bluuebunny/crossref_metadata_2025 huggingface dataset:
USP22-dependent HSP90AB1 expression promotes resistance to HSP90 inhibition in mammary and colorectal cancer
Authors: Kosinsky Robyn Laura , Helms Marlena , Zerche Maria , Wohn Luisa , Dyas Anna , Prokakis Evangelos , Kazerouni Zahra Basir , Bedi Upasana , Wegwitz Florian , Johnsen Steven A.
Published: December 2019

As a member of the 11-gene “death-from-cancer” gene expression signature, overexpression of the Ubiquitin-Specific Protease 22 (USP22) was associated with poor prognosis in various human malignancies. To investigate the function of USP22 in cancer development and progression, we sought to detect common USP22-dependent molecular mechanisms in human colorectal and breast cancer cell lines. We performed mRNA-seq to compare gene expression profiles of various colorectal (SW837, SW480, HCT116) and mammary (HCC1954 and MCF10A) cell lines upon siRNA-mediated knockdown of USP22. Intriguingly, while USP22 depletion had highly heterogeneous effects across the cell lines, all cell lines displayed a common reduction in the expression of Heat Shock Protein 90 Alpha Family Class B Member 1 (HSP90AB1). The downregulation of HSP90AB1 was confirmed at the protein level in these cell lines as well as in colorectal and mammary tumors in mice with tissue-specific Usp22 deletions. Mechanistically, we detected a significant reduction of H3K9ac on the HSP90AB1 gene in USP22-deficient cells. Interestingly, USP22-deficient cells displayed a high dependence on HSP90AB1 expression and diminishing HSP90 activity further using the HSP90 inhibitor Ganetespib resulted in increased therapeutic vulnerability in both colorectal and breast cancer cells in vitro. Accordingly, subcutaneously transplanted CRC cells deficient in USP22 expression displayed increased sensitivity towards Ganetespib treatment in vivo. Together, we discovered that HSP90AB1 is USP22-dependent and that cooperative targeting of USP22 and HSP90 may provide an effective approach to the treatment of colorectal and breast cancer.
Exploring the potential of BH3 mimetic therapy in squamous cell carcinoma of the head and neck
Authors: Carter Rachel J. , Milani Mateus , Butterworth Michael , Alotibi Ahoud , Harper Nicholas , Yedida Govindaraju , Greaves Georgia , Al-Zebeeby Aoula , Jorgensen Andrea L. , Schache Andrew G. , Risk Janet M. , Shaw Richard J. , Jones Terry M. , Sacco Joseph J. , Hurlstone Adam , Cohen Gerald M. , Varadarajan Shankar
Published: December 2019

Squamous cell carcinoma of the head and neck (SCCHN) is the sixth most common cancer worldwide, with overall survival of less than 50%. Current therapeutic strategies involving a combination of surgery, radiation, and/or chemotherapy are associated with debilitating side effects, highlighting the need for more specific and efficacious therapies. Inhibitors of BCL-2 family proteins (BH3 mimetics) are under investigation or in clinical practice for several hematological malignancies and show promise in solid tumors. In order to explore the therapeutic potential of BH3 mimetics in the treatment of SCCHN, we assessed the expression levels of BCL-2, BCL-XL, and MCL-1 via Western blots and immunohistochemistry, in cell lines, primary cells derived from SCCHN patients and in tissue microarrays containing tumor tissue from a cohort of 191 SCCHN patients. All preclinical models exhibited moderate to high levels of BCL-XL and MCL-1, with little or no BCL-2. Although expression levels of BCL-XL and MCL-1 did not correlate with patient outcome, a combination of BH3 mimetics to target these proteins resulted in decreased clonogenic potential and enhanced apoptosis in all preclinical models, including tumor tissue resected from patients, as well as a reduction of tumor volume in a zebrafish xenograft model of SCCHN. Our results show that SCCHN is dependent on both BCL-XL and MCL-1 for apoptosis evasion and combination therapy targeting both proteins may offer significant therapeutic benefits in this disease.
Association of N6-methyladenine DNA with plaque progression in atherosclerosis via myocardial infarction-associated transcripts
Authors: Wu Lianpin , Pei Yuqing , Zhu Yinhuan , Jiang Minghua , Wang Cheng , Cui Wei , Zhang Donghong
Published: December 2019

Modification of the novel N6-methyladenine (m6A) DNA implicates this epigenetic mark in human malignant disease, but its role in atherosclerosis (AS) is largely unknown. Here, we found that the leukocyte level of m6A but not 5mC DNA modification was decreased with increasing of carotid plaque size and thickness in 207 AS patients as compared with 142 sex- and age-matched controls. Serum low-density lipoprotein (LDL) and leukocyte m6A levels were associated with the progression of carotid plaque size and thickness. Both LDL level and plaque thickness were also independently and negatively related to m6A level. Reduced m6A level was further confirmed in leukocytes and endothelium in western diet-induced AS mice and in oxidized-LDL (ox-LDL)-treated human endothelium and monocyte cells. Decreased m6A level was closely related to the upregulation of AlkB homolog 1 (ALKBH1), the demethylase of m6A. Silencing of ALKBH1 or hypoxia-inducible factor 1α (HIF1α) could rescue the ox-LDL–increased level of MIAT, a hypoxia-response gene. Mechanically, ox-LDL induced HIF1α for transfer into the nucleus. Nuclear HIF1α bound to the ALKBH1-demethylated MIAT promoter and transcriptionally upregulated its expression. Therefore, elevated ALKBH1 level in endothelium and leukocytes reduced m6A level, which is a novel and sensitive biomarker for AS progression.
Reciprocal regulation of miR-1205 and E2F1 modulates progression of laryngeal squamous cell carcinoma
Authors: Li Pei , Lin Xi-Jun , Yang Yang , Yang An-Kui , Di Jin-Ming , Jiang Qi-Wei , Huang Jia-Rong , Yuan Meng-Ling , Xing Zi-Hao , Wei Meng-Ning , Li Yao , Yuan Xiao-Hui , Shi Zhi , Liu Hui , Ye Jin
Published: December 2019

