20 million sea-level rise-related internal migrants by 2100 if no adaptation policies are implemented, with approximately three times higher migration in southern and eastern Mediterranean countries compared to northern Mediterranean countries. We show that adaptation policies can reduce the number of internal migrants by a factor of 1.4 to 9, depending on the type of strategies pursued; the implementation of hard protection measures may even lead to migration towards protected coastlines. Overall, spatial migration patterns are robust across all scenarios, with out-migration from a narrow coastal strip and in-migration widely spread across urban settings. However, the type of migration (e.g. proactive/reactive, managed/autonomous) depends on future socioeconomic developments that drive adaptive capacity, calling for decision-making that goes well beyond coastal issues.
Roles of adenine methylation in the physiology of Lacticaseibacillus paracasei
Authors: Zhao Jie , Zhang Meng , Hui Wenyan , Zhang Yue , Wang Jing , Wang Shaojing , Kwok Lai-Yu , Kong Jian , Zhang Heping , Zhang Wenyi
Published: May 2023

Lacticaseibacillus paracasei is an economically important bacterial species, used in the food industry and as a probiotic. Here, we investigate the roles of N6-methyladenine (6mA) modification in L. paracasei using multi-omics and high-throughput chromosome conformation capture (Hi-C) analyses. The distribution of 6mA-modified sites varies across the genomes of 28 strains, and appears to be enriched near genes involved in carbohydrate metabolism. A pglX mutant, defective in 6mA modification, shows transcriptomic alterations but only modest changes in growth and genomic spatial organization.
Large-scale control of the retroflection of the Labrador Current
Authors: Jutras Mathilde , Dufour Carolina O. , Mucci Alfonso , Talbot Lauryn C.
Published: May 2023

The Labrador Current transports cold, relatively fresh, and well-oxygenated waters within the subpolar North Atlantic and towards the eastern American continental shelf. The relative contribution of these waters to either region depends on the eastward retroflection of the Labrador Current at the Grand Banks of Newfoundland. Here, we develop a retroflection index based on the pathway of virtual Lagrangian particles and show that strong retroflection generally occurs when a large-scale circulation adjustment, related to the subpolar gyre, accelerates the Labrador Current and shifts the Gulf Stream northward, partly driven by a northward shift of the wind patterns in the western North Atlantic. Starting in 2008, a particularly strong northward shift of the Gulf Stream dominates the other drivers. A mechanistic understanding of the drivers of the Labrador Current retroflection should help predict changes in the water properties in both export regions, and anticipate their impacts on marine life and deep-water formation.
Improving de novo protein binder design with deep learning
Authors: Bennett Nathaniel R. , Coventry Brian , Goreshnik Inna , Huang Buwei , Allen Aza , Vafeados Dionne , Peng Ying Po , Dauparas Justas , Baek Minkyung , Stewart Lance , DiMaio Frank , De Munck Steven , Savvides Savvas N. , Baker David
Published: May 2023

Recently it has become possible to de novo design high affinity protein binding proteins from target structural information alone. There is, however, considerable room for improvement as the overall design success rate is low. Here, we explore the augmentation of energy-based protein binder design using deep learning. We find that using AlphaFold2 or RoseTTAFold to assess the probability that a designed sequence adopts the designed monomer structure, and the probability that this structure binds the target as designed, increases design success rates nearly 10-fold. We find further that sequence design using ProteinMPNN rather than Rosetta considerably increases computational efficiency.
Broad phosphorylation mediated by testis-specific serine/threonine kinases contributes to spermiogenesis and male fertility
Authors: Zhang Xuedi , Peng Ju , Wu Menghua , Sun Angyang , Wu Xiangyu , Zheng Jie , Shi Wangfei , Gao Guanjun
Published: May 2023

