bluuebunny/crossref_metadata_2025 huggingface dataset:
A novel exchange method to access sulfated molecules
Authors: Alshehri Jaber A. , Benedetti Anna Mary , Jones Alan M.
Published: October 2020

Organosulfates and sulfamates are important classes of bioactive molecules but due to their polar nature, they are both difficult to prepare and purify. We report an operationally simple, double ion-exchange method to access organosulfates and sulfamates. Inspired by the novel sulfating reagent, TriButylSulfoAmmonium Betaine (TBSAB), we developed a 3-step procedure using tributylamine as the novel solubilising partner coupled to commercially available sulfating agents. Hence, in response to an increasing demand for complementary methods to synthesise organosulfates, we developed an alternative sulfation route based on an inexpensive, molecularly efficient and solubilising cation exchanging method using off-the-shelf reagents. The disclosed method is amenable to a range of differentially substituted benzyl alcohols, benzylamines and aniline and can also be performed at low temperature for sensitive substrates in good to excellent isolated yield.
High-purity foam-like micron-sized gold cage material with tunable plasmon properties
Authors: Dong Shuo , Yi Lin , Cheng Lexiao , Li Shijian , Yang Weiming , Wang Zhebin , Jiang Shaoen
Published: October 2020

Herein, by growing mono dispersed gold nanoparticles (MNPAu) on the surface of polystyrene (PS)/nanogold (Au) core–shell composites (PS@Au), we successfully synthesized a micron-sized gold cage (2.6–10.7 μm), referred to as PS@Au@MNPAu for the first time. The new micron-gold cage materials exhibit broadband absorption range from near-ultraviolet to near-infrared, which is unlike the conventional nanogold core–shell structure. The uniform growth of MNPAu on the surface forms a new photonic crystal spectrum. The strong coupling of the spectra causes anomalous absorption in the ultraviolet-near infrared band (400–900 nm). Furthermore, by removing the PS core, a nanogold cavity structure referred to as Au@MNPAu was prepared. This structure demonstrated a high purity (> 97 wt%), low density (9–223 mg/cm3), and high specific surface area (854 m2/g). As the purification process progressed, the MNPAu coupling on the surface of the micro-gold cage strengthened, resulting in the formation of peaks around 370 nm, plasma resonant peaks around 495 nm, and structural bands of photonic crystal peaks around 850 nm. The micron-sized gold cage provides hybridized and tunable plasmonic systems. The theoretical simulations indicate that this plasmon anomalous absorption phenomena can be understood as the novel form of the topological structural transitions near the percolation threshold, which is consistent experimental measurements.
Oncogenic driver mutations predict outcome in a cohort of head and neck squamous cell carcinoma (HNSCC) patients within a clinical trial
Authors: Fernández-Mateos Javier , Pérez-García Jéssica , Seijas-Tamayo Raquel , Mesía Ricard , Rubió-Casadevall Jordi , García-Girón Carlos , Iglesias Lara , Carral Maseda Alberto , Adansa Klain Juan Carlos , Taberna Miren , Vazquez Silvia , Gómez María Asunción , del Barco Edel , Ocana Alberto , González-Sarmiento Rogelio , Cruz-Hernández Juan Jesús
Published: October 2020

234 diagnostic formalin-fixed paraffin-embedded (FFPE) blocks from homogeneously treated patients with locally advanced head and neck squamous cell carcinoma (HNSCC) within a multicentre phase III clinical trial were characterised. The mutational spectrum was examined by next generation sequencing in the 26 most frequent oncogenic drivers in cancer and correlated with treatment response and survival. Human papillomavirus (HPV) status was measured by p16INK4a immunohistochemistry in oropharyngeal tumours. Clinicopathological features and response to treatment were measured and compared with the sequencing results. The results indicated TP53 as the most mutated gene in locally advanced HNSCC. HPV-positive oropharyngeal tumours were less mutated than HPV-negative tumours in TP53 (p < 0.01). Mutational and HPV status influences patient survival, being mutated or HPV-negative tumours associated with poor overall survival (p < 0.05). No association was found between mutations and clinicopathological features. This study confirmed and expanded previously published genomic characterization data in HNSCC. Survival analysis showed that non-mutated HNSCC tumours associated with better prognosis and lack of mutations can be identified as an important biomarker in HNSCC. Frequent alterations in PI3K pathway in HPV-positive HNSCC could define a promising pathway for pharmacological intervention in this group of tumours.
Exploring cyclic networks of multisite modification reveals origins of information processing characteristics
Authors: Suwanmajo Thapanar , Ramesh Vaidhiswaran , Krishnan J.
Published: October 2020

