bluuebunny/crossref_metadata_2025 huggingface dataset:
Clustering of Largely Right-Censored Oropharyngeal Head and Neck Cancer Patients for Discriminative Groupings to Improve Outcome Prediction
Authors: Tosado Joel , Zdilar Luka , Elhalawani Hesham , Elgohari Baher , Vock David M. , Marai G. Elisabeta , Fuller Clifton , Mohamed Abdallah S. R. , Canahuate Guadalupe
Published: March 2020

Clustering is the task of identifying groups of similar subjects according to certain criteria. The AJCC staging system can be thought as a clustering mechanism that groups patients based on their disease stage. This grouping drives prognosis and influences treatment. The goal of this work is to evaluate the efficacy of machine learning algorithms to cluster the patients into discriminative groups to improve prognosis for overall survival (OS) and relapse free survival (RFS) outcomes. We apply clustering over a retrospectively collected data from 644 head and neck cancer patients including both clinical and radiomic features. In order to incorporate outcome information into the clustering process and deal with the large proportion of censored samples, the feature space was scaled using the regression coefficients fitted using a proxy dependent variable, martingale residuals, instead of follow-up time. Two clusters were identified and evaluated using cross validation. The Kaplan Meier (KM) curves between the two clusters differ significantly for OS and RFS (p-value < 0.0001). Moreover, there was a relative predictive improvement when using the cluster label in addition to the clinical features compared to using only clinical features where AUC increased by 5.7% and 13.0% for OS and RFS, respectively.
The reduction of DSS-induced colitis severity in mice exposed to cigarette smoke is linked to immune modulation and microbial shifts
Authors: Lo Sasso Giuseppe , Phillips Blaine W. , Sewer Alain , Battey James N. D. , Kondylis Athanasios , Talikka Marja , Titz Bjoern , Guedj Emmanuel , Peric Dariusz , Bornand David , Dulize Remi , Merg Celine , Corciulo Maica , Ouadi Sonia , Yanuar Rendy , Tung Ching Keong , Ivanov Nikolai V. , Peitsch Manuel C. , Hoeng Julia
Published: March 2020

Exposure to cigarette smoke (CS) causes detrimental health effects, increasing the risk of cardiovascular, pulmonary diseases and carcinogenesis in exposed individuals. The impact of CS on Inflammatory Bowel Disease (IBD) has been established by a number of epidemiological and clinical studies. In fact, CS is associated with a higher risk of developing Crohn’s disease (CD) while inversely correlates with the development, disease risks, and relapse rate of ulcerative colitis (UC). To investigate the effect of CS exposure on experimental colitis, we performed a comprehensive and integrated comparative analysis of colon transcriptome and microbiome in mice exposed to dextran sodium sulfate (DSS) and CS. Colon transcriptome analysis revealed that CS downregulated specific pathways in a concentration-dependent manner, affecting both the inflammatory state and composition of the gut microbiome. Metagenomics analysis demonstrated that CS can modulate DSS-induced dysbiosis of specific bacterial genera, contributing to resolve the inflammation or accelerate recovery. The risks of smoking far outweigh any possible benefit, thus smoking cessation must always be encouraged because of its significant health benefits. However, the inverse association between active smoking and the development of UC cannot be ignored and the present study lays the foundation for investigating potential molecular mechanisms responsible for the attenuation of colitis by certain compounds of tobacco when decoupled from combustion.
Statistical Tests for Force Inference in Heterogeneous Environments
Authors: Serov Alexander S. , Laurent François , Floderer Charlotte , Perronet Karen , Favard Cyril , Muriaux Delphine , Westbrook Nathalie , Vestergaard Christian L. , Masson Jean-Baptiste
Published: March 2020

We devise a method to detect and estimate forces in a heterogeneous environment based on experimentally recorded stochastic trajectories. In particular, we focus on systems modeled by the heterogeneous overdamped Langevin equation. Here, the observed drift includes a "spurious” force term when the diffusivity varies in space. We show how Bayesian inference can be leveraged to reliably infer forces by taking into account such spurious forces of unknown amplitude as well as experimental sources of error. The method is based on marginalizing the force posterior over all possible spurious force contributions. The approach is combined with a Bayes factor statistical test for the presence of forces. The performance of our method is investigated analytically, numerically and tested on experimental data sets. The main results are obtained in a closed form allowing for direct exploration of their properties and fast computation. The method is incorporated into TRamWAy, an open-source software platform for automated analysis of biomolecule trajectories.
Nasalization of Central Retinal Vessel Trunk Predicts Rapid Progression of Central Visual Field in Open-Angle Glaucoma
Authors: Shon Kilhwan , Hye Jo Youn , Won Shin Joong , Kwon Junki , Jeong Daun , Kook Michael S.
Published: March 2020

Central visual field (CVF) loss is important in maintaining vision-related quality of life in eyes with open-angle glaucoma (OAG). The present study investigated whether nasalized location of central retinal vessel trunk (CRVT) at baseline is associated with rapid rate of CVF loss in early-stage OAG eyes. This study included 76 OAG eyes with high nasalization CRVT [HNL] group and 75 OAG eyes with low nasalization CRVT [LNL] group matched for glaucoma severity at baseline that showed progressive visual field (VF) loss. The rates of mean threshold changes at various regions were compared in the two groups using a linear mixed model. Clinical variables associated with rapid rate of CVF progression were also identified using a linear mixed model. The rate of CVF loss in the central 10° was significantly higher in the HNL group than that in the LNL group (−0.452 dB/year vs. −0.291 dB/year, P < 0.001). The average and inferior hemi-macular ganglion cell inner plexiform layer (GCIPL) progression rates were significantly faster in the HNL group than in the LNL group (P < 0.05). Nasalized location of CRVT was an independent predictor of a more rapid VF loss in the central 10° region (P < 0.05).
fMRI Revealed Reduced Amygdala Activation after Nx4 in Mildly to Moderately Stressed Healthy Volunteers in a Randomized, Placebo-Controlled, Cross-Over Trial
Authors: Herrmann Luisa , Vicheva Petya , Kasties Vanessa , Danyeli Lena V. , Szycik Gregor R. , Denzel Dominik , Fan Yan , Meer Johan Van der , Vester Johannes C. , Eskoetter Herbert , Schultz Myron , Walter Martin
Published: March 2020

