bluuebunny/crossref_metadata_2025 huggingface dataset:
Effects of Nitric Oxide on Monocrotaline Induced Right Ventricular Hypertrophy and Lung Mast Cell Hyperplasia in Rats
Authors: Hung Kuen-Shan , Duncan William H
Published: July 2020

Monocrotaline (M) induces pulmonary hypertension (PH) characterized by increased pulmonary arterial pressure, thickened pulmonary arterial walls, and right ventricular hypertrophy (RVH). In addition, numerous mast cells (MC) have been localized in M treated rats and these cells may have a role in causing PH and other lung injury because of their content of serotonin, which is a vasoconstrictor. Nitric oxide (NO) is a vasodilator that has been used in treatments of human patients and experimental animals with PH. The purpose of this study is to determine if NO inhalation can prevent or reverse RVH or MC accumulation induced by M.

Adult male Sprague-Dawley rats were divided into 5 groups (C, M3, MN3, M5, MN5). Group C served as controls without treatments. Groups M3 and M5 received one single subcutaneous injection of M (80mg/kg BW) and were sacrificed at 3 weeks (M3) or 5 weeks (M5) after injection.
Ultrastructural Diagnosis of a Pheochromocytoma at Autopsy
Authors: Siew S , Newton B
Published: July 2020

Pheochromocytoma is a rare tumor found in approximately 2 individuals per million of the population. In 90% of cases, it arises from the chromaffin cells of the adrenal medulla. These cells secrete catecholamines: epinephrine and norepinephrine which have a sympathomimetic action. The classical clinical presentation is paroxysms of extreme elevation of systemic blood pressure. Although pheochromocytoma accounts for only 0.1 % of cases of systemic hypertension, it is important to make the diagnosis, as the sudden release of large quantities of catecholamines into the circulation may prove fatal, as happened in our patient.

We present a case of a 25 year old woman, who collapsed suddenly, while she was feeding her 8 month old baby. She went into ventricular fibrillation and was defibrillated 3 times. There was no response to vigorous resuscitative measures.

Past Medical History: No definitive findings. Vague history of palpitations and an “abnormal heart beat”, which had been considered to be benign.
Quantitation of Peroxisome Proliferation using Silver Enhanced Immunogold Labeling on Glycol Methacrylate (GMA) Sections
Authors: Gagne GD , Illi AH , Hickman D , Fagerland JA
Published: July 2020

Assessment of peroxisome proliferation is important in drug safety studies, since peroxisome proliferation often precedes tumor development in rodents. Proliferation can be measured morphometrically on sections by immunostaining for the peroxisomal enzyme catalase. Previous studies have used tissue embedded in acrylic resins such as LR White, which requires tissue sizes of 1-2 mm. Glycol methacrylate (GMA) is an acrylic resin that preserves antigenicity in much larger pieces of tissue. In this study we applied immunogold-silver staining (IGSS) to GMA sections for the quantitation of peroxisome proliferation in rat livers.

Sprague-Dawley rats were given clofibrate, a known peroxisome proliferator, for 14 days. Livers were removed, fixed in neutral buffered formalin for 4 hours, and embedded in GMA. Sections (3 μm thick) were incubated with antibody to catalase followed by protein A-gold (PAG), and the gold label was amplified using a commercial silver enhancement kit. Tissue sections were counterstained with propidium iodide (PI).
Demonstration of Z-RNA in the Dog Eye Lens Epithelium (Germinative Zone)
Authors: Gagna CE , Chen JH , Kuo HR , Lambert WC
Published: July 2020

The purpose of this scientific investigation was to determine the presence and specific cellular localization of left-handed Z-RNA, within germinative zone (GZ) epithelium of the lens (Fig. 1), using anti-Z-RNA IgG polyclonal antibodies. Right-handed B-DNA has the ability to adopt the Z-DNA conformation in vitro (Sinden, 1994). Right-handed A-RNA can be transformed into Z-RNA under specific conditions (Hall et al., 1984), and Z-RNA has been identified in cultured cells (Zarling et al., 1990). Strong evidence supports the idea of Z-DNA in vivo (Sinden, 1994). Removal of proteins by fixatives can induce supercoiling which stabilizes Z-DNA (Sinden, 1994).

Anti-Z-RNA antibodies were produced in rabbits immunized with injections of Z-RNA: brominated-poly[ribosomal(G-C)]. For light microscopy, immunohistochemical studies (ABC method), normal dog lens tissues (1 yr old) were fixed in Carnoy's, embedded in paraffin and sectioned 2 μm thick. For electron microscopy (immunogold staining), pieces of epithelium from the GZ of normal dog lens (1 yr old) were fixed with 5% glutaraldehyde in 0.05 M phosphate buffer solution, pH 7.3.
Immunocytochemical Localization of Myosin Light Chains in the Abdominal Superficial Flexor Muscles of the American Lobster, Homarus Americanus
Authors: Brown Lisa D , Cantino Marie E
Published: July 2020

Myosin is composed of two high-molecular weight heavy chains and four low-molecular weight hght chains. In both vertebrate and invertebrate skeletal muscle, each myosin heavy chain is associated with two myosin light chains. In skeletal muscle myosins studied by X-ray diffraction, each myosin heavy chain binds one of each of two distinct classes of hght chains. Thus, while isoform distributions may vary within and between fibers, the spatial distribution of each class of light chain should be uniform within the A band and between sarcomeres and fibers. Since no such study exists for crustacean myosin, we investigated the spatial distribution of the hght chains within the superficial flexor muscle (SFM) of the lobster, Homarus americanus, using immunoelectron microscopy. The SFM contains two classes of myosin hght chains, termed “alpha” (Mr = 21,000 to 23,500) and “beta” (Mr = 18,000 to 18,500). Immunocytochemical electron microscopic results suggest that the alpha light chains are not uniformly distributed at the subsarcomere level.
High Pressure Freezing and Freeze Substitution of Primitive Agglutinated Foraminifera
Authors: Goldstein Susan T , Richardson Elizabeth A
Published: July 2020

