bluuebunny/crossref_metadata_2025 huggingface dataset:
Cereblon contributes to the development of pulmonary fibrosis via inactivation of adenosine monophosphate-activated protein kinase α1
Authors: Kang Hyo Jae , Lee Kyung Jin , Woo Jisu , Kim Jiyeon , Kim Yun Kyu , Lee Chang-Hoon , Yoo Chul-Gyu , Lee Kyoung-Hee
Published: May 2021

Pulmonary fibrosis is a progressive and lethal lung disease characterized by the proliferation and differentiation of lung fibroblasts and the accumulation of extracellular matrices. Since pulmonary fibrosis was reported to be associated with adenosine monophosphate-activated protein kinase (AMPK) activation, which is negatively regulated by cereblon (CRBN), we aimed to determine whether CRBN is involved in the development of pulmonary fibrosis. Therefore, we evaluated the role of CRBN in bleomycin (BLM)-induced pulmonary fibrosis in mice and in transforming growth factor-beta 1 (TGF-β1)-induced differentiation of human lung fibroblasts. BLM-induced fibrosis and the mRNA expression of collagen and fibronectin were increased in the lung tissues of wild-type (WT) mice; however, they were significantly suppressed in Crbn knockout (KO) mice. While the concentrations of TGF-β1/2 in bronchoalveolar lavage fluid were increased via BLM treatment, they were similar between BLM-treated WT and Crbn KO mice. Knockdown of CRBN suppressed TGF-β1-induced activation of small mothers against decapentaplegic 3 (SMAD3), and overexpression of CRBN increased it. TGF-β1-induced activation of SMAD3 increased α-smooth muscle actin (α-SMA) and collagen levels. CRBN was found to be colocalized with AMPKα1 in lung fibroblasts. CRBN overexpression inactivated AMPKα1. When cells were treated with metformin (an AMPK activator), the CRBN-induced activation of SMAD3 and upregulation of α-SMA and collagen expression were significantly suppressed, suggesting that increased TGF-β1-induced activation of SMAD3 via CRBN overexpression is associated with AMPKα1 inactivation. Taken together, these data suggest that CRBN is a profibrotic regulator and maybe a potential target for treating lung fibrosis.
Advantages of robotic assistance over a manual approach in simulated subretinal injections and its relevance for gene therapy
Authors: Ladha Reza , Meenink Thijs , Smit Jorrit , de Smet Marc D.
Published: May 2021

Subretinal injection is a method for gene delivery to treat genetic diseases of the photoreceptors and retinal pigment epithelium. A reflux-free subretinal injection is important to allow effective, safe, and cost-effective gene therapy to the retina. We report on a comparison between manual and robotic assistance in simulated subretinal injections using an artificial retina model. Nine surgeons carried out the procedure with and without the Preceyes Surgical System, using an OPMI Lumera 700 Zeiss surgical microscope equipped with intra-operative optical coherence tomography. Success in creating a bleb without reflux, injection duration, drift, tremor, and increase in the diameter of the puncture hole were analyzed. Robotic assistance improved drift (median 16 vs 212 µm), tremor (median 1 vs 18 µm), enlargement of the retinal hole, and allowed for prolonged injection times (median 52 vs 29 sec). Robotic assistance allowed higher rate of bleb formation (8/9 vs 4/9 attempts) with a moderate reduction in reflux (7/9 vs 8/9 attempts) in this artificial model. Robotic assistance can significantly contribute to subretinal injections and provide quantifiable parameters in assessing surgical and clinical success of novel retinal gene therapies.
A pilot study to investigate if the mesenteric circumferential location of colon cancer affects survival when compared to the anti-mesenteric side
Authors: Horwell E. , Sagias F.
Published: May 2021

Colorectal cancer is a leading cause of death in the western world. The main datum that is employed to guide treatment and prognosis are related to the pathological stage and the genetics of the cancer. Recent electron-microscopic study of the colonic border has suggested a difference between the micro-anatomy of the mesenteric border11, compared to the anti-mesenteric. With colorectal cancer increasing in incidence, the more information that we can employ to guide and tailor patient centred management, the better. A pilot study to test the hypothesis that the circumferential location on the colonic wall, mesenteric or anti-mesenteric, has an impact on the mortality rate associated with right-sided colon cancer. All patients undergoing a right hemicolectomy for non-metastatic adenocarcinoma between 2010 and 2013 were included (155 patients in total). T and N stage were recorded. There was no statistical difference between the groups for age or sex. Survival rates were then calculated according to the location of the cancer and analysed using Kaplan–Meir survival calculations. 100 patients were included in the final analysis. 90 patients had cancer on the antimesenteric border. The T and N stage were not statistically different between the two groups. The mean all-cause survival was 44 months for the mesenteric group and 77 for the antimesenteric (P = 0.002). Disease free survival was 41 versus 60 months accordingly (P = 0.021). Mesenteric cancer appears to have a shorter survival time, and may be a good candidate for future prognostication and treatment algorithms. Interesting this survival difference is observed even with a lower average T stage in the mesenteric group. The histological recording of the circumferential location is a zero cost and easy metric to record.
Discovery of primary prostate cancer biomarkers using cross cancer learning
Authors: Zhou Kaiyue , Arslanturk Suzan , Craig Douglas B. , Heath Elisabeth , Draghici Sorin
Published: May 2021