Social stress contributes to major societal health burdens, such as anxiety disorders and nervousness. Nx4 has been found to modulate stress responses. We investigated whether dampening of such responses is associated with neuronal correlates in brain regions involved in stress and anxiety. In a randomized, placebo-controlled, double-blind, cross-over trial, 39 healthy males took a single dose (three tablets) of either placebo or Nx4, 40 to 60 minutes before an fMRI scan session. We here report on drug effects on amygdala responses during a face-matching task, which was performed during a complex test battery further including resting-state brain connectivity and a social stress experiment. The first of the Primary Outcomes, defined in a hierarchical order, concerned reduced amygdala effects after intake of verum compared to placebo. We found a statistically significant reduction in differential activations in the left amygdala for the contrast negative faces versus forms during verum versus placebo condition. Our results indicate that effects of Nx4 can be monitored in the brain. Previously noted effects on stress responses may thus be modulated by affective brain regions including the amygdala.
Oxidation of Nb(110): atomic structure of the NbO layer and its influence on further oxidation
Authors: Zhussupbekov Kuanysh , Walshe Killian , Bozhko Sergey I. , Ionov Andrey , Fleischer Karsten , Norton Emma , Zhussupbekova Ainur , Semenov Valery , Shvets Igor V. , Walls Brian
Published: March 2020

NbO terminated Nb(110) and its oxidation are examined by scanning tunneling microscopy and spectroscopy (STS). The oxide structures are strongly influenced by the structural and electronic properties of the underlying NbO substrate. The NbO is terminated by one-dimensional few-nanometer nanocrystals, which form an ordered pattern. High-resolution STS measurements reveal that the nanocrystals and the regions between the nanocrystals exhibit different electronic characters. Low-dosage oxidation, sufficient for sub-monolayer coverage of the NbO, with subsequent UHV annealing results in the formation of resolved sub-nanometer clusters, positioned in-between the nanocrystals. Higher dosage oxidation results in the formation of a closed Nb2O5−y layer, which is confirmed by X-ray photoelectron spectroscopy measurements. The pentoxide is amorphous at the atomic-scale. However, large scale (tens of nanometers) structures are observed with their symmetry matching that of the underlying nanocrystals.
Modulation of feeding behavior and metabolism by dynorphin
Authors: Ghule Aishwarya , Rácz Ildiko , Bilkei-Gorzo Andras , Leidmaa Este , Sieburg Meike , Zimmer Andreas
Published: March 2020

The neuronal regulation of metabolic and behavioral responses to different diets and feeding regimens is an important research area. Herein, we investigated if the opioid peptide dynorphin modulates feeding behavior and metabolism. Mice lacking dynorphin peptides (KO) were exposed to either a normal diet (ND) or a high-fat diet (HFD) for a period of 12 weeks. Additionally, mice had either time-restricted (TR) or ad libitum (AL) access to food. Body weight, food intake and blood glucose levels were monitored throughout the 12-week feeding schedule. Brain samples were analyzed by immunohistochemistry to detect changes in the expression levels of hypothalamic peptides. As expected, animals on HFD or having AL access to food gained more weight than mice on ND or having TR access. Unexpectedly, KO females on TR HFD as well as KO males on AL ND or AL HFD demonstrated a significantly increased body weight gain compared to the respective WT groups. The calorie intake differed only marginally between the genotypes: a significant difference was present in the female ND AL group, where dynorphin KO mice ate more than WT mice. Although female KO mice on a TR feeding regimen consumed a similar amount of food as WT controls, they displayed significantly higher levels of blood glucose. We observed significantly reduced levels of hypothalamic orexigenic peptides neuropeptide Y (NPY) and orexin-A in KO mice. This decrease became particularly pronounced in the HFD groups and under AL condition. The kappa opiod receptor (KOR) levels were higher after HFD compared to ND feeding in the ventral pallidum of WT mice. We hypothesize that HFD enhances dynorphin signaling in this hedonic center to maintain energy homeostasis, therefore KO mice have a more pronounced phenotype in the HFD condition due to the lack of it. Our data suggest that dynorphin modulates metabolic changes associated with TR feeding regimen and HFD consumption. We conclude that the lack of dynorphin causes uncoupling between energy intake and body weight gain in mice; KO mice maintained on HFD become overweight despite their normal food intake. Thus, using kappa opioid receptor agonists against obesity could be considered as a potential treatment strategy.
Advances of native and non-native Antarctic species to in vitro conservation: improvement of disinfection protocols
Authors: Cuba-Díaz Marely , Rivera-Mora Claudia , Navarrete Eduardo , Klagges Macarena
Published: March 2020

