bluuebunny/crossref_metadata_2025_split huggingface dataset:
Antimicrobial peptide gramicidin S is accumulated in granules of producer cells for storage of bacterial phosphagens
Authors: Berditsch Marina , Trapp Mareike , Afonin Sergii , Weber Christian , Misiewicz Julia , Turkson Joana , Ulrich Anne S. 
Published: March 2017

AbstractMany antimicrobial peptides are synthesized non-ribosomally in bacteria, but little is known about their subcellular route of biosynthesis, their mode of intracellular accumulation, or their role in the physiology of the producer cells. Here, we present a comprehensive view on the biosynthesis of gramicidin S (GS) in Aneurinibacillus migulanus, having observed a peripheral membrane localization of its synthetases. The peptide gets accumulated in nano-globules, which mature by fusion into larger granules and end up within vacuolar structures. These granules serve as energy storage devices, as they contain GS molecules that are non-covalently attached to alkyl phosphates and protect them from dephosphorylation and premature release of energy. This finding of a fundamentally new type of high-energy phosphate storage mechanism can explain the curious role of GS biosynthesis in the physiology of the bacterial producer cells. The unknown role of the GrsT protein, which is part of the non-ribosomal GS synthetase operon, can thus be assumed to be responsible for the biosynthesis of alkyl phosphates. GS binding to alkyl phosphates may suggest its general affinity to phosphagens such as ATP and GTP, which can represent the important intracellular targets in pathogenic bacteria.
Aptamer-based Field-Effect Biosensor for Tenofovir Detection
Authors: Aliakbarinodehi N. , Jolly P. , Bhalla N. , Miodek A. , De Micheli G. , Estrela P. , Carrara S. 
Published: March 2017

AbstractDuring medical treatment it is critical to maintain the circulatory concentration of drugs within their therapeutic range. A novel biosensor is presented in this work to address the lack of a reliable point-of-care drug monitoring system in the market. The biosensor incorporates high selectivity and sensitivity by integrating aptamers as the recognition element and field-effect transistors as the signal transducer. The drug tenofovir was used as a model small molecule. The biointerface of the sensor is a binary self-assembled monolayer of specific thiolated aptamer and 6-mercapto-1-hexanol (MCH), whose ratio was optimized by electrochemical impedance spectroscopy measurements to enhance the sensitivity towards the specific target. Surface plasmon resonance, performed under different buffer conditions, shows optimum specific and little non-specific binding in phosphate buffered saline. The dose-response behavior of the field-effect biosensor presents a linear range between 1 nM and 100 nM of tenofovir and a limit of detection of 1.2 nM. Two non-specific drugs and one non-specific aptamer, tested as stringent control candidates, caused negligible responses. The applications were successfully extended to the detection of the drug in human serum. As demonstrated by impedance measurements, the aptamer-based sensors can be used for real-time drug monitoring.
A cross-functional nanostructured platform based on carbon nanotube-Si hybrid junctions: where photon harvesting meets gas sensing
Authors: Rigoni F. , Pintossi C. , Drera G. , Pagliara S. , Lanti G. , Castrucci P. , De Crescenzi M. , Sangaletti L. 
Published: March 2017

AbstractA combination of the functionalities of carbon nanotube (CNT)-Si hybrid heterojunctions is presented as a novel method to steer the efficiency of the photovoltaic (PV) cell based on these junctions, and to increase the selectivity and sensitivity of the chemiresistor gas sensor operated with the p-doped CNT layer. The electrical characteristics of the junctions have been tracked by exposing the devices to oxidizing (NO2) and reducing (NH3) molecules. It is shown that when used as PV cells, the cell efficiency can be reversibly steered by gas adsorption, providing a tool to selectively dope the p-type layer through molecular adsorption. Tracking of the current-voltage curve upon gas exposure also allowed to use these cells as gas sensors with an enhanced sensitivity as compared to that provided by a readout of the electrical signal from the CNT layer alone. In turn, the chemiresistive response was improved, both in terms of selectivity and sensitivity, by operating the system under illumination, as the photo-induced charges at the junction increase the p-doping of CNTs making them more sensitive to NH3 and less to NO2.
Calretinin and Neuropeptide Y interneurons are differentially altered in the motor cortex of the SOD1G93A mouse model of ALS
Authors: Clark Rosemary M. , Blizzard Catherine A. , Young Kaylene M. , King Anna E. , Dickson Tracey C. 
Published: March 2017