Genetic studies elucidate a link between testis-specific serine/threonine kinases (TSSKs) and male infertility in mammals, but the underlying mechanisms are unclear. Here, we identify a TSSK homolog inDrosophila, CG14305 (termed dTSSK), whose mutation impairs the histone-to-protamine transition during spermiogenesis and causes multiple phenotypic defects in nuclear shaping, DNA condensation, and flagellar organization in spermatids. Genetic analysis demonstrates that kinase catalytic activity of dTSSK, which is functionally conserved with human TSSKs, is essential for male fertility. Phosphoproteomics identify 828 phosphopeptides/449 proteins as potential substrates of dTSSK enriched primarily in microtubule-based processes, flagellar organization and mobility, and spermatid differentiation and development, suggesting that dTSSK phosphorylates various proteins to orchestrate postmeiotic spermiogenesis. Among them, the two substrates, protamine-like protein Mst77F/Ser9and transition protein Mst33A/Ser237, are biochemically validated to be phosphorylated by dTSSK in vitro, and are genetically demonstrated to be involved in spermiogenesis in vivo. Collectively, our findings demonstrate that broad phosphorylation mediated by TSSKs plays an indispensable role in spermiogenesis.
Evaluation of multigene assays as predictors for response to neoadjuvant chemotherapy in early-stage breast cancer patients
Authors: Freeman Jincong Q. , Shubeck Sarah , Howard Frederick M. , Chen Nan , Nanda Rita , Huo Dezheng
Published: May 2023

OncotypeDX and MammaPrint assays have not been validated to predict pathologic complete response (pCR) to neoadjuvant chemotherapy (NACT) in early-stage breast cancer patients. We analyzed the 2010–2019 National Cancer Database and found that high OncotypeDX recurrence scores or high MammaPrint scores were associated with greater odds of pCR. Our findings suggest that OncotypeDX and MammaPrint testing predict pCR after NACT and could facilitate clinical decision-making between clinicians and patients.
A dual-process model for cognitive training
Authors: Ericson Julia , Klingberg Torkel
Published: May 2023

A key goal in cognitive training research is understanding whether cognitive training enhances general cognitive capacity or provides only task-specific improvements. Here, we developed a quantitative model for describing the temporal dynamics of these two processes. We analyzed data from 1300 children enrolled in an 8 week working memory training program that included 5 transfer test sessions. Factor analyses suggested two separate processes: an early task-specific improvement, accounting for 44% of the total increase, and a slower capacity improvement. A hidden Markov model was then applied to individual training data, revealing that the task-specific improvement plateaued on the third day of training on average. Thus, training is not only task specific or transferable but a combination of the two. The models provide methods for quantifying and separating these processes, which is crucial for studying the effects of cognitive training and relating these effects to neural correlates.
Generalising uncertainty improves accuracy and safety of deep learning analytics applied to oncology
Authors: MacDonald Samual , Foley Helena , Yap Melvyn , Johnston Rebecca L. , Steven Kaiah , Koufariotis Lambros T. , Sharma Sowmya , Wood Scott , Addala Venkateswar , Pearson John V. , Roosta Fred , Waddell Nicola , Kondrashova Olga , Trzaskowski Maciej
Published: May 2023

Uncertainty estimation is crucial for understanding the reliability of deep learning (DL) predictions, and critical for deploying DL in the clinic. Differences between training and production datasets can lead to incorrect predictions with underestimated uncertainty. To investigate this pitfall, we benchmarked one pointwise and three approximate Bayesian DL models for predicting cancer of unknown primary, using three RNA-seq datasets with 10,968 samples across 57 cancer types. Our results highlight that simple and scalable Bayesian DL significantly improves the generalisation of uncertainty estimation. Moreover, we designed a prototypical metric—the area between development and production curve (ADP), which evaluates the accuracy loss when deploying models from development to production. Using ADP, we demonstrate that Bayesian DL improves accuracy under data distributional shifts when utilising ‘uncertainty thresholding’. In summary, Bayesian DL is a promising approach for generalising uncertainty, improving performance, transparency, and safety of DL models for deployment in the real world.
A water cooled, high power, dielectric barrier discharge reactor for CO2 plasma dissociation and valorization studies
Authors: Lisi Nicola , Pasqual Laverdura Umberto , Chierchia Rosa , Luisetto Igor , Stendardo Stefano
Published: May 2023