Plants that inhabit Antarctica have raised scientific interest due to their resilience to climate change, abiotic tolerance mechanisms and potential biological applications. In vitro propagation is useful for conservation, genetic material availability of these species and avoiding mass collection in their habitat. In vitro culture protocols for the native plants Colobanthus quitensis and Deschampsia antarctica and the non-native Juncus bufonius have been affected by endophytic microorganisms that proliferate when introduced to tissue cultures. This study evaluated the microbicidal and phytotoxic effect of calcium hypochlorite (Ca(ClO)2), silver nitrate (AgNO3) and silver nanoparticles (AgNPs), and their use at different concentrations for different time periods. The Ca(ClO)2 at 100 mg mL−1 showed the best microbial contamination control in D. antarctica (applied for 20 min) and for the three C. quitensis populations (applied for 15 min). In J. bufonius, AgNO3 at 10 mg mL−1 for 10 min reduced the microbial growth, but oxidative damage was generated. AgNPs did not prevent contamination or have adverse effects on tissues. Survival plantlets from each treatment, population or species were effectively introduced to the tissue culture and their propagation was successful. These results constitute a fundamental advance for the introduction, propagation and conservation of Antarctic species and their use in scientific research.
Attractor Ranked Radial Basis Function Network: A Nonparametric Forecasting Approach for Chaotic Dynamic Systems
Authors: Masnadi-Shirazi Maryam , Subramaniam Shankar
Published: March 2020

The curse of dimensionality has long been a hurdle in the analysis of complex data in areas such as computational biology, ecology and econometrics. In this work, we present a forecasting algorithm that exploits the dimensionality of data in a nonparametric autoregressive framework. The main idea is that the dynamics of a chaotic dynamical system consisting of multiple time-series can be reconstructed using a combination of different variables. This nonlinear autoregressive algorithm uses multivariate attractors reconstructed as the inputs of a neural network to predict the future. We show that our approach, attractor ranked radial basis function network (AR-RBFN) provides a better forecast than that obtained using other model-free approaches as well as univariate and multivariate autoregressive models using radial basis function networks. We demonstrate this for simulated ecosystem models and a mesocosm experiment. By taking advantage of dimensionality, we show that AR-RBFN overcomes the shortcomings of noisy and short time-series data.
Patient-derived small intestinal myofibroblasts direct perfused, physiologically responsive capillary development in a microfluidic Gut-on-a-Chip Model
Authors: Seiler Kristen M. , Bajinting Adam , Alvarado David M. , Traore Mahama A. , Binkley Michael M. , Goo William H. , Lanik Wyatt E. , Ou Jocelyn , Ismail Usama , Iticovici Micah , King Cristi R. , VanDussen Kelli L. , Swietlicki Elzbieta A. , Gazit Vered , Guo Jun , Luke Cliff J. , Stappenbeck Thaddeus , Ciorba Matthew A. , George Steven C. , Meacham J. Mark , Rubin Deborah C. , Good Misty , Warner Brad W.
Published: March 2020

The development and physiologic role of small intestine (SI) vasculature is poorly studied. This is partly due to a lack of targetable, organ-specific markers for in vivo studies of two critical tissue components: endothelium and stroma. This challenge is exacerbated by limitations of traditional cell culture techniques, which fail to recapitulate mechanobiologic stimuli known to affect vessel development. Here, we construct and characterize a 3D in vitro microfluidic model that supports the growth of patient-derived intestinal subepithelial myofibroblasts (ISEMFs) and endothelial cells (ECs) into perfused capillary networks. We report how ISEMF and EC-derived vasculature responds to physiologic parameters such as oxygen tension, cell density, growth factors, and pharmacotherapy with an antineoplastic agent (Erlotinib). Finally, we demonstrate effects of ISEMF and EC co-culture on patient-derived human intestinal epithelial cells (HIECs), and incorporate perfused vasculature into a gut-on-a-chip (GOC) model that includes HIECs. Overall, we demonstrate that ISEMFs possess angiogenic properties as evidenced by their ability to reliably, reproducibly, and quantifiably facilitate development of perfused vasculature in a microfluidic system. We furthermore demonstrate the feasibility of including perfused vasculature, including ISEMFs, as critical components of a novel, patient-derived, GOC system with translational relevance as a platform for precision and personalized medicine research.
Local oral and nasal microbiome diversity in age-related macular degeneration
Authors: Rullo Jacob , Far Parsa Mehraban , Quinn Matthew , Sharma Neel , Bae Steven , Irrcher Isabella , Sharma Sanjay
Published: March 2020

Age-related macular degeneration (AMD) is a chronic degenerative disease of the retina. Recent reports have highlighted the potential role of mucosal surface microbes in the pathogenesis of AMD. In this case-control study, the composition of the nasal and oral microbiota in newly diagnosed neovascular age-related macular degeneration cases (6 male, 7 female) was compared to controls without retinal diseases (2 male, 3 female). PCR amplification of 16S rRNA genes was performed with universal primers amplifying the V4 variable region (515F-806R). Distinct microbial community characterization was achieved using Principal Coordinates Analysis (PCoA) of the Bray-Curtis index with comparative analysis between cases and controls performed within QIIME 2. Sequencing of all cases and controls revealed clear separation with strong beta diversity between oral and nasal microbial communities (p < 0.001). Microbial composition differed between cases and controls in both oral and nasal samples. The top three oral microbes identified as different compared to controls included Burkholderiales (7.41 log2fold change, p = 3.29E-05), Actinomyceataceae (6.22 log2fold change, p = 3.73E-06) and Gemella (5.28 log2fold change, p = 0.0002). The top three nasal microbes identified as different compared to controls included Rothia (13.6 log2fold change, p =  3.63E-18), Actinobacteria (10.29 log2fold change, p = 9.81E-10) and Propionibacteriales (8.73 log2fold change, p = 6.74E-09). These relative shifts in communities of bacteria detected in newly diagnosed neovascular AMD patients may suggest additional mechanistic links in disease pathogenesis.
Sialylated N-glycan profile during acute and chronic infections with Toxoplasma gondii in mice
Authors: Rehan Ibrahim Farag , Mahmoud Motamed Elsayed , Salman Doaa , Elnagar Asmaa , Salman Saleh , Youssef Mohammed , Aziz Amer Ragheb Abdel , Bazh Eman Kamal , Hesham Abd El-Latif
Published: March 2020