Prostate cancer (PCa), the second leading cause of cancer death in American men, is a relatively slow-growing malignancy with multiple early treatment options. Yet, a significant number of low-risk PCa patients are over-diagnosed and over-treated with significant and long-term quality of life effects. Further, there is ever increasing evidence of metastasis and higher mortality when hormone-sensitive or castration-resistant PCa tumors are treated indistinctively. Hence, the critical need is to discover clinically-relevant and actionable PCa biomarkers by better understanding the biology of PCa. In this paper, we have discovered novel biomarkers of PCa tumors through cross-cancer learning by leveraging the pathological and molecular similarities in the DNA repair pathways of ovarian, prostate, and breast cancer tumors. Cross-cancer disease learning enriches the study population and identifies genetic/phenotypic commonalities that are important across diseases with pathological and molecular similarities. Our results show that ADIRF, SLC2A5, C3orf86, HSPA1B are among the most significant PCa biomarkers, while MTRNR2L1, EEPD1, TEPP and VN1R2 are jointly important biomarkers across prostate, breast and ovarian cancers. Our validation results have further shown that the discovered biomarkers can predict the disease state better than any randomly selected subset of differentially expressed prostate cancer genes.
Optimization of whole-brain rabies virus tracing technology for small cell populations
Authors: Roelofs Theresia J. M. , Menting-Henry Shanice , Gol Lieke M. , Speel Annelijn M. , Wielenga Vera H. , Garner Keith M. , Luijendijk Mieneke C. M. , Hennrich Alexandru A. , Conzelmann Karl-Klaus , Adan Roger A. H.
Published: May 2021

The lateral hypothalamus (LH) is critically involved in the regulation of homeostatic energy balance. Some neurons in the LH express receptors for leptin (LepRb), a hormone known to increase energy expenditure and decrease energy intake. However, the neuroanatomical inputs to LepRb-expressing LH neurons remain unknown. We used rabies virus tracing technology to map these inputs, but encountered non-specific tracing. To optimize this technology for a minor cell population (LepRb is not ubiquitously expressed in LH), we used LepRb-Cre mice and assessed how different titers of the avian tumor virus receptor A (TVA) helper virus affected rabies tracing efficiency and specificity. We found that rabies expression is dependent on TVA receptor expression, and that leakiness of TVA receptors is dependent on the titer of TVA virus used. We concluded that a titer of 1.0–3.0 × 107 genomic copies per µl of the TVA virus is optimal for rabies tracing. Next, we successfully applied modified rabies virus tracing technology to map inputs to LepRb-expressing LH neurons. We discovered that other neurons in the LH itself, the periventricular hypothalamic nucleus (Pe), the posterior hypothalamic nucleus (PH), the bed nucleus of the stria terminalis (BNST), and the paraventricular hypothalamic nucleus (PVN) are the most prominent input areas to LepRb-expressing LH neurons.
Virtual splint registration for electromagnetic and optical navigation in orbital and craniofacial surgery
Authors: Schreurs Ruud , Baan F. , Klop C. , Dubois L. , Beenen L. F. M. , Habets P. E. M. H. , Becking A. G. , Maal T. J. J.
Published: May 2021

In intra-operative navigation, a registration procedure is performed to register the patient’s position to the pre-operative imaging data. The registration process is the main factor that determines accuracy of the navigation feedback. In this study, a novel registration protocol for craniofacial surgery is presented, that utilizes a virtual splint with marker points. The accuracy of the proposed method was evaluated by two observers in five human cadaver heads, for optical and electromagnetic navigation, and compared to maxillary bone-anchored fiducial registration (optical and electromagnetic) and surface-based registration (electromagnetic). The results showed minimal differences in accuracy compared to bone-anchored fiducials at the level of the infra-orbital rim. Both point-based techniques had lower error estimates at the infraorbital rim than surface-based registration, but surface-based registration had the lowest loss of accuracy over target distance. An advantage over existing point-based registration methods (bone-anchored fiducials, existing splint techniques) is that radiological imaging does not need to be repeated, since the need for physical fiducials to be present in the image volume is eradicated. Other advantages include reduction of invasiveness compared to bone-achnored fiducials and a possible reduction of human error in the registration process.
Characterization of the human TARDBP gene promoter
Authors: Baralle Marco , Romano Maurizio
Published: May 2021

The expression of TDP-43, the main component of neuronal intracellular inclusions across a broad spectrum of ALS and FTD disorders, is developmentally regulated and studies in vivo have shown that TDP-43 overexpression can be toxic, even before observation of pathological aggregates. Starting from these observations, the regulation of its expression at transcriptional level might represent a further key element for the pathogenesis of neurodegenerative diseases. Therefore, we have characterized the human TARDBP promoter, in order to study the transcriptional mechanisms of expression. Mapping of cis-acting elements by luciferase assays in different cell outlined that the activity of the promoter seems to be higher in SH-SY5Y, Neuro2A, and HeLa than in HEK293. In addition, we tested effects of two SNPs found in the promoter region of ALS patients and observed no significant effect on transcription levels in all tested cell lines. Lastly, while TDP-43 overexpression did not affect significantly the activity of its promoter (suggesting that TDP-43 does not influence its own transcription), the presence of the 5′UTR sequence and of intron-1 splicing seem to impact positively on TDP-43 expression without affecting transcript stability. In conclusion, we have identified the region spanning nucleotides 451–230 upstream from the transcription start site as the minimal region with a significant transcription activity. These results lay an important foundation for exploring the regulation of the TARDBP gene transcription by exogenous and endogenous stimuli and the implication of transcriptional mechanisms in the pathogenesis of TDP-43 proteinopathies.
Changes in retinal layers in type 1 diabetes mellitus without retinopathy measured by spectral domain and swept source OCTs
Authors: Orduna-Hospital Elvira , Sanchez-Cano Ana , Perdices Lorena , Acha Javier , Lopez-Alaminos Elena María , Pinilla Isabel
Published: May 2021

