bluuebunny/crossref_metadata_2025 huggingface dataset:
Thermal groundwaters of the UK: geochemical indications of flow, vulnerability and possible threat to the shallow hydrosphere
Authors: Darling W. George
Published: April 2019

Three types of thermal groundwater are known from the UK: warm springs (≤45°C), mine inflows (≤50°C) and deep basin waters (≤80°C). The warm springs depend on Carboniferous Limestone conveying water to sufficient depth (600–3000 m) to acquire a significantly higher temperature. The springs have residence times of a few thousand years, but also contain ≤5% modern groundwater. Their water quality is little threat to the environment; the main danger to the springs is construction activity near the emergences. Mine inflows significantly >20°C are known only from Cornish granite. High dissolved
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He has been interpreted as indicating long residence of the thermal component, but there is also modern water in the system, leading to uncertainty in the mean age. Unpredictable fracturing could hinder development of this resource, while the seawater-like salinity, combined with the presence of toxic metals, would require treatment or re-injection of the spent water to protect the near-surface environment. Mesozoic sedimentary basin brines reach temperatures >60°C, suitable for district heating. This resource is large and effectively invulnerable. However, these waters are generally more saline than seawater and, while disposal of spent brine could take place into the sea under favourable conditions, re-injection would be necessary for inland sites.
Methylglyoxal triggers human aortic endothelial cell dysfunction via modulation of the KATP/MAPK pathway
Authors: Wang Yihan , Hall Leo M. , Kujawa Marisa , Li Hainan , Zhang Xiang , O’Meara Megan , Ichinose Tomomi , Wang Jie-Mei
Published: April 2019

Endothelial dysfunction is a key risk factor in diabetes-related multiorgan damage. Methylglyoxal (MGO), a highly reactive dicarbonyl generated primarily as a by-product of glycolysis, is increased in both type 1 and type 2 diabetic patients. MGO can rapidly bind with proteins, nucleic acids, and lipids, resulting in structural and functional changes. MGO can also form advanced glycation end products (AGEs). How MGO causes endothelial cell dysfunction, however, is not clear. Human aortic endothelial cells (HAECs) from healthy (H-HAECs) and type 2 diabetic (D-HAECs) donors were cultured in endothelial growth medium (EGM-2). D-HAECs demonstrated impaired network formation (on Matrigel) and proliferation (MTT assay), as well as increased apoptosis (caspase-3/7 activity and TUNEL staining), compared with H-HAECs. High glucose (25 mM) or AGEs (200 ng/ml) did not induce such immediate, detrimental effects as MGO (10 µM). H-HAECs were treated with MGO (10 µM) for 24 h with or without the ATP-sensitive potassium (KATP) channel antagonist glibenclamide (1 µM). MGO significantly impaired H-HAEC network formation and proliferation and induced cell apoptosis, which was reversed by glibenclamide. Furthermore, siRNA against the KATP channel protein Kir6.1 significantly inhibited endothelial cell function at basal status but rescued impaired endothelial cell function upon MGO exposure. Meanwhile, activation of MAPK pathways p38 kinase, c-Jun NH2-terminal kinase (JNK), and extracellular signal-regulated kinase (ERK) (determined by Western blot analyses of their phosphorylated forms, p-JNK, p-p38, and p-ERK) in D-HAECs were significantly enhanced compared with those in H-HAECs. MGO exposure enhanced the activation of all three MAPK pathways in H-HAECs, whereas glibenclamide reversed the activation of p-stress-activated protein kinase/JNK induced by MGO. Glyoxalase-1 (GLO1) is the endogenous MGO-detoxifying enzyme. In healthy mice that received an inhibitor of GLO1, MGO deposition in aortic wall was enhanced and endothelial cell sprouting from isolated aortic segment was significantly inhibited. Our data suggest that MGO triggers endothelial cell dysfunction by activating the JNK/p38 MAPK pathway. This effect arises partly through activation of KATP channels. By understanding how MGO induces endothelial dysfunction, our study may provide useful information for developing MGO-targeted interventions to treat vascular disorders in diabetes.
Electrical stimulation facilitates the angiogenesis of human umbilical vein endothelial cells through MAPK/ERK signaling pathway by stimulating FGF2 secretion
Authors: Geng Kang , Wang Jing , Liu Pengfei , Tian Xinli , Liu Hongjun , Wang Xue , Hu Chunbing , Yan Hong
Published: April 2019

Electrical stimulation (ES) is able to enhance angiogenesis by stimulating fibroblasts. Fibroblast growth factor 2 (FGF2) is an independent angiogenesis inducer. The present study aimed to evaluate the role of ES-induced FGF2 secretion in affecting angiogenesis during wound healing via the mitogen-activated protein kinase/extracellular signal-regulated kinase (MAPK/ERK) signaling pathway. Fibroblasts and human umbilical vein endothelial cells (HUVECs) were exposed to ES, and the HUVECs were cocultured with ES-treated fibroblast culture solution. ES exposure showed no toxic effects on fibroblasts or HUVECs. ES led to enhanced growth of fibroblasts and HUVECs as well as FGF2 secretion, which is induced through the NOS pathway. ES-induced FGF2 secretion was shown to increase vascular endothelial growth factor (VEGF) protein and enhance migration, invasion, and angiogenesis of HUVECs. Also, ES-induced FGF2 secretion activated the MAPK/ERK signaling pathway. However, inhibition of the MAPK/ERK signaling pathway reversed the positive effects of ES-induced FGF2 secretion. In vitro experiments showed positive effects of ES on wound healing. Taken together, the findings suggested that ES promoted FGF2 secretion and then activated the MAPK/ERK signaling pathway by facilitating angiogenesis and promoting wound healing.
Renin-angiotensin system promotes colonic inflammation by inducing TH17 activation via JAK2/STAT pathway
Authors: He Lei , Du Jie , Chen Yinyin , Liu Chunyan , Zhou Min , Adhikari Sarbani , Rubin David T. , Pekow Joel , Li Yan Chun
Published: April 2019