Multisite phosphorylation (and generally multisite modification) is a basic way of encoding substrate function and circuits/networks of post-translational modifications (PTM) are ubiquitous in cell signalling. The information processing characteristics of PTM systems are a focal point of broad interest. The ordering of modifications is a key aspect of multisite modification, and a broad synthesis of the impact of ordering of modifications is still missing. We focus on a basic class of multisite modification circuits: the cyclic mechanism, which corresponds to the same ordering of phosphorylation and dephosphorylation, and examine multiple variants involving common/separate kinases and common/separate phosphatases. This is of interest both because it is encountered in concrete cellular contexts, and because it serves as a bridge between ordered (sequential) mechanisms (representing one type of ordering) and random mechanisms (which have no ordering). We show that bistability and biphasic dose response curves of the maximally modified phosphoform are ruled out for basic structural reasons independent of parameters, while oscillations can result with even just one shared enzyme. We then examine the effect of relaxing some basic assumptions about the ordering of modification. We show computationally and analytically how bistability, biphasic responses and oscillations can be generated by minimal augmentations to the cyclic mechanism even when these augmentations involved reactions operating in the unsaturated limit. All in all, using this approach we demonstrate (1) how the cyclic mechanism (with single augmentations) represents a modification circuit using minimal ingredients (in terms of shared enzymes and sequestration of enzymes) to generate bistability and oscillations, when compared to other mechanisms, (2) new design principles for rationally designing PTM systems for a variety of behaviour, (3) a basis and a necessary step for understanding the origins and robustness of behaviour observed in basic multisite modification systems.
Normal electric field enhanced light-induced polarizations and magnetic detection of valley polarization in silicene
Authors: Shahabi N. , Phirouznia A.
Published: October 2020

The role of staggered potential on light-induced spin and pseudo-spin polarization has been investigated in silicene. It has been shown that non-equilibrium spin and pseudo-spin polarizations are emerged in silicene sheet by applying an external perpendicular electric field in the presence of circularly polarized light emission. This electric field results in pseudo-spin resolved states very close to the Dirac points therefore could be considered as a pseudomagnetic field. It has been shown that staggered potential induced spin-valley locking and pseudo-spin resolved bands are responsible for the enhancement of the spin and pseudo-spin polarizations. Meanwhile, spin-valley locking suggests a coexistence of both spin and valley polarizations with nearly identical (or at least proportional) population imbalance at low Fermi energies which could be employed for magnetic detection of the valley polarization. It has been shown that spin-valley locking results in the protection of the spin polarizations against the relaxations in elastic scattering regime. In addition, the results indicate that the pseudo-spin current can be generated by the circularly polarized light which could be explained by asymmetric light absorption of the states in k-space.
LncRNA-AK149641 regulates the secretion of tumor necrosis factor-α in P815 mast cells by targeting the nuclear factor-kappa B signaling pathway
Authors: Zhou Yao , Gu Li-na , Zhang Jie , Pan Jing , Zhang Jia-min , Zhao De-yu , Liu Feng
Published: October 2020

Long noncoding RNAs play important roles in various biological processes. However, not much is known about their roles in inflammatory response. Mast cells, involved in innate and adaptive immunity, are one of the major effector cells in allergic inflammatory reactions and contribute to the pathogenesis of disorders, including asthma. In the present study, we aimed to verify and elucidate the function and possible role of a novel lncRNA, called lncRNA-AK149641, in the mechanism of lipopolysaccharide (LPS)-induced inflammatory response in P815 mast cells. The results showed that downregulating lncRNA-AK149641 decreased secretion of tumor necrosis factor-α into the supernatants of LPS-stimulated mast cells. Mechanistically, the activity of nuclear factor-kappa B (NF-κB) decreased after downregulating lncRNA-AK149641, as shown by western blot and electrophoretic mobility shift assays. Moreover, RNA binding protein immunoprecipitation (RIP) verified that lncRNA-AK149641 was able to bind to NF-κB in the nucleus. In conclusion, we demonstrated that lncRNA-AK149641 regulated LPS-induced inflammatory response in mast cells through the NF-κB signaling pathway.
Consistent opening of the blood brain barrier using focused ultrasound with constant intravenous infusion of microbubble agent
Authors: Lapin Norman A. , Gill Kirt , Shah Bhavya R. , Chopra Rajiv
Published: October 2020

The blood brain barrier (BBB) is a major obstacle to the delivery of therapeutics to the brain. Focused ultrasound (FUS) in combination with microbubbles can non-invasively open the BBB in a targeted manner. Bolus intravenous injections of microbubbles are standard practice, but dynamic influx and clearance mechanisms prevent delivery of a uniform dose with time. When multiple targets are selected for sonication in a single treatment, uniform serum concentrations of microbubbles are important for consistent BBB opening. Herein, we show that bubble infusions were able to achieve consistent BBB opening at multiple target sites. FUS exposures were conducted with different Definity microbubble concentrations at various acoustic pressures. To quantify the effects of infusion on BBB opening, we calculated the MRI contrast enhancement rate. When infusions were performed at rates of 7.2 µl microbubbles/kg/min or below, we were able to obtain consistent BBB opening without injury at all pressures. However, when infusion rates exceeded 20 µl/kg/min, signs of injury occurred at pressures from 0.39 to 0.56 MPa. When compared to bolus injections, a bubble infusion offers a more controlled and consistent approach to multi-target BBB disruption.
An innovative technique of harvesting soil gas as a highly efficient source of 222Rn for calibration applications in a walk-in type chamber: part-1
Authors: Karunakara N. , Shetty Trilochana , Sahoo B. K. , Kumara K. Sudeep , Sapra B. K. , Mayya Y. S.
Published: October 2020