Aiming at the energy efficient use and valorization of carbon dioxide in the framework of decarbonization studies and hydrogen research, a novel dielectric barrier discharge (DBD) reactor has been designed, constructed and developed. This test rig with water cooled electrodes is capable of a plasma power tunable in a wide range from 20W to 2 kW per unit. The reactor was designed to be ready for catalysts and membrane integration aiming at a broad range plasma conditions and processes, including low to moderate high pressures (0.05–2 bar). In this paper, preliminary studies on the highly endothermic dissociation of CO2, into O2 and CO, in a pure, inert, and noble gas mixture flow are presented. These initial experiments were performed in a geometry with a 3 mm plasma gap in a chamber volume of 40cm3, where the process pressure was varied from few 200 mbar to 1 bar, using pure CO2, and diluted in N2. Initial results confirmed the well-known trade-off between conversion rate (up to 60%) and energy efficiency (up to 35%) into the dissociation products, as measured downstream of the reactor system. Improving conversion rate, energy efficiency and the trade-off curve can be further accomplished by tuning the plasma operating parameters (e.g. the gas flow and system geometry). It was found that the combination of a high-power, water-cooled plasma reactor, together with electronic and waveform diagnostic, optical emission and mass spectroscopies provides a convenient experimental framework for studies on the chemical storage of fast electric power transients and surges.
Blood spinal cord barrier disruption recovers in patients with degenerative cervical myelopathy after surgical decompression: a prospective cohort study
Authors: Schmidt Tobias Philip , Jütten Kerstin , Bertram Ulf , Brandenburg Lars Ove , Pufe Thomas , Delev Daniel , Gombert Alexander , Mueller Christian Andreas , Clusmann Hans , Blume Christian
Published: May 2023

The pathophysiology of degenerative cervical myelopathy (DCM) is characterized by chronic compression-induced damage to the spinal cord leading to secondary harm such as disruption of the blood spinal cord barrier (BSCB). It is therefore the purpose of this study to analyze BSCB disruption in pre- and postoperative DCM patients and to correlate those with the clinical status and postoperative outcome. This prospectively controlled cohort included 50 DCM patients (21 female; 29 male; mean age: 62.9 ± 11.2 years). As neurological healthy controls, 52 (17 female; 35 male; mean age 61.8 ± 17.3 years) patients with thoracic abdominal aortic aneurysm (TAAA) and indication for open surgery were included. All patients underwent a neurological examination and DCM-associated scores (Neck Disability Index, modified Japanese Orthopaedic Association Score) were assessed. To evaluate the BSCB status, blood and cerebrospinal fluid (CSF) samples (lumbar puncture or CSF drainage) were taken preoperatively and in 15 DCM patients postoperatively (4 female; 11 male; mean age: 64.7 ± 11.1 years). Regarding BSCB disruption, CSF and blood serum were examined for albumin, immunoglobulin (Ig) G, IgA and IgM. Quotients for CSF/serum were standardized and calculated according to Reiber diagnostic criteria. Significantly increased preoperative CSF/serum quotients were found in DCM patients as compared to control patients: AlbuminQ (p < .001), IgAQ (p < .001) and IgGQ (p < .001). IgMQ showed no significant difference (T = − 1.15, p = .255). After surgical decompression, neurological symptoms improved in DCM patients, as shown by a significantly higher postoperative mJOA compared to the preoperative score (p = .001). This neurological improvement was accompanied by a significant change in postoperative CSF/serum quotients for Albumin (p = .005) and IgG (p = .004) with a trend of a weak correlation between CSF markers and neurological recovery. This study further substantiates the previous findings, that a BSCB disruption in DCM patients is evident. Interestingly, surgical decompression appears to be accompanied by neurological improvement and a reduction of CSF/serum quotients, implying a BSCB recovery. We found a weak association between BSCB recovery and neurological improvement. A BSCB disruption might be a key pathomechanism in DCM patients, which could be relevant to treatment and clinical recovery.
Historic evolution of population exposure to heatwaves in Xinjiang Uygur Autonomous Region, China
Authors: Dong Diwen , Tao Hui , Zhang Zengxin
Published: May 2023

Heatwaves have pronounced impacts on human health and the environment on a global scale. Although the characteristics of heatwaves has been well documented, there still remains a lack of dynamic studies of population exposure to heatwaves (PEH), particularly in the arid regions. In this study, we analyzed the spatio-temporal evolution characteristics of heatwaves and PEH in Xinjiang using the daily maximum temperature (Tmax), relative humidity (RH), and high-resolution gridded population datasets. The results revealed that the heatwaves in Xinjiang occur more continually and intensely from 1961 to 2020. Furthermore, there is substantial spatial heterogeneity of heatwaves with eastern part of the Tarim Basin, Turpan, and Hami been the most prone areas. The PEH in Xinjiang showed an increasing trend with high areas mainly in Kashgar, Aksu, Turpan, and Hotan. The increase in PEH is mainly contributed from population growth, climate change and their interaction. From 2001 to 2020, the climate effect contribution decreased by 8.5%, the contribution rate of population and interaction effects increased by 3.3% and 5.2%, respectively. This work provides a scientific basis for the development of policies to improve the resilience against hazards in arid regions.
Improved anticancer efficacy of methyl pyropheophorbide-a–incorporated solid lipid nanoparticles in photodynamic therapy
Authors: Yeo Sooho , Lee Tae Heon , Kim Min Je , Shim Young Key , Yoon Il , Song Young Kyu , Lee Woo Kyoung
Published: May 2023