AbstractIncreasing evidence indicates an excitatory/inhibitory imbalance may have a critical role in the pathogenesis of amyotrophic lateral sclerosis (ALS). Impaired inhibitory circuitry is consistently reported in the motor cortex of both familial and sporadic patients, closely associated with cortical hyperexcitability and ALS onset. Inhibitory network dysfunction is presumably mediated by intra-cortical inhibitory interneurons, however, the exact cell types responsible are yet to be identified. In this study we demonstrate dynamic changes in the number of calretinin- (CR) and neuropeptide Y-expressing (NPY) interneurons in the motor cortex of the familial hSOD1G93A ALS mouse model, suggesting their potential involvement in motor neuron circuitry defects. We show that the density of NPY-populations is significantly decreased by ~17% at symptom onset (8 weeks), and by end-stage disease (20 weeks) is significantly increased by ~30%. Conversely, the density of CR-populations is progressively reduced during later symptomatic stages (~31%) to end-stage (~36%), while CR-expressing interneurons also show alteration of neurite branching patterns at symptom onset. We conclude that a differential capacity for interneurons exists in the ALS motor cortex, which may not be a static phenomenon, but involves early dynamic changes throughout disease, implicating specific inhibitory circuitry.
Coherent selection of invisible high-order electromagnetic excitations
Authors: Tseng Ming Lun , Fang Xu , Savinov Vassili , Wu Pin Chieh , Ou Jun-Yu , Zheludev Nikolay I. , Tsai Din Ping 
Published: March 2017

AbstractFar-field spectroscopy and mapping of electromagnetic near-field distribution are the two dominant tools for analysis and characterization of the electromagnetic response in nanophotonics. Despite the widespread use, these methods can fail at identifying weak electromagnetic excitations masked by stronger neighboring excitations. This is particularly problematic in ultrafast nanophotonics, including optical sensing, nonlinear optics and nanolasers, where the broad resonant modes can overlap to a significant degree. Here, using plasmonic metamaterials, we demonstrate that coherent spectroscopy can conveniently isolate and detect such hidden high-order photonic excitations. Our results establish that the coherent spectroscopy is a powerful new tool. It complements the conventional methods for analysis of the electromagnetic response, and provides a new route to designing and characterizing novel photonic devices and materials.
Glycol porphyrin derivatives and temoporfin elicit resistance to photodynamic therapy by different mechanisms
Authors: Kralova Jarmila , Kolar Michal , Kahle Michal , Truksa Jaroslav , Lettlova Sandra , Balusikova Kamila , Bartunek Petr 
Published: March 2017

AbstractThe development of drug resistance is a major problem which often occurs during anticancer chemotherapies. Photodynamic therapy (PDT) has been studied as an alternative treatment modality for drug-resistant tumors, however the question of resistance to PDT and potential cross-resistance with chemotherapy has yet to be fully answered. To investigate the mechanism of resistance to PDT, we developed an in vitro experimental model system in a mouse mammary carcinoma cell line 4T1. We used two ethylene glycol derivatives of tetraphenylporphyrin, and tetraphenylchlorin derivative, temoporfin, as photosensitizers (PS). PDT-resistant clones were obtained by exposure to a set concentration of PS followed by irradiation with increasing light doses. PDT resistance to soluble glycol porphyrins was mediated mainly by increased drug efflux through ABCB1 (P-glycoprotein) as we demonstrated by specific ABCB1 knockdown experiments, which in turn rescued the sensitivity of resistant cells to PDT. In contrast, resistance raised to temoporfin, which is generally more lipophilic than glycol porphyrins, elicited mechanism based on sequestration of the drug to lysosomes. The resistance that is acquired from a particular PS could be overcome by using a different PS, which is not susceptible to the same mechanism(s) of resistance. Elucidation of the underlying mechanisms in various types of resistance might facilitate improvements in PDT treatment design.
Mixed Molybdenum Oxides with Superior Performances as an Advanced Anode Material for Lithium-Ion Batteries
Authors: Wu Di , Shen Rui , Yang Rong , Ji Wenxu , Jiang Meng , Ding Weiping , Peng Luming 
Published: March 2017

