bluuebunny/crossref_metadata_2025_split huggingface dataset:
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

AbstractThe 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

AbstractThe 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

AbstractThe 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

AbstractParticle 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

AbstractThe 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

AbstractIn 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

AbstractThe 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

AbstractA 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

AbstractThree-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

AbstractWe 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

AbstractNature 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

AbstractBisphenol 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

AbstractAt 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

AbstractSince 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

AbstractThe 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.