Photodynamic therapy (PDT) is a promising anticancer treatment because it is patient-friendly and non-invasive. Methyl pyropheophorbide-a (MPPa), one of the chlorin class photosensitizers, is a drug with poor aqueous solubility. The purpose of this study was to synthesize MPPa and develop MPPa-loaded solid lipid nanoparticles (SLNs) with improved solubility and PDT efficacy. The synthesized MPPa was confirmed 1H nuclear magnetic resonance (1H-NMR) spectroscopy and UV–Vis spectroscopy. MPPa was encapsulated in SLN via a hot homogenization with sonication. Particle characterization was performed using particle size and zeta potential measurements. The pharmacological effect of MPPa was evaluated using the 1,3-diphenylisobenzofuran (DPBF) assay and anti-cancer effect against HeLa and A549 cell lines. The particle size and zeta potential ranged from 231.37 to 424.07 nm and − 17.37 to − 24.20 mV, respectively. MPPa showed sustained release from MPPa-loaded SLNs. All formulations improved the photostability of MPPa. The DPBF assay showed that SLNs enhanced the 1O2 generation from MPPa. In the photocytotoxicity analysis, MPPa-loaded SLNs demonstrated cytotoxicity upon photoirradiation but not in the dark. The PDT efficacy of MPPa improved following its entrapment in SLNs. This observation suggests that MPPa-loaded SLNs are suitable for the enhanced permeability and retention effect. Together, these results demonstrate that the developed MPPa-loaded SLNs are promising candidates for cancer treatment using PDT.
Identification of sequence mutations in Phytophthora cactorum genome associated with mefenoxam resistance and development of a molecular assay for the mutant detection in strawberry (F. × ananassa)
Authors: Marin Marcus V. , Baggio Juliana S. , Oh Youngjae , Han Hyeondae , Chandra Saket , Wang Nan-Yi , Lee Seonghee , Peres Natalia A.
Published: May 2023

Phytophthora crown rot (PhCR) caused by Phytophthora cactorum is one of the most damaging diseases of strawberry worldwide. Mefenoxam is one of the major fungicides currently used to manage PhCR. However, the emergence and spread of resistant isolates have made controlling the pathogen in the field problematic. In the present study, using whole genome sequencing analysis, mutations associated with mefenoxam-resistant isolates were identified in six different genomic regions of P. cactorum. The 95.54% reads from a sensitive isolate pool and 95.65% from a resistant isolate pool were mapped to the reference genome of P. cactorum P414. Four point mutations were in coding regions while the other two were in noncoding regions. The genes harboring mutations were functionally unknown. All mutations present in resistant isolates were confirmed by sanger sequencing of PCR products. For the rapid diagnostic assay, SNP-based high-resolution melting (HRM) markers were developed to differentiate mefenoxam-resistant P. cactorum from sensitive isolates. The HRM markers R3-1F/R3-1R and R2-1F/R2-1R were suitable to differentiate both sensitive and resistant profiles using clean and crude DNA extraction. None of the mutations associated with mefenoxam resistance found in this study were in the RNA polymerase subunit genes, the hypothesized target of this compound in oomycetes. Our findings may contribute to a better understanding of the mechanisms of resistance of mefenoxam in oomycetes since serves as a foundation to validate the candidate genes as well as contribute to the monitoring of P. cactorum populations for the sustainable use of this product.
Transfer and transformation characteristics of Zn and Cd in soil-rotation plant (Brassica napus L and Oryza sativa L) system and its influencing factors
Authors: Yan Qiuxiao , Fang Hui , Wang Daoping , Xiao Xuefeng , Deng Tingfei , Li Xiangying , Wei Fuxiao , Liu Jiming , Lin Changhu
Published: May 2023