To evaluate changes in inner retinal layer (IRL) thicknesses in patients with type 1 diabetes mellitus (DM1) with no diabetic retinopathy (DR) using two different optical coherence tomography (OCT) devices. Ninety DM1 and 60 healthy eyes were evaluated using spectral domain (SD)-OCT and swept source (SS)-OCT to measure changes in the retinal nerve fiber layer (RNFL), ganglion cell layer (GCL), inner plexiform layer (IPL) and inner nuclear layer (INL) thicknesses in all Early Treatment of Diabetic Retinopathy Study (ETDRS) macular areas. Functional tests were performed in both groups, including ETDRS with 100, 2.5 and 1.25% contrast, and color vision. The mean ages were 42.93 ± 13.62 and 41.52 ± 13.05 years in the diabetic and control groups, respectively. Visual acuity (VA) with ETDRS 1.25% was lower in the DM1 patients. Both ETDRS 2.5% and color vision were lower in the DM1 group but did not reach statistical significance. Retinal thicknesses in the central area and in the vertical outer areas were higher in the DM1 group. Differences were found in the IRL with no changes in the outer ones. Long-term DM1 patients with no DR maintained visual function, with a decrease in VA with 1.25% ETDRS contrast. Macular thickness measurements were higher using Spectralis SD-OCT than DRI Triton SS-OCT, and DM1 patients had a decrease in IRL thickness, especially in the GCL at the parafoveal level, generating thinning of the RNFL in the peripheral areas. There were no differences in outer retinal layer (ORL) thickness.
Status and development for detection and control of ammonium bisulfate as a by-product of SCR denitrification
Authors: Jiao Kunling , Chen Xiangyang , Bie Xuan , Liu Daokuan , Qiu Mingjie , Ma Shuangchen
Published: May 2021

When denitrification technology using NH3 or urea as the reducing agent is applied to remove NOx from the flue gas, ammonium bisulfate (ABS) by-product will also be generated in the flue gas. ABS has an impact on catalyst life span, denitrification efficiency etc., air preheater and its downstream thermal equipment also have a significant negative impact due to its plugging and corrosion. The requirement for NOx removal efficiency is improved by ultra-low emissions in China. However, wide-load denitrification makes the flue gas composition and temperature changing more complicated. Increasing ammonia injection can improve the NOx removal effect, but too much ammonia injection will lead to the formation of ABS and the increase of deposition risk, the contradiction between these two aspects is amplified by ultra-low emissions and wide-load denitrification in many plants. Coordinating NOx control and reducing the impact of ABS on equipment are issues that the industry needs to solve urgently. In recent years, extensive research on ABS had been carried out deeply, consequently, there has been a relatively in-deepth knowledge foundation for ABS formation, formation temperature, deposition temperature, dew point temperature, decomposition behavior, etc., but the existing researches are insufficient to support the problem of ABS under full load denitrification completely resolved. Therefore, some analysis and detection methods related to ABS are reviewed in this paper, and the impact of ABS on SCR, air preheater and other equipment and the existing research results on reducing the impact of ABS are summarized also. It is hoped that this review will provide a reference for the industry to solve the problems of ABS that hinder wide-load denitrification and affect ultra-low emissions.
A tyrosine kinase inhibitor-induced interferon response positively associates with clinical response in EGFR-mutant lung cancer
Authors: Gurule Natalia J. , McCoach Caroline E. , Hinz Trista K. , Merrick Daniel T. , Van Bokhoven Adriaan , Kim Jihye , Patil Tejas , Calhoun Jacob , Nemenoff Raphael A. , Tan Aik Choon , Doebele Robert C. , Heasley Lynn E.
Published: May 2021

Tyrosine kinase inhibitors (TKIs) targeting EGFR-mutant lung cancers promote a range of tumor regression responses to yield variable residual disease, a likely incubator for acquired resistance. Herein, rapid transcriptional responses induced by TKIs early in treatment that associate with the range of patient responses were explored. RNAseq was performed on EGFR mutant cell lines treated in vitro with osimertinib and on tumor biopsies of eight EGFR mutant lung cancer patients before and after 2 weeks of TKI treatment. Data were evaluated for gene expression programs altered upon TKI treatment. Chemokine and cytokine expression were measured by ELISA and quantitative RT-PCR. IκB Kinase (IKK) and JAK-STAT pathway dependence was tested with pharmacologic and molecular inhibitors. Tumor sections were stained for the T-cell marker CD3. Osimertinib stimulated dynamic, yet wide-ranging interferon (IFN) program regulation in EGFR mutant cell lines. IL6 and CXCL10 induction varied markedly among the EGFR mutant cell lines and was sensitive to IKK and JAK-STAT inhibitors. Analysis of matched patient biopsy pairs revealed marked, yet varied enrichment of IFN transcriptional programs, effector immune cell signatures and T-cell content in treated tumors that positively correlated with time to progression in the patients. EGFR-specific TKIs induce wide-ranging IFN response program activation originating within the cancer cell. The strong association of IFN program induction and duration of clinical response indicates that the TKI-induced IFN program instructs variable recruitment and participation of immune cells in the overall therapeutic response.
Genome-wide bioinformatic analyses predict key host and viral factors in SARS-CoV-2 pathogenesis
Authors: Ferrarini Mariana G. , Lal Avantika , Rebollo Rita , Gruber Andreas J. , Guarracino Andrea , Gonzalez Itziar Martinez , Floyd Taylor , de Oliveira Daniel Siqueira , Shanklin Justin , Beausoleil Ethan , Pusa Taneli , Pickett Brett E. , Aguiar-Pulido Vanessa
Published: May 2021