Previous studies suggest that the renin-angiotensin system (RAS) is a pathogenic factor for colitis. The goal of this study was to elucidate the molecular mechanism whereby angiotensin II (ANG II) promotes colonic inflammation. We found that renin was highly induced in colonic biopsies from patients with ulcerative colitis or Crohn’s disease, and colonic renin and ANG II levels were markedly increased in a 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced colitis model, indicating that the colonic RAS is activated in colitis. Renin transgenic (RenTg) mice exhibited increased phosphorylation in Janus kinase-2 (JAK2) and signal transducer and activator of transcription1/3 (STAT1/3) within colonic mucosa at baseline and following TNBS induction, suggesting that ANG II promotes colonic inflammation via the JAK2/STAT1/3 pathway. Treatment with pan-JAK inhibitor tofacitinib blocked JAK2 and STAT1/3 phosphorylation, attenuated T helper (TH)1 and TH17 responses, alleviated colitis, and prevented death of RenTg mice in TNBS model. ANG II stimulated JAK2/STAT1/3 phosphorylation in both Jurkat T lymphocytes and HCT116 epithelial cells. In vitro polarization assays demonstrated that ANG II directly promoted TH17 polarization, but not TH1 polarization, via JAK2/STAT1/3. ANG II stimulation of transforming growth factor-β1 (TGFβ1), IL-6, myosin light chain kinase, and p53 upregulated modulator of apoptosis in HCT116 cells was also mediated by JAK2/STAT1/3. These observations suggest that ANG II promotes TH17 polarization directly as well as indirectly by inducing production of TH17-polarizing cytokines (e.g., TGFβ1 and IL-6) from colonic epithelial cells, both via the JAK2/STAT pathway. Therefore, colonic RAS promotes colonic inflammation, at least in part, by stimulating TH17 activation.

NEW & NOTEWORTHY This study demonstrates that the local renin-angiotensin system in the colon is activated in colitis development, which promotes mucosal T helper cell activation through the JAK2/STAT pathway. These observations provide molecular evidence that the renin-angiotensin system is a pathogenic factor for the development of inflammatory bowel diseases.
Dyslipidemia and the role of adipose tissue in early pregnancy in the BPH/5 mouse model for preeclampsia
Authors: Reijnders Dorien , Olson Kelsey N. , Liu Chin-Chi , Beckers Kalie F. , Ghosh Sujoy , Redman Leanne M. , Sones Jenny L.
Published: April 2019

The hypertensive pregnancy disorder preeclampsia (PE) is a leading cause of fetal and maternal morbidity/mortality. Obesity increases the risk to develop PE, presumably via the release of inflammatory mediators from the adipose tissue, but the exact etiology remains largely unknown. Using obese PE-like blood pressure high subline 5 (BPH/5) and lean gestational age-matched C57Bl6 mice, we aimed to obtain insight into differential reproductive white adipose tissue (rWAT) gene expression, circulating lipids and inflammation at the maternal-fetal interface during early pregnancy. In addition, we investigated the effect of 7 days 25% calorie restriction (CR) in early pregnancy on gene expression in rWAT and implantation sites. Compared with C57Bl6, female BPH/5 are dyslipidemic before pregnancy and show an amplification of rWAT mass, circulating cholesterol, free fatty acids, and triacylglycerol levels throughout pregnancy. RNA sequencing showed that pregnant BPH/5 mice have elevated gene enrichment in pathways related to inflammation and cholesterol biosynthesis at embryonic day ( e) 7.5. Expression of cholesterol-related HMGCS1, MVD, Cyp51a1, and DHCR was validated by quantitative reverse-transcription-polymerase chain reaction. CR during the first 7 days of pregnancy restored the relative mRNA expression of these genes to a level comparable to C57Bl6 pregnant females and reduced the expression of circulating leptin and proinflammatory prostaglandin synthase 2 in both rWAT and implantation sites in BPH/5 mice at e7.5. Our data suggest a possible role for rWAT in the dyslipidemic state and inflammatory uterine milieu that might underlie the pathogenesis of PE. Future studies should further address the physiological functioning of the adipose tissue in relation to PE-related pregnancy outcomes.
Functional effects of blocking VEGF/VEGFR2 signaling in the rat urinary bladder in acute and chronic CYP-induced cystitis
Authors: Tooke Katharine , Girard Beatrice , Vizzard Margaret A.
Published: April 2019

