bluuebunny/crossref_metadata_2025 huggingface dataset:
Development of a highly controlled system for large-area, directional printing of quasi-1D nanomaterials
Authors: Christou Adamos , Liu Fengyuan , Dahiya Ravinder
Published: October 2021

Printing is a promising method for the large-scale, high-throughput, and low-cost fabrication of electronics. Specifically, the contact printing approach shows great potential for realizing high-performance electronics with aligned quasi-1D materials. Despite being known for more than a decade, reports on a precisely controlled system to carry out contact printing are rare and printed nanowires (NWs) suffer from issues such as location-to-location and batch-to-batch variations. To address this problem, we present here a novel design for a tailor-made contact printing system with highly accurate control of printing parameters (applied force: 0–6 N ± 0.3%, sliding velocity: 0–200 mm/s, sliding distance: 0–100 mm) to enable the uniform printing of nanowires (NWs) aligned along 93% of the large printed area (1 cm2). The system employs self-leveling platforms to achieve optimal alignment between substrates, whereas the fully automated process minimizes human-induced variation. The printing dynamics of the developed system are explored on both rigid and flexible substrates. The uniformity in printing is carefully examined by a series of scanning electron microscopy (SEM) images and by fabricating a 5 × 5 array of NW-based photodetectors. This work will pave the way for the future realization of highly uniform, large-area electronics based on printed NWs.
BRD9 inhibition promotes PUMA-dependent apoptosis and augments the effect of imatinib in gastrointestinal stromal tumors
Authors: Mu Jianfeng , Sun Xuezeng , Zhao Zhipeng , Sun Hao , Sun Pengda
Published: October 2021

Gastrointestinal stromal tumors (GISTs) are primarily characterized by activating mutations of tyrosine kinase or platelet-derived growth factor receptor alpha. Although the revolutionary therapeutic outcomes of imatinib are well known, the long-term benefits of imatinib are still unclear. The effects of BRD9, a recently identified subunit of noncanonical BAF complex (ncBAF) chromatin remodeling complexes, in GISTs are not clear. In the current study, we evaluated the functional role of BRD9 in GIST progression. Our findings demonstrated that the expression of BRD9 was upregulated in GIST tissues. The downregulation or inhibition of BRD9 could significantly reduce cellular proliferation, and facilitates apoptosis in GISTs. BRD9 inhibition could promote PUMA-dependent apoptosis in GISTs and enhance imatinib activity in vitro and in vivo. BRD9 inhibition synergizes with imatinib in GISTs by inducing PUMA upregulation. Mechanism study revealed that BRD9 inhibition promotes PUMA induction via the TUFT1/AKT/GSK-3β/p65 axis. Furthermore, imatinib also upregulates PUMA by targeting AKT/GSK-3β/p65 axis. In conclusion, our results indicated that BRD9 plays a key role in the progression of GISTs. Inhibition of BRD9 is a novel therapeutic strategy in GISTs treated alone or in combination with imatinib.
Isolation of a panel of ultra-potent human antibodies neutralizing SARS-CoV-2 and viral variants of concern
Authors: Gorchakov Andrey A. , Kulemzin Sergey V. , Guselnikov Sergey V. , Baranov Konstantin O. , Belovezhets Tatyana N. , Mechetina Ludmila V. , Volkova Olga Yu. , Najakshin Alexander M. , Chikaev Nikolai A. , Chikaev Anton N. , Solodkov Pavel P. , Larichev Victor F. , Gulyaeva Marina A. , Markhaev Alexander G. , Kononova Yulia V. , Alekseyev Alexander Yu. , Shestopalov Alexander M. , Yusubalieva Gaukhar M. , Klypa Tatiana V. , Ivanov Alexander V. , Valuev-Elliston Vladimir T. , Baklaushev Vladimir P. , Taranin Alexander V.
Published: October 2021

In the absence of virus-targeting small-molecule drugs approved for the treatment and prevention of COVID-19, broadening the repertoire of potent SARS-CoV-2-neutralizing antibodies represents an important area of research in response to the ongoing pandemic. Systematic analysis of such antibodies and their combinations can be particularly instrumental for identification of candidates that may prove resistant to the emerging viral escape variants. Here, we isolated a panel of 23 RBD-specific human monoclonal antibodies from the B cells of convalescent patients. A surprisingly large proportion of such antibodies displayed potent virus-neutralizing activity both in vitro and in vivo. Four of the isolated nAbs can be categorized as ultrapotent with an apparent IC100 below 16 ng/mL. We show that individual nAbs as well as dual combinations thereof retain activity against currently circulating SARS-CoV-2 variants of concern (such as B.1.1.7, B.1.351, B.1.617, and C.37), as well as against other viral variants. When used as a prophylactics or therapeutics, these nAbs could potently suppress viral replication and prevent lung pathology in SARS-CoV-2-infected hamsters. Our data contribute to the rational development of oligoclonal therapeutic nAb cocktails mitigating the risk of SARS-CoV-2 escape.
mTOR-related synaptic pathology causes autism spectrum disorder-associated functional hyperconnectivity
Authors: Pagani Marco , Barsotti Noemi , Bertero Alice , Trakoshis Stavros , Ulysse Laura , Locarno Andrea , Miseviciute Ieva , De Felice Alessia , Canella Carola , Supekar Kaustubh , Galbusera Alberto , Menon Vinod , Tonini Raffaella , Deco Gustavo , Lombardo Michael V. , Pasqualetti Massimo , Gozzi Alessandro
Published: October 2021