The novel betacoronavirus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) caused a worldwide pandemic (COVID-19) after emerging in Wuhan, China. Here we analyzed public host and viral RNA sequencing data to better understand how SARS-CoV-2 interacts with human respiratory cells. We identified genes, isoforms and transposable element families that are specifically altered in SARS-CoV-2-infected respiratory cells. Well-known immunoregulatory genes includingCSF2, IL32, IL-6andSERPINA3were differentially expressed, while immunoregulatory transposable element families were upregulated. We predicted conserved interactions between the SARS-CoV-2 genome and human RNA-binding proteins such as the heterogeneous nuclear ribonucleoprotein A1 (hnRNPA1) and eukaryotic initiation factor 4 (eIF4b). We also identified a viral sequence variant with a statistically significant skew associated with age of infection, that may contribute to intracellular host–pathogen interactions. These findings can help identify host mechanisms that can be targeted by prophylactics and/or therapeutics to reduce the severity of COVID-19.
Polyols as a Toolbox for the Preparation of Inorganic-based Nanostructures
Authors: Antonoglou Orestis , Dendrinou-Samara Catherine
Published: May 2021

The preparation of inorganic nanoparticles (NPs) through wet chemical approaches is very attractive, as chemical differentiations permit fine control of the structure, the chemical nature and the morphology of the nanostructures. However, rationalization is limited, and among the various methods for synthesizing NPs in solution, only a few are easy to use, produce NPs of high crystallinity and quality and can be scaled up. The so-called ‘‘polyol process’’ is recognized as possessing these features after about three decades of development. The present chapter reviews the redox mechanism of polyols, summarizes main findings and concepts for the production of metals, metal oxides and bimetallic nanostructures, and aims to provide the advantages but also the limitations that the polyol synthesis bears.
Role of Phenols and Phenol Derivatives in the Synthesis of Nanoparticles
Authors: Kinayyigit Solen
Published: May 2021

In recent years, there has been intensive research into finding less expensive, non-toxic, and easier wet-chemical synthetic methods in order to control the properties of metal nanoparticles used for a variety of applications. Physical and chemical properties of nanoparticles are highly dependent on size, shape, crystallinity, and composition. Moreover, it is difficult to control nanoparticle behaviours in solution, since they have a tendency to form agglomerations due to their particular size and high surface energy and the dominant van der Waals forces present. Considerable effort has gone into finding novel strategies to produce well-tuned and stable metal nanoparticles as well as optimizing existing synthetic methods through the investigation of the reaction conditions and the pursuit of more effective reagents to reduce a variety of metal complexes. Among such reagents, phenol and its derivatives, also found in biological systems, are proven to be not only good capping agents but also efficient reducing agents that can control the relative rates between nucleation and growth well enough to achieve the desired metal nanoparticles for targeted applications. This chapter is dedicated to the different types of phenols used as reducing and stabilizing agents to produce well-defined metal nanoparticles, namely, Au, Ag, Pd, and MxOn nanoparticles.
Associated anisotropy of intrinsic NAD(P)H for monitoring changes in the metabolic activities of breast cancer cells (4T1) in three-dimensional collagen matrix
Authors: Cong Anh T. Q. , Pimenta Rafaela M. L. , Holy Jon , Heikal Ahmed A.
Published: May 2021

The time-resolved associated anisotropy of intrinsic NAD(P)H can be used for monitoring changes in the metabolic state of living cells or tissues.
Structure illumination microscopy imaging of lipid vesicles in live bacteria with naphthalimide-appended organometallic complexes
Authors: Maria Ranieri Anna , Vezzelli Matteo , Leslie Kathryn G. , Huang Song , Stagni Stefano , Jacquemin Denis , Jiang Haibo , Hubbard Alysia , Rigamonti Luca , Watkin Elizabeth L. J. , Ogden Mark I. , New Elizabeth J. , Massi Massimiliano
Published: May 2021

Staining bacteria is made more informative with a probe that enables imaging using super-resolution microscopy, and ion nanoscopy.
Formaldehyde regulates tetrahydrofolate stability and thymidylate synthase catalysis
Authors: Chen Xiaolei , Chothia Sara Y. , Basran Jaswir , Hopkinson Richard J.
Published: May 2021

NMR studies on the formation and stability of 5,10-methylenetetrahydrofolic acid reveal a non-enzymatic feedback mechanism mediated by formaldehyde.
Effects of molecular shape on alcohol aggregation and water hydrogen bond network behavior in butanol isomer solutions
Authors: Choi Seungeui , Parameswaran Saravanan , Choi Jun-Ho
Published: May 2021

The morphologic image about water-incompatible network and water-compatible network in aqueous butanol isomer solutions. The chain-shapedn-butanol forms water-incompatible network, and the globular-shapedtert-butanol forms water-compatible network. Then-butanol andtert-butanol molecules are presented in gray color, while the water molecules are presented in red color.
Revealing practical specific capacity and carbonyl utilization of multi-carbonyl compounds for organic cathode materials
Authors: Shi Jun-Lin , Xiang Shi-Qin , Su Dai-Jian , He Rongxing , Zhao Liu-Bin
Published: May 2021