High expression of VEGF is associated with immature angiogenesis within the urinary bladder wall and bladder afferent nerve sensitization, leading to visceral hyperalgesia and pelvic pain. Research suggests a shift in VEGF alternative splice variant (VEGF-Axxxa and VEGF-Axxxb) expression with several pathologies (e.g., neuropathic pain and inflammation) as well as differing effects on pain. Translational studies have also demonstrated increased total VEGF expression in the bladders of women with interstitial cystitis/bladder pain syndrome. In the present study, we quantified VEGF alternative splice variant expression in lower urinary tract tissues under control conditions and with cyclophosphamide (CYP)-induced cystitis. Using conscious cystometry and intravesical instillation of a potent and selective VEGF receptor 2 (VEGFR2) tyrosine kinase inhibitor (Ki-8751, 1 mg/kg) in Wistar rats (male and female) with acute and chronic CYP-induced cystitis and control (no CYP) rats, we further determined the functional effects of VEGFR2 blockade on bladder function. With VEGFR2 blockade, bladder capacity increased ( P ≤ 0.01) in male and female control rats as well as in male and female rats with acute ( P ≤ 0.05) or chronic ( P ≤ 0.01 or P ≤ 0.05, respectively) CYP-induced cystitis. Void volume also increased in female control rats ( P ≤ 0.01) and female rats with acute ( P ≤ 0.05) or chronic ( P ≤ 0.05) CYP-induced cystitis as well as in male control rats ( P ≤ 0.05) and male rats with chronic CYP-induced cystitis ( P ≤ 0.01). These data suggest that VEGF may be a biomarker for interstitial cystitis/bladder pain syndrome and that targeting VEGF/VEGFR2 signaling may be an effective treatment.
Brown adipocytes and β3-stimulant-induced brown-like adipocytes contribute to the prevention of renal crystal formation
Authors: Sugino Teruaki , Okada Atsushi , Taguchi Kazumi , Unno Rei , Hamamoto Shuzo , Ando Ryosuke , Mogami Tohru , Kohri Kenjiro , Yamashita Hitoshi , Yasui Takahiro
Published: April 2019

According to recent studies, kidney stones are associated with metabolic syndrome. We focused on brown adipocytes and β3-stimulant-induced brown-like adipocytes to investigate how these adipocytes influence kidney stone disease. For the interscapular brown adipose tissue (iBAT) removal experiment, mice were subjected to either iBAT removal or sham operation (X-BAT group or sham group), and, after 3 wk, renal crystal deposition was induced by intra-abdominal injection of glyoxylate (GOX) for 6 days. For the β3-stimulant experiment, mice were administered intra-abdominal injections of the β3-stimulant (β3-group) or saline (control group) for 6 days. Thereafter, renal crystal deposition was induced by intra-abdominal injection of GOX for 6 days. iBAT removal decreased the expression of Sod1 and increased that of chemokine (C-C motif) ligand 2 ( Ccl2), EGF module-containing mucin-like receptor 1 ( Emr1), and tumor necrosis factor ( Tnf) in the kidneys. Renal crystal deposition was 2.06-fold higher in the X-BAT group than in the sham group. The β3-stimulant caused differentiation of white adipocytes into brown-like adipocytes. In the kidneys of the β3-group, the expression of Ccl2 and Emr1 decreased and that of Sod1 increased. Renal crystal deposition was 0.17-fold lower in the β3-group than in the control group. In summary, iBAT removal promoted kidney inflammation and renal crystal formation. β3-Stimulant-induced brown-like adipocytes reduced inflammation and improved antioxidant action in the kidneys, which suppressed renal crystal formation. This is the first report on the therapeutic role of brown and brown-like adipocytes for kidney stone formation.
Supplemental vibrotactile feedback of real-time limb position enhances precision of goal-directed reaching
Authors: Risi Nicoletta , Shah Valay , Mrotek Leigh A. , Casadio Maura , Scheidt Robert A.
Published: April 2019

We examined vibrotactile stimulation as a form of supplemental limb state feedback to enhance planning and ongoing control of goal-directed movements. Subjects wore a two-dimensional vibrotactile display on their nondominant arm while performing horizontal planar reaching with the dominant arm. The vibrotactile display provided feedback of hand position such that small hand displacements were more easily discriminable using vibrotactile feedback than with intrinsic proprioceptive feedback. When subjects relied solely on proprioception to capture visuospatial targets, performance was degraded by proprioceptive drift and an expansion of task space. By contrast, reach accuracy was enhanced immediately when subjects were provided vibrotactile feedback and further improved over 2 days of training. Improvements reflected resolution of proprioceptive drift, which occurred only when vibrotactile feedback was active, demonstrating that benefits of vibrotactile feedback are due, in part to its integration into the ongoing control of movement. A partial resolution of task space expansion persisted even when vibrotactile feedback was inactive, demonstrating that training with vibrotactile feedback also induced changes in movement planning. However, the benefits of vibrotactile feedback come at a cognitive cost. All subjects adopted a stereotyped strategy wherein they attempted to capture targets by moving first along one axis of the vibrotactile display and then the other. For most subjects, this inefficient approach did not resolve over two bouts of training performed on separate days, suggesting that additional training is needed to integrate vibrotactile feedback into the planning and online control of goal-directed reaching in a way that promotes smooth and efficient movement.

NEW & NOTEWORTHY A two-dimensional vibrotactile display provided state (not error) feedback to enhance control of a moving limb. Subjects learned to use state feedback to perform blind reaches with accuracy and precision exceeding that attained using intrinsic proprioception alone. Feedback utilization incurred substantial cognitive cost: subjects moved first along one axis of the vibrotactile display, then the other. This stereotyped control strategy must be overcome if vibrotactile limb state feedback is to promote naturalistic limb movements.
Visual cortex neurons phase-lock selectively to subsets of LFP oscillations
Authors: Swindale N. V. , Spacek M. A.
Published: April 2019

It is generally thought that apart from receptive field differences, such as preferred orientation and spatial frequency selectivity, primary visual cortex neurons are functionally similar to each other. However, the genetic diversity of cortical neurons plus the existence of inputs additional to those required to explain known receptive field properties might suggest otherwise. Here we report the existence of desynchronized states in anesthetized cat area 17 lasting up to 45 min, characterized by variable narrow-band local field potential (LFP) oscillations in the range 2–100 Hz and the absence of a synchronized 1/ f frequency spectrum. During these periods, spontaneously active neurons phase-locked to variable subsets of LFP oscillations. Individual neurons often ignored frequencies that others phase-locked to. We suggest that these desynchronized periods may correspond to REM sleep-like episodes occurring under anesthesia. Frequency-selective codes may be used for signaling during these periods. Hence frequency-selective combination and frequency-labeled pathways may represent a previously unsuspected dimension of cortical organization.

