bluuebunny/crossref_metadata_2025 huggingface dataset:
What does fluorine do to a protein? Thermodynamic, and highly-resolved structural insights into fluorine-labelled variants of the cold shock protein
Authors: Welte Hannah , Zhou Tiankun , Mihajlenko Xenia , Mayans Olga , Kovermann Michael
Published: February 2020

Fluorine labelling represents one promising approach to study proteins in their native environment due to efficient suppressing of background signals. Here, we systematically probe inherent thermodynamic and structural characteristics of the Cold shock protein B from Bacillus subtilis (BsCspB) upon fluorine labelling. A sophisticated combination of fluorescence and NMR experiments has been applied to elucidate potential perturbations due to insertion of fluorine into the protein. We show that single fluorine labelling of phenylalanine or tryptophan residues has neither significant impact on thermodynamic stability nor on folding kinetics compared to wild type BsCspB. Structure determination of fluorinated phenylalanine and tryptophan labelled BsCspB using X-ray crystallography reveals no displacements even for the orientation of fluorinated aromatic side chains in comparison to wild type BsCspB. Hence we propose that single fluorinated phenylalanine and tryptophan residues used for protein labelling may serve as ideal probes to reliably characterize inherent features of proteins that are present in a highly biological context like the cell.
N-terminal domain of the architectural protein CTCF has similar structural organization and ability to self-association in bilaterian organisms
Authors: Bonchuk Artem , Kamalyan Sofia , Mariasina Sofia , Boyko Konstantin , Popov Vladimir , Maksimenko Oksana , Georgiev Pavel
Published: February 2020

CTCF is the main architectural protein found in most of the examined bilaterian organisms. The cluster of the C2H2 zinc-finger domains involved in recognition of long DNA-binding motif is only part of the protein that is evolutionarily conserved, while the N-terminal domain (NTD) has different sequences. Here, we performed biophysical characterization of CTCF NTDs from various species representing all major phylogenetic clades of higher metazoans. With the exception of Drosophilides, the N-terminal domains of CTCFs show an unstructured organization and absence of folded regions in vitro. In contrast, NTDs of Drosophila melanogaster and virilis CTCFs contain unstructured folded regions that form tetramers and dimers correspondingly in vitro. Unexpectedly, most NTDs are able to self-associate in the yeast two-hybrid and co-immunoprecipitation assays. These results suggest that NTDs of CTCFs might contribute to the organization of CTCF-mediated long-distance interactions and chromosomal architecture.
Comprehensive biophysical and functional study of ziv-aflibercept: characterization and forced degradation
Authors: Hermosilla Jesús , Pérez-Robles Raquel , Salmerón-García Antonio , Casares Salvador , Cabeza Jose , Bones Jonathan , Navas Natalia
Published: February 2020

Aflibercept (AFL) is an Fc fusion protein used in the treatment of colorectal cancers and different ophthalmological diseases. There are two medicines in which AFL is the active substance: Zaltrap and Eylea, referred as ziv-AFL and AFL respectively. No proper accelerated degradation studies were published on either AFL or ziv-AFL. These studies are essential during research, development and manufacturing stages. Here, we characterized ziv-AFL and submitted it to different stress conditions: light, 60 °C, freeze-thaw cycles, changes in pH, high hypertonic solution and strong denaturing conditions. We used an array of techniques to detect aggregation (SE-HPLC/DAD and DLS), changes in secondary structure (Far-UV circular dichroism), changes in conformation or tertiary structure (Intrinsic tryptophan fluorescence) and alterations in functionality (ELISA). Results indicate that aggregation is common degradation pathway. Two different types of aggregates were detected: dimers and high molecular weight aggregates attributed to β-amyloid-like structures. Secondary structure was maintained in most of the stress tests, while conformation was altered by almost all the tests except for the freeze-thaw cycles. Functionality, evaluated by its immunochemical reaction with VEGF, was found to be stable but with decrease when exposed to light and with likely partial inactivation of the drug when pH was altered.
RETRACTED ARTICLE: Inhibition of autophagic flux differently modulates cannabidiol-induced death in 2D and 3D glioblastoma cell cultures
Authors: Ivanov Vladimir N. , Grabham Peter W. , Wu Cheng-Chia , Hei Tom K.
Published: February 2020

Radiotherapy combined with chemotherapy is the major treatment modality for human glioblastoma multiforme (GBM). GBMs eventually relapse after treatment and the average survival of GBM patients is less than two years. There is some evidence that cannabidiol (CBD) can induce cell death and increases the radiosensitivity of GBM by enhancing apoptosis. Beside initiation of death, CBD has been demonstrated as an inducer of autophagy. In the present study, we address the question whether CBD simultaneously induces a protective effect in GBM by upregulating autophagy. Addition of chloroquine that suppressed autophagic flux to 2D GBM cultures increased CBD-induced cell death, presenting proof for the protective autophagy. Blockage of autophagy upregulated radiation-induced cytotoxicity but only modestly affected the levels of cell death in CBD- or CBD/γ-irradiated 3D GBM cultures. Furthermore, CBD enhanced the pro-apoptotic activities of JNK1/2 and MAPK p38 signaling cascades while partially downregulated the pro-survival PI3K-AKT cascade, thereby changing a balance between cell death and survival. Suppression of JNK activation partially reduced CBD-induced cell death in 3D GBM cultures. In contrast, co-treatment of CBD-targeted cells with inhibitors of PI3K-AKT-NF-κB, IKK-NF-κB or JAK2-STAT3 pathways killed surviving GBM cells in both 2D and 3D cultures, potentially improving the therapeutic ratio of GBM.
RNA sequence and length contribute to RNA-induced conformational change of TLS/FUS
Authors: Hamad Nesreen , Mashima Tsukasa , Yamaoki Yudai , Kondo Keiko , Yoneda Ryoma , Oyoshi Takanori , Kurokawa Riki , Nagata Takashi , Katahira Masato
Published: February 2020