The influence of carbonyl type and carbonyl number on the electrochemical performance of a series of multi-carbonyl compounds is investigated.
Constructing an n/n+ homojunction in a monolithic perovskite film for boosting charge collection in inverted perovskite photovoltaics
Authors: Lu Yan-Na , Zhong Jun-Xing , Yu Yinye , Chen Xi , Yao Chan-Ying , Zhang Chengxi , Yang Meifang , Feng Wenhuai , Jiang Yong , Tan Ying , Gong Li , Wei Xingzhan , Zhou Yecheng , Wang Lianzhou , Wu Wu-Qiang
Published: May 2021

A simple heterovalent metal halide surface treatment enables formation of n/n+ perovskite homojunction, which enlarged built-in electric field and accelerated charge extraction at the perovskite/C60 interface, achieving a high efficiency of 22.2%.
Synthesis and antibiofilm activity of 1,2,3-triazole-pyridine hybrids against methicillin-resistant Staphylococcus aureus (MRSA)
Authors: El Malah Tamer , Soliman Hanan A. , Hemdan Bahaa A. , Abdel Mageid Randa E. , Nour Hany F.
Published: May 2021

Antibiotic-resistant bacteria are emerging at an alarming rate, posing a potential threat to human health. A series of 1,2,3-triazole-pyridine hybrids were synthesised as promising antibiofilm agents against planktonic and sessile MRSA.
Pt distribution-controlled Ni–Pt nanocrystalsviaan alcohol reduction technique for the oxygen reduction reaction
Authors: Taniguchi Kaneyuki , Cuya Huaman Jhon L. , Iwata Daichi , Yokoyama Shun , Matsumoto Takatoshi , Suzuki Kazumasa , Miyamura Hiroshi , Balachandran Jeyadevan
Published: May 2021

The catalytic performance and durability of Ni–Pt alloy nanoparticles synthesized using an alcohol reduction technique were enhanced by controlling the metallic Pt distribution.
The chromodepsins – chemistry, biology and biosynthesis of a selective Gq inhibitor natural product family
Authors: Hermes Cornelia , König Gabriele M. , Crüsemann Max
Published: May 2021

This review summarizes research on the chromodepsins, a small natural product family inhibiting Gq proteins, including their discovery, mode of action, biosynthesis, ecology, total synthesis, pharmacological and therapeutic use.
Silica-confined Ru highly dispersed on ZrO2 with enhanced activity and thermal stability in dichloroethane combustion
Authors: Fei Zhaoyang , Wang Zhicheng , Li Dunfei , Xue Fan , Cheng Chao , Liu Qing , Chen Xian , Cui Mifen , Qiao Xu
Published: May 2021

An efficient strategy (spontaneous deposition to enhance noble metal dispersity and core–shell confinement to inhibit noble metal sintering) is presented to synthesize active and thermally stable Ru/ZrO2 catalysts for dichloroethane combustion.
Interaction from structure using machine learning: in and out of equilibrium
Authors: Bag Saientan , Mandal Rituparno
Published: May 2021

A novel machine learning based method is proposed to infer interaction from structure. The study shows that the trained neural network makes excellent prediction both in and out of equilibrium (e.g. in active matter).
Effects of HIF-1α on renal fibrosis in cisplatin-induced chronic kidney disease
Authors: Zhao Hao , Han Yachun , Jiang Na , Li Chenrui , Yang Ming , Xiao Ying , Wei Ling , Xiong Xiaofen , Yang Jinfei , Tang Chengyuan , Xiao Li , Liu Fuyou , Liu Yu , Sun Lin
Published: May 2021

Cisplatin (Cis) can cause chronic kidney disease (CKD) and promote renal fibrosis, but the underlying mechanism is not fully understood. Hypoxia inducible factor-1α (HIF-1α) can promote renal fibrosis in some kidney diseases, but its role in Cis-induced CKD is still unknown. Notch-1 is a recognized molecule that promotes renal fibrosis under pathological circumstances, and evidence shows that HIF-1α and Notch-1 are closely related to each other. In the present study, mice with HIF-1α gene knockout in proximal tubular cells (PTCs) (PT-HIF-1α-KO) were generated and treated with Cis to induce CKD. A human proximal tubular cell line (HK-2) and primary mouse PTCs were used for in vitro studies. The results showed that HIF-1α was increased in the kidneys of Cis-treated wild-type mice, accompanied by elevated Notch-1, Notch-1 intracellular domain (N1ICD), Hes-1 and renal fibrosis. However, these alterations were partially reversed in PT-HIF-1α-KO mice. Similar results were observed in HK-2 cells and primary mouse PTCs. In addition, treating the cells with Cis induced a marked interaction of HIF-1α and N1ICD. Further inhibiting Notch-1 significantly reduced cellular fibrogenesis but did not affect HIF-1α expression. The data suggested that HIF-1α could promote renal fibrosis in Cis-induced CKD by activating Notch-1 both transcriptionally and post-transcriptionally and that HIF-1α may serve as a potential therapeutic target for Cis-induced CKD.
Development and Initial Validation of the Lifetime Exposure to Noise and Solvents Questionnaire in U.S. Service Members and Veterans
Authors: Griest-Hines Susan E. , Bramhall Naomi F. , Reavis Kelly M. , Theodoroff Sarah M. , Henry James A.
Published: May 2021

Purpose

A need exists to investigate the short- and long-term impact of noise exposures during and following military service on auditory health. Currently available questionnaires are limited in their ability to meet this need because of (a) inability to evaluate noise exposures beyond a limited time frame, (b) lack of consensus on scoring, (c) inability to assess impulse exposures (e.g., firearm use), (d) lack of a single questionnaire that assesses both military and nonmilitary exposures, and (e) lack of validity and reliability data. To address these limitations, the Lifetime Exposure to Noise and Solvents Questionnaire (LENS-Q) was developed. The purpose of this report is to describe the development and initial validation of the LENS-Q as a measure of self-reported noise exposure.

