bluuebunny/crossref_metadata_2025 huggingface dataset:
In vitro modelling of alveolar repair at the air-liquid interface using alveolar epithelial cells derived from human induced pluripotent stem cells
Authors: van Riet Sander , Ninaber Dennis K. , Mikkers Harald M. M. , Tetley Teresa D. , Jost Carolina R. , Mulder Aat A. , Pasman Thijs , Baptista Danielle , Poot André A. , Truckenmüller Roman , Mummery Christine L. , Freund Christian , Rottier Robbert J. , Hiemstra Pieter S.
Published: March 2020

Research on acute and chronic lung diseases would greatly benefit from reproducible availability of alveolar epithelial cells (AEC). Primary alveolar epithelial cells can be derived from human lung tissue but the quality of these cells is highly donor dependent. Here, we demonstrated that culture of EpCAM+ cells derived from human induced pluripotent stem cells (hiPSC) at the physiological air-liquid interface (ALI) resulted in type 2 AEC-like cells (iAEC2) with alveolar characteristics. iAEC2 cells expressed native AEC2 markers (surfactant proteins and LPCAT-1) and contained lamellar bodies. ALI-iAEC2 were used to study alveolar repair over a period of 2 weeks following mechanical wounding of the cultures and the responses were compared with those obtained using primary AEC2 (pAEC2) isolated from resected lung tissue. Addition of the Wnt/β-catenin activator CHIR99021 reduced wound closure in the iAEC2 cultures but not pAEC2 cultures. This was accompanied by decreased surfactant protein expression and accumulation of podoplanin-positive cells at the wound edge. These results demonstrated the feasibility of studying alveolar repair using hiPSC-AEC2 cultured at the ALI and indicated that this model can be used in the future to study modulation of alveolar repair by (pharmaceutical) compounds.
Geodynamic subduction models constrained by deep earthquakes beneath the Japan Sea and eastern China
Authors: Čížková Hana , Zahradník Jiří , Liu Junqing , Bina Craig R.
Published: March 2020

Details of Pacific plate subduction under the Japan Sea and associated current seismicity remain challenging. Seismic tomography reveals a continuous slab dipping at ~30° down to ~600 km, and earthquake mechanisms point to down-dip compression. Further, the slab is lying at the 660-km discontinuity, and this zone is aseismic. We suggest that this pattern results from the slab’s negative thermal buoyancy, resistance of the viscous lower mantle, and buoyancy forces associated with the phase transitions at 410 km and 660 km. Our model comprises an ageing subducting plate, nonlinear rheology and major phase transitions. The model explains the observed low dip angle of the slab and predicts a detailed stress pattern related to bending down to 450 km, followed by unbending as the slab is laid flat upon the 660 km boundary. Remarkably, in the bending/unbending regions, down-dip compression occurs close to the slab top/bottom, respectively. As only down-dip compression is observed, we argue that the earthquakes are mapping the top and bottom of the slab. The absence of seismicity in the flat-lying slab is explained by significantly lower stresses and higher temperatures. With this new knowledge, increasingly accurate seismic locations will considerably improve images of finite-extent slab geometry.
Oral lichen planus interactome reveals CXCR4 and CXCL12 as candidate therapeutic targets
Authors: Rivera César , Crisóstomo Mariangela Fernanda , Peña Carolina , González-Díaz Paulina , González-Arriagada Wilfredo Alejandro
Published: March 2020

Today, we face difficulty in generating new hypotheses and understanding oral lichen planus due to the large amount of biomedical information available. In this research, we have used an integrated bioinformatics approach assimilating information from data mining, gene ontologies, protein–protein interaction and network analysis to predict candidate genes related to oral lichen planus. A detailed pathway analysis led us to propose two promising therapeutic targets: the stromal cell derived factor 1 (CXCL12) and the C-X-C type 4 chemokine receptor (CXCR4). We further validated our predictions and found that CXCR4 was upregulated in all oral lichen planus tissue samples. Our bioinformatics data cumulatively support the pathological role of chemokines and chemokine receptors in oral lichen planus. From a clinical perspective, we suggest a drug (plerixafor) and two therapeutic targets for future research.
Enhancement of Radiation Effectiveness in Proton Therapy: Comparison Between Fusion and Fission Methods and Further Approaches
Authors: Tabbakh Farshid , Hosmane Narayan S.
Published: March 2020

Proton therapy as a promising candidate in cancer treatment has attracted much attentions and many studies have been performed to investigate the new methods to enhance its radiation effectiveness. In this regard, two research groups have suggested that using boron isotopes will lead to a radiation effectiveness enhancement, using boron-11 agent to initiate the proton fusion reaction (P-BFT) and using boron-10 agent to capture the low energy secondary neutrons (NCEPT). Since, these two innovative methods have not been approved clinically, they have been recalculated in this report, discussed and compared between them and also with the traditional proton therapy to evaluate their impacts before the experimental investigations. The calculations in the present study were performed by Geant4 and MCNPX Monte Carlo Simulation Codes were utilized for obtaining more precision in our evaluations of these methods impacts. Despite small deviations in the results from the two MC tools for the NCEPT method, a good agreement was observed regarding the delivered dose rate to the tumor site at different depths while, for P-BFT related calculations, the GEANT4 was in agreement with the analytical calculations by means of the detailed cross-sections of proton-11B fusion. Accordingly, both the methods generate excess dose rate to the tumor several orders of magnitude lower than the proton dose rate. Also, it was found that, the P-BFT has more significant enhancement of effectiveness, when compared to the NCEPT, a method with impact strongly depended on the tumor’s depth. On the other hand, the advantage of neutron risk reduction proposed by NCEPT was found to give no considerable changes in the neutron dose absorption by healthy tissues.
Epidural bolus versus continuous epidural infusion analgesia on optic nerve sheath diameter in paediatric patients: A prospective, double-blind, randomised trial
Authors: Lee Bora , Lee Jae Hoon , Kim Min-Soo , Kim Seon Ju , Song Jeehyun , Kim Do-Hyeong , Choi Yong Seon
Published: March 2020