The paper describes a novel technique to harvest 222Rn laden air from soil gas of natural origin as a highly efficient source of 222Rn for calibration applications in a walk-in type 222Rn calibration chamber. The technique makes use of a soil probe of about 1 m to draw soil gas, through a dehumidifier and a delay volume, using an air pump to fill the calibration chamber. 222Rn concentration in the range of a few hundred Bq m−3 to a few tens of kBq m−3 was easily attained in the chamber of volume 22.7 m3 within a short pumping duration of 1 h. A new technique referred to as “semi-dynamic mode of operation” in which soil gas is injected into the calibration chamber at regular intervals to compensate for the loss of 222Rn due to decay and leak is discussed. Harvesting soil gas has many important advantages over the traditional methods of 222Rn generation for calibration experiments using finite sources such as solid flow-through, powdered emanation, and liquid sources. They are: (1) soil gas serves as an instantaneous natural source of 222Rn, very convenient to use unlike the high strength 226Ra sources used in the calibration laboratories, and has no radiation safety issues, (2) does not require licensing from the regulatory authority, and (3) it can be used continuously as a non-depleting reservoir of 222Rn, unlike other finite sources. The newly developed technique would eliminate the need for expensive radioactive sources and thereby offers immense application in a variety of day to day experiments—both in students and research laboratories.
The crystal structure of mycobacterial epoxide hydrolase A
Authors: Schulz Eike C. , Henderson Sara R. , Illarionov Boris , Crosskey Thomas , Southall Stacey M. , Krichel Boris , Uetrecht Charlotte , Fischer Markus , Wilmanns Matthias
Published: October 2020

The human pathogen Mycobacterium tuberculosis is the causative agent of tuberculosis resulting in over 1 million fatalities every year, despite decades of research into the development of new anti-TB compounds. Unlike most other organisms M. tuberculosis has six putative genes for epoxide hydrolases (EH) of the α/β-hydrolase family with little known about their individual substrates, suggesting functional significance for these genes to the organism. Due to their role in detoxification, M. tuberculosis EH’s have been identified as potential drug targets. Here, we demonstrate epoxide hydrolase activity of M. thermoresistibile epoxide hydrolase A (Mth-EphA) and report its crystal structure in complex with the inhibitor 1,3-diphenylurea at 2.0 Å resolution. Mth-EphA displays high sequence similarity to its orthologue from M. tuberculosis and generally high structural similarity to α/β-hydrolase EHs. The structure of the inhibitor bound complex reveals the geometry of the catalytic residues and the conformation of the inhibitor. Comparison to other EHs from mycobacteria allows insight into the active site plasticity with respect to substrate specificity. We speculate that mycobacterial EHs may have a narrow substrate specificity providing a potential explanation for the genetic repertoire of epoxide hydrolase genes in M. tuberculosis.
Tunable particle separation via deterministic absolute negative mobility
Authors: Słapik A. , Spiechowicz J.
Published: October 2020

Particle isolation techniques are in the spotlight of many areas of science and engineering. In food industry, a harmful bacterial activity can be prevented with the help of separation schemes. In health care, isolation techniques are used to distinguish cancer and healthy cells or in therapy for Alzheimer’s and Parkinson’s diseases. We consider a cloud of Brownian particles of different sizes moving in a periodic potential and subjected to an unbiased driving as well as a constant force. We reveal an efficient separation strategy via the counterintuitive effect of negative mobility when particles of a given size are transported in a direction opposite to the applied constant force. We demonstrate a tunable separation solution in which size of the particle undergoing separation may be controlled by variation of the parameters of the external force applied to the system. This approach is an important step towards the development of point-of-care lab-on-a-chip devices.
Twinning in MAPbI3 at room temperature uncovered through Laue neutron diffraction
Authors: Breternitz Joachim , Tovar Michael , Schorr Susan
Published: October 2020

The crystal structure of MAPbI3, the signature compound of the hybrid halide perovskites, at room temperature has been a reason for debate and confusion in the past. Part of this confusion may be due to twinning as the material bears a phase transition just above room temperature, which follows a direct group–subgroup relationship and is prone to twinning. Using neutron Laue diffraction, we illustrate the nature of twinning in the room temperature structure of MAPbI3 and explain its origins from a group-theoretical point-of-view.
Improving reproducibility in animal research by splitting the study population into several ‘mini-experiments’
Authors: von Kortzfleisch Vanessa Tabea , Karp Natasha A. , Palme Rupert , Kaiser Sylvia , Sachser Norbert , Richter S. Helene
Published: October 2020

In light of the hotly discussed ‘reproducibility crisis’, a rethinking of current methodologies appears essential. Implementing multi-laboratory designs has been shown to enhance the external validity and hence the reproducibility of findings from animal research. We here aimed at proposing a new experimental strategy that transfers this logic into a single-laboratory setting. We systematically introduced heterogeneity into our study population by splitting an experiment into several ‘mini-experiments’ spread over different time points a few weeks apart. We hypothesised to observe improved reproducibility in such a ‘mini-experiment’ design in comparison to a conventionally standardised design, according to which all animals are tested at one specific point in time. By comparing both designs across independent replicates, we could indeed show that the use of such a ‘mini-experiment’ design improved the reproducibility and accurate detection of exemplary treatment effects (behavioural and physiological differences between four mouse strains) in about half of all investigated strain comparisons. Thus, we successfully implemented and empirically validated an easy-to-handle strategy to tackle poor reproducibility in single-laboratory studies. Since other experiments within different life science disciplines share the main characteristics with the investigation reported here, these studies are likely to also benefit from this approach.
Neurocranium thickness mapping in early childhood
Authors: Gajawelli Niharika , Deoni Sean , Shi Jie , Linguraru Marius George , Porras Antonio R. , Nelson Marvin D. , Tamrazi Benita , Rajagopalan Vidya , Wang Yalin , Lepore Natasha
Published: October 2020