Postmortem studies have revealed increased density of excitatory synapses in the brains of individuals with autism spectrum disorder (ASD), with a putative link to aberrant mTOR-dependent synaptic pruning. ASD is also characterized by atypical macroscale functional connectivity as measured with resting-state fMRI (rsfMRI). These observations raise the question of whether excess of synapses causes aberrant functional connectivity in ASD. Using rsfMRI, electrophysiology and in silico modelling in Tsc2 haploinsufficient mice, we show that mTOR-dependent increased spine density is associated with ASD -like stereotypies and cortico-striatal hyperconnectivity. These deficits are completely rescued by pharmacological inhibition of mTOR. Notably, we further demonstrate that children with idiopathic ASD exhibit analogous cortical-striatal hyperconnectivity, and document that this connectivity fingerprint is enriched for ASD-dysregulated genes interacting with mTOR or Tsc2. Finally, we show that the identified transcriptomic signature is predominantly expressed in a subset of children with autism, thereby defining a segregable autism subtype. Our findings causally link mTOR-related synaptic pathology to large-scale network aberrations, revealing a unifying multi-scale framework that mechanistically reconciles developmental synaptopathy and functional hyperconnectivity in autism.
Friction modulation in limbless, three-dimensional gaits and heterogeneous terrains
Authors: Zhang Xiaotian , Naughton Noel , Parthasarathy Tejaswin , Gazzola Mattia
Published: October 2021

Motivated by a possible convergence of terrestrial limbless locomotion strategies ultimately determined by interfacial effects, we show how both 3D gait alterations and locomotory adaptations to heterogeneous terrains can be understood through the lens of local friction modulation. Via an effective-friction modeling approach, compounded by 3D simulations, the emergence and disappearance of a range of locomotory behaviors observed in nature is systematically explained in relation to inhabited environments. Our approach also simplifies the treatment of terrain heterogeneity, whereby even solid obstacles may be seen as high friction regions, which we confirm against experiments of snakes ‘diffracting’ while traversing rows of posts, similar to optical waves. We further this optic analogy by illustrating snake refraction, reflection and lens focusing. We use these insights to engineer surface friction patterns and demonstrate passive snake navigation in complex topographies. Overall, our study outlines a unified view that connects active and passive 3D mechanics with heterogeneous interfacial effects to explain a broad set of biological observations, and potentially inspire engineering design.
Regulation of local GTP availability controls RAC1 activity and cell invasion
Authors: Bianchi-Smiraglia Anna , Wolff David W. , Marston Daniel J. , Deng Zhiyong , Han Zhannan , Moparthy Sudha , Wombacher Rebecca M. , Mussell Ashley L. , Shen Shichen , Chen Jialin , Yun Dong-Hyun , O’Brien Cox Anderson , Furdui Cristina M. , Hurley Edward , Feltri Maria Laura , Qu Jun , Hollis Thomas , Kengne Jules Berlin Nde , Fongang Bernard , Sousa Rui J. , Kandel Mikhail E. , Kandel Eugene S. , Hahn Klaus M. , Nikiforov Mikhail A.
Published: October 2021

Physiological changes in GTP levels in live cells have never been considered a regulatory step of RAC1 activation because intracellular GTP concentration (determined by chromatography or mass spectrometry) was shown to be substantially higher than the in vitro RAC1 GTP dissociation constant (RAC1-GTP Kd). Here, by combining genetically encoded GTP biosensors and a RAC1 activity biosensor, we demonstrated that GTP levels fluctuating around RAC1-GTP Kd correlated with changes in RAC1 activity in live cells. Furthermore, RAC1 co-localized in protrusions of invading cells with several guanylate metabolism enzymes, including rate-limiting inosine monophosphate dehydrogenase 2 (IMPDH2), which was partially due to direct RAC1-IMPDH2 interaction. Substitution of endogenous IMPDH2 with IMPDH2 mutants incapable of binding RAC1 did not affect total intracellular GTP levels but suppressed RAC1 activity. Targeting IMPDH2 away from the plasma membrane did not alter total intracellular GTP pools but decreased GTP levels in cell protrusions, RAC1 activity, and cell invasion. These data provide a mechanism of regulation of RAC1 activity by local GTP pools in live cells.
Faecal miRNA profiles associated with age, sex, BMI, and lifestyle habits in healthy individuals
Authors: Francavilla Antonio , Gagliardi Amedeo , Piaggeschi Giulia , Tarallo Sonia , Cordero Francesca , Pensa Ruggero G. , Impeduglia Alessia , Caviglia Gian Paolo , Ribaldone Davide Giuseppe , Gallo Gaetano , Grioni Sara , Ferrero Giulio , Pardini Barbara , Naccarati Alessio
Published: October 2021

For their stability and detectability faecal microRNAs represent promising molecules with potential clinical interest as non-invasive diagnostic and prognostic biomarkers. However, there is no evidence on how stool miRNA profiles change according to an individual’s age, sex, and body mass index (BMI) or how lifestyle habits influence the expression levels of these molecules. We explored the relationship between the stool miRNA levels and common traits (sex, age, BMI, and menopausal status) or lifestyle habits (physical activity, smoking status, coffee, and alcohol consumption) as derived by a self-reported questionnaire, using small RNA-sequencing data of samples from 335 healthy subjects. We detected 151 differentially expressed miRNAs associated with one variable and 52 associated with at least two. Differences in miR-638 levels were associated with age, sex, BMI, and smoking status. The highest number of differentially expressed miRNAs was associated with BMI (n = 92) and smoking status (n = 84), with several miRNAs shared between them. Functional enrichment analyses revealed the involvement of the miRNA target genes in pathways coherent with the analysed variables. Our findings suggest that miRNA profiles in stool may reflect common traits and lifestyle habits and should be considered in relation to disease and association studies based on faecal miRNA expression.
Analysis of the 2016–2018 fluid-injection induced seismicity in the High Agri Valley (Southern Italy) from improved detections using template matching
Authors: Stabile T. A. , Vlček Josef , Wcisło Milosz , Serlenga Vincenzo
Published: October 2021