Method

Six hundred ninety participants, consisting of current Service members and recently military-separated (within about 2.5 years) Veterans, completed the LENS-Q, additional study questionnaires, and comprehensive audiometric testing. Noise exposure scores were computed from LENS-Q responses using a simple scoring algorithm that distinguishes between different cumulative levels of exposure and allows for the inclusion of both continuous and impulse noise exposures.

Results

The LENS-Q demonstrates good construct validity as evidenced by measures of hearing loss, tinnitus, and subjective hearing difficulties all increasing with an increase in noise exposure scores. A logistic regression, adjusting for age and sex, revealed that participants in the highest exposure group were 2.4–3.9 times more likely to experience hearing loss, 2.7–2.8 times more likely to experience tinnitus, and 3.0–3.7 times more likely to report hearing difficulties compared with individuals in the lowest exposure group.

Conclusions

The LENS-Q captures noise exposure over an individual's lifetime and provides an alternative scoring metric capable of representing exposure to both continuous and impulse noise. Findings suggest that the LENS-Q is a valuable tool for capturing and measuring both military and nonmilitary noise exposure.

Supplemental Material

https://doi.org/10.23641/asha.14582937
Observation of bi-directional jets in a prominence
Authors: Hillier A. , Polito V.
Published: May 2021

Quiescent prominences host a large range of flows, many driven by buoyancy, which lead to velocity shear. The presence of these shear flows could bend and stretch the magnetic field resulting in the formation of current sheets which can lead to magnetic reconnection. Though this has been hypothesised to occur in prominences, with some observations that are suggestive of this process, clear evidence has been lacking. In this paper we present observations performed on June 30, 2015 using the Interface Region Imaging Spectrograph Si IV and Mg II slit-jaw imagers of two bi-directional jets that occur inside the body of the prominence. Such jets are highly consistent with what would be expected from magnetic reconnection theory. Using this observation, we estimate that the prominence under study has an ambient field strength in the range of 4.5−9.2 G with ‘turbulent’ field strengths of 1 G. Our results highlight the ability of gravity-driven flows to stretch and fold the magnetic field of the prominence, implying that locally, the quiescent prominence field can be far from a static, force-free magnetic field.
Study of the thermal and nonthermal emission components in M 31: the Sardinia Radio Telescope view at 6.6 GHz
Authors: Fatigoni S. , Radiconi F. , Battistelli E. S. , Murgia M. , Carretti E. , Castangia P. , Concu R. , de Bernardis P. , Fritz J. , Genova-Santos R. , Govoni F. , Guidi F. , Lamagna L. , Masi S. , Melis A. , Paladini R. , Perez-Toledo F. M. , Piacentini F. , Poppi S. , Rebolo R. , Rubino-Martin J. A. , Surcis G. , Tarchi A. , Vacca V.
Published: May 2021

Context.The Andromeda galaxy is the best-known large galaxy besides our own Milky Way. Several images and studies exist at all wavelengths from radio to hard X-ray. Nevertheless, only a few observations are available in the microwave range where its average radio emission reaches the minimum.

Aims.In this paper, we want to study the radio morphology of the galaxy, decouple thermal from nonthermal emission, and extract the star formation rate. We also aim to derive a complete catalog of radio sources for the mapped patch of sky.

Methods.We observed the Andromeda galaxy with the Sardinia Radio Telescope at 6.6 GHz with very high sensitivity and angular resolution, and an unprecedented sky coverage.

Results.Using new 6.6 GHz data and Effelsberg radio telescope ancillary data, we confirm that, globally, the spectral index is ∼0.7−0.8, while in the star forming regions it decreases to ∼0.5. By disentangling (gas) thermal and nonthermal emission, we find that at 6.6 GHz, thermal emission follows the distribution of HII regions around the ring. Nonthermal emission within the ring appears smoother and more uniform than thermal emission because of diffusion of the cosmic ray electrons away from their birthplaces. This causes the magnetic fields to appear almost constant in intensity. Furthermore, we calculated a map of the star formation rate based on the map of thermal emission. Integrating within a radius ofRmax = 15 kpc, we obtained a total star formation rate of 0.19 ± 0.01 M⊙yr−1in agreement with previous results in the literature. Finally, we correlated our radio data with infrared images of the Andromeda galaxy. We find an unexpectedly high correlation between nonthermal and mid-infrared data in the central region, with a correlation parameterr = 0.93. Finally, by computing the logarithmic 24μm/21cmratioq24 μm, we find a decreasing trend with increasing galactocentric distance and an increasing dispersion. The logarithmic far-infrared-to-radio ratio is found to be 2.41 ± 0.04.
The imprint of X-ray photoevaporation of planet-forming discs on the orbital distribution of giant planets
Authors: Monsch Kristina , Picogna Giovanni , Ercolano Barbara , Preibisch Thomas
Published: May 2021

Context. Numerical models have shown that disc dispersal via internal photoevaporation driven by the host star can successfully reproduce the observed pile-up of warm Jupiters near 1–2 au. However, since a range of different mechanisms have been proposed to cause the same feature, clear observational diagnostics of disc dispersal leaving an imprint in the observed distribution of giant planets could help in constraining the dominant mechanisms.