NEW & NOTEWORTHY We investigated spontaneous neuronal firing during periods of desynchronized local field potential (LFP) activity, resembling REM sleep, in anesthetized cats. During these periods, neurons synchronized their spikes to specific phases of multiple LFP frequency components, with some neurons ignoring frequencies that others were synchronized to. Some neurons fired at phase alignments of frequency pairs, thereby acting as phase coincidence detectors. These results suggest that internal brain signaling may use frequency combination codes to generate temporally structured spike trains.
A review on screening tests for vestibular disorders
Authors: Cohen Helen S.
Published: April 2019

Although many studies have reported on tests of the vestibular system a valid and reliable, evidence-based screening battery for easy clinical use remains elusive. Many screening tests attempt to assess the vestibulo-ocular reflex. Therefore, head shaking, the Dix-Hallpike maneuver, the supine roll test, and head impulse tests are discussed. Other tests address the spatial orientation functions of the vestibular system, such as the Bucket Test and the Fukuda Stepping test. Still, other tests are based on the known correlates with balance skills, both static and dynamic, such as tandem walking and the modern variation of the Romberg test, the modified Clinical Test of Sensory Interaction and Balance. This review provides a critical overview of the literature on some of these tests and their value for clinical use and in epidemiological studies.
Resveratrol Suppresses Epithelial-Mesenchymal Transition in GBM by Regulating Smad-Dependent Signaling
Authors: Song Yang , Chen Yong , Li Yunqian , Lyu Xiaoyan , Cui Jiayue , Cheng Ye , Zheng Tianyang , Zhao Liyan , Zhao Gang
Published: April 2019

Glioblastoma (GBM) is the most common and malignant intracranial tumor in adults. Despite continuous improvements in diagnosis and therapeutic method, the prognosis is still far away from expectations. The invasive phenotype of GBM is the main reason for the poor prognosis. Epithelial-mesenchymal transition (EMT) is recognized as a participator in this invasive phenotype. Resveratrol, a natural plant-derived compound, is reported to be able to regulate EMT. In the present study, we used TGF-β1 to induce EMT and aimed to evaluate the effect of resveratrol on EMT and to explore the underline mechanism in GBM. Western blotting was used to detect the expression of EMT-related markers, stemness markers, and Smad-dependent signaling. Wound healing assay and transwell invasion assay were performed to evaluate the migratory and invasive ability of GBM cells. Gliosphere formation assay was used to investigate the effect of resveratrol on the ability of self-renewal. Xenograft experiment was conducted to examine the effect of resveratrol on EMT and Smad-dependent signalingin vivo. Our data validated that resveratrol suppressed EMT and EMT-associated migratory and invasive ability via Smad-dependent signaling in GBM cells. We also confirmed that resveratrol obviously inhibited EMT-induced self-renewal ability of glioma stem cells (GSCs) and inhibited EMT-induced cancer stem cell markers Bmi1 and Sox2, suggesting that resveratrol is able to suppress EMT-generated stem cell-like properties in GBM cells. Furthermore, we also showed the inhibitory effect of resveratrol on EMT in xenograft experimentsin vivo. Overall, our study reveals that resveratrol suppresses EMT and EMT-generated stem cell-like properties in GBM by regulating Smad-dependent signaling and provides experimental evidence of resveratrol for GBM treatment.
Thermostable Cellulases from the Yeast Trichosporon sp.
Authors: Touijer Hanane , Benchemsi Najoua , Ettayebi Mohamed , Janati Idrissi Abdellatif , Chaouni Bouchra , Bekkari Hicham
Published: April 2019

Objectives. Identification of cellulolytic microorganisms is of great interest to the hydrolysis of cellulosic biomass. This study focuses on the identification of cellulolytic yeasts and the optimization of cellulase activities produced by the best performing isolate. Results. 30 cellulolytic yeast isolates were selected. Enzymes produced by an isolate from the Trichosporon genus showed the property to hydrolyze different substrates: carboxymethyl cellulose (CMC), cellulose fiber, and filter paper (FP). The optimum measured temperature was 55°C for CMCase and 60°C for FPase. The optimal pH was 5 for CMCase and 4 to 6 for FPase. The effect of the substrates concentration showed that the best activities were obtained at 100 mg/mL CMC or FP. The highest activities were 0.52 for the CMCase and 0.56 for the cellulase fiber at 10 min incubation, 0.44 IU/mL at 15 min incubation, and 24 h FPase preincubation. Conclusion. Cellulases produced by the studied yeast are capable of hydrolyzing soluble and insoluble substrates at elevated temperatures and at a wide pH range. They are considerable interest in the production of fermentable sugars from lignocellulosic substrates.
An Analytical Model for Bandwidth Enhancement of Air-Coupled Unsealed Helmholtz Structural CMUTs
Authors: Liu Xin , Yu Yuanyu , Wang Jiujiang , Pun Sio Hang , Vai Mang I , Mak Peng Un
Published: April 2019