Translocated in liposarcoma (TLS)/fused in sarcoma (FUS) is a multitasking DNA/RNA binding protein implicated in cancer and neurodegenerative diseases. Upon DNA damage, TLS is recruited to the upstream region of the cyclin D1 gene (CCND1) through binding to the promotor associated non-coding RNA (pncRNA) that is transcribed from and tethered at the upstream region. Binding to pncRNA is hypothesized to cause the conformational change of TLS that enables its inhibitive interaction with histone acetyltransferases and resultant repression of CCND1 expression, although no experimental proof has been obtained. Here, the closed-to-open conformational change of TLS on binding pncRNA was implied by fluorescence resonance energy transfer. A small fragment (31 nucleotides) of the full-length pncRNA (602 nucleotides) was shown to be sufficient for the conformational change of TLS. Dissection of pncRNA identified the G-rich RNA sequence that is critical for the conformational change. The length of RNA was also revealed to be critical for the conformational change. Furthermore, it was demonstrated that the conformational change of TLS is caused by another target DNA and RNA, telomeric DNA and telomeric repeat-containing RNA. The conformational change of TLS on binding target RNA/DNA is suggested to be essential for biological functions.
Similarity of therapeutic networks induced by a multi-component herbal remedy, Ukgansan, in neurovascular unit cells
Authors: Kim Bu-Yeo , Lim Hye-Sun , Kim Yu Jin , Sohn Eunjin , Kim Yun Hee , Koo Imhoi , Jeong Soo-Jin
Published: February 2020

The neurovascular unit, which includes neurons, glial cells, and vascular cells, plays crucial roles in the onset and progression of Alzheimer’s disease (AD). Therefore, effective drugs against AD should be able to target the multi-cellular neurovascular unit and the therapeutic relationships among neurovascular cells should be defined. Here, we examined the therapeutic effects of Ukgansan (UGS), an herbal remedy with multi-targeting capabilities, usingin vitroneurovascular unit models and anin vivomodel of AD. In addition, we compared the therapeutic networks induced by UGS and its components in different neurovascular cell types. We found that UGS and its components protected neurovascular cells against diverse damaging agents and improved the behavioral patterns of AD model mice. A comparison of UGS- or its components-induced therapeutic networks, constructed from high-throughput data on gene expression, pathway activity, and protein phosphorylation, revealed similarities among neurovascular cell types, especially between BV-2 microglia and HBVP (human brain vascular pericytes). These findings, together with the functional connections between neurovascular cells, can explain the therapeutic effects of UGS. Furthermore, they suggest underlying similarities in the therapeutic mechanisms in different neurovascular cell types.
Invasive Wild Pigs as Primary Nest Predators for Wild Turkeys
Authors: Sanders Heather N. , Hewitt David G. , Perotto-Baldivieso Humberto L. , VerCauteren Kurt C. , Snow Nathan P.
Published: February 2020

Depredation of wild turkey (Meleagris gallopavo) nests is a leading cause of reduced recruitment for the recovering and iconic game species. Invasive wild pigs (Sus scrofa) are known to depredate nests, and have been expanding throughout the distributed range of wild turkeys in North America. We sought to gain better insight on the magnitude of wild pigs depredating wild turkey nests. We constructed simulated wild turkey nests throughout the home ranges of 20 GPS-collared wild pigs to evaluate nest depredation relative to three periods within the nesting season (i.e., early, peak, and late) and two nest densities (moderate = 12.5-25 nests/km2, high = 25-50 nests/km2) in south-central Texas, USA during March–June 2016. Overall, the estimated probability of nest depredation by wild pigs was 0.3, equivalent to native species of nest predators in the study area (e.g., gray fox [Urocyon cinereoargenteus], raccoon [Procyon lotor], and coyote [Canis latrans]). Female wild pigs exhibited a constant rate of depredation regardless of nesting period or density of nests. However, male wild pigs increased their rate of depredation in areas with higher nest densities. Management efforts should remove wild pigs to reduce nest failure in wild turkey populations especially where recruitment is low.
Effect of mammalian mesopredator exclusion on vertebrate scavenging communities
Authors: Turner Kelsey L. , Conner L. Mike , Beasley James C.
Published: February 2020

Carrion is a valuable resource used by facultative scavengers across the globe. Due to conflicts with humans, many vertebrate scavengers have experienced population declines due to direct persecution or indirect effects of human activities. However, little is known about the implications of altered scavenger community composition on the fate and efficiency of carrion removal within ecosystems. In particular, mammalian mesopredators are efficient scavengers that are often subjected to control, thus, it is important to understand how the reduction of this scavenger guild influences the fate of carrion resources and efficiency of carrion removal within ecosystems. We evaluated the influence of the absence of mammalian mesopredators on vertebrate scavenging dynamics by comparing the efficiency of carrion removal and species composition at carrion between sites where we experimentally manipulated mesopredator abundance and paired control sites. Overall scavenging rates were high, even within our mesopredator exclusion sites (79% of carcasses). Despite the exclusion of an entire guild of dominant scavengers, we saw little effect on scavenging dynamics due to the extensive acquisition of carrion by avian scavengers. However, we observed a slight reduction in vertebrate scavenging efficiency in sites where mesopredators were excluded. Our results suggest vertebrate communities are highly efficient at carrion removal, as we saw a functional response by avian scavengers to increased carrion availability. These data provide insights into the impact of mesopredator control on food web dynamics, and build upon the growing body of knowledge investigating the role of vertebrate scavengers on ecosystem services provided through carrion removal.
Development of an embedded multimodality imaging platform for onco-pharmacology using a smart anticancer prodrug as an example
Authors: Raes Florian , Badiane Serigne Moussa , Renoux Brigitte , Papot Sébastien , Lerondel Stéphanie , Le Pape Alain
Published: February 2020