The burgeoning functions of many microRNAs (miRs) have been well study in cancer. However, the level and function of miR-1205 in laryngeal squamous cell cancer remains unknown. In the current research, we validated that miR-1205 was notably downregulated in human laryngeal squamous cell carcinoma (LSCC) samples in comparison with tissues adjacent to LSCC, and correlated with T stage, lymph node metastasis, and clinical stage. Using Kaplan–Meier analysis indicates that high expression of miR-1205 has a favorable prognosis for patients with LSCC. Functional assays show that enforced miR-1205 expression attenuates the migration, growth, and invasion of LSCC cells. And E2F1 is verified to be a target of miR-1205, while E2F1 binds to miR-1205 promoter and transcriptionally inhibits miR-1205 expression. Overexpression of E2F1 reverses the inhibitory impacts of miR-1205 on LSCC cells in part. Importantly, E2F1 is abnormally increased in LSCC tissues, and its protein levels were inversely relevant to miR-1205 expression. High E2F1 protein level is in connection with clinical stage, T stage, lymph node metastasis, and poor prognosis. Consequently, reciprocal regulation of miR-1205 and E2F1 plays a crucial role in the progression of LSCC, suggesting a new miR-1205/E2F1-based clinical application for patients of LSCC.
Resistance to BTK inhibition by ibrutinib can be overcome by preventing FOXO3a nuclear export and PI3K/AKT activation in B-cell lymphoid malignancies
Authors: Kapoor Isha , Li Yue , Sharma Arishya , Zhu Huayuan , Bodo Juraj , Xu Wei , Hsi Eric D. , Hill Brian T. , Almasan Alexandru
Published: December 2019

Chronic activation of the Bruton’s tyrosine kinase (BTK)-mediated B-cell receptor (BCR) signaling is a hallmark of many B-cell lymphoid malignancies, including chronic lymphocytic leukemia (CLL) and diffuse large B-cell lymphoma (DLBCL). Ibrutinib, an FDA approved, orally administered BTK inhibitor, has demonstrated high response rates, however, complete responses are infrequent and acquired resistance to BTK inhibition can emerge. In this study, we generated ibrutinib-resistant (IB-R) cell lines by chronic exposure of CLL and activated B-cell (ABC)-DLBCL cells to ibrutinib in order to investigate the mechanism of acquired resistance to ibrutinib. IB-R cell lines demonstrated downregulation of FOXO3a and PTEN levels and activation of AKT, with their levels being low in the nuclei of resistant cells in comparison to the sensitive counterparts. Inhibition of PI3K and AKT using idelalisib and MK2206, respectively increased ibrutinib-induced apoptosis in IB-R cells by downregulation of pAKT473 and restoring FOXO3a levels, demonstrating the importance of these cell survival factors for ibrutinib-resistance. Notably, the exportin 1 inhibitor, selinexor synergized with ibrutinib in IB-R cells and restored nuclear abundance of FOXO3a and PTEN, suggesting that nuclear accumulation of FOXO3a and PTEN facilitates increase in ibrutinib-induced apoptosis in IB-R cells. These data demonstrate that reactivation of FOXO3a nuclear function enhances the efficacy of ibrutinib and overcomes acquired resistance to ibrutinib. Together, these findings reveal a novel mechanism that confers ibrutinib resistance via aberrant nuclear/cytoplasmic subcellular localization of FOXO3a and could be exploited by rational therapeutic combination regimens for effectively treating lymphoid malignancies.
eIF2α signaling regulates autophagy of osteoblasts and the development of osteoclasts in OVX mice
Authors: Li Jie , Li Xinle , Liu Daquan , Hamamura Kazunori , Wan Qiaoqiao , Na Sungsoo , Yokota Hiroki , Zhang Ping
Published: December 2019

Bone loss in postmenopausal osteoporosis is induced chiefly by an imbalance of bone-forming osteoblasts and bone-resorbing osteoclasts. Salubrinal is a synthetic compound that inhibits de-phosphorylation of eukaryotic translation initiation factor 2 alpha (eIF2α). Phosphorylation of eIF2α alleviates endoplasmic reticulum (ER) stress, which may activate autophagy. We hypothesized that eIF2α signaling regulates bone homeostasis by promoting autophagy in osteoblasts and inhibiting osteoclast development. To test the hypothesis, we employed salubrinal to elevate the phosphorylation of eIF2α in an ovariectomized (OVX) mouse model and cell cultures. In the OVX model, salubrinal prevented abnormal expansion of rough ER and decreased the number of acidic vesiculars. It regulated ER stress-associated signaling molecules such as Bip, p-eIF2α, ATF4 and CHOP, and promoted autophagy of osteoblasts via regulation of eIF2α, Atg7, LC3, and p62. Salubrinal markedly alleviated OVX-induced symptoms such as reduction of bone mineral density and bone volume fraction. In primary bone-marrow-derived cells, salubrinal increased the differentiation of osteoblasts, and decreased the formation of osteoclasts by inhibiting nuclear factor of activated T-cells cytoplasmic 1 (NFATc1). Live cell imaging and RNA interference demonstrated that suppression of osteoclastogenesis is in part mediated by Rac1 GTPase. Collectively, this study demonstrates that ER stress-autophagy axis plays an important role in OVX mice. Bone-forming osteoblasts are restored by maintaining phosphorylation of eIF2α, and bone-resorbing osteoclasts are regulated by inhibiting NFATc1 and Rac1 GTPase.
miR-137 alleviates doxorubicin resistance in breast cancer through inhibition of epithelial-mesenchymal transition by targeting DUSP4
Authors: Du Feiya , Yu Ling , Wu Ying , Wang Shuqian , Yao Jia , Zheng Xiaoxiao , Xie Shangzhi , Zhang Shufeng , Lu Xuemei , Liu Yu , Chen Wei
Published: December 2019