The use of programmed intermittent epidural bolus for postoperative analgesia may have greater analgesic efficacy than continuous epidural infusion. However, the rapid delivery speed used with an epidural bolus is more likely to increase intracranial pressure. We compared the effects of lumbar epidural bolus versus continuous infusion epidural analgesia on intracranial pressure in children using optic nerve sheath diameter as a marker. We randomly assigned 40 paediatric patients to bolus or infusion groups. Epidural analgesia (0.15% ropivacaine 0.3 ml·kg−1) was administered via bolus or infusion. Ultrasonography was used to measure the optic nerve sheath diameter before (T0), at 3 min (T1), 10 min (T2), and 70 min (T3) after starting the pump. There were statistically significant between-group differences in optic nerve sheath diameter over time (PGroup x Time = 0.045). From T0–T3, the area under the curve values were similar between the two groups. Although there were differences in the patterns of optic nerve sheath diameter change according to the delivery mode, the use of lumbar epidural bolus did not increase the risk of intracranial pressure increase over that of continuous infusion. Further research is needed to investigate intracranial pressure changes after continuous application of each delivery mode.
Clinical characteristics in patients with ossification of the posterior longitudinal ligament: A prospective multi-institutional cross-sectional study
Authors: Hirai Takashi , Yoshii Toshitaka , Ushio Shuta , Mori Kanji , Maki Satoshi , Katsumi Keiichi , Nagoshi Narihito , Takeuchi Kazuhiro , Furuya Takeo , Watanabe Kei , Nishida Norihiro , Watanabe Kota , Kaito Takashi , Kato Satoshi , Nagashima Katsuya , Koda Masao , Ito Kenyu , Imagama Shiro , Matsuoka Yuji , Wada Kanichiro , Kimura Atsushi , Ohba Tetsuro , Katoh Hiroyuki , Matsuyama Yukihiro , Ozawa Hiroshi , Haro Hirotaka , Takeshita Katsushi , Watanabe Masahiko , Matsumoto Morio , Nakamura Masaya , Yamazaki Masashi , Okawa Atsushi , Kawaguchi Yoshiharu
Published: March 2020

Ossification of the posterior longitudinal ligament (OPLL) can occur throughout the entire spine and can sometimes lead to spinal disorder. Although patients with OPLL sometimes develop physical limitations because of pain, the characteristics of pain and effects on activities of daily living (ADL) have not been precisely evaluated in OPLL patients. Therefore, we conducted a multi-center prospective study to assess whether the symptoms of cervical OPLL are different from those of cervical spondylosis (CS). A total of 263 patients with a diagnosis of cervical OPLL and 50 patients with a diagnosis of CS were enrolled and provided self-reported outcomes, including responses to the Japanese Orthopaedic Association (JOA) Cervical Myelopathy Evaluation Questionnaire (JOACMEQ), JOA Back Pain Evaluation Questionnaire (JOABPEQ), visual analog scale (VAS), and SF-36 scores. The severity of myelopathy was significantly correlated with each domain of the JOACMEQ and JOABPEQ. There was a negative correlation between the VAS score for each domain and the JOA score. There were significantly positive correlations between the JOA score and the Mental Health, Bodily Pain, Physical Functioning, Role Emotional, and Role Physical domains of the SF-36. One-to-one matching resulted in 50 pairs of patients with OPLL and CS. Although there was no significant between-group difference in scores in any of the domains of the JOACMEQ or JOABPEQ, the VAS scores for pain or numbness in the buttocks or limbs were significantly higher in the CS group; however, there was no marked difference in low back pain, chest tightness, or numbness below the chest between the two study groups. The scores for the Role Physical and Body Pain domains of the SF-36 were significantly higher in the OPLL group than in the CS group, and the mean scores for the other domains was similar between the two groups. The results of this study revealed that patients with OPLL were likely to have neck and low back pain and restriction in ADL. No specific type of pain was found in patients with OPLL when compared with those who had CS.
Genome-wide identification of essential genes in Mycobacterium intracellulare by transposon sequencing — Implication for metabolic remodeling
Authors: Tateishi Yoshitaka , Minato Yusuke , Baughn Anthony D. , Ohnishi Hiroaki , Nishiyama Akihito , Ozeki Yuriko , Matsumoto Sohkichi
Published: March 2020