Toxoplasma gondii is associated with physiological and psychiatric perturbations. The immune response is interrelated to the progress of anhedonia and despair symptoms of T. gondii-infected subjects. We recently reported that serum N-glycans were altered in mice displayed depressive-like behaviors. However, a novel biomarker that correlated to T. gondii infection and associated behaviors is demanded. Glycomics has been used to find affected glycoproteins during depression. The objective of this study is to investigate serum N-glycomics changes during infection with T. gondii in BALB/c mice, immunocompetent, or in severe combined immunodeficient mice, and after treatment with an immunostimulant; 1-methyl tryptophan. Glycans were examined through glycoblotting-protocol then investigated by MALDI-TOF/MS. Both depressive and sickness-related behaviors were significantly abundant (P ≤ 0.001 each), during acute T. gondii in immunocompetent mice, compared to controls. Only sickness symptoms were evident in immunodeficient mice infected with T. gondii, as associated with high expression level (P ≤ 0.001) of Peak # 15 (2 × Neu5Gc) compared to controls. The alteration of sialylated N-glycan expressions is important to detect the immune status of animals/humans against T. gondii. Moreover, 1-methyl tryptophan reduced depressive-like behavior (P ≤ 0.001) compared to controls. Therefore, sialylated N-glycan (Neu5Ac/Neu5Gc-terminal) is targeted to be used as a novel biomarker of sickness/depressive-like behaviors.
Novel elvitegravir nanoformulation for drug delivery across the blood-brain barrier to achieve HIV-1 suppression in the CNS macrophages
Authors: Gong Yuqing , Chowdhury Pallabita , Nagesh Prashanth K. B. , Rahman Mohammad A. , Zhi Kaining , Yallapu Murali M. , Kumar Santosh
Published: March 2020

The use of antiretroviral therapy (ART) has remarkably decreased the morbidity associated with HIV-1 infection, however, the prevalence of HIV-1-associated neurocognitive disorders (HAND) is still increasing. The blood-brain barrier (BBB) is the major impediment for penetration of antiretroviral drugs, causing therapeutics to reach only suboptimal level to the brain. Conventional antiretroviral drug regimens are not sufficient to improve the treatment outcomes of HAND. In our recent report, we have developed a poloxamer-PLGA nanoformulation loaded with elvitegravir (EVG), a commonly used antiretroviral drug. The nanoformulated EVG is capable of elevating intracellular drug uptake and simultaneously enhance viral suppression in HIV-1-infected macrophages. In this work, we identified the clinical parameters including stability, biocompatibility, protein corona, cellular internalization pathway of EVG nanoformulation for its potential clinical translation. We further assessed the ability of this EVG nanoformulation to cross the in vitro BBB model and suppress the HIV-1 in macrophage cells. Compared with EVG native drug, our EVG nanoformulation demonstrated an improved BBB model penetration cross the in vitro BBB model and an enhanced HIV-1 suppression in HIV-1-infected human monocyte-derived macrophages after crossing the BBB model without altering the BBB model integrity. Overall, this is an innovative and optimized treatment strategy that has a potential for therapeutic interventions in reducing HAND.
Role of peribrachial fat as a key determinant of brachial artery dilatation for successful arteriovenous fistula maturation in hemodialysis patients
Authors: Lee Hyung Seok , Park Mi Jin , Yoon Sam Youl , Joo Narae , Song Young Rim , Kim Hyung Jik , Kim Sung Gyun , Nizet Victor , Kim Jwa-Kyung
Published: March 2020

The functional quality of the inflow artery is one of the most important determinants of arteriovenous fistula (AVF) success. We evaluated the association of early optimal brachial arterial dilatation with a successful AVF maturation and assessed the role of peribrachial adipose tissue in determining brachial arterial distensibility. All patients underwent a preoperative vascular mapping with Doppler ultrasound (US), and only patients who had suitable vessels for AVF creation were enrolled (n = 162). Peribrachial fat thickness was measured using US. To evaluate the degree of brachial dilatation, follow-up US was performed at 1 month after surgery, and early brachial artery dilation was defined as the change in postoperative arterial diameter compared to the preoperative value. The primary outcome was failure to achieve a clinically functional AVF within 8 weeks. Nonfunctional AVF occurred in 21 (13.0%) patients, and they had a significantly lower brachial dilatation than patients with successful AVF during early period after surgery (0.85 vs. 0.43 mm, p = 0.003). Patients with a brachial dilatation greater than median level showed a 1.8-times higher rate of achieving a successful AVF than those without. Interestingly, the early brachial dilatation showed significant correlations with diabetes (r = −0.260, p = 0.001), peribrachial fat thickness (r = −0.301, p = 0.008), and the presence of brachial artery calcification (r = −0.178, p = 0.036). Even after adjustments for demographic factors, comorbidities, and baseline brachial flow volume, peribrachial fat thickness was an independent determinant for early brachial dilatation (β = −0.286, p = 0.013). A close interplay between the peri-brachial fat and brachial dilatation can be translated into novel clinical tools to predict successful AVF maturation.
TREM-1 activation is a potential key regulator in driving severe pathogenesis of enterovirus A71 infection
Authors: Amrun Siti Naqiah , Tan Jeslin J. L. , Rickett Natasha Y. , Cox Jonathan A. , Lee Bernett , Griffiths Michael J. , Solomon Tom , Perera David , Ooi Mong How , Hiscox Julian A. , Ng Lisa F. P.
Published: March 2020