Acquired resistance to chemotherapy is a major obstacle in breast cancer (BC) treatment. Accumulated evidence has uncovered that microRNAs (miRNAs) are vital regulators of chemoresistance in cancer. Growing studies reveal that miR-137 acts as a suppressor in tumor progression. However, it remains obscure the role of miR-137 in modulating the sensitivity of BC cells to doxorubicin (DOX). In this study, we demonstrate that miR-137 exerts a significant effect on repressing the development of chemoresistance of BC cells in response to DOX via attenuating epithelial-mesenchymal transition (EMT) of tumor cells in vitro and in vivo. MiR-137 overexpression dramatically elevated the sensitivity of BC cells to DOX as well as impaired the DOX-promoted EMT of tumor cells. Mechanistically, miR-137 directly targeted dual-specificity phosphatase 4 (DUSP4) to impact on the EMT and chemoresistance of BC cells upon DOX treatment. Consistently, decreased DUSP4 efficiently enhanced the sensitivity of BC cells to DOX while overexpressed DUSP4 significantly diminished the beneficial effect of miR-137 on BC cells chemoresistance. Moreover, the increased miR-137 heightened the sensitivity of BC cells-derived tumors to DOX through targeting DUSP4 in vivo. Together, our results provide a novel insight into the DOX resistance of BC cells and miR-137 may serve as a new promising therapeutic target for overcoming chemoresistance in BC.
Controlling a Van Hove singularity and Fermi surface topology at a complex oxide heterostructure interface
Authors: Mori Ryo , Marshall Patrick B. , Ahadi Kaveh , Denlinger Jonathan D. , Stemmer Susanne , Lanzara Alessandra
Published: December 2019

The emergence of saddle-point Van Hove singularities (VHSs) in the density of states, accompanied by a change in Fermi surface topology, Lifshitz transition, constitutes an ideal ground for the emergence of different electronic phenomena, such as superconductivity, pseudo-gap, magnetism, and density waves. However, in most materials the Fermi level, $${E}_{{\rm{F}}}$$

E

F

, is too far from the VHS where the change of electronic topology takes place, making it difficult to reach with standard chemical doping or gating techniques. Here, we demonstrate that this scenario can be realized at the interface between a Mott insulator and a band insulator as a result of quantum confinement and correlation enhancement, and easily tuned by fine control of layer thickness and orbital occupancy. These results provide a tunable pathway for Fermi surface topology and VHS engineering of electronic phases.
CD4+ T cell help creates memory CD8+ T cells with innate and help-independent recall capacities
Authors: Ahrends Tomasz , Busselaar Julia , Severson Tesa M. , Bąbała Nikolina , de Vries Evert , Bovens Astrid , Wessels Lodewyk , van Leeuwen Fred , Borst Jannie
Published: December 2019

CD4+ T cell help is required for the generation of CD8+ cytotoxic T lymphocyte (CTL) memory. Here, we use genome-wide analyses to show how CD4+ T cell help delivered during priming promotes memory differentiation of CTLs. Help signals enhance IL-15-dependent maintenance of central memory T (TCM) cells. More importantly, help signals regulate the size and function of the effector memory T (TEM) cell pool. Helped TEM cells produce Granzyme B and IFNγ upon antigen-independent, innate-like recall by IL-12 and IL-18. In addition, helped memory CTLs express the effector program characteristic of helped primary CTLs upon recall with MHC class I-restricted antigens, likely due to epigenetic imprinting and sustained mRNA expression of effector genes. Our data thus indicate that during priming, CD4+ T cell help optimizes CTL memory by creating TEM cells with innate and help-independent antigen-specific recall capacities.
Gut uropathogen abundance is a risk factor for development of bacteriuria and urinary tract infection
Authors: Magruder Matthew , Sholi Adam N. , Gong Catherine , Zhang Lisa , Edusei Emmanuel , Huang Jennifer , Albakry Shady , Satlin Michael J. , Westblade Lars F. , Crawford Carl , Dadhania Darshana M. , Lubetzky Michelle , Taur Ying , Littman Eric , Ling Lilan , Burnham Philip , De Vlaminck Iwijn , Pamer Eric , Suthanthiran Manikkam , Lee John Richard
Published: December 2019

The origin of most bacterial infections in the urinary tract is often presumed to be the gut. Herein, we investigate the relationship between the gut microbiota and future development of bacteriuria and urinary tract infection (UTI). We perform gut microbial profiling using 16S rRNA gene deep sequencing on 510 fecal specimens from 168 kidney transplant recipients and metagenomic sequencing on a subset of fecal specimens and urine supernatant specimens. We report that a 1% relative gut abundance of Escherichia is an independent risk factor for Escherichia bacteriuria and UTI and a 1% relative gut abundance of Enterococcus is an independent risk factor for Enterococcus bacteriuria. Strain analysis establishes a close strain level alignment between species found in the gut and in the urine in the same subjects. Our results support a gut microbiota–UTI axis, suggesting that modulating the gut microbiota may be a potential novel strategy to prevent UTIs.
The Escherichia coli transcriptome mostly consists of independently regulated modules
Authors: Sastry Anand V. , Gao Ye , Szubin Richard , Hefner Ying , Xu Sibei , Kim Donghyuk , Choudhary Kumari Sonal , Yang Laurence , King Zachary A. , Palsson Bernhard O.
Published: December 2019