AbstractA simple and effective carbon-free strategy is carried out to prepare mixed molybdenum oxides as an advanced anode material for lithium-ion batteries. The new material shows a high specific capacity up to 930.6 mAh·g−1, long cycle-life (>200 cycles) and high rate capability. 1D and 2D solid-state NMR, as well as XRD data on lithiated sample (after discharge) show that the material is associated with both insertion/extraction and conversion reaction mechanisms for lithium storage. The well mixed molybdenum oxides at the microscale and the involvement of both mechanisms are considered as the key to the better electrochemical properties. The strategy can be applied to other transition metal oxides to enhance their performance as electrode materials.
Filters that mitigate waveform modulation of radar clutter
Authors: O'Connor Alan C. , Kantor Joshua M. , Jakabosky John 
Published: March 2017

Moving target indication (MTI) radars will require modified signal processing to be able to employ pulse‐to‐pulse agile waveforms. The main problem with conventional processing is that matched‐filter pulse compression leads to range‐sidelobe modulation (RSM) of clutter. Due to the fact that range sidelobes differ on each pulse, clutter energy that leaks into these sidelobes cannot be cancelled by subsequent processing. This study derives a figure‐of‐merit for pulse‐compression filters that quantifies the signal‐to‐interference‐plus‐noise ratio (SINR) loss that results from RSM. Optimising this figure‐of‐merit results in sets of filters that mitigate RSM by producing matched sidelobes. The proposed filters are compared to low‐sidelobe mismatch filters designed separately for each pulse. Simulation results indicate that an MTI radar could achieve a 5–10 dB improvement in SINR by using the proposed filters instead of low‐sidelobe filters.
Oxidative degradation and morphological properties of gamma‐irradiated isotactic polypropylene films
Authors: Mouaci Sarah , Saidi Mohamed , Saidi‐Amroun Nadia 
Published: March 2017

Isotactic polypropylene (iPP) films of 25 μm thickness were subjected to gamma‐ray irradiation for different doses (30, 60, 90 and 100 kGy) at ambient atmosphere and both molecular modifications and surface properties have been investigated by Fourier transform infrared spectroscopy (FTIR) and atomic force microscopy (AFM), respectively. The occurrence of the oxidation process is identified and quantified by the FTIR. In addition, it is found that the carbonyl index increases with the absorbed dose which confirms that the irradiation process induces the diffusion of the oxygen into the iPP matrix. The AFM image (for virgin and higher dose irradiated samples) showed a dramatic change in the surface topography. The gamma radiation induces the formation of the nanostructured iPP surface. The roughness of the polymer surface, measured by AFM, increases after gamma irradiation. These results revealed that the oxidative degradation may be correlated with the morphological properties.
Frequency of Chromosomal Abnormalities in Products of Conception
Authors: Paula Carolina Maria Marques de , Ramos Mariana Gontijo , Costa Helena B. B. L. Martins da , Andrade Cyntia Roberta Almeida , Coxir Sarah Abreu , Penna Maria Lectícia Firpe , Teles Thaís Mesquita Alves 
Published: March 2017

Purpose To describe the frequencies of chromosomal abnormalities found in abortion material, and to observe its correlation to maternal age.
Methods A retrospective study was conducted based on data obtained from the databank of a medical genetics laboratory in Belo Horizonte, MG, Brazil. A total of 884 results from products of conception analysis were included, 204 of which were analyzed by cytogenetics, and 680 by molecular biology based on quantitative fluorescence polymerase chain reaction (QF-PCR). The frequency of individual chromosomal aberrations and the relationship between the presence of anomalies and maternal age were also evaluated.
Results The conventional cytogenetics technique was able to detect 52% of normal and 48% of abnormal results in the analyzed material. Quantitative fluorescence polymerase chain reaction revealed 60% of normal and 40% of abnormal results from the samples evaluated by this method. The presence of trisomy 15 was detected only by cytogenetics, as it was not included in the QF-PCR routine investigation in the laboratory. A significant increase in abnormal results was observed among women aged 35 years or older compared with younger women (p = 0.02).
Conclusion Chromosomal aberrations are still a major cause of spontaneous abortion, and the conventional cytogenetics technique is efficient for miscarriage material analysis, but molecular methods such as QF-PCR are adequate complementary strategies to detect the major chromosomal anomalies, leading to technical reports with reliable results.
Evaluation of the 2015 AGA guidelines on pancreatic cystic neoplasms in a large surgically confirmed multicenter cohort
Authors: Ge Phillip , Muthusamy V. , Gaddam Srinivas , Jaiyeola Diana-Marie , Kim Stephen , Sedarat Alireza , Donahue Timothy , Hosford Lindsay , Wilson Robert , Grande David , Keswani Rajesh , Kushnir Vladimir , Mullady Daniel , Edmundowicz Steven , Early Dayna , Komanduri Srinadh , Wani Sachin , Watson Rabindra 
Published: March 2017