Increasingly, in vivo imaging holds a strategic position in bio-pharmaceutical innovation. We will present the implementation of an integrated multimodal imaging setup enabling the assessment of multiple, complementary parameters. The system allows the fusion of information provided by: Near infrared fluorescent biomarkers, bioluminescence (for tumor proliferation status), Photoacoustic and Ultrasound imaging. We will study representative applications to the development of a smart prodrug, delivering a highly cytotoxic chemotherapeutic agent to cancer tumors. The results realized the ability of this embedded, multimodality imaging platform to firstly detect bioluminescent and fluorescent signals, and secondly, record ultrasound and photoacoustic data from the same animal. This study demonstrated that the prodrug was effective in three different models of hypoxia in human cancers compared to the parental cytotoxic agent and the vehicle groups. Monitoring by photoacoustic imaging during the treatments revealed that the prodrug exhibits an intrinsic capability to prevent the progression of tumor hypoxia. It is essential for onco-pharmacology studies to precisely document the hypoxic status of tumors both before and during the time course of treatments. This approach opens new perspectives for exploitation of preclinical mouse models of cancer, especially when considering associations between hypoxia, neoangiogenesis and antitumor activity.
Inhibition of store-operated calcium channels by N-arachidonoyl glycine (NAGly): no evidence for the involvement of lipid-sensing G protein coupled receptors
Authors: Deveci Aykut , Hasna Jessy , Bouron Alexandre
Published: February 2020

N-arachidonoyl glycine (NAGly) is an endogenous lipid deriving from the endocannabinoid anandamide (AEA). Identified as a ligand of several G-protein coupled receptors (GPCRs), it can however exert biological responses independently of GPCRs. NAGly was recently shown to depress store-operated Ca2+ entry (SOCE) but its mechanism of action remains elusive. The major aim of this study was to gain a better knowledge on the NAGly-dependent impairment of SOCE in neurons of the central nervous system (CNS) from mice. First, we examined the expression of genes encoding for putative lipid sensing GPCRs using transcriptomic data publicly available. This analysis showed that the most abundant GPCRs transcripts present in the cerebral cortices of embryonic brains were coding for lysophosphatidic acid (LPA) and sphingosine-1 phosphate (S1P) receptors. Next, the presence of functional receptors was assessed with live-cell calcium imaging experiments. In primary cortical cells S1P and LPA mobilize Ca2+ from internal stores via a mechanism sensitive to the S1P and LPA receptor antagonists Ex26, H2L5186303, or Ki16425. However, none of these compounds prevented or attenuated the NAGly-dependent impairment of SOCE. We found no evidence for the requirement of lipid sensing GPCRs in this inhibitory process, indicating that NAGly is an endogenous modulator interfering with the core machinery of SOCE. Moreover, these data also raise the intriguing possibility that the depression of SOCE could play a role in the central effects of NAGly.
Evaluation of semiochemical based push-pull strategy for population suppression of ambrosia beetle vectors of laurel wilt disease in avocado
Authors: Rivera Monique J. , Martini Xavier , Conover Derrick , Mafra-Neto Agenor , Carrillo Daniel , Stelinski Lukasz L.
Published: February 2020

Ambrosia beetles (Coleoptera: Curculionidae: Scolytinae and Platypodinae) bore into tree xylem to complete their life cycle, feeding on symbiotic fungi. Ambrosia beetles are a threat to avocado where they have been found to vector a symbiotic fungus, Raffaelea lauricola, the causal agent of the laurel wilt disease. We assessed the repellency of methyl salicylate and verbenone to two putative laurel wilt vectors in avocado, Xyleborus volvulus (Fabricius) and Xyleborus bispinatus (Eichhoff), under laboratory conditions. Then, we tested the same two chemicals released from SPLAT flowable matrix with and without low-dose ethanol dispensers for manipulation of ambrosia beetle populations occurring in commercial avocado. The potential active space of repellents was assessed by quantifying beetle catch on traps placed ‘close’ (~5–10 cm) and ‘far’ (~1–1.5 m) away from repellent dispensers. Ambrosia beetles collected on traps associated with all in-field treatments were identified to species to assess beetle diversity and community variation. Xyleborus volvulus was not repelled by methyl salicylate (MeSA) or verbenone in laboratory assays, while X. bispinatus was repelled by MeSA but not verbenone. Ambrosia beetle trap catches were reduced in the field more when plots were treated with verbenone dispensers (SPLAT) co-deployed with low-dose ethanol dispensers than when treated with verbenone alone. Beetle diversity was highest on traps deployed with low-dose ethanol lures. The repellent treatments and ethanol lures significantly altered the species composition of beetles captured in experiment plots. Our results indicate that verbenone co-deployed with ethanol lures holds potential for manipulating ambrosia beetle vectors via push-pull management in avocado. This tactic could discourage immigration and/or population establishment of ambrosia beetles in commercial avocado and function as an additional tool for management programs of laurel wilt.
Structure of the agonist 12–HHT in its BLT2 receptor-bound state
Authors: Giusti Fabrice , Casiraghi Marina , Point Elodie , Damian Marjorie , Rieger Jutta , Bon Christel Le , Pozza Alexandre , Moncoq Karine , Banères Jean-Louis , Catoire Laurent J.
Published: February 2020