Underlying cellular responses is a transcriptional regulatory network (TRN) that modulates gene expression. A useful description of the TRN would decompose the transcriptome into targeted effects of individual transcriptional regulators. Here, we apply unsupervised machine learning to a diverse compendium of over 250 high-qualityEscherichia coliRNA-seq datasets to identify 92 statistically independent signals that modulate the expression of specific gene sets. We show that 61 of these transcriptomic signals represent the effects of currently characterized transcriptional regulators. Condition-specific activation of signals is validated by exposure ofE. colito new environmental conditions. The resulting decomposition of the transcriptome provides: a mechanistic, systems-level, network-based explanation of responses to environmental and genetic perturbations; a guide to gene and regulator function discovery; and a basis for characterizing transcriptomic differences in multiple strains. Taken together, our results show that signal summation describes the composition of a model prokaryotic transcriptome.
Author Correction: Gene correction for SCID-X1 in long-term hematopoietic stem cells
Authors: Pavel-Dinu Mara , Wiebking Volker , Dejene Beruh T. , Srifa Waracharee , Mantri Sruthi , Nicolas Carmencita E. , Lee Ciaran , Bao Gang , Kildebeck Eric J. , Punjya Niraj , Sindhu Camille , Inlay Matthew A. , Saxena Nivedita , DeRavin Suk See , Malech Harry , Roncarolo Maria Grazia , Weinberg Kenneth I. , Porteus Matthew H.
Published: December 2019

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
Author Correction: Stronger zonal convective clustering associated with a wider tropical rain belt
Authors: Popp Max , Bony Sandrine
Published: December 2019

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
Author Correction: Marrying chemistry with biology by combining on-chip solution-based combinatorial synthesis and cellular screening
Authors: Benz Maximilian , Molla Mijanur R. , Böser Alexander , Rosenfeld Alisa , Levkin Pavel A.
Published: December 2019

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
The GenomeAsia 100K Project enables genetic discoveries across Asia
Authors:   GenomeAsia100K Consortium, Wall Jeffrey D. , Stawiski Eric W. , Ratan Aakrosh , Kim Hie Lim , Kim Changhoon , Gupta Ravi , Suryamohan Kushal , Gusareva Elena S. , Purbojati Rikky Wenang , Bhangale Tushar , Stepanov Vadim , Kharkov Vladimir , Schröder Markus S. , Ramprasad Vedam , Tom Jennifer , Durinck Steffen , Bei Qixin , Li Jiani , Guillory Joseph , Phalke Sameer , Basu Analabha , Stinson Jeremy , Nair Sandhya , Malaichamy Sivasankar , Biswas Nidhan K. , Chambers John C. , Cheng Keith C. , George Joyner T. , Khor Seik Soon , Kim Jong-Il , Cho Belong , Menon Ramesh , Sattibabu Thiramsetti , Bassi Akshi , Deshmukh Manjari , Verma Anjali , Gopalan Vivek , Shin Jong-Yeon , Pratapneni Mahesh , Santhosh Sam , Tokunaga Katsushi , Md-Zain Badrul M. , Chan Kok Gan , Parani Madasamy , Natarajan Purushothaman , Hauser Michael , Allingham R. Rand , Santiago-Turla Cecilia , Ghosh Arkasubhra , Gadde Santosh Gopi Krishna , Fuchsberger Christian , Forer Lukas , Schoenherr Sebastian , Sudoyo Herawati , Lansing J. Stephen , Friedlaender Jonathan , Koki George , Cox Murray P. , Hammer Michael , Karafet Tatiana , Ang Khai C. , Mehdi Syed Q. , Radha Venkatesan , Mohan Viswanathan , Majumder Partha P. , Seshagiri Somasekar , Seo Jeong-Sun , Schuster Stephan C. , Peterson Andrew S.
Published: December 2019

The underrepresentation of non-Europeans in human genetic studies so far has limited the diversity of individuals in genomic datasets and led to reduced medical relevance for a large proportion of the world’s population. Population-specific reference genome datasets as well as genome-wide association studies in diverse populations are needed to address this issue. Here we describe the pilot phase of the GenomeAsia 100K Project. This includes a whole-genome sequencing reference dataset from 1,739 individuals of 219 population groups and 64 countries across Asia. We catalogue genetic variation, population structure, disease associations and founder effects. We also explore the use of this dataset in imputation, to facilitate genetic studies in populations across Asia and worldwide.
Structural and solvent control over activation parameters for a pair of retro Diels-Alder reactions
Authors: Widstrom Andrea L. , Lear Benjamin J.
Published: December 2019

We report the temperature dependent NMR of two Diels-Alder adducts of furan: one formed with maleic anhydride and the other with N-methylmaleimide. These adducts are the products of so-called ‘click’ reactions, widely valued for providing simple, reliable, and robust reactivity. Under our experimental conditions, these adducts undergo a retro Diels-Alder reaction and we use our temperature dependent NMR to determine the rates of these reactions at multiple temperatures—ultimately providing estimates of the activation parameters for the reversion. We repeat these measurements in three solvents. We find that, in all solvents, the barrier to reversion is larger for the adduct formed with N-methylmaleimide. The barrier to reversion for this adduct is relatively insensitive to changes in solvent while the adduct formed with maleic anhydride responds more strongly to changes in solvent polarity. The differences in reaction barrier and solvent dependence arises because the adduct formed with N-methylmalemide is more stable—leading to a larger barrier to reversion—while the adduct formed with maleic anhydride experiences a larger change in dipole during the reaction—leading to a larger solvent dependence.
Electronic structure and core electron fingerprints of caesium-based multi-alkali antimonides for ultra-bright electron sources
Authors: Cocchi Caterina , Mistry Sonal , Schmeißer Martin , Amador Raymond , Kühn Julius , Kamps Thorsten
Published: December 2019