The neurocranium changes rapidly in early childhood to accommodate the growing brain. Developmental disorders and environmental factors such as sleep position may lead to abnormal neurocranial maturation. Therefore, it is important to understand how this structure develops, in order to provide a baseline for early detection of anomalies. However, its anatomy has not yet been well studied in early childhood due to the lack of available imaging databases. In hospitals, CT is typically used to image the neurocranium when a pathology is suspected, but the presence of ionizing radiation makes it harder to construct databases of healthy subjects. In this study, instead, we use a dataset of MRI data from healthy normal children in the age range of 6 months to 36 months to study the development of the neurocranium. After extracting its outline from the MRI data, we used a conformal geometry-based analysis pipeline to detect local thickness growth throughout this age span. These changes will help us understand cranial bone development with respect to the brain, as well as detect abnormal variations, which will in turn inform better treatment strategies for implicated disorders.
Liposomal delivery of azithromycin enhances its immunotherapeutic efficacy and reduces toxicity in myocardial infarction
Authors: Al-Darraji Ahmed , Donahue Renée R. , Tripathi Himi , Peng Hsuan , Levitan Bryana M. , Chelvarajan Lakshman , Haydar Dalia , Gao Erhe , Henson David , Gensel John C. , Feola David J. , Venditto Vincent J. , Abdel-Latif Ahmed
Published: October 2020

A growing body of evidence shows that altering the inflammatory response by alternative macrophage polarization is protective against complications related to acute myocardial infarction (MI). We have previously shown that oral azithromycin (AZM), initiated prior to MI, reduces inflammation and its negative sequelae on the myocardium. Here, we investigated the immunomodulatory role of a liposomal AZM formulation (L-AZM) in a clinically relevant model to enhance its therapeutic potency and avoid off-target effects. L-AZM (40 or 10 mg/kg, IV) was administered immediately post-MI and compared to free AZM (F-AZM). L-AZM reduced cardiac toxicity and associated mortality by 50% in mice. We observed a significant shift favoring reparatory/anti-inflammatory macrophages with L-AZM formulation. L-AZM use resulted in a remarkable decrease in cardiac inflammatory neutrophils and the infiltration of inflammatory monocytes. Immune cell modulation was associated with the downregulation of pro-inflammatory genes and the upregulation of anti-inflammatory genes. The immunomodulatory effects of L-AZM were associated with a reduction in cardiac cell death and scar size as well as enhanced angiogenesis. Overall, L-AZM use enhanced cardiac recovery and survival after MI. Importantly, L-AZM was protective from F-AZM cardiac off-target effects. We demonstrate that the liposomal formulation of AZM enhances the drug’s efficacy and safety in an animal model of acute myocardial injury. This is the first study to establish the immunomodulatory properties of liposomal AZM formulations. Our findings strongly support clinical trials using L-AZM as a novel and clinically relevant therapeutic target to improve cardiac recovery and reduce heart failure post-MI in humans.
Pomegranate: 2D segmentation and 3D reconstruction for fission yeast and other radially symmetric cells
Authors: Baybay Erod Keaton , Esposito Eric , Hauf Silke
Published: October 2020

Three-dimensional (3D) segmentation of cells in microscopy images is crucial to accurately capture signals that extend across optical sections. Using brightfield images for segmentation has the advantage of being minimally phototoxic and leaving all other channels available for signals of interest. However, brightfield images only readily provide information for two-dimensional (2D) segmentation. In radially symmetric cells, such as fission yeast and many bacteria, this 2D segmentation can be computationally extruded into the third dimension. However, current methods typically make the simplifying assumption that cells are straight rods. Here, we report Pomegranate, a pipeline that performs the extrusion into 3D using spheres placed along the topological skeletons of the 2D-segmented regions. The diameter of these spheres adapts to the cell diameter at each position. Thus, Pomegranate accurately represents radially symmetric cells in 3D even if cell diameter varies and regardless of whether a cell is straight, bent or curved. We have tested Pomegranate on fission yeast and demonstrate its ability to 3D segment wild-type cells as well as classical size and shape mutants. The pipeline is available as a macro for the open-source image analysis software Fiji/ImageJ. 2D segmentations created within or outside Pomegranate can serve as input, thus making this a valuable extension to the image analysis portfolio already available for fission yeast and other radially symmetric cell types.
Enhanced observation time of magneto-optical traps using micro-machined non-evaporable getter pumps
Authors: Boudot Rodolphe , McGilligan James P. , Moore Kaitlin R. , Maurice Vincent , Martinez Gabriela D. , Hansen Azure , de Clercq Emeric , Kitching John
Published: October 2020

We show that micro-machined non-evaporable getter pumps (NEGs) can extend the time over which laser cooled atoms can be produced in a magneto-optical trap (MOT), in the absence of other vacuum pumping mechanisms. In a first study, we incorporate a silicon-glass microfabricated ultra-high vacuum (UHV) cell with silicon etched NEG cavities and alumino–silicate glass (ASG) windows and demonstrate the observation of a repeatedly-loading MOT over a 10 min period with a single laser-activated NEG. In a second study, the capacity of passive pumping with laser activated NEG materials is further investigated in a borosilicate glass-blown cuvette cell containing five NEG tablets. In this cell, the MOT remained visible for over 4 days without any external active pumping system. This MOT observation time exceeds the one obtained in the no-NEG scenario by almost five orders of magnitude. The cell scalability and potential vacuum longevity made possible with NEG materials may enable in the future the development of miniaturized cold-atom instruments.
SERS activity of hybrid nano/microstructures Ag-Fe3O4 based on Dimorphotheca ecklonis pollen grains as bio-template
Authors: Ávila-Avilés R. D. , Torres-Gómez N. , Camacho-López M. A. , Vilchis-Nestor A. R.
Published: October 2020