G Protein-Coupled receptors represent the main communicating pathway for signals from the outside to the inside of most of eukaryotic cells. They define the largest family of integral membrane receptors at the surface of the cells and constitute the main target of the current drugs on the market. The low affinity leukotriene receptor BLT2 is a receptor involved in pro- and anti-inflammatory pathways and can be activated by various unsaturated fatty acid compounds. We present here the NMR structure of the agonist 12–HHT in its BLT2-bound state and a model of interaction of the ligand with the receptor based on a conformational homology modeling associated with docking simulations. Put into perspective with the data obtained with leukotriene B4, our results illuminate the ligand selectivity of BLT2 and may help define new molecules to modulate the activity of this receptor.
Masking Phosphate with Rare-Earth Elements Enables Selective Detection of Arsenate by Dipycolylamine-ZnII Chemosensor
Authors: Mekjinda Nutsara , Phunnarungsi Supho , Ruangpornvisuti Vithaya , Ritchie Raymond J. , Hamachi Itaru , Ojida Akio , Wongkongkatep Jirarut
Published: February 2020

Functional reassessment of the phosphate-specific chemosensors revealed their potential as arsenate detectors. A series of dipicolylamine (Dpa)-ZnII chemosensors were screened, among which acridine Dpa-ZnII chemosensor showed the highest capability in sensing arsenate. The presence of excess ZnII improved sensitivity and strengthened the binding between acridine Dpa-ZnII complex to arsenate as well as phosphate. However, due to their response to phosphate, these sensors are not suited for arsenate detection when phosphate is also present. This study demonstrated for the first time that rare-earth elements could effectively mask phosphate, allowing the specific fluorescence detection of arsenate in phosphate-arsenate coexisting systems. In addition, detection of arsenate contamination in the real river water samples and soil samples was performed to prove its practical use. This sensor was further employed for the visualization of arsenate and phosphate uptake in vegetables and flowering plants for the first time, as well as in the evaluation of a potent inhibitor of arsenate/phosphate uptake.
Possible involvement of PS-PLA1 and lysophosphatidylserine receptor (LPS1) in hepatocellular carcinoma
Authors: Uranbileg Baasanjav , Kurano Makoto , Sato Masaya , Ikeda Hitoshi , Ishizawa Takeaki , Hasegawa Kiyoshi , Kokudo Norihiro , Yatomi Yutaka
Published: February 2020

Lysophosphatidylserine (LysoPS) is a lysophospholipid, its generating enzyme, phosphatidylserine-specific phospholipase A1 (PS-PLA1), reportedly plays roles in stomach and colon cancers. Here, we examined the potential roles of LysoPS in hepatocellular carcinoma (HCC). The ninety-seven HCC patients who underwent surgical treatment were enrolled in this study and approved by the institutional review board. Among LysoPS-related enzymes and receptors, increased PS-PLA1 or LysoPS receptor 1 (LPS1) mRNA was observed in HCC tissues compared to non-HCC tissues. PS-PLA1 mRNA in HCC was associated with no clinical parameters, while LPS1 mRNA in HCC was correlated inversely with tumor differentiation. Furthermore, higher serum PS-PLA1 was observed in HCC patients compared to healthy control and correlated with PS-PLA1 mRNA in non-HCC tissues and with serum AST or ALT. Additionally, serum levels of PS-PLA1 were higher in HCC patients with HCV-related liver injury than in those with HBV or non-HBV-, non-HCV-related liver diseases. In conclusion, among LysoPS-related enzymes and receptors, PS-PLA1 and LPS1 mRNA were increased in HCC. Based on the correlation between the serum PS-PLA1 and the mRNA level of PS-PLA1 in non-HCC tissues, the liver may be the main source of serum PS-PLA1, and serum PS-PLA1 levels may be a useful marker for liver injury.
Multiparametric MR Index for the Diagnosis of Non-Alcoholic Steatohepatitis in Patients with Non-Alcoholic Fatty Liver Disease
Authors: Kim Jeong Woo , Lee Young-Sun , Park Yang Shin , Kim Baek-Hui , Lee Soo Yeon , Yeon Jong Eun , Lee Chang Hee
Published: February 2020

Non-alcoholic steatohepatitis (NASH) is a complex disease consisting of various components including steatosis, lobular inflammation, and ballooning degeneration, with or without fibrosis. Therefore, it is difficult to diagnose NASH with only one imaging modality. This study was aimed to evaluate the feasibility of magnetic resonance imaging (MRI) for predicting NASH and to develop a non-invasive multiparametric MR index for the detection of NASH in non-alcoholic fatty liver disease (NAFLD) patients. This prospective study included 47 NAFLD patients who were scheduled to undergo or underwent ultrasound-guided liver biopsy within 2 months. Biopsy specimens were graded as NASH or non-NASH. All patients underwent non-enhanced MRI including MR spectroscopy (MRS), MR elastography (MRE), and T1 mapping. Diagnostic performances of MRS, MRE, and T1 mapping for grading steatosis, activity, and fibrosis were evaluated. A multiparametric MR index combining fat fraction (FF), liver stiffness (LS) value, and T1 relaxation time was developed using linear regression analysis. Receiver operating characteristic (ROC) curve analysis was performed to evaluate the diagnostic performance of the newly devised MR index. Twenty NASH patients and 27 non-NASH patients were included. Using MRS, MRE, and T1 mapping, the mean areas under the curve (AUCs) for grading steatosis, fibrosis, and activity were 0.870, 0.951, and 0.664, respectively. The multiparametric MR index was determined as 0.037 × FF (%) + 1.4 × LS value (kPa) + 0.004 × T1 relaxation time (msec) −3.819. ROC curve analysis of the MR index revealed an AUC of 0.883. The cut-off value of 6 had a sensitivity of 80.0% and specificity of 85.2%. The multiparametric MR index combining FF, LS value, and T1 relaxation time showed high diagnostic performance for detecting NASH in NAFLD patients.
Impact of mental disorders and chronic physical conditions on quality-adjusted life years in Singapore
Authors: Abdin Edimansyah , Chong Siow Ann , Vaingankar Janhavi Ajit , Shafie Saleha , Verma Swapna , Luo Nan , Tan Kelvin Bryan , James Lyn , Heng Derrick , Subramaniam Mythily
Published: February 2020