Improving the capability of seismic network to detect weak seismic events is one of the timeless challenges in seismology: the greater is the number of detected and locatable seismic events, the greater insights on the mechanisms responsible for seismic activation may be gained. Here we implement and apply a single-station template matching algorithm to detect events belonging to the fluid-injection induced seismicity cluster located in the High Agri Valley, Southern Italy, using the continuous seismic data stream of the closest station of the INSIEME network. To take into account the diversity of waveforms, albeit belonging to the same seismic cluster, eight different master templates were adopted. Afterwards, using all the stations of the network, we provide a seismic catalogue consisting of 196 located earthquakes, in the magnitude range − 1.2 ≤ Ml ≤ 1.2, with a completeness magnitudeMc = − 0.5 ± 0.1. This rich seismic catalogue allows us to describe the damage zone of a SW dipping fault, characterized by a variety of fractures critically stressed in the dip range between ~ 45° and ~ 75°. The time-evolution of seismicity clearly shows seismic swarm distribution characteristics with many events of similar magnitude, and the seismicity well correlates with injection operational parameters (i.e. injected volumes and injection pressures).
Climate driven spatiotemporal variations in seabird bycatch hotspots and implications for seabird bycatch mitigation
Authors: Bi Rujia , Jiao Yan , Browder Joan A.
Published: October 2021

Bycatch in fisheries is a major threat to many seabird species. Understanding and predicting spatiotemporal changes in seabird bycatch from fisheries might be the key to mitigation. Inter-annual spatiotemporal patterns are evident in seabird bycatch of the U.S. Atlantic pelagic longline fishery monitored by the National Marine Fisheries Service Pelagic Observer Program (POP) since 1992. A newly developed fast computing Bayesian approximation method provided the opportunity to use POP data to understand spatiotemporal patterns, including temporal changes in location of seabird bycatch hotspots. A Bayesian model was developed to capture the inherent spatiotemporal structure in seabird bycatch and reduce the bias caused by physical barriers such as coastlines. The model was applied to the logbook data to estimate seabird bycatch for each longline set, and the mid-Atlantic bight and northeast coast were the fishing areas with the highest fleet bycatch estimate. Inter-annual changes in predicted bycatch hotspots were correlated with Gulf Stream meanders, suggesting that predictable patterns in Gulf Stream meanders could enable advanced planning of fishing fleet schedules and areas of operation. The greater the Gulf Stream North Wall index, the more northerly the seabird bycatch hotspot two years later. A simulation study suggested that switching fishing fleets from the hindcasted actual bycatch hotspot to neighboring areas and/or different periods could be an efficient strategy to decrease seabird bycatch while largely maintaining fishers’ benefit.
Lactobacillus rhamnosus and Bifidobacterium longum alleviate colitis and cognitive impairment in mice by regulating IFN-γ to IL-10 and TNF-α to IL-10 expression ratios
Authors: Ma Xiaoyang , Shin Yoon-Jung , Jang Hyo-Min , Joo Min-Kyung , Yoo Jong-Wook , Kim Dong-Hyun
Published: October 2021

Gut lactobacilli and bifidobacteria on the immune homeostasis. Therefore, to understand the mechanism in vivo, we selected human fecal Lactobacillus rhamnosus NK210 and Bifidobacterium longum NK219, which strongly suppressed the IFN-γ to IL-10 expression (IIE) ratio in lipopolysaccharide-stimulated macrophages. Thereafter, we examined their effects on the endotoxin, antibiotics, or antitumor drug-stimulated immune imbalance in mice. Intraperitoneal injection of lipopolysaccharide and oral gavage of ampicillin increased IFN-γ and TNF-α expression in the spleen, colon, and hippocampus, while IL-10 expression decreased. However, intraperitoneal injection of cyclophosphamide suppressed IFN-γ, TNF-α, and IL-10 expression. LPS exposure induced splenic natural killer cell cytotoxicity against YAC-1 cells (sNK-C) and peritoneal macrophage phagocytosis against Candida albicans (pMA-P) activities, while cyclophosphamide and ampicillin treatments suppressed sNK-C and pMA-P activities. However, LPS, ampicillin, cyclophosphamide all increased IIE and TNF-α to IL-10 expression (TIE) ratios. Oral administration of NK210 and/or NK219 significantly reduced LPS-induced sNK-C, pMA-P, and IFN-γ expression, while cyclophosphamide- or ampicillin-suppressed sNK-C and pMA-P activities, cyclophosphamide-suppressed IFN-γ, TNF-α, and IL-10 expression, and ampicillin-suppressed IL-10 expression increased. Nevertheless, they suppressed LPS-, ampicillin-, or cyclophosphamide-induced IIE and TIE ratios, cognitive impairment, and gut dysbiosis. In particular, NK219, but not NK210, increased the IIE expression ratio in vitro and in vivo, and enhanced sNK-C and pMA-P activities in normal control mice, while cognitive function and gut microbiota composition were not significantly affected. These findings suggest that NK210, Lactobacillus sp, and NK219, Bifidobacterium additively or synergistically alleviate gut dysbiosis, inflammation, and cognitive impairment with immune imbalance by controlling IIE and TIE ratios.
Ameliorative effect of curcumin and zinc oxide nanoparticles on multiple mechanisms in obese rats with induced type 2 diabetes
Authors: Abdulmalek Shaymaa , Eldala Asmaa , Awad Doaa , Balbaa Mahmoud
Published: October 2021