Nature provides remarkable examples of mass-produced microscale particles with structures and chemistries optimized by evolution for particular functions. Synthetic chemical tailoring of such sustainable biogenic particles may be used to generate new multifunctional materials. Herein, we report a facile method for the synthesis of hybrid nano/microstructures Ag-Fe3O4 based on Dimorphotheca ecklonis pollen grains as bio-template. Silver nanoparticles was biosynthesized using pollen grains as a reduction and stabilization agent as well as a bio-template promoting the adhesion of silver nanoparticles to pollen surface. Fe3O4 nanoparticles were synthesized by co-precipitation method from FeSO4. Hybrid nano/microstructures Ag-Fe3O4 based on Dimorphotheca ecklonis pollen grains as bio-template were obtained and characterized using Scanning Electron Microscopy and Transmission Electron Microscopy to study the morphology and structure; Energy-Dispersive X-ray Spectroscopy to determine the chemical composition distribution; and Confocal Fluorescence Microscopy to demonstrate the fluorescence properties of hybrid nano-microstructures. Furthermore, these hybrid nano-microstructures have been studied by Surface-Enhanced Raman Scattering (SERS), using methylene blue as a target molecule; the hybrid nano-microstructures have shown 14 times signal amplification.
Bisphenol A impaired cell adhesion by altering the expression of adhesion and cytoskeleton proteins on human podocytes
Authors: Moreno-Gómez-Toledano Rafael , Arenas María I. , González-Martínez Clara , Olea-Herrero Nuria , Reventún Paula , Di Nunzio Michele , Sánchez-Esteban Sandra , Arilla-Ferreiro Eduardo , Saura Marta , Bosch Ricardo J.
Published: October 2020

Bisphenol A (BPA), a chemical -xenoestrogen- used in food containers is present in the urine of almost the entire population. Recently, several extensive population studies have proven a significant association between urinary excretion of BPA and albuminuria. The alteration of glomerular podocytes or "podocytopathy" is a common event in chronic albuminuric conditions. Since many podocytes recovered from patients' urine are viable, we hypothesized that BPA could impair podocyte adhesion capabilities. Using an in vitro adhesion assay, we observed that BPA impaired podocyte adhesion, an effect that was abrogated by Tamoxifen (an estrogen receptor blocker). Genomic and proteomic analyses revealed that BPA affected the expression of several podocyte cytoskeleton and adhesion proteins. Western blot and immunocytochemistry confirmed the alteration in the protein expression of tubulin, vimentin, podocin, cofilin-1, vinculin, E-cadherin, nephrin, VCAM-1, tenascin-C, and β-catenin. Moreover, we also found that BPA, while decreased podocyte nitric oxide production, it lead to overproduction of ion superoxide. In conclusion, our data show that BPA induced a novel type of podocytopathy characterizes by an impairment of podocyte adhesion, by altering the expression of adhesion and cytoskeleton proteins. Moreover, BPA diminished production of podocyte nitric oxide and induced the overproduction of oxygen-free metabolites. These data provide a mechanism by which BPA could participate in the pathogenesis and progression of renal diseases.
Pulmonary injury risk curves and behavioral changes from blast overpressure exposures of varying frequency and intensity in rats
Authors: Sajja Venkatasivasai Sujith , Statz Jonathan K. , Walker LCDR Peter B. , Gist Irene D. , Wilder Donna M. , Ahlers Stephen T. , Long Joseph B.
Published: October 2020

At present, there are no set guidelines establishing cumulative limits for blast exposure numbers and intensities in military personnel, in combat or training operations. The objective of the current study was to define lung injury, pathology, and associated behavioral changes from primary repeated blast lung injury under appropriate exposure conditions and combinations (i.e. blast overpressure (BOP) intensity and exposure frequency) using an advanced blast simulator. Male Sprague Dawley rats were exposed to BOP frontally and laterally at a pressure range of ~ 8.5–19 psi, for up to 30 daily exposures. The extent of lung injury was identified at 24 h following BOP by assessing the extent of surface hemorrhage/contusion, Hematoxylin and Eosin staining, and behavioral deficits with open field activity. Lung injury was mathematically modeled to define the military standard 1% lung injury threshold. Significant levels of histiocytosis and inflammation were observed in pressures ≥ 10 psi and orientation effects were observed at pressures ≥ 13 psi. Experimental data demonstrated ~ 8.5 psi is the threshold for hemorrhage/contusion, up to 30 exposures. Modeling the data predicted injury risk up to 50 exposures with intensity thresholds at 8 psi for front exposure and 6psi for side exposures, which needs to be validated further.
Posture-induced changes in the vessels of the head and neck: evaluation using conventional supine CT and upright CT
Authors: Kosugi Kenzo , Yamada Yoshitake , Yamada Minoru , Yokoyama Yoichi , Fujiwara Hirokazu , Yoshida Keisuke , Yoshida Kazunari , Toda Masahiro , Jinzaki Masahiro
Published: October 2020