The current study aims to evaluate the burden of disease in Singapore by estimating the quality-adjusted life years (QALYs) lost due to mental disorders and chronic physical conditions. The second Singapore Mental Health Study (SMHS-2016) was conducted in 2016 among 6126 respondents aged 18 years and above. The World Health Organization Composite International Diagnostic Interview version 3.0 (WHO-CIDI 3.0) and a modified version of the CIDI chronic medical disorders checklist were used to assess the 12-month diagnoses of mental and chronic physical disorders while the SF-6D scores derived from the 12-item Short Form Health Survey instrument was used to estimate the QALYs lost. The mean SF-6D score in this population was 0.87. The largest reduction in SF-6D scores among people with mental disorders was observed in Generalized Anxiety Disorder (GAD), followed by Major Depressive Disorder (MDD), alcohol abuse, bipolar disorder and Obsessive Compulsive Disorder (OCD) while the largest reduction in SF-6D score among people with chronic physical conditions was observed in ulcer, followed by lung disease, chronic pain and cardiovascular disease. At the population level, chronic pain was associated with the greatest QALY loss followed by MDD (14,204 and 6,889 respectively). Lung disease was associated with the smallest QALY loss (376). These findings highlight chronic pain, MDD, OCD, cardiovascular disease and GAD as the five leading contributors of QALYs lost in the general population which deserve prioritisation in public health prevention programmes.
Assessment of the Stability of the Palatal Rugae in a 3D-3D Superimposition Technique Following Slow Maxillary Expansion (SME)
Authors: Lanteri Valentina , Cossellu Gianguido , Farronato Marco , Ugolini Alessandro , Leonardi Rosalia , Rusconi Francesca , De Luca Stefano , Biagi Roberto , Maspero Cinzia
Published: February 2020

The Palatal Rugae are considered a useful human identification marker for both orthodontists and forensic personnel. The principal aim of the present study was to evaluate the stability of palatal rugae with a 3D-3D superimposition procedure following Slow Maxillary Expansion (SME), in order to assess whether they kept their uniqueness and validity for human identification, even after a specific dental treatment. For this purpose, a sample of 27 digital dental models - belonging to growing patients (13 males and 14 females), aged between 8.5 and 15 years, who underwent SME therapy - was retrospectively studied and compared with a control group of 27 untreated subjects - (13 males and 14 females). Digital dental models were obtained pre-treatment and at device removal; both were processed by means of an intraoral scanner. A superimposition procedure was thus performed to reach the minimum point-to-point distance between two models of palatal rugae. Intra- and inter-observer differences were statistically analyzed by paired Wilcoxon test and Intra-class Correlation coefficient (ICC), showing values larger than 0.93. There was no difference in Root-Mean-Square (RMS) values between untreated control subjects and subjects treated with Leaf Expander (p = 0.062). A RMS value of 0.43 was the threshold to distinguish the pooled group (“Untreated” and “Leaf”) from any mismatch. According to the obtained results, this study failed to reject the null hypothesis and presented no differences between the RMS values of the Test group and the RMS values of the untreated control group. This work highlighted the usefulness of 3D superimposition procedure for purposes of human identification, in subjects undergoing dental treatment. However, keeping in sight the forensic use of this technique as a helpful probation element in court, further studies should be performed to confirm these findings.
The STING pathway does not contribute to behavioural or mitochondrial phenotypes in Drosophila Pink1/parkin or mtDNA mutator models
Authors: Lee Juliette J. , Andreazza Simonetta , Whitworth Alexander J.
Published: February 2020

Mutations in PINK1 and Parkin/PRKN cause the degeneration of dopaminergic neurons in familial forms of Parkinson’s disease but the precise pathogenic mechanisms are unknown. The PINK1/Parkin pathway has been described to play a central role in mitochondrial homeostasis by signalling the targeted destruction of damaged mitochondria, however, how disrupting this process leads to neuronal death was unclear until recently. An elegant study in mice revealed that the loss of Pink1 or Prkn coupled with an additional mitochondrial stress resulted in the aberrant activation of the innate immune signalling, mediated via the cGAS/STING pathway, causing degeneration of dopaminergic neurons and motor impairment. Genetic knockout of Sting was sufficient to completely prevent neurodegeneration and accompanying motor deficits. To determine whether Sting plays a conserved role in Pink1/parkin related pathology, we tested for genetic interactions between Sting and Pink1/parkin in Drosophila. Surprisingly, we found that loss of Sting, or its downstream effector Relish, was insufficient to suppress the behavioural deficits or mitochondria disruption in the Pink1/parkin mutants. Thus, we conclude that phenotypes associated with loss of Pink1/parkin are not universally due to aberrant activation of the STING pathway.
Novel Ocellatin Peptides Mitigate LPS-induced ROS Formation and NF-kB Activation in Microglia and Hippocampal Neurons
Authors: Sousa Nayara A. , Oliveira Guilherme A. L. , de Oliveira Ana Patrícia , Lopes André Luís F. , Iles Bruno , Nogueira Kerolayne M. , Araújo Thiago S. L. , Souza Luan K. M. , Araújo Alyne R. , Ramos-Jesus Joilson , Plácido Alexandra , Amaral Constança , Campelo Yuri D. M. , Barbosa Eder Alves , Portugal Camila C. , Socodato Renato , Lobo Andrea , Relvas Joao , Bemquerer Marcelo , Eaton Peter , Leite José Roberto S. A. , Medeiros Jand Venes R.
Published: February 2020