The present study was carried out to investigate the therapeutic effect of synthesized naturally compounds, curcumin nanoparticles (CurNPs) and metal oxide, zinc oxide nanoparticles (ZnONPs) on a high-fat diet (HFD)/streptozotocin (STZ)-induced hepatic and pancreatic pathophysiology in type 2 diabetes mellitus (T2DM) via measuring AKT pathway and MAPK pathway. T2DM rats were intraperitoneally injected with a low dose of 35 mg/kg STZ after being fed by HFD for 8 weeks. Then the rats have orally received treatments for 6 weeks. HFD/STZ-induced hepatic inflammation, reflected by increased phosphorylation of p38-MAPK pathway’s molecules, was significantly decreased after nanoparticle supplementation. In addition, both nanoparticles significantly alleviated the decreased phosphorylation of AKT pathway. Further, administration of ZnONPs, CurNPs, conventional curcumin, and ZnSO4(zinc sulfate), as well as metformin, effectively counteracted diabetes-induced oxidative stress and inflammation in the internal hepatic and pancreatic tissues. Based on the results of the current study, ZnONPs and CurNPs could be explored as a therapeutic adjuvant against complications associated with T2DM. Both nanoparticles could effectively delay the progression of several complications by activating AKT pathway and down-regulating MAPK pathway. Our findings may provide an experimental basis for the application of nanoparticles in the treatment of T2DM with low toxicity.
Genomic investigations provide insights into the mechanisms of resilience to heterogeneous habitats of the Indian Ocean in a pelagic fish
Authors: Sebastian Wilson , Sukumaran Sandhya , Abdul Azeez S. , Muraleedharan K. R. , Dinesh Kumar P. K. , Zacharia P. U. , Gopalakrishnan A.
Published: October 2021

The adaptive genetic variation in response to heterogeneous habitats of the Indian Ocean was investigated in the Indian oil sardine using ddRAD sequencing to understand the subpopulation structure, stock complexity, mechanisms of resilience, and vulnerability in the face of climate change. Samples were collected from different ecoregions of the Indian ocean and ddRAD sequencing was carried out. Population genetic analyses revealed that samples from the Gulf of Oman significantly diverged from other Indian Ocean samples. SNP allele-environment correlation revealed the presence of candidate loci correlated with the environmental variables like annual sea surface temperature, chlorophyll-a, and dissolved oxygen concentration which might represent genomic regions allegedly diverging as a result of local adaptation. Larval dispersal modelling along the southwest coast of India indicated a high dispersal rate. The two major subpopulations (Gulf of Oman and Indian) need to be managed regionally to ensure the preservation of genetic diversity, which is crucial for climatic resilience.
Risk factors for the development of esophageal candidiasis among patients in community hospital
Authors: Ogiso Hideyuki , Adachi Seiji , Mabuchi Masatoshi , Horibe Yohei , Ohno Tomohiko , Suzuki Yusuke , Yamauchi Osamu , Kojima Takao , Takada Eri , Iwama Midori , Saito Koshiro , Iwashita Takuji , Ibuka Takashi , Yasuda Ichiro , Shimizu Masahito
Published: October 2021

The aim of this study was to clarify risk factors for esophageal candidiasis (EC) in immunocompetent patients in a community hospital. 7736 patients who underwent esophagogastroduodenoscopy at our hospital from April 2012 to July 2018 were enrolled. The relationships between EC and the following factors: age, gender, body mass index, lifestyle, lifestyle-related diseases, medication, and endoscopic findings were analyzed. EC was observed in 184 of 7736 cases (2.4% morbidity rate). Multivariate analysis revealed that significant risk factors for the development of EC were: diabetes mellitus {odds ratio (OR): 1.52}, proton pump inhibitor (PPI) use (OR: 1.69), atrophic gastritis (AG) (OR: 1.60), advanced gastric cancer (OR: 4.66), and gastrectomy (OR: 2.32). When severe EC (Kodsi grade ≥ II) was compared to mild EC (grade I), the most significant risk factors were advanced gastric cancer (OR: 17.6) and gastrectomy (OR: 23.4). When considering the risk of AG and PPI use with EC development, the risk increased as follows: AG (OR: 1.59), PPI use (OR: 2.25), and both (OR: 3.13). PPI use, AG, advanced gastric cancer and post-gastrectomy are critical risk factors for the development of EC. We suggest close monitoring for EC development when PPIs are administered to patients with these factors.
UV induced changes in proteome of rats plasma are reversed by dermally applied cannabidiol
Authors: Gęgotek Agnieszka , Atalay Sinemyiz , Skrzydlewska Elżbieta
Published: October 2021