Rice–rape rotation is a widely practiced cropping system in China. However, changes in soil properties and management could change the bioavailability of Cd, In order to explore the occurrence state, transportation and transformation characteristics of heavy metals Cd and Zn in rice-rape rotation system in Guizhou karst area with high background value of Cd. In the karst rice–rape rotation area, the physical and chemical properties of soil, chemical specifications and activities of Cd and Zn at different soil depths and during various crop growth stages, and the bioaccumulation of Cd and Zn in different tissues of rice and rape were studied by field experiment and laboratory analysis. The bioaccumulation of Cd and Zn and the effects of physical and chemical soil properties on the activities and bioavailabilities of Cd and Zn during rice–rape rotation were explored. The findings revealed that soil particle size, composition, pH, redox potential, soil organic matter, and Cd and Zn contents varied dramatically, especially in deep soils. The physical and chemical properties of the deep and surface soils were significantly related to the bioaccumulation of Cd and Zn. Cd and Zn are activated during crop rotation. Cd was easier to be enriched in rice, while Zn was easier to be enriched in rape. The correlation between Cd and Zn contents in Brassica campestris L and their enrichment abilities were not significant, but that in Oryza sativa L were significant. During rice-rape rotation, the chemical speciations and activities of Cd and Zn changed with the changes of soil properties and waterlogging environment. This study had important basic guiding significance for the evaluation, prevention and control of heavy metal pollution, and improving soil quality in different rotation systems in karst areas, and was conducive to promoting the safe production of rape and rice.
Fickian yet non-Gaussian diffusion of a quasi-2D colloidal system in an optical speckle field: experiment and simulations
Authors: Ciarlo Antonio , Pastore Raffaele , Greco Francesco , Sasso Antonio , Pesce Giuseppe
Published: May 2023

We investigate a quasi-2D suspension of Brownian particles in an optical speckle field produced by holographic manipulation of a laser wavefront. This system was developed to study, in a systematic and controllable way, a distinctive instance of diffusion, called Fickian yet Non Gaussian diffusion (FnGD), observed, during the last decade, for colloidal particles in a variety of complex and biological fluids. Our setup generates an optical speckle field that behaves like a disordered set of optical traps. First, we describe the experimental setup and the dynamics of the particles, focusing on mean square displacements, displacement distributions and kurtosis. Then, we present Brownian Dynamics simulations of point-like particles in a complex energy landscape, mimicking that generated by the optical speckle field. We show that our simulations can capture the salient features of the experimental results, including the emergence of FnGD, also covering times longer than the ones so far achieved in experiments. Some deviations are observed at long time only, with the Gaussian restoring being slower in simulations than in experiments. Overall, the introduced numerical model might be exploited to guide the design of upcoming experiments targeted, for example, to fully monitor the recovery of Gaussianity.
Mitochondrial citrate metabolism and efflux regulate BeWo differentiation
Authors: Mahr Renee M. , Jena Snehalata , Nashif Sereen K. , Nelson Alisa B. , Rauckhorst Adam J. , Rome Ferrol I. , Sheldon Ryan D. , Hughey Curtis C. , Puchalska Patrycja , Gearhart Micah D. , Taylor Eric B. , Crawford Peter A. , Wernimont Sarah A.
Published: May 2023

Cytotrophoblasts fuse to form and renew syncytiotrophoblasts necessary to maintain placental health throughout gestation. During cytotrophoblast to syncytiotrophoblast differentiation, cells undergo regulated metabolic and transcriptional reprogramming. Mitochondria play a critical role in differentiation events in cellular systems, thus we hypothesized that mitochondrial metabolism played a central role in trophoblast differentiation. In this work, we employed static and stable isotope tracing untargeted metabolomics methods along with gene expression and histone acetylation studies in an established BeWo cell culture model of trophoblast differentiation. Differentiation was associated with increased abundance of the TCA cycle intermediates citrate and α-ketoglutarate. Citrate was preferentially exported from mitochondria in the undifferentiated state but was retained to a larger extent within mitochondria upon differentiation. Correspondingly, differentiation was associated with decreased expression of the mitochondrial citrate transporter (CIC). CRISPR/Cas9 disruption of the mitochondrial citrate carrier showed that CIC is required for biochemical differentiation of trophoblasts. Loss of CIC resulted in broad alterations in gene expression and histone acetylation. These gene expression changes were partially rescued through acetate supplementation. Taken together, these results highlight a central role for mitochondrial citrate metabolism in orchestrating histone acetylation and gene expression during trophoblast differentiation.
Explainable semi-supervised deep learning shows that dementia is associated with small, avocado-shaped clocks with irregularly placed hands
Authors: Bandyopadhyay Sabyasachi , Wittmayer Jack , Libon David J. , Tighe Patrick , Price Catherine , Rashidi Parisa
Published: May 2023