Cutaneous secretions of amphibians have bioactive compounds, such as peptides, with potential for biotechnological applications. Therefore, this study aimed to determine the primary structure and investigate peptides obtained from the cutaneous secretions of the amphibian, Leptodactylus vastus, as a source of bioactive molecules. The peptides obtained possessed the amino acid sequences, GVVDILKGAAKDLAGH and GVVDILKGAAKDLAGHLASKV, with monoisotopic masses of [M + H]± = 1563.8 Da and [M + H]± = 2062.4 Da, respectively. The molecules were characterized as peptides of the class of ocellatins and were named as Ocellatin-K1(1–16) and Ocellatin-K1(1–21). Functional analysis revealed that Ocellatin-K1(1–16) and Ocellatin-K1(1–21) showed weak antibacterial activity. However, treatment of mice with these ocellatins reduced the nitrite and malondialdehyde content. Moreover, superoxide dismutase enzymatic activity and glutathione concentration were increased in the hippocampus of mice. In addition, Ocellatin-K1(1–16) and Ocellatin-K1(1–21) were effective in impairing lipopolysaccharide (LPS)-induced reactive oxygen species (ROS) formation and NF-kB activation in living microglia. We incubated hippocampal neurons with microglial conditioned media treated with LPS and LPS in the presence of Ocellatin-K1(1–16) and Ocellatin-K1(1–21) and observed that both peptides reduced the oxidative stress in hippocampal neurons. Furthermore, these ocellatins demonstrated low cytotoxicity towards erythrocytes. These functional properties suggest possible to neuromodulatory therapeutic applications.
Aluminum and aluminum oxide nanomaterials uptake after oral exposure - a comparative study
Authors: Krause Benjamin C. , Kriegel Fabian L. , Rosenkranz Daniel , Dreiack Nadine , Tentschert Jutta , Jungnickel Harald , Jalili Pegah , Fessard Valerie , Laux Peter , Luch Andreas
Published: February 2020

The knowledge about a potential in vivo uptake and subsequent toxicological effects of aluminum (Al), especially in the nanoparticulate form, is still limited. This paper focuses on a three day oral gavage study with three different Al species in Sprague Dawley rats. The Al amount was investigated in major organs in order to determine the oral bioavailability and distribution. Al-containing nanoparticles (NMs composed of Al0 and aluminum oxide (Al2O3)) were administered at three different concentrations and soluble aluminum chloride (AlCl3·6H2O) was used as a reference control at one concentration. A microwave assisted acid digestion approach followed by inductively coupled plasma mass spectrometry (ICP-MS) analysis was developed to analyse the Al burden of individual organs. Special attention was paid on how the sample matrix affected the calibration procedure. After 3 days exposure, AlCl3·6H2O treated animals showed high Al levels in liver and intestine, while upon treatment with Al0 NMs significant amounts of Al were detected only in the latter. In contrast, following Al2O3 NMs treatment, Al was detected in all investigated organs with particular high concentrations in the spleen. A rapid absorption and systemic distribution of all three Al forms tested were found after 3-day oral exposure. The identified differences between Al0 and Al2O3 NMs point out that both, particle shape and surface composition could be key factors for Al biodistribution and accumulation.
Publisher Correction: Exploring the Pharmacological Mechanism of Quercetin-Resveratrol Combination for Polycystic Ovary Syndrome: A Systematic Pharmacological Strategy-Based Research
Authors: Yang Kailin , Zeng Liuting , Bao Tingting , Long Zhiyong , Jin Bing
Published: February 2020

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
Publisher Correction: Dichotomic effects of clinically used drugs on tumor growth, bone remodeling and pain management
Authors: Barrière David André , Midavaine Élora , Doré-Savard Louis , Kirby Karyn , Tremblay Luc , Beaudoin Jean-François , Beaudet Nicolas , Longpré Jean-Michel , Lecomte Roger , Lepage Martin , Sarret Philippe
Published: February 2020

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
Author Correction: Impact of ezetimibe on plasma lipoprotein(a) concentrations as monotherapy or in combination with statins: a systematic review and meta-analysis of randomized controlled trials
Authors: Sahebkar Amirhossein , Simental-Mendía Luis E. , Pirro Matteo , Banach Maciej , Watts Gerald F. , Sirtori Cesare , Al-Rasadi Khalid , Atkin Stephen L.
Published: February 2020

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
Author Correction: Anti-apoptotic activity of ETB receptor agonist, IRL-1620, protects neural cells in rats with cerebral ischemia
Authors: Briyal Seema , Ranjan Amaresh K. , Hornick Mary G. , Puppala Anupama K. , Luu Thanh , Gulati Anil
Published: February 2020

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
Serotonin 5-HT4 receptor boosts functional maturation of dendritic spines via RhoA-dependent control of F-actin
Authors: Schill Yvonne , Bijata Monika , Kopach Olga , Cherkas Volodymyr , Abdel-Galil Dalia , Böhm Katrin , Schwab Markus H. , Matsuda Michiyuki , Compan Valerie , Basu Subhadip , Bijata Krystian , Wlodarczyk Jakub , Bard Lucie , Cole Nicholas , Dityatev Alexander , Zeug Andre , Rusakov Dmitri A. , Ponimaskin Evgeni
Published: February 2020