Hand, foot and mouth disease (HFMD), caused by enterovirus A71 (EV-A71), presents mild to severe disease, and sometimes fatal neurological and respiratory manifestations. However, reasons for the severe pathogenesis remain undefined. To investigate this, infection and viral kinetics of EV-A71 isolates from clinical disease (mild, moderate and severe) from Sarawak, Malaysia, were characterised in human rhabdomyosarcoma (RD), neuroblastoma (SH-SY5Y) and peripheral blood mononuclear cells (PBMCs). High resolution transcriptomics was used to decipher EV-A71-host interactions in PBMCs. Ingenuity analyses revealed similar pathways triggered by all EV-A71 isolates, although the extent of activation varied. Importantly, several pathways were found to be specific to the severe isolate, including triggering receptor expressed on myeloid cells 1 (TREM-1) signalling. Depletion of TREM-1 in EV-A71-infected PBMCs with peptide LP17 resulted in decreased levels of pro-inflammatory genes for the moderate and severe isolates. Mechanistically, this is the first report describing the transcriptome profiles during EV-A71 infections in primary human cells, and the potential involvement of TREM-1 in the severe disease pathogenesis, thus providing new insights for future treatment targets.
Complex approach for analysis of snake venom α-neurotoxins binding to HAP, the high-affinity peptide
Authors: Kudryavtsev Denis S. , Tabakmakher Valentin М. , Budylin Gleb S. , Egorova Natalia S. , Efremov Roman G. , Ivanov Igor A. , Belukhina Svetlana Yu. , Jegorov Artjom V. , Kasheverov Igor E. , Kryukova Elena V. , Shelukhina Irina V. , Shirshin Evgeny A. , Zhdanova Nadezhda G. , Zhmak Maxim N. , Tsetlin Victor I.
Published: March 2020

Snake venom α-neurotoxins, invaluable pharmacological tools, bind with high affinity to distinct subtypes of nicotinic acetylcholine receptor. The combinatorial high-affinity peptide (HAP), homologous to the C-loop of α1 and α7 nAChR subunits, binds biotinylated α-bungarotoxin (αBgt) with nanomolar affinity and might be a protection against snake-bites. Since there are no data on HAP interaction with other toxins, we checked its binding of α-cobratoxin (αCtx), similar to αBgt in action on nAChRs. Using radioiodinated αBgt, we confirmed a high affinity of HAP for αBgt, the complex formation is supported by mass spectrometry and gel chromatography, but only weak binding was registered with αCtx. A combination of protein intrinsic fluorescence measurements with the principal component analysis of the spectra allowed us to measure the HAP-αBgt binding constant directly (29 nM). These methods also confirmed weak HAP interaction with αCtx (>10000 nM). We attempted to enhance it by modification of HAP structure relying on the known structures of α-neurotoxins with various targets and applying molecular dynamics. A series of HAP analogues have been synthesized, HAP[L9E] analogue being considerably more potent than HAP in αCtx binding (7000 nM). The proposed combination of experimental and computational approaches appears promising for analysis of various peptide-protein interactions.
A soluble truncated tau species related to cognitive dysfunction is elevated in the brain of cognitively impaired human individuals
Authors: Liu Peng , Smith Benjamin R. , Montonye Michelle L. , Kemper Lisa J. , Leinonen-Wright Kailee , Nelson Kathryn M. , Higgins LeeAnn , Guerrero Candace R. , Markowski Todd W. , Zhao Xiaohui , Petersen Ashley J. , Knopman David S. , Petersen Ronald C. , Ashe Karen H.
Published: March 2020

Neurofibrillary tangles are a pathological hallmark of Alzheimer’s disease, and their levels correlate with the severity of cognitive dysfunction in humans. However, experimental evidence suggests that soluble tau species cause cognitive deficits and memory impairment. Our recent study suggests that caspase-2 (Casp2)-catalyzed tau cleavage at aspartate 314 mediates synaptic dysfunction and memory impairment in mouse and cellular models of neurodegenerative disorders. Δtau314, the C-terminally-truncated cleavage products, are soluble and present in human brain. In addition, levels of Δtau314 proteins are elevated in the brain of the cognitively impaired individuals compared to the cognitively normal individuals, indicating a possible role for Δtau314 proteins in cognitive deterioration. Here we show that (1) Δtau314 proteins are present in the inferior temporal gyrus of human brains; (2) Δtau314 proteins are generated from all six tau splicing isoforms, (3) levels of both Casp2 and Δtau314 proteins are elevated in cognitively impaired individuals compared to cognitively normal individuals, and (4) levels of Δtau314 proteins show a modest predictive value for dementia. These findings advance our understanding of the characteristics of Δtau314 proteins and their relevance to cognitive dysfunction and shed light on the contribution of Casp2-mediated Δtau314 production to cognitive deterioration.
Basic Hallmarks of Urothelial Cancer Unleashed in Primary Uroepithelium by Interference with the Epigenetic Master Regulator ODC1
Authors: Erichsen Lars , Seifert Hans-Helge , Schulz Wolfgang A. , Hoffmann Michèle J. , Niegisch Günter , Araúzo-Bravo Marcos J. , Bendhack Marcelo L. , Poyet Cedric , Hermanns Thomas , Beermann Agnes , Hassan Mohamed , Theis Lisa , Mahmood Wardah , Santourlidis Simeon
Published: March 2020