The clock drawing test is a simple and inexpensive method to screen for cognitive frailties, including dementia. In this study, we used the relevance factor variational autoencoder (RF-VAE), a deep generative neural network, to represent digitized clock drawings from multiple institutions using an optimal number of disentangled latent factors. The model identified unique constructional features of clock drawings in a completely unsupervised manner. These factors were examined by domain experts to be novel and not extensively examined in prior research. The features were informative, as they distinguished dementia from non-dementia patients with an area under receiver operating characteristic (AUC) of 0.86 singly, and 0.96 when combined with participants’ demographics. The correlation network of the features depicted the “typical dementia clock” as having a small size, a non-circular or“avocado-like”shape, and incorrectly placed hands. In summary, we report a RF-VAE network whose latent space encoded novel constructional features of clocks that classify dementia from non-dementia patients with high performance.
Innovative solid desiccant dehumidification using distributed microwaves
Authors: Ybyraiymkul Doskhan , Chen Qian , Burhan Muhammad , Akhtar Faheem Hassan , AlRowais Raid , Shahzad Muhammad Wakil , Ja M. Kum , Ng Kim Choon
Published: May 2023

Dehumidification is one of the key challenges facing the air conditioning (AC) industry in the treatment of moist air. Over many decades, the dual role of heat exchangers of AC chillers for the sensible and latent cooling of space has hindered the thermal-lift reduction in the refrigeration cycle due to the requirements of water vapor removal at dew-point and heat rejection to the ambient air. These practical constraints of AC chillers have resulted in the leveling of energy efficiency of mechanical vapor compressors (MVC) for many decades. One promising approach to energy efficiency improvement is the decoupling of dehumidification from sensible processes so that innovative but separate processes can be applied. In this paper, an advanced microwave dehumidification method is investigated in the laboratory, where the microwave (2.45 GHz) energy can be irradiated onto the dipole structure of water vapor molecules, desorbing rapidly from the pores of adsorbent. Results show a significant improvement in performance for microwave dehumidification, up to fourfold, as compared to data available in the literature.
The difference in the cellular uptake of tocopherol and tocotrienol is influenced by their affinities to albumin
Authors: Nakatomi Takashi , Itaya-Takahashi Mayuko , Horikoshi Yosuke , Shimizu Naoki , Parida Isabella Supardi , Jutanom Mirinthorn , Eitsuka Takahiro , Tanaka Yoshikazu , Zingg Jean-Marc , Matsura Tatsuya , Nakagawa Kiyotaka
Published: May 2023

Vitamin E is classified into tocopherol (Toc) and tocotrienol (T3) based on its side chains. T3 generally has higher cellular uptake than Toc, though the responsible mechanism remains unclear. To elucidate this mechanism, we hypothesized and investigated whether serum albumin is a factor that induces such a difference in the cellular uptake of Toc and T3. Adding bovine serum albumin (BSA) to serum-depleted media increased the cellular uptake of T3 and decreased that of Toc, with varying degrees among α-, β-, γ-, and δ-analogs. Such enhanced uptake of α-T3 was not observed when cells were incubated under low temperature (the uptake of α-Toc was also reduced), suggesting that Toc and T3 bind to albumin to form a complex that results in differential cellular uptake of vitamin E. Fluorescence quenching study confirmed that vitamin E certainly bound to BSA, and that T3 showed a higher affinity than Toc. Molecular docking further indicated that the differential binding energy of Toc or T3 to BSA is due to the Van der Waals interactions via their side chain. Overall, these results suggested that the affinity of Toc and T3 to albumin differs due to their side chains, causing the difference in their albumin-mediated cellular uptake. Our results give a better mechanistic insight into the physiological action of vitamin E.
Numerical analysis of predatory potentiality of Toxorhynchites splendens against larval Aedes albopictus in laboratory and semi-field conditions
Authors: Malla Rajesh Kumar , Mandal Koushik Kumar , Burman Sunanda , Das Shubhaisi , Ghosh Anupam , Chandra Goutam
Published: May 2023