The global incidence of the human nontuberculous mycobacteria (NTM) disease is rapidly increasing. However, knowledge of gene essentiality under optimal growth conditions and conditions relevant to the natural ecology of NTM, such as hypoxia, is lacking. In this study, we utilized transposon sequencing to comprehensively identify genes essential for growth in Mycobacterium intracellulare. Of 5126 genes of M. intracellulare ATCC13950, 506 genes were identified as essential genes, of which 280 and 158 genes were shared with essential genes of M. tuberculosis and M. marinum, respectively. The shared genes included target genes of existing antituberculous drugs including SQ109, which targets the trehalose monomycolate transporter MmpL3. From 175 genes showing decreased fitness as conditionally essential under hypoxia, preferential carbohydrate metabolism including gluconeogenesis, glyoxylate cycle and succinate production was suggested under hypoxia. Virulence-associated genes including proteasome system and mycothiol redox system were also identified as conditionally essential under hypoxia, which was further supported by the higher effective suppression of bacterial growth under hypoxia compared to aerobic conditions in the presence of these inhibitors. This study has comprehensively identified functions essential for growth of M. intracellulare under conditions relevant to the host environment. These findings provide critical functional genomic information for drug discovery.
Hippocampal mitochondrial dysfunction and psychiatric-relevant behavioral deficits in spinocerebellar ataxia 1 mouse model
Authors: Tichanek Filip , Salomova Martina , Jedlicka Jan , Kuncova Jitka , Pitule Pavel , Macanova Tereza , Petrankova Zuzana , Tuma Zdenek , Cendelin Jan
Published: March 2020

Spinocerebellar ataxia 1 (SCA1) is a devastating neurodegenerative disease associated with cerebellar degeneration and motor deficits. However, many patients also exhibit neuropsychiatric impairments such as depression and apathy; nevertheless, the existence of a causal link between the psychiatric symptoms and SCA1 neuropathology remains controversial. This study aimed to explore behavioral deficits in a knock-in mouse SCA1 (SCA1154Q/2Q) model and to identify the underlying neuropathology. We found that the SCA1 mice exhibit previously undescribed behavioral impairments such as increased anxiety- and depressive-like behavior and reduced prepulse inhibition and cognitive flexibility. Surprisingly, non-motor deficits characterize the early SCA1 stage in mice better than does ataxia. Moreover, the SCA1 mice exhibit significant hippocampal atrophy with decreased plasticity-related markers and markedly impaired neurogenesis. Interestingly, the hippocampal atrophy commences earlier than the cerebellar degeneration and directly reflects the individual severity of some of the behavioral deficits. Finally, mitochondrial respirometry suggests profound mitochondrial dysfunction in the hippocampus, but not in the cerebellum of the young SCA1 mice. These findings imply the essential role of hippocampal impairments, associated with profound mitochondrial dysfunction, in SCA1 behavioral deficits. Moreover, they underline the view of SCA1 as a complex neurodegenerative disease and suggest new avenues in the search for novel SCA1 therapies.
EAC-1A: A novel large-volume lunar regolith simulant
Authors: Engelschiøn V. S. , Eriksson S. R. , Cowley A. , Fateri M. , Meurisse A. , Kueppers U. , Sperl M.
Published: March 2020

The European Astronaut Centre (EAC) is currently constructing the European Lunar Exploration Laboratory (LUNA), a large training and operations facility to be located adjacent to EAC at the DLR (German Aerospace Centre) campus in Cologne, Germany. With an estimated representative lunar testbed area of approximately 660 m2, a large volume of lunar regolith simulant material is needed for this purpose. In this study, a basanitic sandy silt from a quarry located in the Siebengebirge Volcanic Field is evaluated as a large-volume source of material. The focus of this project has been to conduct a physical and chemical characterisation of the fine-grained material to be used in LUNA; the European Astronaut Centre lunar regolith simulant 1 (EAC-1 A). The physical characterisation tests undertaken include sphericity, density measurements, cohesion and static angle of repose, with mineralogical investigations via petrographical analysis with optical microscope and SEM, XRF, XRD and DSC measurements. The results of the EAC-1A tests are compared to published data on existing widely used lunar regolith simulants, namely JSC-1A, JSC-2A, NU-LHT-3M, DNA and FJS-1.
Reactive oxygen species scavenging mechanisms associated with polyethylene glycol mediated osmotic stress tolerance in Chinese potato
Authors: Sahoo Manas Ranjan , Devi Tongbram Roshni , Dasgupta Madhumita , Nongdam Potshangbam , Prakash Narendra
Published: March 2020

Influence of polyethylene glycol (PEG) mediated osmotic stress on reactive oxygen species (ROS) scavenging machinery of Chinese potato (Solenostemon rotundifolius (Poir.) J. K. Morton) was investigated. Five genotypes of Chinese potato were raised in Murashige and Skoog (MS) basal medium containing 6–benzylaminopurine (BAP, 1 mg L–1) along with various concentrations of PEG–6000 mediated stress conditions (0, –0.2 and –0.5 MPa) and evaluated for osmotic stress tolerance in vitro. The medium containing PEG–6000 had a detrimental effect on plantlet growth and development while compared with the control. Accumulation of H2O2 was lower in Sreedhara and Subala and higher in Nidhi under PEG stress, which was evident by in situ detection in leaves. Lipid peroxidation product such as malondialdehyde (MDA) content was increased due to PEG stress which was more in susceptible genotype than that in tolerant ones. An enhanced ROS–scavenging antioxidant enzyme was observed under stress with respect to the control. The enzymes of ascorbate–glutathione cycle showed an important role in scavenging ROS. The imposition of PEG stress also increased the non–enzymatic antioxidants viz., the ascorbate and reduced glutathione content which was prominent in tolerant genotypes in comparison to susceptible. The present study indicated that, Sreedhara and Subala showed more tolerance to osmotic stress with better ROS scavenging machineries which would be the lines of interest for augmenting future breeding strategies in this climate resilient minor tuber crop.
Dietary intake of bioactive ingredients impacts liver and adipose tissue transcriptomes in a porcine model of prepubertal early obesity
Authors: Ballester Maria , Quintanilla Raquel , Ortega Francisco J. , Serrano José C. E. , Cassanyé Anna , Rodríguez-Palmero Maria , Moreno-Muñoz José A. , Portero-Otin Manuel , Tibau Joan
Published: March 2020