Freeze substitution techniques can provide exceptional fixation of many types of small biological materials. Ultrastructural studies on the Foraminiferida (marine rhizopods) traditionally have used standard chemical fixation protocols. The relatively large size (-25 μm - several cm) and the presence of a mineralized shell in most taxa precludes the application of many cryo-techniques. High pressure freezing, however, provides a method for freezing organisms as large as many of the smaller foraminifera often without extensive ice damage. Gamonts (sexual generation) from three representatives of the suborder Astrorhizina ﹛Myxotheca sp., Cribrothalammina alba, and Hyperammina sp.) were selected because they are among the most primitive foraminifera and have only very finely agglutinated shells with non-mineralized, organic cements. Myxotheca sp. and C. alba were originally collected from salt marsh environments on Sapelo Island, Georgia, and Hyperammina sp. was isolated from fine-grained carbonate sediments of the Florida Keys.
Analysis of Endocytosis and Food Plaquette Formation in the Ciliated Protozoan Hyalophysa.
Authors: Landers Stephen C , Treadaway Rex A
Published: July 2020

The ciliated protozoan Hyalophysa is a symbiont of a variety of crustaceans, including grass shrimp, hermit crabs, and blue crabs. At the molting of the host, the attached protozoans excyst and swim into the exoskeleton to feed by pinocytosis on exuvial fluid. The feeding trophonts expand to many times their original size, transforming into cells that are little more than large food vacuoles with a rim of cytoplasm stretched around the perimeter. After feeding for the only time during their life cycle, they settle on the substrate to encyst and divide into daughter tomites, and in doing so they divide the food vacuole. The tomites then leave the cyst and attach to a crustacean for their next opportunity to feed at molting.

We have followed endocytosis in Hyalophysa using two dyes, nigrosin and congo red, in order to understand the digestive process.
Pollination in Arabidopsis Thaliana
Authors: Lennon K , Lord E
Published: July 2020

In flowering plants, pollination and the process of fertilization are complex processes involving a series of cell-to-cell communication events. Though details of the progression of the pollen tube through the pistil, beginning with germination of the pollen grain on the stigma and culminating with delivery of the sperm cells to the embryo sac, are well established for several higher plant species, the mechanisms involved have yet to be elucidated. It has been shown that the transmitting tissue, which coincides with the path of pollen tubes in the gynoecium, is composed of highly secretory cells characterized by an extensive extracellular matrix (ECM). The actual roles that this ECM plays in pollination are currently unknown, although functions proposed include mechanical and/or chemotropic pollen tube guidance as well as pollen tube nutrition.
The Efficacy of Individual Psychological Interventions With	Non-Clinical Older Adults
Authors: Vedel Anna , Larsen Lars , Aamand Anna
Published: July 2020

Abstract. A number of reviews and meta-analyses have consistently documented the positive effect of individual psychological intervention with clinical older adults suffering from late-life depression, anxiety disorders, or other mental illnesses. However, many older adults without clinical disorders might seek and benefit from individual psychological interventions too. Given the aging populations across the globe, knowing the potential efficacy of individual psychological interventions with non-clinical older adults therefore is important. However, the research on this topic has not been reviewed systematically. This was the primary aim of the present review. Secondarily, we wanted to find out how many of these studies were conducted in a European context. A systematic literature search identified nine eligible studies yielding an aggregated sample size of 983. Two of these were European. Eight of the nine studies (including one European) reported significant positive effects of individual psychological interventions, that is, increases in psychological well-being and decreases in depression symptoms and distress. Effect sizes were extracted or calculated when possible to estimate the magnitude of the intervention effects. These effect sizes varied across studies and ranged from trivial in size to large and even very large, the median being a medium effect size. The results from the present review suggest that non-clinical older adults benefit from individual psychological interventions. However, the limited number of studies available for review precludes conclusions regarding the comparative efficacy of different types of psychological interventions in this population. Directions for future research are discussed.
Reconciling Geophysical and Petrological Estimates of the Thermal Structure of Southern Tibet
Authors: Craig T. J. , Kelemen P. B. , Hacker B. R. , Copley A.
Published: July 2020

The thermal structure of the Tibetan plateau—the largest orogenic system on Earth—remains largely unknown. Numerous avenues provide fragmentary pressure/temperature information, both at the present (predominantly informed though geophysical observation) and on the evolution of the thermal structure over the recent past (combining petrological, geochemical, and geophysical observables). However, these individual constraints have proven hard to reconcile with each other. Here, we show that models for the simple underthrusting of India beneath southern Tibet are capable of matching all available constraints on its thermal structure, both at the present day and since the Miocene. Many parameters in such models remain poorly constrained, and we explore the various trade‐offs among the competing influences these parameters may have. However, three consistent features to such models emerge: (i) that present‐day geophysical observations require the presence of relatively cold underthrust Indian lithosphere beneath southern Tibet; (ii) that geochemical constraints require the removal of Indian mantle from beneath southern Tibet at some point during the early Miocene, although the mechanism of this removal, and whether it includes the removal of any crustal material, is not constrained by our models; and (iii) that the combination of the southern extent of Miocene mantle‐derived magmatism and the present‐day geophysical structure and earthquake distribution of southern Tibet require that the time‐averaged rate of underthrusting of India relative to central Tibet since the middle Miocene has been faster than it is at present.
Locally Thin Crust and High Crustal VP/VS Ratio Beneath the Armenian Volcanic Highland of the Lesser Caucasus: A Case for Recent Delamination
Authors: Lin Chih‐Ming , Tseng Tai‐Lin , Meliksetian Khachatur , Karakhanyan Arkady , Huang Bor‐Shouh , Babayan Hektor , Hu Jyr‐Ching , Gevorgyan Mikayel , Chang Shuo‐Fen , Levonyan Ara
Published: July 2020