Larvae of the elephant mosquitoes, Toxorhynchites spp. (Diptera: Culicidae) are predacious on larvae of other mosquito species and some small aquatic organisms; this predatory behavior can be applied in (mosquito) vector control. The present study examined the feeding behavior of Toxorhynchites splendens on Aedes albopictus in relation to search area [volume of water (X1)] and prey density (X2), prey instars, predatory preference and larvae's functional response on variable prey densities. Experiments were conducted to determine changes in the feeding activity of T. splendens with different search areas and showed that rate of prey consumption was inversely proportional to the search area as evidenced by a negative value of X1 in the regression equation and positively related to prey density. The non-linear polynomial logistic regression estimated a significant linear parameter (P1 < 0) for the functional response analysis suggesting a Type II functional response. Differences in feeding response related to the different combinations of prey instars were statistically not significant (p > 0.05), expressing that all the instars of prey were equally susceptible to the predator. Toxorhynchites splendens preferred to consume Ae. albopictus larvae rather than Tubifex when supplied together as a food source.
Prenatal DEHP exposure predicts neurological disorders via transgenerational epigenetics
Authors: Tran Mita T. M. T. , Kuo Fu-Chen , Low Jie-Ting , Chuang Yu-Ming , Sultana Sofia , Huang Wen-Long , Lin Zhe-Young , Lin Guan-Ling , Wu Chia-Fang , Li Sih-Syuan , Suen Jau-Ling , Hung Chih-Hsing , Wu Ming-Tsang , Chan Michael W. Y.
Published: May 2023

Recent experimental and observational research has suggested that childhood allergic asthma and other conditions may be the result of prenatal exposure to environmental contaminants, such as di-(2-ethylhexyl) phthalate (DEHP). In a previous epidemiological study, we found that ancestral exposure (F0 generation) to endocrine disruptors or the common plasticizer DEHP promoted allergic airway inflammation via transgenerational transmission in mice from generation F1 to F4. In the current study, we employed a MethylationEPIC Beadchip microarray to examine global DNA methylation in the human placenta as a function of maternal exposure to DEHP during pregnancy. Interestingly, global DNA hypomethylation was observed in placental DNA following exposure to DEHP at high concentrations. Bioinformatic analysis confirmed that DNA methylation affected genes related to neurological disorders, such as autism and dementia. These results suggest that maternal exposure to DEHP may predispose offspring to neurological diseases. Given the small sample size in this study, the potential role of DNA methylation as a biomarker to assess the risk of these diseases deserves further investigation.
Human sperm cooperate to transit highly viscous regions on the competitive pathway to fertilization
Authors: Xiao Sa , Riordon Jason , Lagunov Alex , Ghaffarzadeh Mahta , Hannam Thomas , Nosrati Reza , Sinton David
Published: May 2023

Human sperm compete for fertilization. Here, we find that human sperm, unexpectedly, cooperate under conditions mimicking the viscosity contrasts in the female reproductive tract. Sperm attach at the head region to migrate as a cooperative group upon transit into and through a high viscosity medium (15-100 cP) from low viscosity seminal fluid. Sperm groups benefit from higher swimming velocity, exceeding that of individual sperm by over 50%. We find that sperm associated with a group possess high DNA integrity (7% fragmentation index) – a stark contrast to individual sperm exhibiting low DNA integrity (> 50% fragmentation index) – and feature membrane decapacitation factors that mediate sperm attachment to form the group. Cooperative behaviour becomes less prevalent upon capacitation and groups tend to disband as the surrounding viscosity reduces. When sperm from different male sources are present, related sperm preferentially form groups and achieve greater swimming velocity, while unrelated sperm are slowed by their involvement in a group. These findings reveal cooperation as a selective mode of human sperm motion – sperm with high DNA integrity cooperate to transit the highly viscous regions in the female tract and outcompete rival sperm for fertilization – and provide insight into cooperation-based sperm selection strategies for assisted reproduction.
Interplay between alpha and theta band activity enables management of perception-action representations for goal-directed behavior
Authors: Wendiggensen Paul , Prochnow Astrid , Pscherer Charlotte , Münchau Alexander , Frings Christian , Beste Christian
Published: May 2023