The development of novel photocathode materials for ultra-bright electron sources demands efficient and cost-effective strategies that provide insight and understanding of the intrinsic material properties given the constraints of growth and operational conditions. To address this question, we propose a viable way to establish correlations between calculated and measured data on core electronic states of Cs-K-Sb materials. To do so, we combine first-principles calculations based on all-electron density-functional theory on the three alkali antimonides Cs3Sb, Cs2KSb, and CsK2Sb with x-ray photoemission spectroscopy (XPS) on Cs-K-Sb photocathode samples. Within the GW approximation of many-body perturbation theory, we obtain quantitative predictions of the band gaps of these materials, which range from 0.57 eV in Cs2KSb to 1.62 eV in CsK2Sb and manifest direct or indirect character depending on the relative potassium content. Our theoretical electronic-structure analysis also reveals that the core states of these systems have binding energies that depend only on the atomic species and their crystallographic sites, with largest shifts of the order of 2 eV and 0.5 eV associated to K 2p and Sb 3d states, respectively. This information can be correlated to the maxima in the XPS survey spectra, where such peaks are clearly visible. In this way, core-level shifts can be used as fingerprints to identify specific compositions of Cs-K-Sb materials and their relation with the measured values of quantum efficiency. Our results represent the first step towards establishing a robust connection between the experimental preparation and characterization of photocathodes, the ab initio prediction of their electronic structure, and the modeling of emission and beam formation processes.
Measurement of Cyanobacterial Bloom Magnitude using Satellite Remote Sensing
Authors: Mishra Sachidananda , Stumpf Richard P. , Schaeffer Blake A. , Werdell P. Jeremy , Loftin Keith A. , Meredith Andrew
Published: December 2019

Cyanobacterial harmful algal blooms (cyanoHABs) are a serious environmental, water quality and public health issue worldwide because of their ability to form dense biomass and produce toxins. Models and algorithms have been developed to detect and quantify cyanoHABs biomass using remotely sensed data but not for quantifying bloom magnitude, information that would guide water quality management decisions. We propose a method to quantify seasonal and annual cyanoHAB magnitude in lakes and reservoirs. The magnitude is the spatiotemporal mean of weekly or biweekly maximum cyanobacteria biomass for the season or year. CyanoHAB biomass is quantified using a standard reflectance spectral shape-based algorithm that uses data from Medium Resolution Imaging Spectrometer (MERIS). We demonstrate the method to quantify annual and seasonal cyanoHAB magnitude in Florida and Ohio (USA) respectively during 2003–2011 and rank the lakes based on median magnitude over the study period. The new method can be applied to Sentinel-3 Ocean Land Color Imager (OLCI) data for assessment of cyanoHABs and the change over time, even with issues such as variable data acquisition frequency or sensor calibration uncertainties between satellites. CyanoHAB magnitude can support monitoring and management decision-making for recreational and drinking water sources.
Carcinoembryonic antigen cell adhesion molecule 6 (CEACAM6) in Pancreatic Ductal Adenocarcinoma (PDA): An integrative analysis of a novel therapeutic target
Authors: Pandey Ritu , Zhou Muhan , Islam Shariful , Chen Baowei , Barker Natalie K , Langlais Paul , Srivastava Anup , Luo Moulun , Cooke Laurence S. , Weterings Eric , Mahadevan Daruka
Published: December 2019

We investigated biomarker CEACAM6, a highly abundant cell surface adhesion receptor that modulates the extracellular matrix (ECM) in pancreatic ductal adenocarcinoma (PDA). The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) RNA-Seq data from PDA patients were analyzed for CEACAM6 expression and evaluated for overall survival, association, enrichment and correlations. A CRISPR/Cas9 Knockout (KO) of CEACAM6 in PDA cell line for quantitative proteomics, mitochondrial bioenergetics and tumor growth in mice were conducted. We found CEACAM6 is over-expressed in primary and metastatic basal and classical PDA subtypes. Highest levels are in classical activated stroma subtype. CEACAM6 over-expression is universally a poor prognostic marker in KRAS mutant and wild type PDA. High CEACAM6 expression is associated with low cytolytic T-cell activity in both basal and classical PDA subtypes and correlates with low levels of T-REG markers. In HPAF-II cells knockout of CEACAM6 alters ECM-cell adhesion, catabolism, immune environment, transmembrane transport and autophagy. CEACAM6 loss increases mitochondrial basal and maximal respiratory capacity. HPAF-II CEACAM6−/− cells are growth suppressed by >65% vs. wild type in mice bearing tumors. CEACAM6, a key regulator affects several hallmarks of PDA including the fibrotic reaction, immune regulation, energy metabolism and is a novel therapeutic target in PDA.
The mixed quantum Rabi model
Authors: Duan Liwei , Xie You-Fei , Chen Qing-Hu
Published: December 2019

The analytical exact solutions to the mixed quantum Rabi model (QRM) including both one- and two-photon terms are found by using Bogoliubov operators. Transcendental functions in terms of 4 × 4 determinants responsible for the exact solutions are derived. These so-called G-functions with pole structures can be reduced to the previous ones in the unmixed QRMs. The zeros of G-functions reproduce completely the regular spectra. The exceptional eigenvalues can also be obtained by another transcendental function. From the pole structure, we can derive two energy limits when the two-photon coupling strength tends to the collapse point. All energy levels only collapse to the lower one, which diverges negatively. The level crossings in the unmixed QRMs are relaxed to avoided crossings in the present mixed QRM due to absence of parity symmetry. In the weak two-photon coupling regime, the mixed QRM is equivalent to an one-photon QRM with an effective positive bias, suppressed photon frequency and enhanced one-photon coupling, which may pave a highly efficient and economic way to access the deep-strong one-photon coupling regime.
Investigating Emotion in Malay, Australian and Iranian Individuals with and without Depression
Authors: Jobson Laura , Mirabolfathi Vida , Moshirpanahi Shiva , Parhoon Hadi , Gillard Julia , Mukhtar Firdaus , Moradi Ali Reza , Mohan Sindhu Nair
Published: December 2019