UV radiation is known to induce a multiple changes in the metabolism of skin-building cells, what can affect the functioning not only neighboring cells, but also, following signal transduction releasing into the blood vessels, the entire body. Therefore, the aim of this study was to analyze the proteomic disturbances occurred in plasma of chronically UVA/UVB irradiated rats and define the effect on these changes of skin topically applied cannabidiol (CBD). Obtained results showed significant changes in the expression of numerous anti-inflammatory and signaling proteins including: NFκB inhibitor, 14-3-3 protein, protein kinase C, keratin, and protein S100 after UV irradiation and CBD treatment. Moreover, the effects of UVA and UVB were manifested by increased level of lipid peroxidation products—protein adducts formation. CBD partially prevented all of these changes, but in a various degree depending on the UV radiation type. Moreover, topical treatment with CBD resulted in the penetration of CBD into the blood and, as a consequence, in direct modifications to the plasma protein structure by creating CBD adducts with molecules, such as proline-rich protein 30, transcription factor 19, or N-acetylglucosamine-6-sulfatase, what significantly changed the activity of these proteins. In conclusion, it may be suggested that CBD applied topically may be an effective compound against systemic UV-induced oxidative stress, but its effectiveness requires careful analysis of CBD's effects on other tissues of the living organism.
Linking climate and infectious disease trends in the Northern/Arctic Region
Authors: Ma Yan , Destouni Georgia , Kalantari Zahra , Omazic Anna , Evengård Birgitta , Berggren Camilla , Thierfelder Tomas
Published: October 2021

Recognition of climate-sensitive infectious diseases is crucial for mitigating health threats from climate change. Recent studies have reasoned about potential climate sensitivity of diseases in the Northern/Arctic Region, where climate change is particularly pronounced. By linking disease and climate data for this region, we here comprehensively quantify empirical climate-disease relationships. Results show significant relationships of borreliosis, leptospirosis, tick-borne encephalitis (TBE), Puumala virus infection, cryptosporidiosis, and Q fever with climate variables related to temperature and freshwater conditions. These data-driven results are consistent with previous reasoning-based propositions of climate-sensitive infections as increasing threats for humans, with notable exceptions for TBE and leptospirosis. For the latter, the data imply decrease with increasing temperature and precipitation experienced in, and projected for, the Northern/Arctic Region. This study provides significant data-based underpinning for simplified empirical assessments of the risks of several infectious diseases under future climate change.
Cell viability and electrical response of breast cancer cell treated in aqueous graphene oxide solution deposition on interdigitated electrode
Authors: Ramli Muhammad M. , Rosman A. S. , Mazlan N. S. , Ahmad M. F. , Halin D. S. C. , Mohamed R. , Osman Nurul H. , Reshak Ali H.
Published: October 2021

Breast cancer is one of the most reported cancers that can lead to death. Despite the advances in diagnosis and treatment procedures, the possibility of cancer recurrences is still high in many cases. With that in consideration, researchers from all over the world are showing interest in the unique features of Graphene oxide (GO), such as its excellent and versatile physicochemical properties, to explore further its potential and benefits towards breast cancer cell treatment. In this study, the cell viability and electrical response of GO, in terms of resistivity and impedance towards the breast cancer cells (MCF7) and normal breast cells (MCF10a), were investigated by varying the pH and concentration of GO. Firstly, the numbers of MCF7 and MCF10a were measured after being treated with GO for 24 and 48 h. Next, the electrical responses of these cells were evaluated by using interdigitated gold electrodes (IDEs) that are connected to an LCR meter. Based on the results obtained, as the pH of GO increased from pH 5 to pH 7, the number of viable MCF7 cells decreased while the number of viable MCF10a slightly increased after the incubation period of 48 h. Similarly, the MCF7 also experienced higher cytotoxicity effects when treated with GO concentrations of more than 25 µg/mL. The findings from the electrical characterization of the cells observed that the number of viable cells has corresponded to the impedance of the cells. The electrical impedance of MCF7 decreased as the number of highly insulating viable cell membranes decreased. But in contrast, the electrical impedance of MCF10a increased as the number of highly insulating viable cell membranes increased. Hence, it can be deduced that the GO with higher pH and concentration influence the MCF7 cancer cell line and MCF10a normal breast cell.
Intact predictive motor sequence learning in autism spectrum disorder
Authors: Rybicki A. J. , Galea J. M. , Schuster B. A. , Hiles C. , Fabian C. , Cook J. L.
Published: October 2021

Atypical motor learning has been suggested to underpin the development of motoric challenges (e.g., handwriting difficulties) in autism. Bayesian accounts of autistic cognition propose a mechanistic explanation for differences in the learning process in autism. Specifically, that autistic individuals overweight incoming, at the expense of prior, information and are thus less likely to (a) build stable expectations of upcoming events and (b) react to statistically surprising events. Although Bayesian accounts have been suggested to explain differences in learning across a range of domains, to date, such accounts have not been extended to motor learning. 28 autistic and 35 non-autistic controls (IQ > 70) completed a computerised task in which they learned sequences of actions. On occasional “surprising” trials, an expected action had to be replaced with an unexpected action. Sequence learning was indexed as the reaction time difference between blocks which featured a predictable sequence and those that did not. Surprise-related slowing was indexed as the reaction time difference between surprising and unsurprising trials. No differences in sequence-learning or surprise-related slowing were observed between the groups. Bayesian statistics provided anecdotal to moderate evidence to support the conclusion that sequence learning and surprise-related slowing were comparable between the two groups. We conclude that individuals with autism do not show atypicalities in response to surprising events in the context of motor sequence-learning. These data demand careful consideration of the way in which Bayesian accounts of autism can (and cannot) be extended to the domain of motor learning.
NR4A2 expression is not altered in placentas from cases of growth restriction or preeclampsia, but is reduced in hypoxic cytotrophoblast
Authors: de Alwis Natasha , Beard Sally , Binder Natalie K. , Pritchard Natasha , Kaitu’u-Lino Tu’uhevaha J. , Walker Susan P. , Stock Owen , Groom Katie M. , Petersen Scott , Henry Amanda , Said Joanne M. , Seeho Sean , Kane Stefan C. , Tong Stephen , Hannan Natalie J.
Published: October 2021