Goal-directed behavior requires integrated mental representations of perceptions and actions. The neurophysiological underpinnings of these processes, however, are not yet understood. It is particularly undetermined, which oscillatory activities in which brain regions are involved in the management of perception-action representations. We examine this question with a focus on response inhibition processes and show that the dynamics of perception-action representations reflected in theta band activity (TBA) are particularly evident in the supplementary motor area and the occipito-temporal cortex. Mental representations coded in alpha band activity (ABA) during perception-action integration are associated with the occipito-temporal cortex. Crucially, perception-action representations are exchanged between theta and alpha frequency bands. The results imply that ABA functions as dynamic top-down control over binding, retrieval and reconfiguration processes during response inhibition, which in turn are reflected by TBA. Our study thus highlights how the interplay of oscillatory activity enables the management of perception-action representations for goal-directed behavior.
Dislocation loop bias and void swelling in irradiated α-iron from mesoscale and atomistic simulations
Authors: Yu Ziang , Xu Haixuan
Published: May 2023

Dislocation loops are ubiquitous in irradiated materials, and dislocation loop bias plays a critical role in void swelling. However, due to complicated interactions between dislocation loops and point defects, it is challenging to evaluate the bias factors of dislocation loops. Here, we determine the bias of sessile < 100 > loops in α-iron using a recently developed atomistic approach based on the lifetime of point defects. We establish a mechanistic understanding of the loop interaction based on the diffusion tendency of point defects near the loop core region. Mobile self-interstitial atoms tend to be absorbed from the edge of the loop, and a trapping region perpendicular to the habit plane of the loop exists. The dislocation loop bias is found to be substantially lower than those of straight dislocations in α-iron and should be included in swelling rate estimates. With the obtained sink strength and bias values, agreement is achieved with experimental results for both absolute values and temperature dependence.
Dealloying of Pt1Bi2 intermetallic toward optimization of electrocatalysis on a Bi-continuous nanoporous core–shell structure
Authors: Wang Yacheng , Wang Wubin , Hu Wangyan , Zhang Dongtang , Guo Guangsheng , Wang Xiayan
Published: May 2023

During the process of dealloying, passivation of the particle surface by the migration of precious metals is prevented due to fluctuations on the surface.
Dansyl-triazole-based fluorescent macrocycle for selective detection of nitro-antibiotic drugs and protein interaction
Authors: Thurakkal Liya , Mol K. M. Rakhi , Porel Mintu
Published: May 2023

A novel dansyl-triazole-based fluorescent macrocycle with high Stokes shift and positive solvatochromism has been developed for sensing nitro-containing antibiotics from real water and in paper strips.
Functions and applications of artificial intelligence in droplet microfluidics
Authors: Liu Huan , Nan Lang , Chen Feng , Zhao Yue , Zhao Yongxi
Published: May 2023

This review summarizes the implementations of droplet microfluidics based on AI, including droplet generation, biological analysis, and material synthesis.
Trace doping of cobalt oxide using lanthanum for effective catalytic oxidation of carbon monoxide
Authors: Zhicheng Zhou , Tingting Jiang , Tao Liu , Shourong Zheng
Published: May 2023

Trace doping La into Co3O4 enhanced the catalytic activity and water resistance for CO oxidation significantly.
A three-in-one C60-integrated PEO-based solid polymer electrolyte enables superior all-solid-state lithium–sulfur batteries
Authors: Wei Benben , Huang Shuo , Song Yuhang , Wang Xuan , Liu Min , Jin Hongyun , Cao Guozhong
Published: May 2023

The 0D C60simultaneously improves the ionic conductivity of PEO, suppresses lithium dendrite penetration, and inhibits polysulfide shuttle.
Deformable channel non‐local network for crowd counting
Authors: Zhang Ting , Wang Huake , Zhang Kaibing , Hou Xingsong
Published: May 2023

Both global dependency and local correlation are crucial for solving the scale variation of crowd. However, most of previous methods fail to take two factors into consideration simultaneously. Against the aforementioned issue, a deformable channel non‐local network, abbreviated as DCNLNet for crowd counting, which can simultaneously learn global context information and adaptive local receptive field is proposed. Specifically, the proposed DCNLNet consists of two well‐crafted designed modules: deformable channel non‐local block (DCNL) and spatial attention feature fusion block (SAFF). The DCNL encodes long‐range dependencies between pixels and the adaptive local correlation with channel non‐local and deformable convolution, respectively, benefiting for improving the spatial discrimination of features. While the SAFF aims to aggregate the cross‐level information, which interacts these features from different depths and learns specific weights for the feature maps with spatial attention. Extensive experiments are performed on three crowd counting benchmark datasets and experimental results indicate that the proposed DCNLNet achieves compelling performance compared to other representative counting models.