Capacitive micromachined ultrasonic transducers (CMUTs) were reported to own high potential in air-coupled ultrasonic applications such as noncontact nondestructive examination and gas flow measurement. The unsealed CMUTs which utilized the squeeze film effect were reported to overcome the narrow output pressure bandwidth of the conventional sealed CMUTs in air operation. This kind of unsealed CMUTs can also be regarded as Helmholtz resonators. In this work, we present the air-coupled unsealed Helmholtz structural CMUTs which utilize both the squeeze film effect and the Helmholtz resonant effect to enhance the output pressure bandwidth. Based on the mechanism of vibration coupling between membrane and air pistons in membrane holes, we propose an analytical model to aid the design process of this kind of CMUTs. We also use finite element method (FEM) to investigate this kind of CMUTs for our analytical model validation. The FEM results show that the significant bandwidth enhancement can be achieved when the Helmholtz resonant frequency is designed close to the fundamental resonant frequency of the CMUT membrane. Compared with the conventional sealed CMUT cell, the 4-hole unsealed Helmholtz structural CMUT cell improves both the 3-dB fractional bandwidth and SPL-bandwidth product around 35 times. Furthermore, it is found that, with more holes under the same hole area ratio or with a smaller ratio of the cavity height to the viscous boundary layer thickness, the Helmholtz resonant effect becomes weaker and thus the output pressure bandwidth decreases.
Leonurus cardiaca L. as a Source of Bioactive Compounds: An Update of the European Medicines Agency Assessment Report (2010)
Authors: Fierascu Radu Claudiu , Fierascu Irina , Ortan Alina , Fierascu Ioana Catalina , Anuta Valentina , Velescu Bruno Stefan , Pituru Silviu Mirel , Dinu-Pirvu Cristina Elena
Published: April 2019

Leonurus cardiaca L. (motherwort) is a perennial herb, native to Asia and southeastern Europe, with widespread global occurrence in present days. The plant was historically used as cardiotonic and for treating gynaecological afflictions (such as amenorrhea, dysmenorrhea, menopausal anxiety, or postpartum depression). Although its use in oriental and occidental medicine is relatively well documented, the recent progress registered raises the need for an update of the Medicines Agency assessment report on Leonurus cardiaca L., herba (2010). The current study presents the progress made within the 2010-2018 timeframe regarding the potential applications and scientific evidences supporting the traditional use of motherwort, in the same time suggesting future research opportunities.
Partial Component Consensus of Discrete‐Time Multiagent Systems
Authors: Hu Wenjun , Zhang Gang , Ma Zhongjun , Wu Binbin
Published: April 2019

The multiagent system has the advantages of simple structure, strong function, and cost saving, which has received wide attention from different fields. Consensus is the most basic problem in multiagent systems. In this paper, firstly, the problem of partial component consensus in the first‐order linear discrete‐time multiagent systems with the directed network topology is discussed. Via designing an appropriate pinning control protocol, the corresponding error system is analyzed by using the matrix theory and the partial stability theory. Secondly, a sufficient condition is given to realize partial component consensus in multiagent systems. Finally, the numerical simulations are given to illustrate the theoretical results.
The Protective Roles of Estrogen Receptor β in Renal Calcium Oxalate Crystal Formation via Reducing the Liver Oxalate Biosynthesis and Renal Oxidative Stress-Mediated Cell Injury
Authors: Zhu Wei , Zhao Zhijian , Chou Fu-Ju , Zuo Li , Liu Tongzu , Bushinsky David , Chang Chawnshang , Zeng Guohua , Yeh Shuyuan
Published: April 2019

Females develop kidney stones less frequently than males do. However, it is unclear if this gender difference is related to altered estrogen/estrogen receptor (ER) signaling. Here, we found that ER beta (ERβ) signals could suppress hepatic oxalate biosynthesis via transcriptional upregulation of the glyoxylate aminotransferase (AGT1) expression. Results from multiple in vitro renal cell lines also found that ERβ could function via suppressing the oxalate-induced injury through increasing the reactive oxygen species (ROS) production that led to a decrease of the renal calcium oxalate (CaOx) crystal deposition. Mechanism study results showed that ERβ suppressed oxalate-induced oxidative stress via transcriptional suppression of the NADPH oxidase subunit 2 (NOX2) through direct binding to the estrogen response elements (EREs) on the NOX2 5′ promoter. We further applied two in vivo mouse models with glyoxylate-induced renal CaOx crystal deposition and one rat model with 5% hydroxyl-L-proline-induced renal CaOx crystal deposition. Our data demonstrated that mice lacking ERβ (ERβKO) as well as mice or rats treated with ERβ antagonist PHTPP had increased renal CaOx crystal deposition with increased urinary oxalate excretion and renal ROS production. Importantly, targeting ERβ-regulated NOX2 with the NADPH oxidase inhibitor, apocynin, can suppress the renal CaOx crystal deposition in the in vivo mouse model. Together, results from multiple in vitro cell lines and in vivo mouse/rat models all demonstrate that ERβ may protect against renal CaOx crystal deposition via inhibiting the hepatic oxalate biosynthesis and oxidative stress-induced renal injury.
Mistletoe and Immunomodulation: Insights and Implications for Anticancer Therapies
Authors: Oei Shiao Li , Thronicke Anja , Schad Friedemann
Published: April 2019