Nuclear Receptor Subfamily 4 Group A Member 2 (NR4A2) transcripts are elevated in the circulation of individuals whose pregnancies are complicated by preterm fetal growth restriction (FGR). In this paper, we show that the cases with preeclampsia (PE) have increased circulating NR4A2 transcripts compared to those with normotensive FGR. We aimed to establish whether the dysfunctional placenta mirrors the increase in NR4A2 transcripts and further, to uncover the function of placental NR4A2. NR4A2 expression was detected in preterm and term placental tissue; expressed higher at term. NR4A2 mRNA expression and protein were not altered in placentas from preterm FGR or PE pregnancies. Hypoxia (1% O2 compared to 8% O2) significantly reduced cytotrophoblast NR4A2 mRNA expression, but not placental explant NR4A2 expression. Silencing cytotrophoblast NR4A2 expression under hypoxia (via short interfering (si)RNAs) did not alter angiogenic Placental Growth Factor, nor anti-angiogenic sFlt-1 mRNA expression or protein secretion, but increased expression of cellular antioxidant, oxidative stress, inflammatory, and growth genes. NR4A2 expression was also not altered in a model of tumour necrosis factor-α-induced endothelial dysfunction, or with pravastatin treatment. Further studies are required to identify the origin of the circulating transcripts in pathological pregnancies, and investigate the function of placental NR4A2.
K15 promoter-driven enforced expression of NKIRAS exhibits tumor suppressive activity against the development of DMBA/TPA-induced skin tumors
Authors: Tago Kenji , Ohta Satoshi , Aoki-Ohmura Chihiro , Funakoshi-Tago Megumi , Sashikawa Miho , Matsui Takeshi , Miyamoto Yuki , Wada Taeko , Oshio Tomoyuki , Komine Mayumi , Matsugi Jitsuhiro , Furukawa Yusuke , Ohtsuki Mamitaro , Yamauchi Junji , Yanagisawa Ken
Published: October 2021

NKIRAS1 and NKIRAS2 (also called as κB-Ras) were identified as members of the atypical RAS family that suppress the transcription factor NF-κB. However, their function in carcinogenesis is still controversial. To clarify how NKIRAS acts on cellular transformation, we generated transgenic mice in which NKIRAS2 was forcibly expressed using a cytokeratin 15 (K15) promoter, which is mainly activated in follicle bulge cells. The ectopic expression of NKIRAS2 was mainly detected in follicle bulges of transgenic mice with NKIRAS2 but not in wild type mice. K15 promoter-driven expression of NKIRAS2 failed to affect the development of epidermis, which was evaluated using the expression of K10, K14, K15 and filaggrin. However, K15 promoter-driven expression of NKIRAS2 effectively suppressed the development of skin tumors induced by treatment with 7,12-dimethylbenz(a)anthracene (DMBA)/12-O-tetradecanoylphorbol 13-acetate (TPA). This observation suggested that NKIRAS seemed to function as a tumor suppressor in follicle bulges. However, in the case of oncogenic HRAS-driven cellular transformation of murine fibroblasts, knockdown of NKIRAS2 expression drastically suppressed HRAS-mutant-provoked cellular transformation, suggesting that NKIRAS2 was required for the cellular transformation of murine fibroblasts. Furthermore, moderate enforced expression of NKIRAS2 augmented oncogenic HRAS-provoked cellular transformation, whereas an excess NKIRAS2 expression converted its functional role into a tumor suppressive phenotype, suggesting that NKIRAS seemed to exhibit a biphasic bell-shaped enhancing effect on HRAS-mutant-provoked oncogenic activity. Taken together, the functional role of NKIRAS in carcinogenesis is most likely determined by not only cellular context but also its expression level.
Vancomycin-induced nephrotoxicity in non-intensive care unit pediatric patients
Authors: Kwak Shinhyeung , Kim Jeong Yeon , Cho Heeyeon
Published: October 2021

Previous data suggested several risk factors for vancomycin-induced nephrotoxicity (VIN), including higher daily dose, long-term use, underlying renal disease, intensive care unit (ICU) admission, and concomitant use of nephrotoxic medications. We conducted this study to investigate the prevalence and risk factors of VIN and to estimate the cut-off serum trough level for predicting acute kidney injury (AKI) in non-ICU pediatric patients. This was a retrospective, observational, single-center study at Samsung Medical Center tertiary hospital, located in Seoul, South Korea. We reviewed the medical records of non-ICU pediatric patients, under 19 years of age with no evidence of previous renal insufficiency, who received vancomycin for more than 48 h between January 2009 and December 2018. The clinical characteristics were compared between patients with AKI and those without to identify the risk factors associated with VIN, and the cut-off value of serum trough level to predict the occurrence of VIN was calculated by the Youden’s index. Among 476 cases, 22 patients (4.62%) developed AKI. The Youden’s index indicated that a maximum serum trough level of vancomycin above 24.35 μg/mL predicted VIN. In multivariate analysis, longer hospital stay, concomitant use of piperacillin-tazobactam and serum trough level of vancomycin above 24.35 μg/mL were associated independently with VIN. Our findings suggest that concomitant use of nephrotoxic medication and higher serum trough level of vancomycin might be associated with the risk of VIN. This study suggests that measuring serum trough level of vancomycin can help clinicians prevent VIN in pediatric patients.
Conic tangents based high precision extraction method of concentric circle centers and its application in camera parameters calibration
Authors: Hao Fei , Su Jinjiang , Shi Jingjing , Zhu Chaohan , Song Jiatong , Hu Yuntao
Published: October 2021