Activity-dependent remodeling of excitatory connections underpins memory formation in the brain. Serotonin receptors are known to contribute to such remodeling, yet the underlying molecular machinery remains poorly understood. Here, we employ high-resolution time-lapse FRET imaging in neuroblastoma cells and neuronal dendrites to establish that activation of serotonin receptor 5-HT4 (5-HT4R) rapidly triggers spatially-restricted RhoA activity and G13-mediated phosphorylation of cofilin, thus locally boosting the filamentous actin fraction. In neuroblastoma cells, this leads to cell rounding and neurite retraction. In hippocampal neurons in situ, 5-HT4R-mediated RhoA activation triggers maturation of dendritic spines. This is paralleled by RhoA-dependent, transient alterations in cell excitability, as reflected by increased spontaneous synaptic activity, apparent shunting of evoked synaptic responses, and enhanced long-term potentiation of excitatory transmission. The 5-HT4R/G13/RhoA signaling thus emerges as a previously unrecognized molecular pathway underpinning use-dependent functional remodeling of excitatory synaptic connections.
Heme binding of transmembrane signaling proteins undergoing regulated intramembrane proteolysis
Authors: Kupke Thomas , Klare Johann P. , Brügger Britta
Published: February 2020

Transmembrane signaling proteins play a crucial role in the transduction of information across cell membranes. One function of regulated intramembrane proteolysis (RIP) is the release of signaling factors from transmembrane proteins. To study the role of transmembrane domains (TMDs) in modulating structure and activity of released signaling factors, we purified heterologously expressed human transmembrane proteins and their proteolytic processing products from Escherichia coli. Here we show that CD74 and TNFα are heme binding proteins. Heme coordination depends on both a cysteine residue proximal to the membrane and on the oligomerization of the TMD. Furthermore, we show that the various processing products have different modes of heme coordination. We suggest that RIP changes the mode of heme binding of these proteins and generates heme binding peptides with yet unexplored functions. The identification of a RIP modulated cofactor binding of transmembrane signaling proteins sheds new light on the regulation of cell signaling pathways.
Application of a Y-type-DNA-functionalized nanogold probe featuring specific telomerase recognition and doxorubicin release in cancer cells
Authors: Zhang Shulin , Liang Kaili , Li Ping , Liu Ju , Tang Bo
Published: February 2020

A Y-type-DNA-functionalized nanogold probe was synthesized to identify telomerase and trigger drug release in cancer cells.
Human fibroblast-macrophage tissue spheroids demonstrate ratio-dependent fibrotic activity for in vitro fibrogenesis model development
Authors: Tan Yu , Suarez Allister , Garza Matthew , Khan Aadil A. , Elisseeff Jennifer , Coon Devin
Published: February 2020

A scaffold-free 3D human fibroblast-macrophage spheroid system was developed for an improved in vitro model of human fibrosis. The optimized model demonstrated high fibroblast activity, M1 macrophage activation and dense collagen production.
Glycoluril derived cucurbituril analogues and the emergence of the most recent example: tiarauril
Authors: Dhiman Rajni , Pen Satyavisal , Chandrakumar Pradeep Kumar , Frankcombe Terry J. , Day Anthony I.
Published: February 2020

Cucurbituril analogues can bear some of the chemical and physical characteristics of their parental origin and are derived wholly or in part from glycolurils (including homologues).
Synthesis and evaluation of anticancer activity of new 9-acridinyl amino acid derivatives
Authors: Rupar Jelena , Dobričić Vladimir , Grahovac Jelena , Radulović Siniša , Skok Žiga , Ilaš Janez , Aleksić Mara , Brborić Jasmina , Čudina Olivera
Published: February 2020

Compounds 6, 7, 8 and 9 exhibit lower or similar IC50 values compared to amsacrine and showed a lack of toxicity towards unstimulated normal human leucocytes.
Triterpenoids
Authors: Hill Robert A. , Connolly Joseph D.
Published: February 2020

This review covers newly isolated triterpenoids that have been reported during 2015.
Engineering digital polymer based on thiol–maleimide Michael coupling toward effective writing and reading
Authors: Liu Baolei , Shi Qiunan , Hu Lihua , Huang Zhihao , Zhu Xiulin , Zhang Zhengbiao
Published: February 2020

Based on thiol–maleimide Michael coupling, a digital polymer allowing efficient message writing and reading was rationally designed.
Effect of the coordination of π-acceptor 4-cyanopyridine ligand on the structural and electronic properties ofmeso-tetra(para-methoxy) andmeso-tetra(para-chlorophenyl) porphyrin cobalt(ii) coordination compounds. Application in the catalytic degradation of methylene blue dye
Authors: Guergueb Mouhieddinne , Nasri Soumaya , Brahmi Jihed , Loiseau Frédérique , Molton Florian , Roisnel Thierry , Guerineau Vincent , Turowska-Tyrk Ilona , Aouadi Kaïss , Nasri Habib
Published: February 2020

Preparation and UV/vis, IR, MS,1H NMR, cyclic voltammetry and molecular structures of two new Co(ii) complexes withpara-methoxy-phenyl andpara-chloromeso-porphyrins and 4-cyanopyridine ligand (1–2). Catalytic oxidation data of MB dye using1–2.
Magnetic properties of 3d transition metal (Sc–Ni) doped plumbene
Authors: Hashemi Daniel , Iizuka Hideo
Published: February 2020

Distance dependent exchange coupling between two transition metal (TM) impurities doped in plumbene in sites along the zigzag (zi) and the armchair (aj) directions.
Titanium phosphonate oxo-alkoxide “clusters”: solution stability and facile hydrolytic transformation into nano titania
Authors: Svensson Fredric G. , Daniel Geoffrey , Tai Cheuk-Wai , Seisenbaeva Gulaim A. , Kessler Vadim G.
Published: February 2020

Oligonuclear Ti(iv) oxo-alkoxide-phosphonate complexes, produced by reaction of tBuPO(OH)2 with Ti(OR)4, are easily topotactically hydrolyzed forming intricate nanostructures.
The influence of dopants on aW-phase antimonene: theoretical investigations
Authors: Zhou Qingxiao , Zhang Qian , Ju Weiwei , Liu Yanling , Li Jiahui
Published: February 2020