Urothelial carcinoma (UC) is a common disease causing significant morbidity and mortality as well as considerable costs for health systems. Extensive aberrant methylation of DNA is broadly documented in early UC, contributing to genetic instability, altered gene expression and tumor progression. However the triggers initiating aberrant methylation are unknown. Recently we discovered that several genes encoding key enzymes of methyl group and polyamine metabolism, including Ornithine Decarboxylase 1(ODC1), are affected by DNA methylation in early stage UC. In this study, we investigated the hypothesis that these epigenetic alterations act in a feed-forward fashion to promote aberrant DNA methylation in UC. We demonstrate that siRNA-mediated knockdown ofODC1expression elicits genome-wide LINE-1 demethylation, induction of LINE-1 transcripts and double-strand DNA breaks and decreases viability in primary cultured uroepithelial cells. Similarly, following siRNA-mediated knockdown ofODC1, UC cells undergo double-strand DNA breaks and apoptosis. Collectively, our findings provide evidence thatODC1gene hypermethylation could be a starting point for the onset of genome-wide epigenetic aberrations in urothelial carcinogenesis. Furthermore, LINE-1 induction enabled byODC1interference provides a new experimental model to study mechanisms and consequences of LINE-1 activation in the etiology and progression of UC as well as presumably other cancers.
The LRRK2 N-terminal domain influences vesicle trafficking: impact of the E193K variant
Authors: Marku Algerta , Carrion Maria Dolores Perez , Pischedda Francesca , Marte Antonella , Casiraghi Zeila , Marciani Paola , von Zweydorf Felix , Gloeckner Christian Johannes , Onofri Franco , Perego Carla , Piccoli Giovanni
Published: March 2020

The LRRK2 protein consists of multiple functional domains, including protein-binding domains at its N and C-terminus. Mutations in the Leucine-rich repeat kinase 2 gene (LRRK2) have been linked to familial and sporadic Parkinson’s disease (PD). We have recently described a novel variant falling within the N-terminal armadillo repeats, E193K. Herein, our aim is to investigate the functional impact of LRRK2 N-terminal domain and the E193K variant on vesicle trafficking. By combining Total Internal Reflection Fluorescence (TIRF) microscopy and a synaptopHluorin assay, we found that expression of a construct lacking the N-terminal domain increases the frequency and amplitude of spontaneous synaptic events. Complementary biochemical approaches showed that the E193K variant alters the binding properties of LRRK2, decreases LRRK2 binding to synaptic vesicles, and promotes vesicle fusion. Our results confirm the physiological and pathological relevance of the nature of the LRRK2-associated macro-molecular complex solidifying the idea that different pathological mutations critically alter the scaffolding function of LRRK2 resulting in a perturbation of the vesicular trafficking as a common denominator.
Generation of Non-aliased Two-dimensional Acoustic Vortex with Enclosed Metasurface
Authors: Liu Jing-jing , Liang Bin , Yang Jing , Yang Jun , Cheng Jian-chun
Published: March 2020

Two-dimensional (2D) acoustic vortex allows new physics and applications different from three-dimensional counterparts, yet existing mechanisms usually have to rely on active array composed of transducers which may result in complexity, high cost and, in particular, undesired spatial aliasing effect. We propose to generate 2D acoustic vortex inside an enclosed metasurface illuminated by axisymmetric wave carrying no orbital angular momentum. We derive the criterion on unit size for eliminating spatial aliasing effect which is challenging for conventional active approaches and design a membrane-based metasurface to implement our mechanism. The performance of our strategy is demonstrated via precise production of different orders of non-aliased vortices regardless of center-to-center alignment, with undistorted Bessel-like pattern extending to the whole inner region. We anticipate our design with simplicity, compactness, precision and flexibility to open up possibility to design novel vortex devices and find important applications in diverse scenarios such as on-chip particle manipulations.
Neotropical termite microbiomes as sources of novel plant cell wall degrading enzymes
Authors: Romero Victorica Matias , Soria Marcelo A. , Batista-García Ramón Alberto , Ceja-Navarro Javier A. , Vikram Surendra , Ortiz Maximiliano , Ontañon Ornella , Ghio Silvina , Martínez-Ávila Liliana , Quintero García Omar Jasiel , Etcheverry Clara , Campos Eleonora , Cowan Donald , Arneodo Joel , Talia Paola M.
Published: March 2020

In this study, we used shotgun metagenomic sequencing to characterise the microbial metabolic potential for lignocellulose transformation in the gut of two colonies of Argentine higher termite species with different feeding habits, Cortaritermes fulviceps and Nasutitermes aquilinus. Our goal was to assess the microbial community compositions and metabolic capacity, and to identify genes involved in lignocellulose degradation. Individuals from both termite species contained the same five dominant bacterial phyla (Spirochaetes, Firmicutes, Proteobacteria, Fibrobacteres and Bacteroidetes) although with different relative abundances. However, detected functional capacity varied, with C. fulviceps (a grass-wood-feeder) gut microbiome samples containing more genes related to amino acid metabolism, whereas N. aquilinus (a wood-feeder) gut microbiome samples were enriched in genes involved in carbohydrate metabolism and cellulose degradation. The C. fulviceps gut microbiome was enriched specifically in genes coding for debranching- and oligosaccharide-degrading enzymes. These findings suggest an association between the primary food source and the predicted categories of the enzymes present in the gut microbiomes of each species. To further investigate the termite microbiomes as sources of biotechnologically relevant glycosyl hydrolases, a putative GH10 endo-β-1,4-xylanase, Xyl10E, was cloned and expressed in Escherichia coli. Functional analysis of the recombinant metagenome-derived enzyme showed high specificity towards beechwood xylan (288.1 IU/mg), with the optimum activity at 50 °C and a pH-activity range from 5 to 10. These characteristics suggest that Xy110E may be a promising candidate for further development in lignocellulose deconstruction applications.
Reliability of CT radiomic features reflecting tumour heterogeneity according to image quality and image processing parameters
Authors: Park Bum Woo , Kim Jeong Kon , Heo Changhoe , Park Kye Jin
Published: March 2020