A high-precision camera intrinsic parameters calibration method based on concentric circles was proposed. Different from Zhang’s method, its feature points are the centers of concentric circles. First, the collinearity of the projection of the center of concentric circles and the centers of two ellipses which are imaged from the concentric circles was proved. Subsequently, a straight line passing through the center of concentric circles was determined with four tangent lines of concentric circles. Finally, the projection of the center of concentric circles was extracted with the intersection of the straight line and the line determined by the two ellipse centers. Simulation and physical experiments are carried out to analyze the factors affecting the accuracy of circle center coordinate extraction and the results show that the accuracy of the proposed method is higher. On this basis, several key parameters of the calibration target design are determined through simulation experiments and then the calibration target is printed to calibrate a binocular system. The results show that the total reprojection error of the left camera is reduced by 17.66% and that of the right camera is reduced by 21.58% compared with those of Zhang’s method. Therefore, the proposed calibration method has higher accuracy.
Integrated study on the comprehensive magnetic-field configuration performance in the 150 kW superconducting magnetoplasmadynamic thruster
Authors: Zheng Jinxing , Liu Haiyang , Song Yuntao , Zhou Cheng , Li Yong , Li Ming , Tang Haibin , Wang Ge , Cong Yuntian , Wang Baojun , Wang Yibai , Wu Peng , Qu Timing , Zhu Xiaoliang , Zhu Lei , Liu Fei , Cheng Yuan , Zhao Boqiang
Published: October 2021

Higher magnetic fields are always favoured in the magnetoplasmadynamic thruster (MPDT) due to its superior control of the plasma profile and acceleration process. This paper introduces the world's first integrated study on the 150 kW level AF-MPDT equipped with a superconductive coil. A completely new way of using superconducting magnet technology to confine plasma with high energy and extremely high temperatures is proposed. Using the PIC method of microscopic particle simulation, the plasma magnetic nozzle effect and performance of the MPDT under different magnetic-field conditions were studied. The integrated experiment used demonstrated that, in conjunction with the superconducting coil, greater homogeneity and a stronger magnetic field not only caused more even cathode ablation and improved its lifespan but also improved the performance of the MPDT (maximum thrust was 4 N at 150 kW, 0.56 T). Maximum thrust efficiency reached 76.6% and the specific impulse reached 5714 s.
Convolutional neural network for human cancer types prediction by integrating protein interaction networks and omics data
Authors: Chuang Yi-Hsuan , Huang Sing-Han , Hung Tzu-Mao , Lin Xiang-Yu , Lee Jung-Yu , Lai Wen-Sen , Yang Jinn-Moon
Published: October 2021

Many studies have proven the power of gene expression profile in cancer identification, however, the explosive growth of genomics data increasing needs of tools for cancer diagnosis and prognosis in high accuracy and short times. Here, we collected 6136 human samples from 11 cancer types, and integrated their gene expression profiles and protein–protein interaction (PPI) network to generate 2D images with spectral clustering method. To predict normal samples and 11 cancer tumor types, the images of these 6136 human cancer network were separated into training and validation dataset to develop convolutional neural network (CNN). Our model showed 97.4% and 95.4% accuracies in identification of normal versus tumors and 11 cancer types, respectively. We also provided the results that tumors located in neighboring tissues or in the same cell types, would induce machine make error classification due to the similar gene expression profiles. Furthermore, we observed some patients may exhibit better prognosis if their tumors often misjudged into normal samples. As far as we know, we are the first to generate thousands of cancer networks to predict and classify multiple cancer types with CNN architecture. We believe that our model not only can be applied to cancer diagnosis and prognosis, but also promote the discovery of multiple cancer biomarkers.
Economical droplet-based microfluidic production of [18F]FET and [18F]Florbetaben suitable for human use
Authors: Lisova Ksenia , Wang Jia , Hajagos Tibor Jacob , Lu Yingqing , Hsiao Alexander , Elizarov Arkadij , van Dam R. Michael
Published: October 2021

Current equipment and methods for preparation of radiopharmaceuticals for positron emission tomography (PET) are expensive and best suited for large-scale multi-doses batches. Microfluidic radiosynthesizers have been shown to provide an economic approach to synthesize these compounds in smaller quantities, but can also be scaled to clinically-relevant levels. Batch microfluidic approaches, in particular, offer significant reduction in system size and reagent consumption. Here we show a simple and rapid technique to concentrate the radioisotope, prior to synthesis in a droplet-based radiosynthesizer, enabling production of clinically-relevant batches of [18F]FET and [18F]FBB. The synthesis was carried out with an automated synthesizer platform based on a disposable Teflon-silicon surface-tension trap chip. Up to 0.1 mL (4 GBq) of radioactivity was used per synthesis by drying cyclotron-produced aqueous [18F]fluoride in small increments directly inside the reaction site. Precursor solution (10 µL) was added to the dried [18F]fluoride, the reaction chip was heated for 5 min to perform radiofluorination, and then a deprotection step was performed with addition of acid solution and heating. The product was recovered in 80 µL volume and transferred to analytical HPLC for purification. Purified product was formulated via evaporation and resuspension or a micro-SPE formulation system. Quality control testing was performed on 3 sequential batches of each tracer. The method afforded production of up to 0.8 GBq of [18F]FET and [18F]FBB. Each production was completed within an hour. All batches passed quality control testing, confirming suitability for human use. In summary, we present a simple and efficient synthesis of clinically-relevant batches of [18F]FET and [18F]FBB using a microfluidic radiosynthesizer. This work demonstrates that the droplet-based micro-radiosynthesizer has a potential for batch-on-demand synthesis of 18F-labeled radiopharmaceuticals for human use.
Multilayer radiation shield for satellite electronic components protection
Authors: Daneshvar Hamideh , Milan Kavoos Ghordoei , Sadr Ali , Sedighy Seyed Hassan , Malekie Shahryar , Mosayebi Armin
Published: October 2021