The Arabia‐Eurasia continental collision created the Caucasus Mountains and the Anatolian and Iranian plateaus. Between the two plateaus, the Armenian Highland features young Holocene‐aged volcanoes. In this study, the P‐wave receiver functions from a new seismic array reveal a thick crust (up to ~52 km thick) beneath the Central Greater Caucasus and an unusually thin crust (32–35 km thick) beneath the northwestern part of Armenia near the Aragats stratovolcano and Gegham volcanic ridge formed by Pleistocene to Holocene monogenetic cinder cones. The average crustal VP/VS ratio in the Armenian Highland is anomalously high (≥1.9), with the highest value approaching 2.1 under the Gegham Ridge. Such high VP/VS ratios cannot be explained by an overall mafic crustal composition. Instead, the presence of partial melts is inferred in the lower crust based on the depth of the low‐velocity structure obtained by inversion of receiver function waveforms. Our study suggests that the postcollisional volcanism was potentially facilitated by the small‐scale removal of lithospheric mantle, resulting in a localized thinner crust balanced by thermal buoyancy and dynamic flow in the uppermost mantle beneath the Armenian Highland.
A Spectrally Consistent Globally Defined Geodetic Mean Dynamic Ocean Topography
Authors: Siegismund Frank
Published: July 2020

The space‐borne geodetic temporal mean dynamic topography (MDT) is obtained from the difference of altimetric mean sea surface (MSS) h and the geoid height N. With the geostrophic surface currents obtained from its gradient, the MDT is an essential parameter when describing the ocean dynamics. Spectral consistency of h and N is crucial to minimize MDT errors. Frequently, h is globalized to allow for a spherical harmonic analysis, and small scales beyond maximum degree and order (d/o) resolved in the geoid are cut off. However, common globalization causes ocean‐land steps in h−N and spectral inconsistencies of N and h over land. To overcome both issues, a methodology is proposed based on globalization of the MDT. A Laplacian smoother with the coastal MDT values as boundary condition is applied, resulting in a smooth surface over land and a continuous ocean‐land transition. The new methodology strongly reduces Gibbs effects and the need to work with high‐resolution MDTs to minimize them. Reduction of resolution is tested to reduce MDT uncertainties caused by the commission error expected to increase with decreasing scale. Applying drifter data and a high‐resolution hydrodynamic ocean model, it is shown that for the Gulf Stream and the Kuroshio, geodetic MDTs applying recent combined geoid models contain physical information up to at least d/o 420 (48‐km spatial scale). For oceanic regions with strong geoid gradients, a higher‐resolution MDT might be needed to prevent Gibbs effects caused by remaining inconsistencies between the geoid and the MSS.
Lunar Secondary Craters and Estimated Ejecta Block Sizes Reveal a Scale‐Dependent Fragmentation Trend
Authors: Singer Kelsi N. , Jolliff Bradley L. , McKinnon William B.
Published: July 2020

Planetary impact events eject large volumes of surface material. Crater excavation processes are difficult to study, and in particular the details of individual ejecta fragments are not well understood. A related, enduring issue in planetary mapping is whether a given crater resulted from a primary impact (asteroid or comet) or instead is a secondary crater created by an ejecta fragment. With mapping and statistical analyses of six lunar secondary crater fields (including Orientale, Copernicus, and Kepler) we provide three new constraints on these issues: (1) estimation of the maximum secondary crater size as a function of distance from a primary crater on the Moon, (2) estimation of the size and velocity of ejecta fragments that formed these secondaries, and (3) estimation of the fragment size ejected at escape velocity. Through this analysis, we confirmed and extended a suspected scale‐dependent trend in ejecta size‐velocity distributions. Maximum ejecta fragment sizes fall off much more steeply with increasing ejection velocity for larger primary impacts (compared to smaller primary impacts). Specifically, we characterize the maximum ejecta sizes for a given ejection velocity with a power law and find that the velocity exponent varies between approximately −0.3 and −3 for the range of primary craters investigated here (0.83–660 km in diameter). Data for the Jovian moons Europa and Ganymede confirm similar trends for icy surfaces. This result is not predicted by analytical theories of formation of Grady‐Kipp fragments or spalls during impacts and suggests that further modeling investigations are warranted to explain this scale‐dependent effect.
Observations and a Model of Net Calcification Declines in Palau's Largest Coral Reef Lagoon Between 1992 and 2015
Authors: Lentz Steven J. , Cohen Anne L. , Shamberger Kathryn E. F. , Barkley Hannah
Published: July 2020