In early tumor development, cancer cells develop a plethora of strategies to escape surveillance from the adaptive and innate immune system. Cancer immunotherapies, in particular immune checkpoint inhibitors, are becoming a highly promising cancer therapeutic approach that has remarkable increased progress in combating various cancer types. Unfortunately, their mechanisms of action induce some complications, such as inflammatory reactions and immune-related adverse events. In the management of side effects during anticancer therapy, complementary and integrative therapy approaches are becoming of growing interest. Particularly, mistletoe, Viscum album L. (VA), has a long traditional history of about 100 years as an add-on therapy of cancer treatment in German-speaking countries. Besides antitumoral and quality of life-promoting activities, VA applications reduce side effects of modern conventional anticancer therapies and exert immunomodulatory characteristics. As these properties may provide a good basis for a combination with modern oncological therapies, the biological activities of VA applications and mechanisms involved have to be understood. In this review, the impact of VA compounds on different cellular pathways and immunological reactions in the fight against cancerous cells is discussed.
Reduction of Motion Artifacts in the Recovery of Undersampled DCE MR Images Using Data Binning and L+S Decomposition
Authors: Bilal Muhammad , Anis Haris , Khan Najeeb , Qureshi Ijaz , Shah Jawad , Kadir Kushsairy A.
Published: April 2019

Background. Motion is a major source of blurring and ghosting in recovered MR images. It is more challenging in Dynamic Contrast Enhancement (DCE) MRI because motion effects and rapid intensity changes in contrast agent are difficult to distinguish from each other. Material and Methods. In this study, we have introduced a new technique to reduce the motion artifacts, based on data binning and low rank plus sparse (L+S) reconstruction method for DCE MRI. For Data binning, radial k-space data is acquired continuously using the golden-angle radial sampling pattern and grouped into various motion states or bins. The respiratory signal for binning is extracted directly from radially acquired k-space data. A compressed sensing- (CS-) based L+S matrix decomposition model is then used to reconstruct motion sorted DCE MR images. Undersampled free breathing 3D liver and abdominal DCE MR data sets are used to validate the proposed technique. Results. The performance of the technique is compared with conventional L+S decomposition qualitatively along with the image sharpness and structural similarity index. Recovered images are visually sharper and have better similarity with reference images. Conclusion. L+S decomposition provides improved MR images with data binning as preprocessing step in free breathing scenario. Data binning resolves the respiratory motion by dividing different respiratory positions in multiple bins. It also differentiates the respiratory motion and contrast agent (CA) variations. MR images recovered for each bin are better as compared to the method without data binning.
Fast Phased Array Calibration by Power-Only Measurements Twice for Each Antenna Element
Authors: He Guolong , Gao Xin , Zhou Hui
Published: April 2019

This paper proposes a novel power-only measurement method for phased array antenna calibration. Besides the total array power, only one phase shift and two power measurements for each array element are required to determine the element complex electric field distortion, one by shifting the element’s phase of π/2 and the other by turning the element under test off. The theory of the proposed calibration method is given, and the closed form formulation of the element amplitude and phase distortions is derived. From the mathematical point of view, it is the minimum required measurements that use two scalar values to determine one complex vector. Numerical simulations and experiments are conducted to validate and demonstrate the effectiveness of the proposed calibration method.
The Effect of Microsized Aluminum Powder on Thermal Decomposition of HNIW (CL-20)
Authors: Mao Xiaoxiang , Zhu Chenguang , Li Yanchun , Li Yifan , Jiang Longfei , Wang Xiaoming
Published: April 2019

DSC experiments were conducted on the 2,4,6,8,10,12-hexanitro-2,4,6,8,10,12-hexaaza-tetracyclo-[5.5.0.05,9.03,11]-dodecane (also known as HNIW or CL-20) and CL-20 containing 10 wt.% microsized aluminum (Al) powders. The kinetic parameters of CL-20 and CL-20/Al were obtained by ASTM685 and Friedman methods, respectively, indicating that Al powder decreases the activation energy of CL-20 slightly and has a catalytic effect on the thermal decomposition of CL-20. By the method of nonlinear multivariate regression, kinetic models of CL-20 and CL-20/Al were derived as fα=1−αn1+kcat⋅α, where the lgkcat of CL-20 and CL-20/Al is 1.97 and 2.12, respectively, showing that the autocatalytic ability of CL-20 had been increased by adding Al powder. From the SEM images of CL-20/Al and the XRD pattern of the decomposition residues of CL-20/Al, it can be inferred that partial combustion of Al particles happened in the microscale view and led to the release of heat.
Morphological and Genetic Structure of Two Equivalent Astyanax Species (Characiformes: Characidae) in the Region of Paranaíba Arc
Authors: Rodrigues Rocha Renan , de Mesquita Alves Rosana , Pasa Rubens , Frehner Kavalco Karine
Published: April 2019

The Astyanax scabripinnis complex is composed of a large number of almost morphological indistinguishable species, including Astyanax paranae and Astyanax rivularis, which exist in the Paraná and São Francisco Basins, respectively, and sometimes are considered subspecies of the A. scabripinnis group or even are cited just as A. scabripinnis. The two river basins are separated by the Upper Paranaíba Arc, likely the main cause of the isolation of these species. We used geometric morphometric tools and DNA analyses of populations of both species to identify the differences between them. Geometric morphometrics separated the two species into distinct groups, whose main difference was the body depth. This is generally related to the speed of the water flow in the river basins. The maximum likelihood phylogram based on mitochondrial DNA sequences formed two main clades: one composed of the population of A. rivularis and the other, of A. paranae. In the haplotype network, the species were similarly separated into two groups from the same ancestral haplotype, with A. rivularis dispersing into two lineages in the São Francisco River Basin. The distribution of A. paranae is a consequence of a secondary dispersion event in the Paraná River Basin. It forms two lineages from a haplotype derived from the ancestor. The vicariant effect of separate basins, through the elevation of the Upper Paranaíba Arc, led to the allopatric speciation of the populations originating the present species. The results of geometric morphometrics and molecular data of the fish show the importance of this geological event in the biogeography and evolutionary history of the ichthyofauna of the region and indicate that the isolation of these species seems to be effective.
Evaluation of Structural Properties and Catalytic Activities in Knoevenagel Condensation Reaction of Zeolitic Imidazolate Framework-8 Synthesized under Different Conditions
Authors: Du Pham Dinh , Duy Thanh Nguyen Viet , Hieu Nguyen Trung
Published: April 2019