In this paper, various multi-layer shields are designed, optimized, and analyzed for electron and proton space environments. The design process is performed for various suitable materials for the local protection of sensitive electronic devices using MCNPX code and the Genetic optimization Algorithm. In the optimizations process, the total ionizing dose is 53.3% and 72% greater than the aluminum shield for proton and electron environments, respectively. Considering the importance of the protons in the LEO orbits, the construction of the shield was based on designing a proton source. A sample shield is built using a combination of Aluminum Bronze and molybdenum layers with a copper carrier to demonstrate the idea. Comparisons of radiation attenuation coefficient results indicate a good agreement between the experimental, simulation, and analytical calculations results. The good specifications of the proposed multi-layer shield prove their capability and ability to use in satellite missions for electronic device protection.
A neutralizing IL-11 antibody reduces vessel hyperplasia in a mouse carotid artery wire injury model
Authors: Schumacher David , Liehn Elisa A. , Nilcham Pakhwan , Mayan David Castaño , Rattanasopa Chutima , Anand Kaviya , Crespo-Avilan Gustavo E. , Hernandez-Resendiz Sauri , Singaraja Roshni R. , Cook Stuart A. , Hausenloy Derek J.
Published: October 2021

Vascular restenosis remains a major problem in patients with coronary artery disease (CAD) and peripheral artery disease (PAD). Neointimal hyperplasia, defined by post-procedure proliferation and migration of vascular smooth muscle cells (VSMCs) is a key underlying pathology. Here we investigated the role of Interleukin 11 (IL-11) in a mouse model of injury-related plaque development. Apoe−/− mice were fed a hyperlipidaemic diet and subjected to carotid wire injury of the right carotid. Mice were injected with an anti-IL11 antibody (X203), IgG control antibody or buffer. We performed ultrasound analysis to assess vessel wall thickness and blood velocity. Using histology and immunofluorescence approaches, we determined the effects of IL-11 inhibition on VSMC and macrophages phenotypes and fibrosis. Treatment of mice with carotid wire injury using X203 significantly reduced post-endothelial injury vessel wall thickness, and injury-related plaque, when compared to control. Immunofluorescence staining of the injury-related plaque showed that X203 treatment did not reduce macrophage numbers, but reduced the number of VSMCs and lowered matrix metalloproteinase 2 (MMP2) levels and collagen content in comparison to control. X203 treatment was associated with a significant increase in smooth muscle protein 22α (SM22α) positive cells in injury-related plaque compared to control, suggesting preservation of the contractile VSMC phenotype. Interestingly, X203 also reduced the collagen content of uninjured carotid arteries as compared to IgG, showing an additional effect on hyperlipidemia-induced arterial remodeling in the absence of mechanical injury. Therapeutic inhibition of IL-11 reduced vessel wall thickness, attenuated neointimal hyperplasia, and has favorable effects on vascular remodeling following wire-induced endothelial injury. This suggests IL-11 inhibition as a potential novel therapeutic approach to reduce arterial stenosis following revascularization in CAD and PAD patients.
Cardiometabolic syndrome and associated factors among Ethiopian public servants, Addis Ababa, Ethiopia
Authors: Geto Zeleke , Challa Feyissa , Lejisa Tadesse , Getahun Tigist , Sileshi Meron , Nagasa Bikila , Tolcha Yosef , Daniel Yeabkal , Getnet Misrak , Molla Meseret Derbew , Degef Maria , Bekele Abebe , Seifu Daniel
Published: October 2021

Non-communicable diseases (NCDs) are increasingly becoming the global cause of premature death encompassing cardiovascular diseases (CVDs), cancer, respiratory diseases and diabetes mellitus. However, cardiometabolic risk factors in the general population, especially among the high-risk groups have rarely been assessed in Ethiopia. The study aimed to assess the prevalence of metabolic syndrome, its components and associated factors among staff in the Ethiopian Public Health Institute (EPHI). An institutional-based cross-section study was conducted from March to June 2018 among EPHI staff members. A total of 450 study participants were involved in the study, and the World Health Organization NCD STEPS survey instrument version 3.1 was used for the assessment. The biochemical parameters were analyzed by using COBAS 6000 analyzer. Statistical package for the social science (SPSS) version 20 was used for data analysis. Both bivariate and multivariate logistic regression analyses were used to identify associated risk factors. p value < 0.05 was considered for statistical significance. The overall prevalence of metabolic syndrome was 27.6% and 16.7% according to IDF and NCEP criteria respectively, with males having greater prevalence than females (35.8% vs 19.4%). Central obesity, low high-density lipoprotein (HDL) and hypertension had a prevalence of 80.2%, 41.3%, and 23.6%, respectively. In multivariate analysis increasing age and having a higher body mass index (25–29.9) were significantly associated with metabolic syndromes. The magnitude of metabolic syndrome was relatively high among public employees. Preventive intervention measures should be designed on the modification of lifestyle, nutrition and physical activities, and early screening for early identification of cardiometabolic risks factors should be practised to reduce the risk of developing cardiovascular diseases.