This study investigated the influence of culture and depression on (1) emotion priming reactions, (2) the recall of subjective experience of emotion, and (3) emotion meaning. Members of individualistic culture (Australia, n = 42) and collectivistic culture (Iran, n = 32, Malaysia, n = 74) with and without depression completed a biological motion task, subjective experience questionnaire and emotion meaning questionnaire. Those with depression, regardless of cultural group, provided significantly fewer correct responses on the biological motion task than the control group. Second, the collectivistic control groups reported greater social engaging emotion than the Australian control group. However, the three depressed groups did not differ culturally. The Australian depressed group reported significantly greater interpersonally engaging emotion than the Australian control group. Third, the collectivistic groups reported significantly greater social worth, belief changes and sharing of emotion than the individualistic group. Depression did not influence these cultural effects. Instead we found that those with depression, when compared to controls, considered emotions as subjective phenomena, that were qualifying for relationships with others, and associated with greater agency appraisals. The applicability of the biocultural framework of emotion in depression was considered.
Adipose-derived stromal/stem cells improve epidermal homeostasis
Authors: Moriyama Mariko , Sahara Shunya , Zaiki Kaori , Ueno Ayumi , Nakaoji Koichi , Hamada Kazuhiko , Ozawa Toshiyuki , Tsuruta Daisuke , Hayakawa Takao , Moriyama Hiroyuki
Published: December 2019

Wound healing is regulated by complex interactions between the keratinocytes and other cell types including fibroblasts. Recently, adipose-derived mesenchymal stromal/stem cells (ASCs) have been reported to influence wound healing positively via paracrine involvement. However, their roles in keratinocytes are still obscure. Therefore, investigation of the precise effects of ASCs on keratinocytes in an in vitro culture system is required. Our recent data indicate that the epidermal equivalents became thicker on a collagen vitrigel membrane co-cultured with human ASCs (hASCs). Co-culturing the human primary epidermal keratinocytes (HPEK) with hASCs on a collagen vitrigel membrane enhanced their abilities for cell proliferation and adhesion to the membrane but suppressed their differentiation suggesting that hASCs could maintain the undifferentiated status of HPEK. Contrarily, the effects of co-culture using polyethylene terephthalate or polycarbonate membranes for HPEK were completely opposite. These differences may depend on the protein permeability and/or structure of the membrane. Taken together, our data demonstrate that hASCs could be used as a substitute for fibroblasts in skin wound repair, aesthetic medicine, or tissue engineering. It is also important to note that a co-culture system using the collagen vitrigel membrane allows better understanding of the interactions between the keratinocytes and ASCs.
A study of dynamic adsorption of propylene and ethylene emitted from the process of coal self-heating
Authors: Wojtacha-Rychter Karolina , Smoliński Adam
Published: December 2019

The gaseous products emitted in the self-heating process constitute one of the parameters suggested for detecting coal spontaneous combustion in underground mining. The objective of the study is to investigate the changes of ethylene and propylene content in a gaseous mixture which flowed through a fixed bed column filled with bituminous coal of different grain size. The mixtures of fire gases were obtained from laboratory simulated heating of coal at the temperatures of 373 K, 423 K, 473 K and 523 K. Hydrocarbons of various initial concentrations were introduced to the adsorption column at the constant flow rate of 2∙10−7 m3/s. The experimental findings show that decreasing the adsorbent granulation and gases concentration causes an extended breakthrough and coal bed saturation times. In all the tests, the saturation time was gained faster for ethylene than for propylene. Thus, the content of tested hydrocarbons, which are some of the indicators for assessing the degree of the coal self-heating process, in mine air may change in time as a result of the adsorption phenomenon. It occurs particularly at the early stage of the self-heating process and in places where coal dust has been left.
Microbiome differences in disease-resistant vs. susceptible Acropora corals subjected to disease challenge assays
Authors: Rosales Stephanie M. , Miller Margaret W. , Williams Dana E. , Traylor-Knowles Nikki , Young Benjamin , Serrano Xaymara M.
Published: December 2019

In recent decades coral gardening has become increasingly popular to restore degraded reef ecosystems. However, the growth and survivorship of nursery-reared outplanted corals are highly variable. Scientists are trying to identify genotypes that show signs of disease resistance and leverage these genotypes in restoring more resilient populations. In a previous study, a field disease grafting assay was conducted on nursery-reared Acropora cervicornis and Acropora palmata to quantify relative disease susceptibility. In this study, we further evaluate this field assay by investigating putative disease-causing agents and the microbiome of corals with disease-resistant phenotypes. We conducted 16S rRNA gene high-throughput sequencing on A. cervicornis and A. palmata that were grafted (inoculated) with a diseased A. cervicornis fragment. We found that independent of health state, A. cervicornis and A. palmata had distinct alpha and beta diversity patterns from one another and distinct dominant bacteria. In addition, despite different microbiome patterns between both inoculated coral species, the genus Sphingomonadaceae was significantly found in both diseased coral species. Additionally, a core bacteria member from the order Myxococcales was found at relatively higher abundances in corals with lower rates of disease development following grafting. In all, we identified Sphingomonadaceae as a putative coral pathogen and a bacterium from the order Myxococcales associated with corals that showed disease resistant phenotypes.
Speed of structured light pulses in free space
Authors: Petrov N. I.
Published: December 2019