Absract
Background and study aims The American Gastroenterological Association (AGA) recently published guidelines for the management of asymptomatic pancreatic cystic neoplasms (PCNs). We aimed to evaluate the diagnostic characteristics of the AGA guidelines in appropriately recommending surgery for malignant PCNs.
Patients and methods A retrospective multicenter study was performed of patients who underwent endoscopic ultrasound (EUS) for evaluation of PCNs who ultimately underwent surgical resection from 2004 – 2014. Demographics, EUS characteristics, fine-needle aspiration (FNA) results, type of resection, and final pathologic diagnosis were recorded. Patients were categorized into 2 groups (surgery or surveillance) based on what the AGA guidelines would have recommended. Performance characteristics for the diagnosis of cancer or high-grade dysplasia (HGD) on surgical pathology were calculated.
Results Three hundred patients underwent surgical resection for PCNs, of whom the AGA guidelines would have recommended surgery in 121 (40.3 %) and surveillance in 179 (59.7 %) patients. Among patients recommended for surgery, 45 (37.2 %) had cancer, whereas 76 (62.8 %) had no cancer/HGD. Among patients recommended for surveillance, 170 (95.0 %) had no cancer/HGD; however, 9 (5.0 %) patients had cancer that would have been missed. For the finding of cancer/HGD on surgical pathology, the AGA guidelines had 83.3 % sensitivity (95 % CI 70.7 – 92.1), 69.1 % specificity (95 % CI 62.9 – 74.8), 37.2 % positive predictive value (95 % CI 28.6 – 46.4), 95.0 % negative predictive value (95 % CI 90.7 – 97.7), and 71.7 % accuracy (95 % CI 67.4 – 74.6).
Conclusions The 2015 AGA guidelines would have resulted in 60 % fewer patients being referred for surgical resection, and accurately recommended surveillance in 95 % of patients with asymptomatic PCNs. Future prospective studies are required to validate these guidelines.Meeting presentations: Presented in part at Digestive Diseases Week 2016
Inhibition of atherogenesis by the COP9 signalosome subunit 5 in vivo
Authors: Asare Yaw , Ommer Miriam , Azombo Florence. A. , Alampour-Rajabi Setareh , Sternkopf Marieke , Sanati Maryam , Gijbels Marion J. , Schmitz Corinna , Sinitski Dzmitry , Tilstam Pathricia V. , Lue Hongqi , Gessner André , Lange Denise , Schmid Johannes A. , Weber Christian , Dichgans Martin , Jankowski Joachim , Pardi Ruggero , de Winther Menno P. J. , Noels Heidi , Bernhagen Jürgen 
Published: March 2017