Since the venous system is affected by gravity, upright computed tomography (CT) in addition to conventional supine CT has great potential for evaluating postural changes in the venous system. We evaluated the morphological differences in the head and neck vessels by performing a contrast CT study in both the supine and the sitting positions. In this study, the 20 included participants (10 men and 10 women) were healthy adults aged 30 to 55 years. The cross-sectional area of the cervical vessels, craniocervical junction veins, and intracranial vessels were obtained quantitatively. Venous sinuses and venous plexuses that were difficult to measure were evaluated qualitatively. The average change in areas from a supine to an upright posture was − 77.87 ± 15.99% (P < 0.0001) in the right internal jugular vein (IJV), − 69.42 ± 23.15% (P < 0.0001) in the left IJV, − 61.52 ± 12.81% (P < 0.0001) in the right external jugular vein (EJV), and − 58.91 ± 17.37% (P < 0.0001) in the left EJV. In contrast, the change in the anterior condylar vein (ACV) from a supine to an upright posture was approximately + 144% (P < 0.005) on the right side and + 110% (P < 0.05) on the left side. In addition, according to the qualitative analysis, the posterior venous structures including the anterior condylar confluence (ACC) of the craniocervical junction became more prominent in an upright posture. Despite these changes, the intracranial vessels showed almost no change between postures. From a supine to an upright position, the IJVs and EJVs above the heart collapsed, and venous channels including the ACCs and ACVs opened, switching the main cerebral venous drainage from the IJVs to the vertebral venous system. Upright head CT angiography can be useful for investigating physiological and pathophysiological hemodynamics of the venous system accompanying postural changes.
Hyperphosphorylated tau aggregation and cytotoxicity modulators screen identified prescription drugs linked to Alzheimer's disease and cognitive functions
Authors: Liu Mengyu , Dexheimer Thomas , Sui Dexin , Hovde Stacy , Deng Xiexiong , Kwok Roland , Bochar Daniel A. , Kuo Min-Hao
Published: October 2020

The neurodegenerative Alzheimer’s disease (AD) affects more than 30 million people worldwide. There is thus far no cure or prevention for AD. Aggregation of hyperphosphorylated tau in the brain correlates with the cognitive decline of patients of AD and other neurodegenerative tauopathies. Intracerebral injection of tau aggregates isolated from tauopathy brains causes similar pathology in the recipient mice, demonstrating the pathogenic role of abnormally phosphorylated tau. Compounds controlling the aggregation of hyperphosphorylated tau therefore are probable modulators for the disease. Here we report the use of recombinant hyperphosphorylated tau (p-tau) to identify potential tauopathy therapeutics and risk factors. Hyperphosphorylation renders tau prone to aggregate and to impair cell viability. Taking advantage of these two characters of p-tau, we performed a screen of a 1280-compound library, and tested a selective group of prescription drugs in p-tau aggregation and cytotoxicity assays. R-(−)-apomorphine and raloxifene were found to be p-tau aggregation inhibitors that protected p-tau-treated cells. In contrast, a subset of benzodiazepines exacerbated p-tau cytotoxicity apparently via enhancing p-tau aggregation. R-(−)apomorphine and raloxifene have been shown to improve cognition in animals or in humans, whereas benzodiazepines were linked to increased risks of dementia. Our results demonstrate the feasibility and potential of using hyperphosphorylated tau-based assays for AD drug discovery and risk factor identification.
Modeling a population of retinal ganglion cells with restricted Boltzmann machines
Authors: Volpi Riccardo , Zanotto Matteo , Maccione Alessandro , Di Marco Stefano , Berdondini Luca , Sona Diego , Murino Vittorio
Published: October 2020

The retina is a complex circuit of the central nervous system whose aim is to encode visual stimuli prior the higher order processing performed in the visual cortex. Due to the importance of its role, modeling the retina to advance in interpreting its spiking activity output is a well studied problem. In particular, it has been shown that latent variable models can be used to model the joint distribution of Retinal Ganglion Cells (RGCs). In this work, we validate the applicability of Restricted Boltzmann Machines to model the spiking activity responses of a large a population of RGCs recorded with high-resolution electrode arrays. In particular, we show that latent variables can encode modes in the RGC activity distribution that are closely related to the visual stimuli. In contrast to previous work, we further validate our findings by comparing results associated with recordings from retinas under normal and altered encoding conditions obtained by pharmacological manipulation. In these conditions, we observe that the model reflects well-known physiological behaviors of the retina. Finally, we show that we can also discover temporal patterns, associated with distinct dynamics of the stimuli.
Effects of sodium citrate on the structure and microbial community composition of an early-stage multispecies biofilm model
Authors: Yao Yuan , Pu Yang , Ngan Wing Yui , Kan Karin , Pan Jie , Li Meng , Habimana Olivier
Published: October 2020