Global prevalence of obesity has increased to epidemic proportions over the past 40 years, with childhood obesity reaching alarming rates. In this study, we determined changes in liver and adipose tissue transcriptomes of a porcine model for prepubertal early obesity induced by a high-calorie diet and supplemented with bioactive ingredients. A total of 43 nine-weeks-old animals distributed in four pens were fed with four different dietary treatments for 10 weeks: a conventional diet; a western-type diet; and a western-type diet with Bifidobacterium breve and rice hydrolysate, either adding or not omega-3 fatty acids. Animals fed a western-type diet increased body weight and total fat content and exhibited elevated serum concentrations of cholesterol, whereas animals supplemented with bioactive ingredients showed lower body weight gain and tended to accumulate less fat. An RNA-seq experiment was performed with a total of 20 animals (five per group). Differential expression analyses revealed an increase in lipogenesis, cholesterogenesis and inflammatory processes in animals on the western-type diet while the supplementation with bioactive ingredients induced fatty acid oxidation and cholesterol catabolism, and decreased adipogenesis and inflammation. These results reveal molecular mechanisms underlying the beneficial effects of bioactive ingredient supplementation in an obese pig model.
Autoselective transport of mammalian cells with a chemotactic droplet
Authors: Holler Silvia , Hanczyc Martin M.
Published: March 2020

Liquid chemical droplets, as models of artificial life, when pushed away from equilibrium possess some life-like behaviors such as fission, fusion, movement and chemotaxis. Chemotaxis, directed motion in response to external gradients, is typically an important process in living systems, but certain artificial systems are also capable of this activity. Previously it was shown that droplet-based chemotactic systems when interfaced with biological systems can act as transporters to move cargo such as hydrogel alginate capsules containing living cells. Here the effectiveness of our system to transport different mammalian cell lines (H460, H1299, A549, HEK293T and HS68) was tested. It was discovered that some lung cancer cell lines release surfactants only when placed in the hydrogel capsules. These surfactants establish the interface between the encapsulated cells and the droplet and also support the chemotaxis of the droplet. Because of this, the droplet-mediated transport system is selective for living cells that produce biosurfactants. This is an example of how the integration of artificial life and biological life could be designed where the systems augment each other and function together as a unit. In this case the living system produces the surfactants that the droplet needs for cargo transport and the artificial system provides the transport for the otherwise sessile mammalian cells. Future applications of droplet-based cell handling that is able to distinguish between cells based not only on viability but cell type, developmental stage or other quantifiable traits are considered.
Transport and kinase activities of CbrA of Pseudomonas putida KT2440
Authors: Wirtz Larissa , Eder Michelle , Schipper Kerstin , Rohrer Stefanie , Jung Heinrich
Published: March 2020

The CbrA/CbrB system is a two-component signal transduction system known to participate in the regulation of the cellular carbon/nitrogen balance and to play a central role in carbon catabolite repression in Pseudomonas species. CbrA is composed of a domain with similarity to proteins of the solute/sodium symporter family (SLC5) and domains typically found in bacterial sensor kinases. Here, the functional properties of the sensor kinase CbrA and its domains are analyzed at the molecular level using the system of the soil bacterium P. putida KT2440 as a model. It is demonstrated that CbrA can bind and transport L-histidine. Transport is specific for L-histidine and probably driven by an electrochemical proton gradient. The kinase domain is not required for L-histidine uptake by the SLC5 domain of CbrA, and has no significant impact on transport kinetics. Furthermore, it is shown that the histidine kinase can autophosphorylate and transfer the phosphoryl group to the response regulator CbrB. The SLC5 domain is not essential for these activities but appears to modulate the autokinase activity. A phosphatase activity of CbrA is not detected. None of the activities is significantly affected by L-histidine. The results demonstrate that CbrA functions as a L-histidine transporter and sensor kinase.
Selective inhibition of electrical conduction within the pulmonary veins by α1-adrenergic receptors activation in the Rat
Authors: Bredeloux Pierre , Findlay Ian , Pasqualin Côme , Hocini Mélèze , Bernus Olivier , Maupoil Véronique
Published: March 2020

Pulmonary veins (PV) are involved in the pathophysiology of paroxysmal atrial fibrillation. In the rat, left atrium (LA) and PV cardiomyocytes have different reactions to α1-adrenergic receptor activation. In freely beating atria-PV preparations, we found that electrical field potential (EFP) originated from the sino-atrial node propagated through the LA and the PV. The α1-adrenergic receptor agonist cirazoline induced a progressive loss of EFP conduction in the PV whereas it was maintained in the LA. This could be reproduced in preparations electrically paced at 5 Hz in LA. During pacing at 10 Hz in the PV where high firing rate ectopic foci can occur, cirazoline stopped EFP conduction from the PV to the LA, which allowed the sino-atrial node to resume its pace-making function. Loss of conduction in the PV was associated with depolarization of the diastolic membrane potential of PV cardiomyocytes. Adenosine, which reversed the cirazoline-induced depolarization of the diastolic membrane potential of PV cardiomyocytes, restored full over-shooting action potentials and EFP conduction in the PV. In conclusion, selective activation of α1-adrenergic receptors results in the abolition of electrical conduction within the PV. These results highlight a potentially novel pharmacological approach to treat paroxysmal atrial fibrillation by targeting directly the PV myocardium.
Differential stromal reprogramming in benign and malignant naturally occurring canine mammary tumours identifies disease-modulating stromal components
Authors: Amini Parisa , Nassiri Sina , Malbon Alexandra , Markkanen Enni
Published: March 2020