Net ecosystem calcification (NEC) rates of Palau's largest lagoon and barrier reef system between 1992 and 2015 are estimated from sparse total alkalinity (TA) and salinity measurements and a tidal exchange model in which surface lagoon water transported offshore on the ebb tide is replaced by saltier (denser) ocean water that sinks to the bottom after entering the lagoon on the flood tide. Observed lagoon salinities are accurately reproduced by the model with no adjustable parameters. To accurately reproduce observed lagoon TA, NEC for the lagoon‐barrier reef system was 70 mmols m−2 day−1 from 1992 to 1998, 35 mmols m−2 day−1 from 1999 to 2012, and 25 mmols m−2 day−1 from 2013 to 2015. This indicates that Palau's largest lagoon and barrier reef system has not recovered, as of 2015, from the 50% decline in NEC in 1998 caused by the loss of coral cover following a severe bleaching event. The cause of the further decline in NEC in 2012–2013 is unclear. Lagoon residence times vary from 8 days during spring tides to 14 days during neap tides and drive substantial spring‐neap variations in lagoon TA (~25% of the mean salinity‐normalized ocean‐lagoon TA difference). Sparse measurements that do not resolve these spring‐neap variations can exhibit apparent long‐term variations in alkalinity that are not due to changes in NEC.
Microphysical and Transportive Contributions to Normal and Anomalous Polarity Subregions in the 29–30 May 2012 Kingfisher Storm
Authors: Chmielewski Vanna C. , MacGorman Donald R. , Ziegler Conrad L. , DiGangi Elizabeth , Betten Daniel , Biggerstaff Michael
Published: July 2020

A developing supercell storm on 29–30 May 2012 in north‐central Oklahoma was observed with the Oklahoma Lightning Mapping Array (OKLMA) and three mobile radars. The storm's vertical charge structure inferred from the OKLMA was anomalous overall but varied considerably even within 10 km of the bounded weak echo region (BWER) and the bounded weak lightning region (BWLR) or lightning hole. Near the BWER, three distinct charge structures were observed—an inverted dipole, an inverted tripole, and a bottom‐heavy normal tripole. One column within each structure was analyzed relative to the Doppler‐derived wind field and environmental properties derived by a diabatic Lagrangian analysis (DLA). Within each column, back trajectories of graupel and hail particles additionally illustrate the history of the diagnosed in‐cloud microphysical properties, which are expected to influence noninductive electrification and may have contributed to the observed charge profiles. This study objectively demonstrates the complicated scenarios presented by the three‐dimensional motions around and through the updraft and provides likely constraints on how each of the three distinct vertical charge distributions could have been produced within this focused region of the storm.
Exercise training modulates the gut microbiota profile and impairs inflammatory signaling pathways in obese children
Authors: Quiroga Rocío , Nistal Esther , Estébanez Brisamar , Porras David , Juárez-Fernández María , Martínez-Flórez Susana , García-Mediavilla María Victoria , de Paz José A. , González-Gallego Javier , Sánchez-Campos Sonia , Cuevas María J.
Published: July 2020

Childhood obesity has reached epidemic levels and is a serious health concern associated with metabolic syndrome, nonalcoholic fatty liver disease, and gut microbiota alterations. Physical exercise is known to counteract obesity progression and modulate the gut microbiota composition. This study aims to determine the effect of a 12-week strength and endurance combined training program on gut microbiota and inflammation in obese pediatric patients. Thirty-nine obese children were assigned randomly to the control or training group. Anthropometric and biochemical parameters, muscular strength, and inflammatory signaling pathways in mononuclear cells were evaluated. Bacterial composition and functionality were determined by massive sequencing and metabolomic analysis. Exercise reduced plasma glucose levels and increased dynamic strength in the upper and lower extremities compared with the obese control group. Metagenomic analysis revealed a bacterial composition associated with obesity, showing changes at the phylum, class, and genus levels. Exercise counteracted this profile, significantly reducing the Proteobacteria phylum and Gammaproteobacteria class. Moreover, physical activity tended to increase some genera, such as Blautia, Dialister, and Roseburia, leading to a microbiota profile similar to that of healthy children. Metabolomic analysis revealed changes in short-chain fatty acids, branched-chain amino acids, and several sugars in response to exercise, in correlation with a specific microbiota profile. Finally, the training protocol significantly inhibited the activation of the obesity-associated NLRP3 signaling pathway. Our data suggest the existence of an obesity-related deleterious microbiota profile that is positively modified by physical activity intervention. Exercise training could be considered an efficient nonpharmacological therapy, reducing inflammatory signaling pathways induced by obesity in children via microbiota modulation.
Supertransport of excitons in atomically thin organic semiconductors at the 2D quantum limit
Authors: Sharma Ankur , Zhang Linglong , Tollerud Jonathan O. , Dong Miheng , Zhu Yi , Halbich Robert , Vogl Tobias , Liang Kun , Nguyen Hieu T. , Wang Fan , Sanwlani Shilpa , Earl Stuart K. , Macdonald Daniel , Lam Ping Koy , Davis Jeffrey A. , Lu Yuerui
Published: July 2020