We systemically investigate the effect of dopants on the geometrics, electronic and magnetic properties of asymmetric washboard structure of antimonene (aW-Sb) by using density functional theory (DFT) calculations.
Unlocking the potential of late-stage functionalisation: an accurate and fully automated method for the rapid characterisation of multiple regioisomeric products
Authors: Richardson Jeffery , Sharman Gary , Martínez-Olid Francisco , Cañellas Santiago , Gomez Jose Enrique
Published: February 2020

An automated pipeline for structure determination is outlined that will help unlock the potential of late-stage functionalisation (LSF).
How a local active force modifies the structural properties of polymers
Authors: Natali Laura , Caprini Lorenzo , Cecconi Fabio
Published: February 2020

We study the dynamics of a polymer, described as a variant of a Rouse chain, driven by an active terminal monomer (head).
High-throughput computational discovery of K2CdO2 as an ion conductor for solid-state potassium-ion batteries
Authors: Xiao Ruijuan , Li Hong , Chen Liquan
Published: February 2020

A new type of potassium ion conductor, K2CdO2, and its derivative are discovered by high-throughput computations.
Cytotoxic and osteogenic effects of crocin and bicarbonate from calcium phosphates for potential chemopreventative and anti-inflammatory applications in vitro and in vivo
Authors: Koski Caitlin , Sarkar Naboneeta , Bose Susmita
Published: February 2020

Delayed healing and nonhealing of bone defects or resected bone sites remains an important clinical concern in the biomedical field.
Modulating the properties of flow-assembled chitosan membranes in microfluidics with glutaraldehyde crosslinking
Authors: Hu Piao , Raub Christopher B. , Choy John S. , Luo Xiaolong
Published: February 2020

Glutaraldehyde crosslinking significantly enhances the mechanical robustness of the originally compromised flow-assembled chitosan membranes after Pluronic passivation in microfluidics.
On the importance of pyrolysis for inkjet-printed oxide piezoelectric thin films
Authors: Godard Nicolas , Mahjoub Mohamed Aymen , Girod Stéphanie , Schenk Tony , Glinšek Sebastjan , Defay Emmanuel
Published: February 2020

Inkjet printing is an attractive low-cost method for the deposition of piezoelectric lead zirconate titanate thin films. Pyrolysis temperature and time are crucial processing parameters to obtain dense layers with state-of-the-art properties.
Engineering polymers with improved charge transport properties from bithiophene-containing polyamides
Authors: Özen Bilal , Candau Nicolas , Temiz Cansel , Grozema Ferdinand C. , Fadaei Tirani Farzaneh , Scopelliti Rosario , Chenal Jean-Marc , Plummer Christopher J. G. , Frauenrath Holger
Published: February 2020

Incorporation of bithiophene segments in the polyamides results in semiconducting properties, while mechanical properties of typical engineering polyamides are maintained.
Highly sensitive and strongly fluorescent gum tragacanth based superabsorbent hydrogel as a new biosensor for glucose optical detection
Authors: Qasemi Soudabeh , Ghaemy Mousa
Published: February 2020

A highly synergistic biosensor for glucose detection based on a FRET system by stabilizing QDs, organic dye, and enzyme inside a superabsorbent hydrogel.
A label-free protamine-assisted colorimetric sensor for highly sensitive detection of S1 nuclease activity
Authors: Wen Jiahui , Liu Yongming , Li Jingwen , Lin Hao , Zheng Yiran , Chen Yan , Fu Xiuli , Chen Lingxin
Published: February 2020

A label-free, simple and rapid colorimetric method for the sensitive detection of S1 nuclease activity based on protamine-assisted aggregation of gold nanoparticles.
Observing the structure-dependent electrocatalytic activity of bimetallic Pd–Au nanorods at the single-particle level
Authors: Chen Ming-Ming , Xu Cong-Hui , Zhao Wei , Chen Hong-Yuan , Xu Jing-Juan
Published: February 2020

The structure-dependent electrocatalytic activity of bimetallic Pd–Au nanorods is observed by ECL microscopy at the single-particle level.
Arylation and alkenylation of activated alkyl halides using sulfonamides
Authors: Johnson Stuart , Kovács Ervin , Greaney Michael F.
Published: February 2020

A variety of quaternary aryl amino acid derivatives can be synthesised using tandem SN2/Smiles rearrangement chemistry involving aryl sulfonamides and α-chloro carbonyl compounds.
Spatially-resolved investigation of the water inhibition of methane oxidation over palladium
Authors: Coney Ciaran , Stere Cristina , Millington Paul , Raj Agnes , Wilkinson Sam , Caracotsios Michael , McCullough Geoffrey , Hardacre Christopher , Morgan Kevin , Thompsett David , Goguet Alexandre
Published: February 2020

Pd/Al2O3catalysts are known to be active for low temperature methane oxidation reactions, however it has been shown that gases normally associated with methane gas streams (H2O, CO2, H2S) can have an inhibitory effect on the total oxidation reaction.
Mechanisms and performance of calcium peroxide-enhanced Fe(ii) coagulation for treatment of Microcystis aeruginosa-laden water
Authors: Xin Huaijia , Yang Shu , Tang Yulin , Wu Mengyi , Deng Yang , Xu Bin , Gao Naiyun
Published: February 2020

Pre-oxidation has been extensively studied as a pre-treatment for enhancement of algae-laden water coagulation.
Thermoelectric performance of nanostructured In/Pb codoped SnTe with band convergence and resonant level prepared via a green and facile hydrothermal method
Authors: Lu Wenqi , He Tiantian , Li Shuang , Zuo Xinru , Zheng Yao , Lou Xunuo , Zhang Jian , Li Di , Liu Jizi , Tang Guodong
Published: February 2020

The enhanced thermoelectric performance is achieved in nanostructured SnTe with band convergence and resonant level prepared by a green and facile hydrothermal method.