The reliability of radiomics features (RFs) is crucial for quantifying tumour heterogeneity. We assessed the influence of imaging, segmentation, and processing conditions (quantization range, bin number, signal-to-noise ratio [SNR], and unintended outliers) on RF measurement. Low SNR and unintended outliers increased the standard deviation and mean values of histograms to calculate the first-order RFs. Variations in imaging processing conditions significantly altered the shape of the probability distribution (centre of distribution, extent of dispersion, and segmentation of probability clusters) in second-order RF matrices (i.e. grey-level co-occurrence and grey-level run length), thereby eventually causing fluctuations in RF estimation. Inconsistent imaging and processing conditions decreased the number of reliably measured RFs in terms of individual RF values (intraclass correlation coefficient ≥0.75) and inter-lesion RF ratios (coefficient of variation <15%). No RF could be reliably estimated under inconsistent SNR and inclusion of outlier conditions. By contrast, with high SNR and no outliers, all first-order RFs, 11 (42%) grey-level co-occurrence RFs and five (42%) grey-level run length RFs showed acceptable reliability. Our study suggests that optimization of SNR, exclusion of outliers, and application of relevant quantization range and bin number should be performed to ensure the robustness of radiomics studies assessing tumor heterogeneity.
Silent circulation of dengue virus in Aedes albopictus (Diptera: Culicidae) resulting from natural vertical transmission
Authors: Ferreira-de-Lima Victor Henrique , Andrade Pâmela dos Santos , Thomazelli Luciano Matsumiya , Marrelli Mauro Toledo , Urbinatti Paulo Roberto , Almeida Rosa Maria Marques de Sá , Lima-Camara Tamara Nunes
Published: March 2020

Vertical transmission in Aedes aegypti and Aedes albopictus is considered a maintenance mechanism for dengue virus (DENV) during unfavorable conditions and may be implicated in dengue outbreaks. Since DENV infection dynamics vary among wild-type viruses and vector populations, vertical transmission rates can also vary between regions. However, even though São Paulo is the most populous city in the Americas and has experienced major dengue epidemics, natural vertical transmission had never been detected in this area before. Here we confirm and describe for the first time natural vertical transmission of DENV-3 in two pools of male Ae. albopictus from the city of São Paulo. The detection of DENV-3 in years when no human autochthonous cases of this serotype were recorded suggests that silent circulation of DENV-3 is occurring and indicates that green areas may be maintaining serotypes that are not circulating in the human population, possibly by a vertical transmission mechanism.
Multi-target immunofluorescence by separation of antibody cross-labelling via spectral-FLIM-FRET
Authors: Rohilla Sumeet , Krämer Benedikt , Koberling Felix , Gregor Ingo , Hocke Andreas C.
Published: March 2020

In biomedical research, indirect immunofluorescence labelling by use of primary and secondary antibodies is central for revealing the spatial distribution of multiple cellular antigens. However, labelling is regularly restricted to few antigens since species variation of primary and corresponding secondary antibodies is limited bearing the risk of unspecific cross-labelling. Here, we introduce a novel microscopic procedure for leveraging undesirable cross-labelling effects among secondary antibodies thereby increasing the number of fluorophore channels. Under cross-labelling conditions, commonly used fluorophores change chemical-physical properties by ‘Förster resonance energy transfer’ leading to defined changes in spectral emission and lifetime decay. By use of spectral fluorescence lifetime imaging and pattern-matching, we demonstrate precise separation of cross-labelled cellular antigens where conventional imaging completely fails. Consequently, this undesired effect serves for an innovative imaging procedure to separate critical antigens where antibody species variation is limited and allows for multi-target labelling by attribution of new fluorophore cross-labelling channels.
Matrix stiffness-regulated cellular functions under different dimensionalities
Authors: Zhong Jiajun , Yang Yuexiong , Liao Liqiong , Zhang Chao
Published: March 2020

The microenvironments that cells encounter with in vitro.
Synthesis of 3-(2-quinolyl) chromones from ynones and quinolineN-oxidesviatandem reactions under transition metal- and additive-free conditions
Authors: Liu Jing , Ba Dan , Chen Yanhui , Wen Si , Cheng Guolin
Published: March 2020

The synthesis of 3-(2-quinolyl) chromones from ynones and quinolineN-oxidesviaa sequential [3+2] cycloaddition/ring-opening/O-arylation reaction under transition metal- and additive-free conditions is reported.
Scope and mechanism of nitrile dihydroboration mediated by a β-diketiminate manganese hydride catalyst
Authors: Nguyen Thao T. , Kim Jun-Hyeong , Kim Suyeon , Oh Changjin , Flores Marco , Groy Thomas L. , Baik Mu-Hyun , Trovitch Ryan J.
Published: March 2020

Nitrile insertion allows for manganese-catalyzed nitrile dihydroboration at 80 °C.
Low-dimensional projection approach for efficient sampling of molecular recognition and polymer aggregation
Authors: Nakata Hiroya , Choi Cheol Ho
Published: March 2020

The one-dimensional projection (ODP) approach is extended to two-dimensional umbrella sampling (TDUS) and is applied to three different complex systems in combination with a reactive force field (ReaxFF).
Solar-driven all-solid-state lithium–air batteries operating at extreme low temperatures
Authors: Song Hucheng , Wang Sheng , Song Xiaoying , Wang Jue , Jiang Kezhu , Huang Shihua , Han Min , Xu Jun , He Ping , Chen Kunji , Zhou Haoshen
Published: March 2020

Plasmon-enhanced solar photothemal battery (STPB) technology allows all-solid-state lithium–air batteries to operate at temperatures as low as −73 °C.
Screening of by-products from the food industry as growth promoting agents in serum-free media for skeletal muscle cell culture
Authors: Andreassen R. Christel , Pedersen Mona E. , Kristoffersen Kenneth A. , Beate Rønning Sissel
Published: March 2020