While cancer-associated stroma (CAS) in malignant tumours is well described, stromal changes in benign forms of naturally occurring tumours remain poorly characterized. Spontaneous canine mammary carcinomas (mCA) are viewed as excellent models of human mCA. We have recently reported highly conserved stromal reprogramming between canine and human mCA based on transcriptome analysis of laser-capture-microdissected FFPE specimen. To identify stromal changes between benign and malignant mammary tumours, we have analysed matched normal and adenoma-associated stroma (AAS) from 13 canine mammary adenomas and compared them to previous data from 15 canine mCA. Our analyses reveal distinct stromal reprogramming even in small benign tumours. While similarities between AAS and CAS exist, the stromal signature clearly distinguished adenomas from mCA. The distinction between AAS and CAS is further substantiated by differential enrichment in several hallmark signalling pathways as well as differential abundance in cellular composition. Finally, we identify COL11A1, VIT, CD74, HLA-DRA, STRA6, IGFBP4, PIGR, and TNIP1 as strongly discriminatory stromal genes between adenoma and mCA, and demonstrate their prognostic value for human breast cancer. Given the relevance of canine CAS as a model for the human disease, our approach identifies disease-modulating stromal components with implications for both human and canine breast cancer.
Frequency-domain CBE imaging for ultrasound localization of the HIFU focal spot: a feasibility study
Authors: Yang Kun , Li Qiang , Liu Hao-Li , Chen Chin-Kuo , Huang Cheng-Wei , Chen Jheng-Ru , Tsai Yu-Wei , Zhou Zhuhuang , Tsui Po-Hsiang
Published: March 2020

High-intensity focused ultrasound (HIFU) is a well-accepted tool for noninvasive thermal therapy. To control the quality of HIFU treatment, the focal spot generated in tissues must be localized. Ultrasound imaging can monitor heated regions; in particular, the change in backscattered energy (CBE) allows parametric imaging to visualize thermal information in the tissue. Conventional CBE imaging constructed in the spatial domain may be easily affected by noises when the HIFU focal spot is visualized. This study proposes frequency-domain CBE imaging to improve noise tolerance and image contrast in HIFU focal spot monitoring. Phantom experiments were performed in a temperature-controlled environment. HIFU of 2.12 MHz was applied to the phantoms, during which a clinical scanner equipped with a 3-MHz convex array transducer was used to collect raw image data consisting of backscattered signals for B-mode, spatial-, and frequency-domain CBE imaging. Concurrently, temperature changes were measured at the focal spot using a thermocouple for comparison with CBE values by calculating the correlation coefficient r. To further analyze CBE image contrast levels, a contrast factor was introduced, and an independent t-test was performed to calculate the probability value p. Experimental results showed that frequency-domain CBE imaging performed well in thermal distribution visualization, enabling quantitative detection of temperature changes. The CBE value calculated in the frequency domain also correlated strongly with that obtained using the conventional spatial-domain approach (r = 0.97). In particular, compared with the image obtained through the conventional method, the contrast of the CBE image obtained using the method based on frequency-domain analysis increased by 2.5-fold (4 dB; p < 0.05). Frequency-domain computations may constitute a new strategy when ultrasound CBE imaging is used to localize the focal spot in HIFU treatment planning.
Bioenergetic functions in subpopulations of heart mitochondria are preserved in a non-obese type 2 diabetes rat model (Goto-Kakizaki)
Authors: Lai N. , Kummitha C. M. , Loy F. , Isola R. , Hoppel C. L.
Published: March 2020

A distinct bioenergetic impairment of heart mitochondrial subpopulations in diabetic cardiomyopathy is associated with obesity; however, many type 2 diabetic (T2DM) patients with high-risk for cardiovascular disease are not obese. In the absence of obesity, it is unclear whether bioenergetic function in the subpopulations of mitochondria is affected in heart with T2DM. To address this issue, a rat model of non-obese T2DM was used to study heart mitochondrial energy metabolism, measuring bioenergetics and enzyme activities of the electron transport chain (ETC). Oxidative phosphorylation in the presence of substrates for ETC and ETC activities in both populations of heart mitochondria in T2DM rats were unchanged. Despite the preservation of mitochondrial function, aconitase activity in T2DM heart was reduced, suggesting oxidative stress in mitochondria. Our study indicate that metabolic function of heart mitochondria is unchanged in the face of oxidative stress and point to a critical role of obesity in T2DM cardiomyopathy.
Trends and Projections in Breast Cancer Mortality among four Asian countries (1990–2017): Evidence from five Stochastic Mortality Models
Authors: Mubarik Sumaira , Wang Fang , Fawad Muhammad , Wang Yafeng , Ahmad Ishfaq , Yu Chuanhua
Published: March 2020

The current study aimed to explore some important insights into the breast cancer mortality (BCM) trends and projections among four Asian countries by using five advanced stochastic mortality models. BCM data over 28 years from 1990–2017 with ages 20–84 were retrieved from the Global Burden of Disease (GBD) Study 2017 for four Asian countries, namely, China, India, Pakistan, and Thailand. Five stochastic mortality models with the family of generalized age-period-cohort were implemented to find the present and future BCM trends in these four Asian countries. Based on Cairns-Blake-Dowd (CBD) model and Lee-Carter model (LCM), overall, results revealed that BCM increased with the passage of time. Aging factor was the most influential factor of elevated BCM in each Asian country under consideration. Projection of BCM showed that mortality rates might continue to grow with time, especially in older ages in each Asian country under study. The highest forecasted BCM rates were observed in Pakistan as compared to other countries. The obvious increase in BCM suggested that earlier tactics should be implemented to reduce the subsequent morbidity and mortality due to breast cancer. The last but not least, some additional tactics to mitigate the BCM in older ages must be adopted.
High-level Fusion Coupled with Mahalanobis Distance Weighted (MDW) Method for Multivariate Calibration
Authors: Li Qianqian , Wu Zhisheng , Lin Ling , Zeng Jingqi , Zhang Jixiong , Yan Hong , Min Shungeng
Published: March 2020