In the present study, the zeolitic imidazolate framework-8 (ZIF-8) was synthesized at both room temperature and high temperatures. The effects of solvents, molar ratios of precursors, reaction time, and temperature on the structural properties of the as-prepared materials were investigated. Moreover, the surface morphologies of the obtained specimens were characterized using X-ray diffraction, scanning electron microscopy, Fourier-transform infrared spectroscopy, and nitrogen adsorption methods. The results show that ZIF-8 was formed in methanol and water at room temperature and in dimethylformamide (DMF) at high temperatures. Further, in methanol, the molar ratios of precursors and reaction time have negligible effects on the morphologies and structures of ZIF-8; however, in DMF, the reaction temperature has a significant influence on the microstructures of ZIF-8. The catalytic activities of the obtained materials were evaluated using the Knoevenagel condensation reaction, and ZIF-8 proves to be an excellent solid base catalyst.
Comparison of Intravenous Dexmedetomidine versus Esmolol for Attenuation of Hemodynamic Response to Tracheal Intubation after Rapid Sequence Induction: A Systematic Review and Meta-Analysis
Authors: Li Zhao , Xu Li , Zheng Jinwei , Wang Qingxiu
Published: April 2019

The present study aims to investigate whether intravenous dexmedetomidine shows superiority to esmolol for hemodynamic response to tracheal intubation after rapid sequence induction. In the present meta-analysis, PubMed, EMBASE, and the Cochrane Library were searched for trials comparing dexmedetomidine with esmolol for the attenuation of the hemodynamic response to intubation. Ten trials were selected in the present meta-analysis. Compared to esmolol, the use of dexmedetomidine maintains stable heart rates (HR), systolic blood pressure (SBP), diastolic blood pressure (DBP), and mean arterial pressure (MAP) at 1 min, 3 min, and 5 min after tracheal intubation. Dexmedetomidine causes less hemodynamic response to tracheal intubation after rapid sequence induction compared with esmolol.
Disruptive Effect of Organotin on Thyroid Gland Function Might Contribute to Hypothyroidism
Authors: de Oliveira Miriane , Rodrigues Bruna Moretto , Olimpio Regiane Marques Castro , Graceli Jones Bernardes , Gonçalves Bianca Mariani , Costa Sarah Maria Barneze , da Silva Tabata Marinda , De Sibio Maria Teresa , Moretto Fernanda Cristina Fontes , Mathias Lucas Solla , Cardoso Dariane Beatriz Marino , Tilli Helena Paim , Freitas-Lima Leandro Ceotto , Nogueira Celia Regina
Published: April 2019

A considerable increase in endocrine abnormalities has been reported over the last few decades worldwide. A growing exposure to endocrine-disrupting chemicals (EDCs) can be one of the causes of endocrine disorders in populations, and these disorders are not only restricted to the metabolic hormone system but can also cause abnormal functions. Thyroid hormone (TH) disruption is defined as an abnormal change in TH production, transport, function, or metabolism, which results in some degree of impairment in body homeostasis. Many EDCs, including organotin compounds (OTCs), are environmental contaminants that are commonly found in antifouling paints used on ships and in several other industrial procedures. OTCs are obesogenic and can disrupt TH metabolism; however, abnormalities in thyroid function resulting from OTC exposure are less well understood. OTCs, one of the most prevalent EDCs that are encountered on a daily basis, modulate the thyroid axis. In most toxicology studies, it has been reported that OTCs might contribute to hypothyroidism.
Real-Time Vehicle Detection Algorithm Based on Vision and Lidar Point Cloud Fusion
Authors: Wang Hai , Lou Xinyu , Cai Yingfeng , Li Yicheng , Chen Long
Published: April 2019

Vehicle detection is one of the most important environment perception tasks for autonomous vehicles. The traditional vision-based vehicle detection methods are not accurate enough especially for small and occluded targets, while the light detection and ranging- (lidar-) based methods are good in detecting obstacles but they are time-consuming and have a low classification rate for different target types. Focusing on these shortcomings to make the full use of the advantages of the depth information of lidar and the obstacle classification ability of vision, this work proposes a real-time vehicle detection algorithm which fuses vision and lidar point cloud information. Firstly, the obstacles are detected by the grid projection method using the lidar point cloud information. Then, the obstacles are mapped to the image to get several separated regions of interest (ROIs). After that, the ROIs are expanded based on the dynamic threshold and merged to generate the final ROI. Finally, a deep learning method named You Only Look Once (YOLO) is applied on the ROI to detect vehicles. The experimental results on the KITTI dataset demonstrate that the proposed algorithm has high detection accuracy and good real-time performance. Compared with the detection method based only on the YOLO deep learning, the mean average precision (mAP) is increased by 17%.
Evaluation of Enterprise Learning Performance in the Process of Cooperation Innovation Using Heronian Mean Operator
Authors: Yin Shi , Li Baizhou
Published: April 2019