Hydrolysates from food by-products allow higher cell growth and metabolic activity than commercially available serum in skeletal muscle cell culture and can potentially be used to produce a tailor-made serum-free media.
The potential of proteins, hydrolysates and peptides as growth factors forLactobacillusandBifidobacterium: current research and future perspectives
Authors: Zhang Chi , Zhang Yinxiao , Li He , Liu Xinqi
Published: March 2020

Probiotics are live microorganisms that provide health benefits to the host when consumed in adequate concentrations.
Metal/semiconductor interfaces in nanoscale objects: synthesis, emerging properties and applications of hybrid nanostructures
Authors: Volokh Michael , Mokari Taleb
Published: March 2020

Multi-component crystals of various shapes, sizes and compositions (hybrid nanostructures) are much sought-after functional materials. Herein, the synthesis and emerging properties of nanomaterials with metal/semiconductor interface(s) are reviewed.
Temperature-dependent heating efficiency of magnetic nanoparticles for applications in precision nanomedicine
Authors: Barrera Gabriele , Allia Paolo , Tiberto Paola
Published: March 2020

The power released by magnetic nanoparticles submitted to an alternating driving field is temperature dependent owing to the variation of the fundamental magnetic properties.
Strongly visible light-absorbing metal–organic frameworks functionalized by cyclometalated ruthenium(ii) complexes
Authors: Thoresen Eirik Mydske , Øien-Ødegaard Sigurd , Kaur Gurpreet , Tilset Mats , Lillerud Karl Petter , Amedjkouh Mohamed
Published: March 2020

The metal–organic framework (MOF) UiO-67 was functionalized by incorporating different cyclometalated ruthenium(ii) complexes using three different methods: premade linker synthesis, postsynthetic functionalization, and postsynthetic linker exchange.
MOF-derived ZnCo2O4 porous micro-rice with enhanced electro-catalytic activity for the oxygen evolution reaction and glucose oxidation
Authors: Zhang Daojun , Wang Zimo , Li Jiakai , Hu Chengming , Zhang Xiaobei , Jiang Bei , Cao Zhi , Zhang Jingchao , Zhang Renchun
Published: March 2020

A porous ZnCo2O4 micro-rice like microstructure was synthesized via calcination of a Zn–Co MOF precursor at an appropriate temperature.
Super-capacity information-carrying systems encoded with spontaneous Raman scattering
Authors: Tang Yuchen , He Caili , Zheng Xingxing , Chen Xuqi , Gao Tingjuan
Published: March 2020

Super-capacity information-carrying systems are fabricated by tuning vibrational signals into octal numeral intensities in multiple bands of Raman-silent regions.
Enhanced catalytic reaction at an air–liquid–solid triphase interface
Authors: Chen Liping , Feng Xinjian
Published: March 2020

Gaseous reactant involved liquid–solid diphase interface reactions can be significantly enhanced using rationally designed and constructed air–liquid–solid triphase systems.
Cyclodextrin-modified poly(octamethylene citrate) polymers towards enhanced sorption properties
Authors: Kasprzyk Wiktor , Bednarz Szczepan , Bogdał Dariusz , Ameer Guillermo A. , Świergosz Tomasz
Published: March 2020

We describe the synthesis of poly(1,8-octamethylene citrate) materials modified in the bulk with 2-hydroxypropyl-β-cyclodextrin, biodegradable elastomers with intrinsic sorption properties for drug delivery.
Diffusive transport of nanoscale objects through cell membranes: a computational perspective
Authors: Xu Ziyang , Gao Lijuan , Chen Pengyu , Yan Li-Tang
Published: March 2020

Clarifying the diffusion dynamics of nanoscale objects with cell membrane is critical for revealing fundamental physics in biological systems. This perspective highlights the advances in computational and theoretical aspects of this emerging field.
Correlations between temperature-dependent rheology and electrostatic interactions in reverse wormlike micelles induced by inorganic salts
Authors: Chang Hung-Ming , Lin Chia-Yi , Tung Shih-Huang
Published: March 2020

Temperature-dependent rheological properties are correlated with the strength of the electrostatic interaction that drives the formation of reverse wormlike micelles.
NMR-based metabolomics and fluxomics: developments and future prospects
Authors: Giraudeau Patrick
Published: March 2020

Recent NMR developments are acting as game changers for metabolomics and fluxomics – a critical and perspective review.
Bimetallic coatings synergistically enhance the speeds of photocatalytic TiO2 micromotors
Authors: Xiao Zuyao , Chen Jingyuan , Duan Shifang , Lv Xianglong , Wang Jizhuang , Ma Xing , Tang Jinyao , Wang Wei
Published: March 2020

A bimetallic cap containing sputtered silver is a better catalyst that significantly improves the performance of catalytically powered micromotors.
Five water-stable luminescent CdII-based metal–organic frameworks as sensors for highly sensitive and selective detection of acetylacetone, Fe3+ and Cr2O72− ions
Authors: Shi Yong-Sheng , Liu Dong , Fu Lianshe , Li Yue-Hua , Dong Gui-Ying
Published: March 2020

Five CdII-based MOFs with different topologies were prepared, in which 2 and 3 are rare examples which display excellent sensitivity, selectivity, recyclability and structural stability for detection of acac/Fe3+ and acac/Cr2O72−, respectively.
Porosity determination of nano- and sub-micron particles by single particle inductively coupled plasma mass spectrometry
Authors: Kéri Albert , Sápi András , Ungor Ditta , Sebők Dániel , Csapó Edit , Kónya Zoltán , Galbács Gábor
Published: March 2020

By comparing the spICP-MS signal intensities of solid and porous nanoparticles of the same composition and size, the porosity of particles can be determined.