Long-range and fast transport of coherent excitons is important for the development of high-speed excitonic circuits and quantum computing applications. However, most of these coherent excitons have only been observed in some low-dimensional semiconductors when coupled with cavities, as there are large inhomogeneous broadening and dephasing effects on the transport of excitons in their native states in materials. Here, by confining coherent excitons at the 2D quantum limit, we first observed molecular aggregation-enabled ‘supertransport’ of excitons in atomically thin two-dimensional (2D) organic semiconductors between coherent states, with a measured high effective exciton diffusion coefficient of ~346.9 cm2/s at room temperature. This value is one to several orders of magnitude higher than the values reported for other organic molecular aggregates and low-dimensional inorganic materials. Without coupling to any optical cavities, the monolayer pentacene sample, a very clean 2D quantum system (~1.2 nm thick) with high crystallinity (J-type aggregation) and minimal interfacial states, showed superradiant emission from Frenkel excitons, which was experimentally confirmed by the temperature-dependent photoluminescence (PL) emission, highly enhanced radiative decay rate, significantly narrowed PL peak width and strongly directional in-plane emission. The coherence in monolayer pentacene samples was observed to be delocalised over ~135 molecules, which is significantly larger than the values (a few molecules) observed for other organic thin films. In addition, the supertransport of excitons in monolayer pentacene samples showed highly anisotropic behaviour. Our results pave the way for the development of future high-speed excitonic circuits, fast OLEDs, and other optoelectronic devices.
BRN2 expression increases anoikis resistance in melanoma
Authors: Pierce Carly J. , Simmons Jacinta L. , Broit Natasa , Karunarathne Deshapriya , Ng Mei Fong , Boyle Glen M.
Published: July 2020

Melanoma tumors are highly heterogeneous, comprising of many cell populations that vary in their potential for growth and invasion. Differential transcription factor expression contributes to these phenotypic traits. BRN2, a member of the POU domain family of transcription factors is thought to play important roles in melanoma invasion and metastasis. However, the function of BRN2 during the metastatic process of melanoma remains largely unknown. We therefore investigated the effect of BRN2 expression in melanoma cells with no or low constitutive expression using a doxycycline-inducible system. Induction of BRN2 expression led to reduced proliferation and partial resistance to an inhibitor of mutated BRAF. Whole-genome profiling analysis revealed novel targets and signaling pathway changes related to prevention of cell death induced by detachment from the extracellular matrix, known as anoikis resistance. Further investigation confirmed increased survival of BRN2-expressing cell lines in non-adherent conditions. Functionally, expression of BRN2 promoted induction of c-MET levels as well as increased phosphorylation of STAT3. Treatment with crizotinib, a c-MET inhibitor, decreased cellular viability of BRN2-expressing cells under non-adherent conditions to death by anoikis. Alternative inhibitors of c-MET showed similar results. These results highlight the importance of a largely overlooked transcription factor in the progression and metastasis of melanoma, and may suggest a strategy to target BRN2-expressing cells resistant to therapy and cell death by anoikis.
Total burden of disease in cancer patients at diagnosis—a Danish nationwide study of multimorbidity and redeemed medication
Authors: Loeppenthin Katrine , Dalton Susanne Oksbjerg , Johansen Christoffer , Andersen Elisabeth , Christensen Mikkel Bring , Pappot Helle , Petersen Lone Nørgaard , Thisted Lise Bjerrum , Frølich Anne , Mortensen Christiane Ehlers , Lassen Ulrik , Ørsted Jytte , Bidstrup Pernille Envold
Published: July 2020

Background

Multimorbidity is a growing challenge worldwide. In this nationwide study, we investigated the prevalence of multimorbidity and polypharmacy at the time of diagnosis across 20 cancers.

Methods

We conducted a nationwide register-based cohort study of all Danish residents with a first primary cancer diagnosed between 1 January 2005 and 31 December 2015. Multimorbidity was defined as one or more of 20 conditions (131 specific diagnoses) registered in the Danish National Patient Registry < 5 years before the cancer diagnosis. Polypharmacy was defined as five or more medications registered in the Danish National Prescription Registry and redeemed twice 2–12 months before the cancer diagnosis.

Results

We included 261,745 patients with a first primary cancer, of whom 55% had at least one comorbid condition at diagnosis and 27% had two or more. The most prevalent conditions at the time of cancer diagnosis were cardiovascular disease, chronic obstructive pulmonary disease, diabetes, stroke and depression/anxiety disorder. Polypharmacy was present in one-third of the cancer patients with antihypertensives, anti-thrombotic agents, anti-hyperlipidaemic agents, analgesics and diuretics as the most prevalent redeemed medications.

Conclusion

Among patients with a newly established cancer diagnosis, 55% had at least one comorbid condition and 32% were exposed to polypharmacy.
RETRACTED ARTICLE: Downregulation of RKIP promotes radioresistance of nasopharyngeal carcinoma by activating NRF2/NQO1 axis via downregulating miR-450b-5p
Authors: Huang Wei , Shi Guangqing , Yong Zhong , Li Jian , Qiu Juan , Cao Yan , Zhao Yongfeng , Yuan Li
Published: July 2020