In recent years, most biofilm studies have focused on fundamental investigations using multispecies biofilm models developed preferentially in simulated naturally occurring low-nutrient medium than in artificial nutrient-rich medium. Because biofilm development under low-nutrient growth media is slow, natural media are often supplemented with an additional carbon source to increase the rate of biofilm formation. However, there are knowledge gaps in interpreting the effects of such supplementation on the resulting biofilm in terms of structure and microbial community composition. We investigated the effects of supplementation of a simulated freshwater medium with sodium citrate on the resulting structure, bacterial community composition, and microbial network interactions of an early-stage multispecies biofilm model. Qualitative and quantitative analyses of acquired confocal laser scanning microscopy data confirmed that sodium citrate supplementation distinctly increased biofilm biomass. Sequencing data revealed that the microbial community structure of biofilms grown in sodium citrate-supplemented conditions was characterized with increased relative abundance and dominance of Proteobacteria compared with that of biofilms grown in sodium citrate-free conditions. Our findings suggest that the supplementation of a low-nutrient medium with a carbon source in experiments involving multispecies biofilms may lead to structural and compositional biases of the microbial community, causing changes in biofilm phenotype.
Beyond MHz image recordings using LEDs and the FRAME concept
Authors: Kornienko Vassily , Kristensson Elias , Ehn Andreas , Fourriere Antoine , Berrocal Edouard
Published: October 2020

Many important scientific questions in physics, chemistry and biology rely on high-speed optical imaging techniques for their investigations. These techniques are either passive, relying on the rapid readout of photoactive elements, or active, relying on the illumination properties of specially designed pulse trains. Currently, MHz imaging speeds are difficult to realize; passive methods, being dictated by electronics, cause the unification of high spatial resolution with high frame rates to be very challenging, while active methods rely on expensive and complex hardware such as femto- and picosecond laser sources. Here we present an accessible temporally resolved imaging system for shadowgraphy based on multiplexed LED illumination that is capable of producing four images at MHz frame rates. Furthermore as the LEDs are independent of each other, any light burst configuration can be obtained, allowing for instance the simultaneous determination of low- and high speed events in parallel. To the best of the authors’ knowledge, this is the fastest high speed imaging system that does not rely on pulsed lasers or fast detectors, in this case reaching up to 4.56 MHz.
Using Bayesian spatial models to map and to identify geographical hotspots of multidrug-resistant tuberculosis in Portugal between 2000 and 2016
Authors: Oliveira Olena , Ribeiro Ana Isabel , Krainski Elias Teixeira , Rito Teresa , Duarte Raquel , Correia-Neves Margarida
Published: October 2020

Multidrug-resistant tuberculosis (MDR-TB) is a major threat to the eradication of tuberculosis. TB control strategies need to be adapted to the necessities of different countries and adjusted in high-risk areas. In this study, we analysed the spatial distribution of the MDR- and non-MDR-TB cases across municipalities in Continental Portugal between 2000 and 2016. We used Bayesian spatial models to estimate age-standardized notification rates and standardized notification ratios in each area, and to delimitate high- and low-risk areas, those whose standardized notification ratio is significantly above or below the country’s average, respectively. The spatial distribution of MDR- and non-MDR-TB was not homogeneous across the country. Age-standardized notification rates of MDR-TB ranged from 0.08 to 1.20 and of non-MDR-TB ranged from 7.73 to 83.03 notifications per 100,000 population across the municipalities. We identified 36 high-risk areas for non-MDR-TB and 8 high-risk areas for MDR-TB, which were simultaneously high-risk areas for non-MDR-TB. We found a moderate correlation (ρ = 0.653; 95% CI 0.457–0.728) between MDR- and non-MDR-TB standardized notification ratios. We found heterogeneity in the spatial distribution of MDR-TB across municipalities and we identified priority areas for intervention against TB. We recommend including geographical criteria in the application of molecular drug resistance to provide early MDR-TB diagnosis, in high-risk areas.
Grain refinement of commercially pure aluminum with addition of Ti and Zr elements based on crystallography orientation
Authors: Chen Zhongwei , Yan Kang
Published: October 2020

The edge-to-edge matching (E2EM) model and electron back-scatter diffraction (EBSD) technique are used to explore the grain refinement mechanism of commercially pure Al through the addition of Ti and Zr elements. EBSD results show that there are favorable crystallography orientation relationships (ORs) between both Al3Ti and Al3Zr particles with α-Al matrix. Due to these ORs Al3Ti and Al3Zr particles act as the heterogeneous nucleation site during solidification nucleation of Al–Ti and Al–Zr alloys, respectively. Furthermore, both Al3Ti and Al3Zr particles have small values of interplanar spacing mismatch and interatomic spacing misfit with respect to α-Al matrix by using E2EM. It shows that micro-addition of Ti and Zr element is efficient heterogeneous nucleation refiner in commercial purity Al or Al alloys. Besides, there may be some other mechanisms in grain refinement of Al alloys with addition of Ti grain refiner.
Potential mechanisms involving the immobilization of Cd, As and Cr during swine manure composting
Authors: Guo Hao-Nan , Wang Li-Xia , Liu Hong-Tao
Published: October 2020

This study aims to investigate the relationship between key physicochemical parameters related to composting process and bioavailability of Cd, As and Cr during swine manure composting through regulating different initial carbon to nitrogen (C/N) ratios (15:1, 20:1, 25:1) and bulking agent types (straw, green waste). Results showed that higher initial C/N ratio of 20:1 or 25:1 and straw as bulking agent were optimal to reduce the bioavailability of Cd, As and Cr (62.4%, 20.6% and 32.2% reduction, respectively). Redundancy analysis implied that the bioavailability of Cd was significantly associated with total phosphorus and total nitrogen, deducing the formation of phosphate precipitation and biosorption might participated in the reaction process, while that of As and Cr were mainly influenced by organic matter (OM), cation exchange capacity (CEC) and OM, CEC, electric conductivity, respectively. A total of 48.5%, 64.6% and 62.2% of Cd, As and Cr redistribution information could be explained by the above parameters. Further correlation analysis revealed that bioavailable As and Cr were negatively correlated with humic acid to fulvic acid ratio. In summary, this study confirms that the mechanisms of phosphate precipitation, biosorption and humification played critical role in reducing Cd, As and Cr bioavailability during swine manure composting.
Benefits of glioma resection in the corpus callosum
Authors: Forster Marie-Therese , Behrens Marion , Lortz Irina , Conradi Nadine , Senft Christian , Voss Martin , Rauch Maximilian , Seifert Volker
Published: October 2020