A plane monochromatic wave propagates in vacuum at the velocity c. However, wave packets limited in space and time are used to transmit energy and information. Here it has been shown based on the wave approach that the on-axis part of the pulsed beams propagates in free space at a variable speed, exhibiting both subluminal and superluminal behaviours in the region close to the source, and their velocity approaches the value of c with distance. Although the pulse can travel over small distances faster than the speed of light in vacuum, the average on-axis velocity, which is estimated by the arrival time of the pulse at distances z ≫ ld (ld is the Rayleigh diffraction range) and z > cτ (τ is the pulse width) is less than c. The total pulsed beam propagates at a constant subluminal velocity over the whole distance. The mutual influence of the spatial distribution of radiation and the temporal shape of the pulse during nonparaxial propagation in vacuum is studied. It is found that the decrease in the width of the incident beam and the increase in the central wavelength of the pulse lead to a decrease in the propagation velocity of the wave packet.
Biological Data in the Light of Toxicological Risk Assessment
Authors: Vitcheva Vessela
Published: December 2019

The practice of modern toxicology has generated and continues to generate enormous amounts of data to be used for safety evaluation and decision-making in human toxicological and ecotoxicological risk assessment as well as elucidation of possible modes of action (MoA) and adverse outcome pathways (AOP). The major goal of toxicity testing is to generate and collect appropriate results from a battery of studies and to assess, interpret and use the data correctly. Although these data were not generated at high speed, large collections of data have been assembled over the years. In addition, new in vitro methods generate high-throughput bioactivity data, together with omics technologies, for elucidation of mechanisms and support of chemical safety assessment. This chapter gives an overview on the different types of studies carried out to generate biological data by in vivo and in vitro testing and toxicity assays, focusing on data generated according to classic toxicological hazard assessment for human health, as an overview of requirements for regulatory toxicological evaluation that predictive toxicology would target. These data are generated mostly in rather time-consuming studies; however, high-throughput in vitro technologies have increased the volume, speed and variety of data generation. The main principles of the tests, the toxicity endpoints and the possible applications of the data obtained along with the main steps in data quality assessment and interpretation are discussed.
Profiling the Tox21 Chemical Library for Environmental Hazards: Applications in Prioritisation, Predictive Modelling, and Mechanism of Toxicity Characterisation
Authors: Sakamuru S. , Zhu H. , Xia M. , Simeonov A. , Huang R.
Published: December 2019

The Toxicology for the 21st Century (Tox21) program is an initiative between multiple U.S. federal agencies aiming to predict chemical toxicity based on the data from in vitro assays, which would greatly reduce the effort of traditional whole animal studies. The program has constructed a library of ∼10 000 environmental chemicals and drugs, representing a wide range of structural diversity, which is being tested in triplicate against a battery of cell-based assays in a quantitative high-throughput screening (qHTS) format. A standardised process has also been established to enable assay development, automated robotic screening, massive data acquisition, new data analysis approaches needed to integrate and characterise the data, and data sharing. To date, the Tox21 program has generated over 120 million data points that have been made publicly available, thus contributing to the big data in toxicology. In this chapter, examples are given to show how to build in vivo toxicity prediction models based on in vitro activity profiles of compounds and prioritise compounds for further in-depth toxicological studies. These data sets were also successfully used in a “crowd-source” challenge with its goal to encourage public participation to develop new methods and models for toxicity prediction.
Chemometrical Analysis of Proteomics Data
Authors: Vračko Marjan
Published: December 2019

Today we witness an explosion of data emerging from proteomic research, i.e., information about the entire protein status of the cells. This chapter is focused on chemometrical analysis of the proteomics data as an example of the handling of large amounts of data points and extracting information and building knowledge, such as the identification of protein changes associated with specific toxic endpoints and conclusion on potential biomarkers. Data compression using graphical and numerical representation of proteomics data as well as chemometrical analysis tools such as clustering, classification and genetic algorithm will be briefly described. Bio-descriptors will be discussed and the added value of using them in combination with chemical descriptors for modelling. Furthermore, application examples of the methods and tools will be shown, demonstrating how knowledge can be extracted from proteomics data to support the understanding of toxicity mechanisms and help build predictive models.
An electroanalytical platform for nereistoxin-related insecticide detection based on DNA conformational switching and exonuclease III assisted target recycling
Authors: Xie Shunbi , Tang Chunyan , Liu Huan , Zhang Tian-e , Tang Ying , Teng Liumei , Zhang Jin
Published: December 2019

An electroanalytical platform for NRT-related insecticide detection is proposed based on NRT induced DNA conformational switching and Exo III assisted target recycling.
Application of ratiometric fluorescence sensor-based microwave-assisted synthesized CdTe quantum dots and mesoporous structured epitope-imprinted polymers for highly efficient determination of tyrosine phosphopeptide
Authors: Saeedzadeh Amiri Nasibeh , Milani Hosseini Mohammad-Reza
Published: December 2019

Molecularly imprinted polymer coated quantum dot sensor modified with ratiometric fluorescence methods and mesoporous structured epitope imprinted silica materials (QDs@SiO2@EMSiO2) have been fabricated for detection of tyrosine phosphopeptide.
A qualitative recognition method based on Karhunen–Loeve decomposition for near-infrared (NIR) and mid infrared (MIR) spectroscopy analysis
Authors: Zhao Zhong , Li Bin , Liu Wei , Yuan Hongfu , Song Chunfeng
Published: December 2019

Qualitative recognition is an important research area of NIR and MIR spectroscopy analyses.
Immunochromatographic tests for the detection of microcystin-LR toxin in water and fish samples
Authors: Zvereva Elena A. , Hendrickson Olga D. , Zherdev Anatoly V. , Dzantiev Boris B.
Published: December 2019

Immunochromatographic analysis of microcystin-LR with indirect antibody labeling by gold nanoparticles has been proposed and successfully applied for fish and water samples.
A simple “on–off–on” ECL sensor for glucose determination based on Pd nanowires and Ag doped g-C3N4 nanosheets
Authors: Fan Yu , Chen Shihong , Wei Shaping , Guo Jinlin , Li Yang
Published: December 2019