Near infrared spectra (NIR) technology is a widespread detection method with high signal to noise ratio (SNR) while has poor modeling interpretation due to the overlapped features. Alternatively, mid-infrared spectra (MIR) technology demonstrates more chemical features and gives a better explanation of the model. Yet, it has the defects of low SNR. With the purpose of developing a model with plenty of characteristics as well as with higher SNR, NIR and MIR technologies are combined to perform high-level fusion strategy for quantitative analysis. A novel chemometrical method named as Mahalanobis distance weighted (MDW) is proposed to integrate NIR and MIR techniques comprehensively. Mahalanobis distance (MD) based on the principle of spectral similarity is obtained to calculate the weight of each sample. Specifically, the weight is assigned to the inverse ratio of the corresponding MD. Besides, the proposed MDW method is applied to NIR and MIR spectra of active ingredients in deltamethrin and emamectin benzoate formulations for quantitative analysis. As a consequence, the overall results show that the MDW method is promising with noticeable improvement of predictive performance than individual methods when executing high-level fusion for quantitative analysis.
Oxidation of Benzyl Alcohol Compounds in the Presence of Carbon
Hybrid Supported Platinum Nanoparticles (Pt@CHs) in Oxygen Atmosphere
Authors: Göksu Haydar , Burhan Hakan , Mustafov Sibel Demiroğlu , Şen Fatih
Published: March 2020

A novel catalyst which carbon hybrid supported platinum nanoparticles
were synthesized by our group for the oxidation of benzyl alcohol derivatives. In
this study, this catalyst was utilized for the oxidation of benzyl alcohol
derivatives to benzaldehyde compounds in aqueous toluene at 80 °C. The benzaldehyde
derivatives were synthesized in high yields and mild conditions in the presence of
the catalyst by the developed method. Additionally, the prepared nanoparticles have
been characterized by Transmission Electron Microscopy (TEM), the high-resolution
electron micrograph (HR-TEM), X-ray Photoelectron Spectroscopy (XPS), and X-ray
Diffraction (XRD). The mean particle size of the nanoparticles determined by the XRD
technique was found to be 2.83 nm in parallel with TEM analysis. TEM analysis also
indicated that the Pt nanoparticles were evenly dispersed on the support material.
Finally, the Pt@CHs catalyst was shown also stable and reusable for the oxidation
reaction, providing ≤95% conversion after its 3rd consecutive use in the oxidation
reaction of various compounds.
The transcriptome of the newt Cynops orientalis provides new insights into evolution and function of sexual gene networks in sarcopterygians
Authors: Biscotti Maria Assunta , Carducci Federica , Barucca Marco , Gerdol Marco , Pallavicini Alberto , Schartl Manfred , Canapa Adriana , Adolfi Mateus Contar
Published: March 2020

Amphibians evolved in the Devonian period about 400 Mya and represent a transition step in tetrapod evolution. Among amphibians, high-throughput sequencing data are very limited for Caudata, due to their largest genome sizes among terrestrial vertebrates. In this paper we present the transcriptome from the fire bellied newt Cynops orientalis. Data here presented display a high level of completeness, comparable to the fully sequenced genomes available from other amphibians. Moreover, this work focused on genes involved in gametogenesis and sexual development. Surprisingly, the gsdf gene was identified for the first time in a tetrapod species, so far known only from bony fish and basal sarcopterygians. Our analysis failed to isolate fgf24 and foxl3, supporting the possible loss of both genes in the common ancestor of Rhipidistians. In Cynops, the expression analysis of genes described to be sex-related in vertebrates singled out an expected functional role for some genes, while others displayed an unforeseen behavior, confirming the high variability of the sex-related pathway in vertebrates.
In vitro hepatic aflatoxicol production is related to a higher resistance to aflatoxin B1 in poultry
Authors: Murcia Hansen W. , Diaz Gonzalo J.
Published: March 2020

A study was conducted to determine the cytosolic in vitro hepatic enzymatic kinetic parameters Vmax, KM, and intrinsic clearance (CLint) for aflatoxin B1 (AFB1) reductase [aflatoxicol (AFL) production] and AFL dehydrogenase (AFB1 production) in four commercial poultry species (chicken, quail, turkey and duck). Large differences were found in AFB1 reductase activity, being the chicken the most efficient producer of AFL (highest CLint value). Oxidation of AFL to AFB1 showed only slight differences among the different poultry species. On average all species produced AFB1 from AFL at a similar rate, except for the turkey which produced AFB1 from AFL at a significantly lower rate than chickens and quail, but not ducks. Although the turkey and duck showed differences in AFL oxidation Vmax and KM parameters, their CLint values did not differ significantly. The ratio AFB1 reductase/AFL dehydrogenase enzyme activity was inversely related to the known in vivo sensitivity to AFB1 being highest for the chicken, lowest for the duck and intermediate for turkeys and quail. Since there is no evidence that AFL is a toxic metabolite of AFB1, these results suggest that AFL production is a detoxication reaction in poultry. Conversion of AFB1 to AFL prevents the formation of the AFB1-8,9-exo-epoxide which, upon conversion to AFB1-dihydrodiol, is considered to be the metabolite responsible for the acute toxic effects of AFB1.
Crystal structure of pathogenic Staphylococcus aureus lipase complex with the anti-obesity drug orlistat
Authors: Kitadokoro Kengo , Tanaka Mutsumi , Hikima Takaaki , Okuno Yukiko , Yamamoto Masaki , Kamitani Shigeki
Published: March 2020