In order to clarify the achievement and efficiency of enterprise learning in the process of cooperative innovation, a comprehensive criteria framework for the evaluation of enterprise learning performance is constructed taking the learning process and learning results as the construction idea based on organizational learning theory. And this paper proposes a novel dynamic evaluation method considering the interaction between attributes of learning performance. In this study, the criterion framework for the evaluation of enterprise learning performance in the process of cooperative innovation includes learning process performance and learning outcomes performance. The original matrices are given by managers and experts using fuzzy set theory, and a dynamic time sequence weight vector is calculated based on information entropy and time degree. The weight of learning performance attributes under different time series is calculated based on entropy measure method. The interactive information of learning performance attributes is integrated through the weight of learning performance attributes and the three‐parameter weighted Heronian mean operator considering the interaction between attributes. And then, the dynamic and comprehensive evaluation result of learning performance in the process of cooperative innovation could be computed by integrating the learning performance information under different time series with time sequence weight vector. Finally, a real case is studied to verify the scientificity and validity of the criteria framework for the evaluation of enterprise learning performance and the method proposed in this study. This study not only helps cooperative enterprises get feedback in time and adjust cooperative relationships and learning styles but also enriches the theory of interorganizational management and provides a theoretical basis for the process of enterprise cooperative innovation.
Activation of the Unfolded Protein Response via Inhibition of Protein Disulfide Isomerase Decreases the Capacity for DNA Repair to Sensitize Glioblastoma to Radiotherapy
Authors: Liu Yajing , Ji Wenbin , Shergalis Andrea , Xu Jiaqi , Delaney Amy M. , Calcaterra Andrew , Pal Anupama , Ljungman Mats , Neamati Nouri , Rehemtulla Alnawaz
Published: April 2019

Patients with glioblastoma multiforme (GBM) survive on average 12 to 14 months after diagnosis despite surgical resection followed by radiotheraphy and temozolomide therapy. Intrinsic or acquired resistance to chemo- and radiotherapy is common and contributes to a high rate of recurrence. To investigate the therapeutic potential of protein disulfide isomerase (PDI) as a target to overcome resistance to chemoradiation, we developed a GBM tumor model wherein conditional genetic ablation of prolyl 4-hydroxylase subunit beta (P4HB), the gene that encodes PDI, can be accomplished. Loss of PDI expression induced the unfolded protein response (UPR) and decreased cell survival in two independent GBM models. Nascent RNA Bru-seq analysis of PDI-depleted cells revealed a decrease in transcription of genes involved in DNA repair and cell-cycle regulation. Activation of the UPR also led to a robust decrease in RAD51 protein expression as a result of its ubiquitination-mediated proteosomal degradation. Clonogenic survival assays demonstrated enhanced killing of GBM cells in response to a combination of PDI knockdown and ionizing radiation (IR) compared with either modality alone, which correlated with a decreased capacity to repair IR-induced DNA damage. Synergistic tumor control was also observed with the combination of PDI inhibition and IR in a mouse xenograft model compared with either single agent alone. These findings provide a strong rationale for the development of PDI inhibitors and their use in combination with DNA damage-inducing, standard-of-care therapies such as IR.

Significance:

These findings identify PDIA1 as a therapeutic target in GBM by demonstrating efficacy of its inhibition in combination with radiotherapy through a novel mechanism involving downregulation of DNA repair genes.
tRNA Fragments Show Intertwining with mRNAs of Specific Repeat Content and Have Links to Disparities
Authors: Telonis Aristeidis G. , Loher Phillipe , Magee Rogan , Pliatsika Venetia , Londin Eric , Kirino Yohei , Rigoutsos Isidore
Published: April 2019

tRNA-derived fragments (tRF) are a class of potent regulatory RNAs. We mined the datasets from The Cancer Genome Atlas (TCGA) representing 32 cancer types with a deterministic and exhaustive pipeline for tRNA fragments. We found that mitochondrial tRNAs contribute disproportionally more tRFs than nuclear tRNAs. Through integrative analyses, we uncovered a multitude of statistically significant and context-dependent associations between the identified tRFs and mRNAs. In many of the 32 cancer types, these associations involve mRNAs from developmental processes, receptor tyrosine kinase signaling, the proteasome, and metabolic pathways that include glycolysis, oxidative phosphorylation, and ATP synthesis. Even though the pathways are common to multiple cancers, the association of specific mRNAs with tRFs depends on and differs from cancer to cancer. The associations between tRFs and mRNAs extend to genomic properties as well; specifically, tRFs are positively correlated with shorter genes that have a higher density in repeats, such as ALUs, MIRs, and ERVLs. Conversely, tRFs are negatively correlated with longer genes that have a lower repeat density, suggesting a possible dichotomy between cell proliferation and differentiation. Analyses of bladder, lung, and kidney cancer data indicate that the tRF-mRNA wiring can also depend on a patient's sex. Sex-dependent associations involve cyclin-dependent kinases in bladder cancer, the MAPK signaling pathway in lung cancer, and purine metabolism in kidney cancer. Taken together, these findings suggest diverse and wide-ranging roles for tRFs and highlight the extensive interconnections of tRFs with key cellular processes and human genomic architecture.

Significance:

Across 32 TCGA cancer contexts, nuclear and mitochondrial tRNA fragments exhibit associations with mRNAs that belong to concrete pathways, encode proteins with particular destinations, have a biased repeat content, and are sex dependent.