Aims. We aim to assess the impact of disc dispersal via X-ray-driven photoevaporation (XPE) on giant planet separations in order to provide theoretical constraints on the location and size of any possible features related to this process within the observed semi-major axis distribution of giant planets.

Methods. For this purpose, we perform a set of 1D planet population syntheses with varying initial conditions and correlate the gas giants’ final parking locations with the X-ray luminosities of their host stars in order to quantify observables of this process within the semi-major axis versus host star X-ray luminosity plane of these systems.

Results. We find that XPE does create an under-density of gas giants near the gravitational radius, with corresponding pile-ups inside and/or outside this location. However, the size and location of these features are strongly dependent on the choice of initial conditions in our model, such as the assumed formation location of the planets.

Conclusions. XPE can strongly affect the migration process of giant planets and leave potentially observable signatures within the observed orbital separations of giant planets. However, due to the simplistic approach employed in our model, which lacks a self-consistent treatment of planet formation within an evolving disc, a quantitative analysis of the final planet population orbits is not possible. Our results, however, should strongly motivate future studies to include realistic disc dispersal mechanisms in global planet population synthesis models with self-consistent planet formation modules.
G 112-43/44: A metal-poor binary star with a unique chemical composition and Helmi stream kinematics
Authors: Nissen P. E. , Silva-Cabrera J. S. , Schuster W. J.
Published: May 2021

Context. Correlations between high-precision elemental abundance ratios and the kinematics of halo stars provide interesting information about the formation and early evolution of the Galaxy.

Aims. Element abundances of G 112-43/44, a metal-poor wide-orbit binary star with extreme kinematics, are revisited.

Methods. High-precision studies of the chemical compositions of 94 metal-poor dwarf stars in the solar neighbourhood are used to compare abundance ratios for G 112-43/44 with ratios for stars that have similar metallicities, taking into account the effect of deviations from local thermodynamic equilibrium on the derived abundances. Gaia EDR3 data are used to compare the kinematics.

Results. The X/Fe abundance ratios of the two components of G 112-43/44 agree within ±0.05 dex for nearly all elements, but there is a hint of a correlation between the difference in [X/H] and the elemental condensation temperature, which may be due to planet-star interactions. The Mg/Fe, Si/Fe, Ca/Fe, and Ti/Fe ratios of G 112-43/44 agree with the corresponding ratios for accreted (Gaia-Enceladus) stars, but Mn/Fe, Ni/Fe, Cu/Fe, and Zn/Fe are significantly enhanced, with Δ [Zn/Fe] reaching 0.25 dex. The kinematics show that G 112-43/44 belongs to the Helmi streams in the solar neighbourhood. In view of this, we discuss if the abundance peculiarities of G 112-43/44 can be explained by chemical enrichment from supernova events in the progenitor dwarf galaxy of the Helmi streams. Interestingly, yields calculated for a helium shell detonation Type Ia supernova model can explain the enhancement of Mn/Fe, Ni/Fe, Cu/Fe, and Zn/Fe in G 112-43/44 and three other α-poor stars in the Galactic halo with abundances from the literature, one of which has Helmi stream kinematics. However, the helium shell detonation model also predicts enhanced abundance ratios of Ca/Fe, Ti/Fe, and Cr/Fe, in disagreement with the observed ratios.
Catalytic Synthesis of PEGylated EGCG Conjugates that Disaggregate Alzheimer’s Tau
Authors: Eisenberg David S. , Harran Patrick G. , El Khoury Anton , Seidler Paul M.
Published: May 2021

The naturally occurring flavonoid (–)-epigallocatechin gallate (EGCG) is a potent disaggregant of tau fibrils. Guided by the recent cryo-electron microscopy (cryoEM) structure of EGCG bound to fibrils of tau derived from an Alzheimer’s brain donor, methods to site-specifically modify the EGCG D-ring with aminoPEGylated linkers are reported. The resultant molecules inhibit tau fibril seeding by Alzheimer’s brain extracts. Formulations of aminoPEGylated EGCG conjugated to the (quasi)-brain-penetrant nanoparticle Ferumoxytol inhibit seeding by AD-tau with linker length affecting activity. The protecting group-free catalytic cycloaddition of amino azides to mono-propargylated EGCG described here provides a blueprint for access to stable nanoparticulate forms of EGCG potentially useful as therapeutics to eliminate Alzheimer’s-related tau tangles.
Nickel-Catalyzed Homocoupling of Aryl Ethers with Magnesium Anthracene Reductant
Authors: Higashida Kosuke , Sawamura Masaya , Rawat Vishal Kumar
Published: May 2021

Nickel-catalyzed reductive homocoupling of aryl ethers has been achieved with Mg(anthracene)(thf)3 as a readily available low-cost reductant. DFT calculations provided a rationale for the specific efficiency of the diorganomagnesium-type two-electron reducing agent. The calculations show that the dianionic anthracene-9,10-diyl ligand reduces the two aryl ether substrates, resulting in the homocoupling reaction through supply of electrons to the Ni-Mg bimetallic system to form organomagnesium nickel(0)-ate complexes, which cause two sequential C–O bond cleavage reactions. The calculations also showed cooperative actions of Lewis acidic magnesium atoms and electron-rich nickel atoms in the C–O cleavage reactions.
Dual Ligand-Enabled Late-Stage Fujiwara–Moritani Reactions
Authors: van Gemmeren Manuel , Santiago Carlos , Chen Hao , Mondal Arup
Published: May 2021