Staphylococcus aureus lipase (SAL), a triacylglycerol esterase, is an important virulence factor and may be a therapeutic target for infectious diseases. Herein, we determined the 3D structure of native SAL, the mutated S116A inactive form, and the inhibitor complex using the anti-obesity drug orlistat to aid in drug development. The determined crystal structures showed a typical α/β hydrolase motif with a dimeric form. Fatty acids bound near the active site in native SAL and inactive S116A mutant structures. We found that orlistat potently inhibits SAL activity, and it covalently bound to the catalytic Ser116 residue. This is the first report detailing orlistat–lipase binding. It provides structure-based information on the production of potent anti-SAL drugs and lipase inhibitors. These results also indicated that orlistat can be repositioned to treat bacterial diseases.
Patterns of Rift Valley fever virus seropositivity in domestic ruminants in central South Africa four years after a large outbreak
Authors: Ngoshe Yusuf B. , Avenant Alida , Rostal Melinda K. , Karesh William B. , Paweska Janusz T. , Bagge Whitney , Jansen van Vuren Petrus , Kemp Alan , Cordel Claudia , Msimang Veerle , Thompson Peter N.
Published: March 2020

Rift Valley fever (RVF) is a mosquito-borne viral zoonosis showing complex epidemiological patterns that are poorly understood in South Africa. Large outbreaks occur in the central interior at long, irregular intervals, most recently in 2010–2011; however, the level of herd immunity of ruminant livestock, a key determinant of outbreaks, is unknown. During 2015–2016 a cross-sectional study on 234 randomly-selected farms investigated the prevalence, patterns of, and factors associated with, antibodies to RVF virus (RVFV) in livestock in an area heavily affected by that outbreak. A RVFV inhibition ELISA was used to screen 977 cattle, 1,549 sheep and 523 goats and information on potential risk factors was collected using a comprehensive questionnaire. The estimated RVFV seroprevalence, adjusted for survey design, was 42.9% in cattle, 28.0% in sheep and 9.3% in goats, showing a high degree of farm-level clustering. Seroprevalence increased with age and was higher on private vs. communal land, on farms with seasonal pans (temporary, shallow wetlands) and perennial rivers and in recently vaccinated animals. Seropositivity amongst unvaccinated animals born after the last outbreak indicates likely viral circulation during the post-epidemic period. The current level of herd immunity in livestock may be insufficient to prevent another large outbreak, should suitable conditions recur.
Bofutsushosan improves gut barrier function with a bloom of Akkermansia muciniphila and improves glucose metabolism in mice with diet-induced obesity
Authors: Fujisaka Shiho , Usui Isao , Nawaz Allah , Igarashi Yoshiko , Okabe Keisuke , Furusawa Yukihiro , Watanabe Shiro , Yamamoto Seiji , Sasahara Masakiyo , Watanabe Yoshiyuki , Nagai Yoshinori , Yagi Kunimasa , Nakagawa Takashi , Tobe Kazuyuki
Published: March 2020

Obesity and insulin resistance are associated with dysbiosis of the gut microbiota and impaired intestinal barrier function. Herein, we report that Bofutsushosan (BFT), a Japanese herbal medicine, Kampo, which has been clinically used for constipation in Asian countries, ameliorates glucose metabolism in mice with diet–induced obesity. A 16S rRNA sequence analysis of fecal samples showed that BFT dramatically increased the relative abundance of Verrucomicrobia, which was mainly associated with a bloom of Akkermansia muciniphila (AKK). BFT decreased the gut permeability as assessed by FITC-dextran gavage assay, associated with increased expression of tight-junction related protein, claudin-1, in the colon. The BFT treatment group also showed significant decreases of the plasma endotoxin level and expression of the hepatic lipopolysaccharide-binding protein. Antibiotic treatment abrogated the metabolic effects of BFT. Moreover, many of these changes could be reproduced when the cecal contents of BFT-treated donors were transferred to antibiotic-pretreated high fat diet-fed mice. These data demonstrate that BFT modifies the gut microbiota with an increase in AKK, which may contribute to improving gut barrier function and preventing metabolic endotoxemia, leading to attenuation of diet-induced inflammation and glucose intolerance. Understanding the interaction between a medicine and the gut microbiota may provide insights into new pharmacological targets to improve glucose metabolism.
Temporal Signal-to-Noise Changes in Combined Multislice- and In-Plane-Accelerated Echo-Planar Imaging with a 20- and 64-Channel Coil
Authors: Seidel Philipp , Levine Seth M. , Tahedl Marlene , Schwarzbach Jens V.
Published: March 2020