Dysregulation of RKIP and NRF2 has been widely involved in the therapy resistance of multiple malignances, however, their relation and the corresponding mechanisms, especially in radiation response, have not been elucidated. In this study, we revealed that RKIP could negatively regulate the expression of NRF2 in nasopharyngeal carcinoma (NPC) cells. Depletion or ectopic expression of NRF2 countered the pro- or anti- radioresistant effects of RKIP knockdown or overexpression on NPC cells, respectively, both in vitro and in vivo. Furthermore, our results indicated that NQO1 was positively regulated by NRF2 and served as the downstream effector of RKIP/NRF2 axis in regulation of NPC radioresistance. Mechanistically, miR-450b-5p, being positively regulated by RKIP in NPC cells, could sensitize NPC cells to irradiation by directly targeting and suppressing the level of NRF2. Besides, we analyzed the level of aforementioned molecules in NPC tissues. The results indicated that RKIP was significantly downregulated, NRF2 and NQO1 were notably upregulated in NPC tissues compared with in normal nasopharyngeal mucosa (NNM) tissues. Furthermore, RKIP and miR-450b-5p were remarkably lower, yet NRF2 and NQO1 were notably higher, in radioresistant NPC tissues relative to in radiosensitive NPC tissues. Consistent with the pattern in NPC cells, the RKIP/miR-450b-5p/NRF2/NQO1 axis was significantly correlated in NPC tissues. Downregulation of RKIP and miR-450b-5p, and upregulation of NRF2 and NQO1, positively correlated to malignant pathological parameters such as primary T stage, Lymph node (N) metastasis, and TNM stage. Finally, RKIP and miR-450b-5p served as favorable prognostic indicators, and NRF2 and NQO1 acted as unfavorable prognostic biomarkers in patients with NPC. Collectively, our outcomes reveal that RKIP downregulation promotes radioresistance of NPC by downregulating miR-450b-5p and subsequently upregulating and activating NRF2 and NQO1, highlighting RKIP/miR-450b-5p/NRF2/NQO1 axis as a potential therapeutic target for improving the radiosensitivity of NPC.
Uncovering mutation-specific morphogenic phenotypes and paracrine-mediated vessel dysfunction in a biomimetic vascularized mammary duct platform
Authors: Kutys Matthew L. , Polacheck William J. , Welch Michaela K. , Gagnon Keith A. , Koorman Thijs , Kim Sudong , Li Linqing , McClatchey Andrea I. , Chen Christopher S.
Published: July 2020

The mammary gland is a highly vascularized tissue capable of expansion and regression during development and disease. To enable mechanistic insight into the coordinated morphogenic crosstalk between the epithelium and vasculature, we introduce a 3D microfluidic platform that juxtaposes a human mammary duct in proximity to a perfused endothelial vessel. Both compartments recapitulate stable architectural features of native tissue and the ability to undergo distinct forms of branching morphogenesis. Modeling HER2/ERBB2 amplification or activating PIK3CA(H1047R) mutation each produces ductal changes observed in invasive progression, yet with striking morphogenic and behavioral differences. Interestingly, PI3KαH1047R ducts also elicit increased permeability and structural disorganization of the endothelium, and we identify the distinct secretion of IL-6 as the paracrine cause of PI3KαH1047R-associated vascular dysfunction. These results demonstrate the functionality of a model system that facilitates the dissection of 3D morphogenic behaviors and bidirectional signaling between mammary epithelium and endothelium during homeostasis and pathogenesis.
Genomic basis of homoploid hybrid speciation within chestnut trees
Authors: Sun Yongshuai , Lu Zhiqiang , Zhu Xingfu , Ma Hui
Published: July 2020

Hybridization can drive speciation. We examine the hypothesis that Castanea henryi var. omeiensis is an evolutionary lineage that originated from hybridization between two near-sympatric diploid taxa, C. henryi var. henryi and C. mollissima. We produce a high-quality genome assembly for mollissima and characterize evolutionary relationships among related chestnut taxa. Our results show that C. henryi var. omeiensis has a mosaic genome but has accumulated divergence in all 12 chromosomes. We observe positive correlation between admixture proportions and recombination rates across the genome. Candidate barrier genomic regions, which isolate var. henryi and mollissima, are re-assorted in the hybrid lineage. We further find that the putative barrier segments concentrate in genomic regions with less recombination, suggesting that interaction between natural selection and recombination shapes the evolution of hybrid genomes during hybrid speciation. This study highlights that reassortment of parental barriers is an important mechanism in generating biodiversity.
Prognostic implications of the expression levels of different immunoglobulin heavy chain-encoding RNAs in early breast cancer
Authors: Larsson Christer , Ehinger Anna , Winslow Sofia , Leandersson Karin , Klintman Marie , Dahl Ludvig , Vallon-Christersson Johan , Häkkinen Jari , Hegardt Cecilia , Manjer Jonas , Saal Lao , Rydén Lisa , Malmberg Martin , Borg Åke , Loman Niklas
Published: July 2020

The extent and composition of the immune response in a breast cancer is one important prognostic factor for the disease. The aim of the current work was to refine the analysis of the humoral component of an immune response in breast tumors by quantifying mRNA expression of different immunoglobulin classes and study their association with prognosis. We used RNA-Seq data from two local population-based breast cancer cohorts to determine the expression ofIGJand immunoglobulin heavy (IGH) chain-encoding RNAs. The association with prognosis was investigated and public data sets were used to corroborate the findings. Except forIGHEandIGHD, mRNAs encoding heavy chains were generally detected at substantial levels and correlated with other immune-related genes. HighIGHG1mRNA was associated with factors related to poor prognosis such as estrogen receptor negativity, HER2 amplification, and high grade, whereas highIGHA2mRNA levels were primarily associated with lower age at diagnosis. HighIGHA2andIGJmRNA levels were associated with a more favorable prognosis both in univariable and multivariable Cox models. When adjusting for other prognostic factors, highIGHG1mRNA levels were positively associated with improved prognosis. To our knowledge, these results are the first to demonstrate that expression of individual Ig class types has prognostic implications in breast cancer.
Acid-catalysed α-O-4 aryl-ether bond cleavage in methanol/(aqueous) ethanol: understanding depolymerisation of a lignin model compound during organosolv pretreatment
Authors: Jasiukaitytė-Grojzdek Edita , Huš Matej , Grilc Miha , Likozar Blaž
Published: July 2020