In this study, we describe the use of dual ligand-based palladium catalysts for the late-stage olefination of arenes. Building upon a method previously developed for simple arenes, a variety of complex arene substrates were functionalized. Importantly, the method uses the arene as a limiting reactant and is therefore suitable for valuable starting materials that cannot be used in excess. The regioselectivity of the transformation is controlled by the steric and electronic properties of the substrate, providing access to regioisomers that would be challenging to prepare through other synthetic approaches.
The Pathophysiology of Hypercoagulability and Infertility
Authors: Malinowski Ann Kinga
Published: May 2021

Alongside an interplay of a multitude of factors, attainment of a favorable pregnancy outcome is predicated on successful implantation, which in itself is a complex process anchored by balanced interchange with the hemostatic system. Among other etiologies, failure of implantation can result in infertility, and lead affected couples to consider assisted reproductive technology (ART) in an effort to fulfill their desire for procreation. Given the critical role of the hemostatic system in the process of implantation, documentation of a hypercoagulable state during controlled ovarian stimulation in the context of in vitro fertilization, as well as the potential association of its derangement in the setting of thrombophilia, with infertility, ART, ovarian hyperstimulation syndrome, and failure of implantation are explored. Additionally, current evidence addressing the relationship between ART and thromboembolism is examined, as is the role of therapy with heparin and aspirin to decrease thrombotic risk and improve ART-related pregnancy outcomes. Evidence-based recommendations from relevant professional societies are summarized.
Understanding Ionic Solutions More Clearly
Authors: Lim Alane
Published: May 2021

A systematic review of ionic solution simulations reconciles differences in published theories.
Development of novel projection-type imaging mass spectrometer
Authors: Aoki J. , Toyoda M.
Published: May 2021

We developed a novel imaging mass spectrometer based on our accumulating technology for projection-type imaging mass spectrometry, the simulation of an accurate ion trajectory, and the theory for ion optics. The newly developed apparatus yields high spatial resolution with a substantially shorter image-acquisition time compared with conventional scanning-type imaging mass spectrometers. In order to maintain a high mass resolution, a multi-turn time-of-flight mass spectrometer is combined with post-extraction differential acceleration methods. Consequently, a mass resolution of m/Δm ∼ 10 000 and a spatial resolution of 1 μm were achieved simultaneously in this study. Application of our newly established apparatus to biological samples accomplished successful imaging mass spectrometry by exhibiting an organ-specific distribution of endogenous ions as well as a localized distribution of exogenously applied ions with an ultra-high spatial resolution image in the size of 18.5 megapixels.
Liquid oxygenated hydrocarbons produced during reforming of CH4 and CO2 in a surface dielectric barrier discharge: Effects of steam on conversion and products distribution
Authors: Rahmani Abdelkader , Aubert Xavier , Fagnon Nicolas , Nikravech Mehrdad
Published: May 2021

We have developed a low-temperature atmospheric surface dielectric barrier discharge reactor that transforms biogas into liquid chemicals. The influence of steam on the conversion of methane and carbon dioxide and the distribution of products vs specific energy input was investigated. The conversion rates of 44% for CH4 and 22% for CO2 were reached based on our operational conditions. The lowest energetic cost of 26 eV/molecule was reached when steam was added at the in-feed. The selectivity of 3 wt. % for liquid hydrocarbon was achieved. More than 12 chemicals were produced as a result of biogas (CH4 + CO2) transformation. Methanol, ethanol, isopropanol, and acetone constituted the most abundant oxygenated hydrocarbon liquids at room temperature. The main gaseous products were H2, CO, C2H4, and C2H6.
Direct treatment of pepper (Capsicum annuum L.) and melon (Cucumis melo) seeds by amplitude-modulated dielectric barrier discharge in air
Authors: Homola Tomáš , Prukner Václav , Artemenko Anna , Hanuš Jan , Kylián Ondřej , Šimek Milan
Published: May 2021

This study evaluates low-temperature plasma generated by an amplitude-modulated dielectric barrier discharge (DBD) as a direct surface treatment of pepper and melon plant seeds. An analysis of the discharge and its products revealed the influence of the seeds inserted into the plasma on the total plasma power and concentration of O3 and NOx, which are the dominant reactive oxygen and nitrogen species produced by the plasma. The plasma treatment of the seeds led to higher viability and higher imbibition rate during the first hour of exposure to the wet environment. X-ray photoelectron spectroscopy (XPS) analysis confirmed changes in the O:C ratio for plasma-treated pepper and melon seeds. However, prolonged plasma treatment for 300 s affected pepper and melon seeds differently. While the O:C ratio gradually increased with plasma treatment time for pepper seeds, that for melon seeds decreased considerably for longer treatment times. Furthermore, detailed XPS analysis of pepper seeds revealed a profound increase in magnesium and calcium, which are often present in seed macronutrients, and a minor increase in potassium, silicon, sulfur, and phosphorus, which are present in micronutrients. These observations can be related to the possible redistribution of the elements owing to the plasma treatment, and thus the treatment might have an essential influence on the seed bulk. The findings presented in this study help elucidate the plasma interaction with surfaces of pepper and melon seeds and confirm the feasibility of the direct plasma treatment using power-modulated DBDs for applications in agriculture.