Echo-planar imaging (EPI) is the most common method of functional MRI for acquiring the blood oxygenation level-dependent (BOLD) contrast, allowing the acquisition of an entire brain volume within seconds. However, because imaging protocols are limited by hardware (e.g., fast gradient switching), researchers must compromise between spatial resolution, temporal resolution, or whole-brain coverage. Earlier attempts to circumvent this problem included developing protocols in which slices of a volume were acquired faster (i.e., in-plane acceleration (S)) or simultaneously (i.e., multislice acceleration (M)). However, applying acceleration methods can lead to a reduction in the temporal signal-to-noise ratio (tSNR): a critical measure of signal stability over time. Using a 20- and 64-channel receiver coil, we show that enabling S-acceleration consistently yielded a substantial decrease in tSNR, regardless of the receiver coil, whereas M-acceleration yielded less pronounced tSNR decrease. Moreover, tSNR losses tended to occur in temporal, insular, and medial brain regions and were more noticeable with the 20-channel coil, while with the 64-channel coil, the tSNR in lateral frontoparietal regions remained relatively stable up to six-fold M-acceleration producing comparable tSNR to that of no acceleration. Such methodological explorations can guide researchers and clinicians in optimizing imaging protocols depending on the brain regions under investigation.
Designing vegetation barriers for urban air pollution abatement: a practical review for appropriate plant species selection
Authors: Barwise Yendle , Kumar Prashant
Published: March 2020

Vegetation can form a barrier between traffic emissions and adjacent areas, but the optimal configuration and plant composition of such green infrastructure (GI) are currently unclear. We examined the literature on aspects of GI that influence ambient air quality, with a particular focus on vegetation barriers in open-road environments. Findings were critically evaluated in order to identify principles for effective barrier design, and recommendations regarding plant selection were established with reference to relevant spatial scales. As an initial investigation into viable species for UK urban GI, we compiled data on 12 influential traits for 61 tree species, and created a supplementary plant selection framework. We found that if the scale of the intervention, the context and conditions of the site and the target air pollutant type are appreciated, the selection of plants that exhibit certain biophysical traits can enhance air pollution mitigation. For super-micrometre particles, advantageous leaf micromorphological traits include the presence of trichomes and ridges or grooves. Stomatal characteristics are more significant for sub-micrometre particle and gaseous pollutant uptake, although we found a comparative dearth of studies into such pollutants. Generally advantageous macromorphological traits include small leaf size and high leaf complexity, but optimal vegetation height, form and density depend on planting configuration with respect to the immediate physical environment. Biogenic volatile organic compound and pollen emissions can be minimised by appropriate species selection, although their significance varies with scale and context. While this review assembled evidence-based recommendations for practitioners, several important areas for future research were identified.
Digital phenotyping, behavioral sensing, or personal sensing: names and transparency in the digital age
Authors: Mohr David C. , Shilton Katie , Hotopf Matthew
Published: March 2020

Data from networked sensors, such as those in our phones, are increasingly being explored and used to identify behaviors related to health and mental health. While computer scientists have referred to this field as context sensing, personal sensing, or mobile sensing, medicine has more recently adopted the term digital phenotyping. This paper discusses the implications of these labels in light of privacy concerns, arguing language that is transparent and meaningful to the people whose data we are acquiring.
The Na,K-ATPase acts upstream of phosphoinositide PI(4,5)P2 facilitating unconventional secretion of Fibroblast Growth Factor 2
Authors: Legrand Cyril , Saleppico Roberto , Sticht Jana , Lolicato Fabio , Müller Hans-Michael , Wegehingel Sabine , Dimou Eleni , Steringer Julia P. , Ewers Helge , Vattulainen Ilpo , Freund Christian , Nickel Walter
Published: March 2020

FGF2 is a tumor cell survival factor that is exported from cells by an ER/Golgi-independent secretory pathway. This unconventional mechanism of protein secretion is based on direct translocation of FGF2 across the plasma membrane. The Na,K-ATPase has previously been shown to play a role in this process, however, the underlying mechanism has remained elusive. Here, we define structural elements that are critical for a direct physical interaction between FGF2 and the α1 subunit of the Na,K-ATPase. In intact cells, corresponding FGF2 mutant forms were impaired regarding both recruitment at the inner plasma membrane leaflet and secretion. Ouabain, a drug that inhibits both the Na,K-ATPase and FGF2 secretion, was found to impair the interaction of FGF2 with the Na,K-ATPase in cells. Our findings reveal the Na,K-ATPase as the initial recruitment factor for FGF2 at the inner plasma membrane leaflet being required for efficient membrane translocation of FGF2 to cell surfaces.
Author Correction: Genome-wide association study of knee pain identifies associations with GDF5 and COL27A1 in UK Biobank
Authors: Meng Weihua , Adams Mark J. , Palmer Colin N. A. ,   The 23andMe Research Team, Agee Michelle , Alipanahi Babak , Bell Robert K. , Bryc Katarzyna , Elson Sarah L. , Fontanillas Pierre , Furlotte Nicholas A. , Hicks Barry , Hinds David A. , Huber Karen E. , Jewett Ethan M. , Jiang Yunxuan , Kleinman Aaron , Lin Keng-Han , Litterman Nadia K. , McCreight Jennifer C. , McIntyre Matthew H. , McManus Kimberly F. , Mountain Joanna L. , Noblin Elizabeth S. , Northover Carrie A. M. , Pitts Steven J. , Poznik G. David , Sathirapongsasuti J. Fah , Shelton Janie F. , Shringarpure Suyash , Tian Chao , Tung Joyce Y. , Vacic Vladimir , Wang Xin , Wilson Catherine H. , Shi Jingchunzi , Auton Adam , Ryan Kathleen A. , Jordan Joanne M. , Mitchell Braxton D. , Jackson Rebecca D. , Yau Michelle S. , McIntosh Andrew M. , Smith Blair H.
Published: March 2020

An amendment to this paper has been published and can be accessed via a link at the top of the paper.