The selective lignin conversion into bio-based organic mono-aromatics is a major general challenge due to complex structure itself/additional macromolecule modifications, caused by the cleavage of the ether chemical bonds during the lignocellulosic biomass organosolv pulping in acidified aqueous ethanol. Herein, the acido-lysis of connected benzyl phenyl (BPE), being a representative model compound with α-O-4 linkage, was investigated in methanol, EtOH and 75 vol% EtOH/water mixture solutions, progressing each time with protonating sulfuric acid. The effect of the physical solvent properties, acidity of the reaction process media and temperature on rate was determined. Experiments suggested BPE following SN1 mechanism due to the formation of a stable primary carbocation/polarity. The product species distribution in non-aqueous functional alcohols was strongly affected. The addition of H2O was advantageous, especially for alkoxylation. Yield was reduced by a factor of 3, consequently preserving reactive hydroxyl group. Quantitative experimental results indicated key performance parameters to achieve optimum. Organosolv lignins were further isolated under significantly moderate conditions. Consecutive structural differences observed supported findings, obtained when using BPE. H2O presence was again found to grant a higher measured –OH content. Mechanistic pathway analysis thus represents the first step when continuing to kinetics, structure–activity relationships or bio-refining industrial resources.
Third Harmonic Generation microscopy distinguishes malignant cell grade in human breast tissue biopsies
Authors: Gavgiotaki Evangelia , Filippidis George , Tsafas Vassilis , Bovasianos Savvas , Kenanakis George , Georgoulias Vasilios , Tzardi Maria , Agelaki Sofia , Athanassakis Irene
Published: July 2020

The ability to distinguish and grade malignant cells during surgical procedures in a fast, non-invasive and staining-free manner is of high importance in tumor management. To this extend, Third Harmonic Generation (THG), Second Harmonic Generation (SHG) and Fourier-Transform Infrared (FTIR) spectroscopy were applied to discriminate malignant from healthy cells in human breast tissue biopsies. Indeed, integration of non-linear processes into a single, unified microscopy platform offered complementary structural information within individual cells at the submicron level. Using a single laser beam, label-free THG imaging techniques provided important morphological information as to the mean nuclear and cytoplasmic area, cell volume and tissue intensity, which upon quantification could not only distinguish cancerous from benign breast tissues but also define disease severity. Simultaneously, collagen fibers that could be detected by SHG imaging showed a well structured continuity in benign tumor tissues, which were gradually disoriented along with disease severity. Combination of THG imaging with FTIR spectroscopy could provide a clearer distinction among the different grades of breast cancer, since FTIR analysis showed increased lipid concentrations in malignant tissues. Thus, the use of non-linear optical microscopy can be considered as powerful and harmless tool for tumor cell diagnostics even during real time surgery procedures.
Electrospray mechanism for quantum dot thin-film formation using an electrohydrodynamic jet and light-emitting device application
Authors: Nguyen Tuan Canh , Choi Woon-Seop
Published: July 2020

A novel electrohydrodynamic (EHD) electrospray coating mechanism was proposed for the continuous fabrication of large-area quantum dot (QD) thin films for high-performance light-emitting diodes (LEDs). The size of QD droplets was systemically controlled using the stable EHD electrospray mode from a mixed solvent, which is a crucial factor for the formation of large and smooth QD thin films. The minimum amount of material consumption was achieved during the process by applying the unique coating system. A QD-LED device based on electrodeposited QDs showed a maximum luminance of 12,082 cd m−2, maximum current efficiency of nearly 4.0 cd A−1, and maximum EQE of 1.86%. This system demonstrates not only high reproducibility but could also pave the way for commercializing high-quality QD-LED devices.
Preparation and physical characteristics of graphene ceramics
Authors: Głuchowski P. , Tomala R. , Jeżowski A. , Szewczyk D. , Macalik B. , Smolina I. , Kurzynowski T. , Stręk W.
Published: July 2020

Graphene, a two-dimensional structure of carbon, due to its structure has unique physico-chemical properties that can be used in numerous research and industry areas. Although this structure is already well known, there are still technological (and cost) barriers which do not allow to produce this material in large quantities and hence prevent its use in various applications. For this reason, many technologies are currently being developed to obtain graphene in forms that would enable its widespread use. The graphene-like ceramics were fabricated by the high isostatic pressure method at different temperatures. This technique allows to obtain dense ceramics with various shapes. The structure and morphology of sintered graphene were investigated by XRD, SEM and the Raman spectroscopy. The hardness, thermal conductivity and electric transport measurements recorded in a wide range of temperatures were used to analyze the physical properties of the obtained ceramics.
Robustaflavone induces G0/G1 cell cycle arrest and apoptosis in human umbilical vein endothelial cells and exhibits anti-angiogenic effects in vivo
Authors: Sim Woo Kyung , Park Jong-Hwa , Kim Ki-Young , Chung In Sik
Published: July 2020