One-dimensional Pd nanowires (PdNWs) and Ag doped g-C3N4 nanosheets (Ag-g-C3N4 NSs) were prepared and applied to construct a simple “on–off–on” ECL sensor for glucose detection.
UV-induced hydrogen transfer in DNA base pairs promoted by dark nπ* states
Authors: Szkaradek Kinga E. , Stadlbauer Petr , Šponer Jiří , Góra Robert W. , Szabla Rafał
Published: December 2019

Formation of an excited-state complex enables ultrafast photorelaxation of dark nπ* states in GC and HC base pairs.
Engineered assembly of a protein–cucurbituril biohybrid
Authors: Guagnini Francesca , Engilberge Sylvain , Ramberg Kiefer O. , Pérez Javier , Crowley Peter B.
Published: December 2019

AdditionalQ7binding sites drive protein aggregation in solution and statistical disorder in the crystalline biohybrid suggest new possibilities for protein-based materials.
Energy–entropy competition in cation–hydroxyl interactions at the liquid water–Pt(111) interface
Authors: Kristoffersen Henrik H. , Chan Karen , Vegge Tejs , Hansen Heine Anton
Published: December 2019

At water–Pt(111) interfaces, cation–*OH interactions are found to consist of both internal energy stabilizations and entropy costs emphasizing the complexity of such systems.
Catalytic asymmetric [4+2] cycloaddition of 1-((2-aryl)vinyl)naphthalen-2-ols with in situ generated ortho-quinone methides for the synthesis of polysubstituted chromanes
Authors: You Yong , Li Ting-Ting , Yuan Shu-Pei , Xie Ke-Xin , Wang Zhen-Hua , Zhao Jian-Qiang , Zhou Ming-Qiang , Yuan Wei-Cheng
Published: December 2019

An asymmetric [4+2] cycloaddition of 1-((2-aryl)vinyl)naphthalen-2-ols with in situ generated ortho-quinone methides enables the highly enantioselective synthesis of polysubstituted chromanes.
A new iodate-phosphate Pb2(IO3)(PO4) achieving great improvement in birefringence activated by (IO3)−groups
Authors: Zhang Xiao-Han , Yang Bing-Ping , Chen Jin , Hu Chun-Li , Fang Zhi , Wang Zujian , Mao Jiang-Gao
Published: December 2019

The first divalent-metal iodate-phosphate, Pb2(IO3)(PO4), has been prepared, showing great improvement in birefringence because of the highly anisotropic (IO3)−groups.
A heterometallic D–A hybrid heterostructural framework with enhanced visible-light photocatalytic properties
Authors: Liu Jian-Jun , You Ming-Hua , Li Meng-Hua , Huang Chang-Cang , Lin Mei-Jin
Published: December 2019

A heterometallic D–A hybrid heterostructural framework from the ternary combination of CuI, lanthanide cations and viologen tectons exhibited enhanced photocatalytic activities for degradation of organic dyes.
Space-selective crystallization of glass by an optical vortex beam
Authors: Lipatiev Alexey S. , Lotarev Sergey V. , Smayev Mikhail P. , Lipateva Tatiana O. , Karateev Igor A. , Presnyakov Mikhail Yu. , Fedotov Sergey S. , Sigaev Vladimir N.
Published: December 2019

We report on the improvement of ultrafast laser-written track quality by using an optical vortex.
Compressive-force induced activation of apo-calmodulin in protein signalling
Authors: Chowdhury Susovan Roy , Jaiswal Sunidhi , Lu H. Peter
Published: December 2019

Biologically-available piconewton compressive force can activate apo-calmodulin without the existence of calcium ions: the discovery of a new force-activation alternative pathway in calmodulin cell signaling.
The impact of photocatalytic paint porosity on indoor NOx and HONO levels
Authors: Gandolfo Adrien , Bartolomei Vincent , Truffier-Boutry Delphine , Temime-Roussel Brice , Brochard Gregory , Bergé Virginie , Wortham Henri , Gligorovski Sasho
Published: December 2019

Photocatalytic materials are a potentially effective remediation technology for indoor air purification.
Engineering functional inorganic nanobiomaterials: controlling interactions between 2D-nanosheets and enzymes
Authors: Puglia Megan K. , Malhotra Mansi , Kumar Challa V.
Published: December 2019

A discussion of recent advances in controlling the enzyme-nanosheet interface, and rational methods to engineer interactions at these interface to build better nanobiomaterials and biodevices is presented.
Entropymetry for non-destructive structural analysis of LiCoO2cathodes
Authors: Kim Hye Jin , Park Youngkyu , Kwon Yoonjin , Shin Jaeho , Kim Young-Han , Ahn Hyun-Seok , Yazami Rachid , Choi Jang Wook
Published: December 2019

Entropymetry is proposed as a non-destructive diagnosis tool in detecting structural evolution of LiCoO2and its nickel-doped derivatives.
Electrochemical valorization of carboxylates in aqueous solution for the production of biofuels, fine chemicals, and hydrogen
Authors: Yuan Gang , Wang Li , Zhang Xiangwen , Luque Rafael , Wang Qingfa
Published: December 2019

Naturally separated biofuels, hydrogen, and fine chemicals are simultaneously produced in aqueous solutions of biomass-derived carboxylates using aqueous substitution synthesized anodes.
The direct transformation of bioethanol fermentation residues for production of high-quality resins
Authors: Pang Bo , Cao Xue-Fei , Sun Shao-Ni , Wang Xi-Luan , Wen Jia-Long , Lam Su Shiung , Yuan Tong-Qi , Sun Run-Cang
Published: December 2019

The direct transformation of bioethanol fermentation residues for production of high-quality green resins.