Due to anticipated postoperative neuropsychological sequelae, patients with gliomas infiltrating the corpus callosum rarely undergo tumor resection and mostly present in a poor neurological state. We aimed at investigating the benefit of glioma resection in the corpus callosum, hypothesizing neuropsychological deficits were mainly caused by tumor presence. Between 01/2017 and 1/2020, 21 patients who underwent glioma resection in the corpus callosum were prospectively enrolled into this study. Neuropsychological function was assessed preoperatively, before discharge and after 6 months. Gross total tumor resection was possible in 15 patients, and in 6 patients subtotal tumor resection with a tumor reduction of 97.7% could be achieved. During a median observation time of 12.6 months 9 patients died from glioblastoma after a median of 17 months. Preoperatively, all cognitive domains were affected in up to two thirds of patients, who presented a median KPS of 100% (range 60–100%). After surgery, the proportion of impaired patients increased in all neurocognitive domains. Most interestingly, after 6 months, significantly fewer patients showed impairments in attention, executive functioning, memory and depression, which are domains considered crucial for everyday functionality. Thus, the results of our study strongly support our hypothesis that in patients with gliomas infiltrating the corpus callosum the benefit of tumor resection might outweigh morbidity.
Predictive factors of selective mineralocorticoid receptor antagonist treatment in chronic central serous chorioretinopathy
Authors: Gergely Róbert , Kovács Illés , Récsán Zsuzsanna , Sándor Gábor László , Czakó Cecília , Nagy Zoltán Zsolt , Ecsedy Mónika
Published: October 2020

To compare the macular morphology of good and poor responders to eplerenone treatment in chronic central serous chorioretinopathy (CSCR) patients. Thirty eyes of 29 patients with chronic CSCR were treated with 50 mg/day oral eplerenone and followed up for 1 year. The integrity of outer retinal layers at baseline was assessed using optical coherence tomography. Patients who showed complete resolution of subretinal fluid at 1 year were assigned to the good responder group (Group 1), whilst those who showed moderate or no resolution were classified as poor responders (Group 2). Ellipsoid zone interruption, ELM interruption and hyperreflective foci in outer segment (OS) and outer nuclear layer (ON layer) was significantly more frequent in Group 2 than in Group 1 (p < 0.05 for all parameteres). Outer segment elongation was significantly more frequently seen in Group 1 than in Group 2 (p < 0.05) Multivariable regression analysis showed that intact ellipsoid zone at baseline is an independent predictor of good therapeutic response, with an odds ratio of 26.00 (95% CI 3.69–183.45; p = 0.001) after controlling for the effect of hyperreflective foci and ELM integrity. There is higher chance of the resolution of subretinal fluid after eplerenone treatment in CSCR patients with intact outer retinal layers at baseline. Baseline morphologic evaluation of the outer retinal layers on OCT scans can be useful in predicting the response to mineralocorticoid antagonist therapy in these patients.
Development of an antibody-dependent cellular cytotoxicity reporter assay for measuring anti-Middle East Respiratory Syndrome antibody bioactivity
Authors: Cao Junxia , Wang Lan , Yu Chuanfei , Wang Kaiqin , Wang Wenbo , Yan Jinghua , Li Yan , Yang Yalan , Wang Xiaomin , Wang Junzhi
Published: October 2020

Middle East Respiratory Syndrome coronavirus (MERS-CoV) is a highly virulent pathogen that causes Middle East Respiratory Syndrome (MERS). Anti-MERS-CoV antibodies play an integral role in the prevention and treatment against MERS-CoV infections. Bioactivity is a key quality attribute of therapeutic antibodies, and high accuracy and precision are required. The major methods for evaluating the antiviral effect of antiviral antibodies include neutralization assays using live viruses or pseudoviruses are highly variable. Recent studies have demonstrated that the antibody-dependent cellular cytotoxicity (ADCC) activity of antiviral antibodies is more consistent with the virus clearance effect in vivo than neutralization activity. However, no reports evaluating the ADCC activity of anti-MERS antibodies have been published to date. Here, we describe the development of a robust and reliable cell-based reporter gene assay for the determination of ADCC activity of anti-MERS antibodies using 293T/MERS cells stably expressing the spike protein of MERS-CoV (MERS-S) as target cells and the engineered Jurkat/NFAT-luc/FcγRIIIa stably expressing FcγRIIIA and NFAT reporter gene as effector cells. According to the ICH-Q2 analytical method guidelines, we carefully optimized the experimental conditions and assessed the performance of our assay. In addition, we found that the ADCC activity of afucosylated anti-MERS antibodies is higher than their fucosylated counterparts. The establishment of this ADCC determination system provides a novel method for evaluating the bioactivity of anti-MERS antibodies and improving ADCC activity through modification of N-glycosylation of the Fc segment.