We investigated the anti-angiogenic and pro-apoptotic effects of robustaflavone (RF), a naturally occurring biflavonoid, on human umbilical vein endothelial cells (HUVECs). RF inhibited HUVEC proliferation and showed cytotoxicity that inhibited HUVEC viability. RF-induced apoptosis was characterized by flow cytometry and caspase 3 analysis. We found that RF increased the number of sub-G1 cells and terminal deoxynucleotidyl transferase dUTP nick end-labeled cells. Additionally, RF induced caspase 3 and poly (ADP-ribose) polymerase activation. Potential molecular targets were identified using a human apoptosis antibody array. RF upregulated Bax, Bad, cleaved caspase 3, p21, and phosphorylated p53 levels. RF induced mitochondrial membrane potential loss and the release of cytochrome c and apoptosis-inducing factor. Cell cycle arrest at G0/G1 phase and the downregulation of Cdk4, Cdk6, and cyclin D1 expression were induced by RF. In vivo anti-angiogenic effects were investigated using a tumor allograft animal model and a Matrigel plug assay. RF reduced the volumes and weights of CT-26 cell-derived tumors. The blood vessel density was significantly decreased in RF-treated tumors. RF also inhibited VEGF-A-stimulated blood vessel formation in vivo in Matrigel plugs. These results suggest that RF can potentially inhibit angiogenesis-dependent tumor growth and metastasis.
Development of simple and efficient Lab-on-a-Disc platforms for automated chemical cell lysis
Authors: Jahromi Arash Khorrami , Saadatmand Maryam , Eghbal Manouchehr , Yeganeh Laleh Parsa
Published: July 2020

Cell lysis is the most important first step for molecular biology and diagnostic testing. Recently, microfluidic systems have attracted considerable attention due to advantages associated with automation, integration and miniaturization, especially in resource-limited settings. In this work, novel centrifugal microfluidic platforms with new configurations for chemical cell lysis are presented. The developed systems employ passive form of pneumatic and inertial forces for effective mixing of lysis reagents and cell samples as well as precise fluidic control. Characterizations of the developed Lab-on-a-Discs (LoaDs) have been conducted with dyed deionized (DI) waters and white blood cells (WBCs) to demonstrate the suitability of the proposed systems in terms of mixing, fluidic control and chemical cell lysis. By making comparison between the results of a well-established manual protocol for chemical cell lysis and the proposed chemical cell lysis discs, it has been proved that the developed systems are capable of realizing automated cell lysis with high throughput in terms of proper values of average DNA yield (ranging from 20.6 to 29.8 ng/µl) and purity (ranging from 1.873 to 1.907) as well as suitability of the released DNA for polymerase chain reaction (PCR). By considering the manual chemical lysis protocol as a reference, the efficiency of the LoaDs has been determined 95.5% and 91% for 10 min and 5 min lysis time, respectively. The developed LoaDs provide simple, efficient, and fully automated chemical cell lysis units, which can be easily integrated into operational on-disc elements to obtain sample-to answer settings systems.
High-performance thermochromic VO2-based coatings with a low transition temperature deposited on glass by a scalable technique
Authors: Kolenatý David , Vlček Jaroslav , Bárta Tomáš , Rezek Jiří , Houška Jiří , Haviar Stanislav
Published: July 2020

We report on high-performance thermochromic ZrO2/V0.982W0.018O2/ZrO2 coatings with a low transition temperature prepared on glass by a low-temperature scalable deposition technique. The V0.982W0.018O2 layers were deposited by a controlled high-power impulse magnetron sputtering of V target, combined with a simultaneous pulsed DC magnetron sputtering of W target to reduce the transition temperature to 20–21 °C, at a low substrate surface temperature of 330 °C in an argon–oxygen gas mixture. ZrO2 antireflection layers both below and above the thermochromic V0.982W0.018O2 layers were deposited at a low substrate temperature (< 100 °C). A coating design utilizing a second-order interference in the ZrO2 layers was applied to increase both the luminous transmittance (Tlum) and the modulation of the solar transmittance (ΔTsol). The ZrO2/V0.982W0.018O2/ZrO2 coatings exhibit Tlum up to 60% at ΔTsol close to 6% for a V0.982W0.018O2 thickness of 45 nm, and Tlum up to 50% at ΔTsol above 10% for a V0.982W0.018O2 thickness of 69 nm.
A novel diterpene agent isolated from Microbispora hainanensis strain CSR-4 and its in vitro and in silico inhibition effects on acetylcholine esterase enzyme
Authors: Thawai Chitti , Bunbamrung Nantiya , Pittayakhajonwut Pattama , Chongruchiroj Sumet , Pratuangdejkul Jaturong , He Ya-Wen , Tadtong Sarin , Sareedenchai Vipaporn , Prombutara Pinidphon , Qian Yang
Published: July 2020

An actinomycete strain CSR-4 was isolated from the rhizosphere soil ofZingiber montanum.Taxonomic characterization revealed strain CSR-4 was a member of the genusMicrobispora. Whole-genome sequence analysis exhibited the highest average nucleotide identity (ANI) value (95.34%) and digital DNA–DNA hybridization (DDH) value (74.7%) between strain CSR-4 and the closest relativeM. hainanensisDSM 45428T, which was in line with the assignment to same species. In addition, a new diterpene compound, 2α-hydroxy-8(14), 15-pimaradien-17, 18-dioic acid, and nine known compounds were isolated from the ethyl acetate crude extract of fermentation broth. Interestingly, a new diterpene displayed the suppressive effect on the recombinant human acetylcholinesterase (rhAChE) enzymes (IC5096.87 ± 2.31 μg/ml). In silico studies based on molecular docking and molecular dynamics (MD) simulations were performed to predict a binding mode of the new compound into the binding pocket of the rhAChE enzyme and revealed that some amino acids in the peripheral anions site (PAS), anionic subsite, oxyanion site and catalytic active site (CAS) of the rhAChE have interacted with the compound. Therefore, our new compound could be proposed as a potential active human AChE inhibitor. Moreover, the new compound can protect significantly the neuron cells (% neuron viability = 88.56 ± 5.19%) from oxidative stress induced by serum deprivation method at 1 ng/ml without both neurotoxicities on murine P19-derived neuron cells and cytotoxicity against Vero cells.