Significance
Atherosclerosis is an inflammatory condition of the artery wall and main cause of myocardial infarction and stroke. Inflammatory processes evoking atherogenic lesions involve NF‐κB–dependent endothelial-cell activation and monocyte/macrophage recruitment. Constitutive photomorphogenesis 9 (COP9) signalosome (CSN) subunit 5 (CSN5) and the CSN control cullin/RING E3 ligase-dependent degradation of cell-cycle regulators and inhibitor of κB‐α by cleaving neural precursor cell-expressed, developmentally down-regulated-8 (NEDD8) from cullins. CSN5 promotes tumorigenesis in humans. We generated a conditional KO mouse in which macrophage/granulocyte-CSN5 is deleted. We show that CSN5 suppresses macrophage inflammation and that mice lacking myeloid CSN5 develop larger atherosclerotic lesions. The NEDDylation inhibitor MLN4924 attenuates early atherosclerosis and inhibits inflammation in macrophages and endothelial cells. With MLN4924 in clinical trials, deNEDDylation approaches may qualify as therapeutics to reduce early-stage atherogenesis.
Parasitophorous vacuole poration precedes its rupture and rapid host erythrocyte cytoskeleton collapse in
Plasmodium falciparum
egress
Authors: Hale Victoria L. , Watermeyer Jean M. , Hackett Fiona , Vizcay-Barrena Gema , van Ooij Christiaan , Thomas James A. , Spink Matthew C. , Harkiolaki Maria , Duke Elizabeth , Fleck Roland A. , Blackman Michael J. , Saibil Helen R. 
Published: March 2017

Significance
Malaria parasites develop within red blood cells inside a membrane-enclosed parasitophorous vacuole. An essential step in their life cycle is the exit of mature parasites from the blood cell, a multistage process termed egress. To do this, the parasites orchestrate a highly regulated sequence of membrane permeabilization and breakage steps culminating in the explosive release of parasites for a new round of infection. Here, we describe a previously unidentified permeabilization of the vacuolar membrane at the start of egress, preceding membrane rupture, suggesting a new initiation step in egress. We also show that, in the final minutes of egress, the blood cell membrane abruptly loses its structural rigidity and collapses around the parasites, showing a precise timing for cytoskeletal breakdown.
Computational investigation of surface freezing in a molecular model of water
Authors: Haji-Akbari Amir , Debenedetti Pablo G. 
Published: March 2017

Significance
Ice nucleation at interfaces plays an important role in atmospheric processes. Because of the insufficient spatiotemporal resolution of the existing experimental techniques, however, it is very difficult to understand how interfaces affect freezing at the molecular level. In particular, whether a vapor–liquid interface enhances or suppresses freezing at its vicinity is still a major unresolved question in contemporary ice physics. We address this question computationally by directly calculating the ice nucleation rate in a freestanding nanofilm of supercooled water modeled using an accurate molecular model and observe seven orders of magnitude enhancement. We observe that freezing initiates away from the air–water interface, in regions of the film favorable to the formation of cubic ice.
Diagnosis of prostate cancer by desorption electrospray ionization mass spectrometric imaging of small metabolites and lipids
Authors: Banerjee Shibdas , Zare Richard N. , Tibshirani Robert J. , Kunder Christian A. , Nolley Rosalie , Fan Richard , Brooks James D. , Sonn Geoffrey A. 
Published: March 2017

SignificanceDesorption electrospray ionization mass spectrometry imaging (DESI-MSI) is a label-free molecular imaging technique that provides a window into the biochemical processes present in benign and malignant prostate tissue. This is important both in improving the understanding of tissue biology and in achieving rapid cancer diagnosis. We applied DESI-MSI to record lipid, carbohydrate, and most importantly, small metabolite images from 54 normal and malignant prostate tissue specimens. Several Krebs cycle intermediates were present at different concentrations in prostate cancer compared with normal tissue. Statistical calculations identified panels of metabolites that could readily distinguish prostate cancer from normal tissue with nearly 90% accuracy in a validation set. The results also indicated that the ratio of glucose to citrate ion signals could be used to accurately identify prostate cancer.
Small molecule selectively suppresses MYC transcription in cancer cells
Authors: Bouvard Claire , Lim Sang Min , Ludka John , Yazdani Nahid , Woods Ashley K. , Chatterjee Arnab K. , Schultz Peter G. , Zhu Shoutian 
Published: March 2017

Significance
Oncogene MYC is up-regulated in up to 75% of all cancers. Suppression of MYC expression or inhibition of MYC function by mutant protein has been shown efficacious in a variety of cancer models. Even though selective MYC-targeting agents have been long sought after, no drugs are available yet. Herein, we demonstrate that a pharmacological agent, stauprimide, selectively suppresses MYC transcription in a variety of cancer cells in vitro and inhibits tumor growth in xenograft mouse models. This study provides not only a proof-of-concept for pharmacologically targeting MYC transcription as an effective strategy for cancer treatment, but also evidence to support further development of stauprimide as an anticancer drug candidate.