bluuebunny/crossref_metadata_2025_split huggingface dataset:
Tissue Harvesting Site and Culture Medium Affect Attachment, Growth, and Phenotype of Ex Vivo Expanded Oral Mucosal Epithelial Cells
Authors: Islam Rakibul , Eidet Jon Roger , Badian Reza A. , Lippestad Marit , Messelt Edward , Griffith May , Dartt Darlene A. , Utheim Tor Paaske 
Published: March 2017

AbstractTransplantation of cultured oral mucosal epithelial cells (OMECs) is a promising treatment strategy for limbal stem cell deficiency. In order to improve the culture method, we investigated the effects of four culture media and tissue harvesting sites on explant attachment, growth, and phenotype of OMECs cultured from Sprague-Dawley rats. Neither choice of media or harvesting site impacted the ability of the explants to attach to the culture well. Dulbecco’s modified Eagle’s medium/Ham’s F12 (DMEM) and Roswell Park Memorial Institute 1640 medium (RPMI) supported the largest cellular outgrowth. Fold outgrowth was superior from LL explants compared to explants from the buccal mucosa (BM), HP, and transition zone of the lower lip (TZ) after six-day culture. Putative stem cell markers were detected in cultures grown in DMEM and RPMI. In DMEM, cells from TZ showed higher colony-forming efficiency than LL, BM, and HP. In contrast to RPMI, DMEM both expressed the putative stem cell marker Bmi-1 and yielded cell colonies. Our data suggest that OMECs from LL and TZ cultured in DMEM give rise to undifferentiated cells with high growth capacity, and hence are the most promising for treatment of limbal stem cell deficiency.
Delivery of ENaC siRNA to epithelial cells mediated by a targeted nanocomplex: a therapeutic strategy for cystic fibrosis
Authors: Manunta Maria D. I. , Tagalakis Aristides D. , Attwood Martin , Aldossary Ahmad M. , Barnes Josephine L. , Munye Mustafa M. , Weng Alexander , McAnulty Robin J , Hart Stephen L. 
Published: March 2017

AbstractThe inhibition of ENaC may have therapeutic potential in CF airways by reducing sodium hyperabsorption, restoring lung epithelial surface fluid levels, airway hydration and mucociliary function. The challenge has been to deliver siRNA to the lung with sufficient efficacy for a sustained therapeutic effect. We have developed a self-assembling nanocomplex formulation for siRNA delivery to the airways that consists of a liposome (DOTMA/DOPE; L), an epithelial targeting peptide (P) and siRNA (R). LPR formulations were assessed for their ability to silence expression of the transcript of the gene encoding the α-subunit of the sodium channel ENaC in cell lines and primary epithelial cells, in submerged cultures or grown in air-liquid interface conditions. LPRs, containing 50 nM or 100 nM siRNA, showed high levels of silencing, particularly in primary airway epithelial cells. When nebulised these nanocomplexes still retained their biophysical properties and transfection efficiencies. The silencing ability was determined at protein level by confocal microscopy and western blotting. In vivo data demonstrated that these nanoparticles had the ability to silence expression of the α-ENaC subunit gene. In conclusion, these findings show that LPRs can modulate the activity of ENaC and this approach might be promising as co-adjuvant therapy for cystic fibrosis.
The Role of Heparanase in the Pathogenesis of Acute Pancreatitis: A Potential Therapeutic Target
Authors: Khamaysi Iyad , Singh Preeti , Nasser Susan , Awad Hoda , Chowers Yehuda , Sabo Edmond , Hammond Edward , Gralnek Ian , Minkov Irena , Noseda Alessandro , Ilan Neta , Vlodavsky Israel , Abassi Zaid 
Published: March 2017

AbstractAcute pancreatitis (AP) is one of the most common diseases in gastroenterology. However, neither the etiology nor the pathophysiology of the disease is fully understood and no specific or effective treatment has been developed. Heparanase is an endoglycosidase that cleaves heparan sulfate (HS) side chains of HS sulfate proteoglycans into shorter oligosaccharides, activity that is highly implicated in cellular invasion associated with cancer metastasis and inflammation. Given that AP involves a strong inflammatory aspect, we examined whether heparanase plays a role in AP. Here, we provide evidence that pancreatic heparanase expression and activity are significantly increased following cerulein treatment. Moreover, pancreas edema and inflammation, as well as the induction of cytokines and signaling molecules following cerulein treatment were attenuated markedly by heparanase inhibitors, implying that heparanase plays a significant role in AP. Notably, all the above features appear even more pronounced in transgenic mice over expressing heparanase, suggesting that these mice can be utilized as a sensitive model system to reveal the molecular mechanism by which heparanase functions in AP. Heparanase, therefore, emerges as a potential new target in AP, and heparanase inhibitors, now in phase I/II clinical trials in cancer patients, are hoped to prove beneficial also in AP.
Ultra-thin clay layers facilitate seismic slip in carbonate faults
Authors: Smeraglia Luca , Billi Andrea , Carminati Eugenio , Cavallo Andrea , Di Toro Giulio , Spagnuolo Elena , Zorzi Federico 
Published: March 2017

AbstractMany earthquakes propagate up to the Earth’s surface producing surface ruptures. Seismic slip propagation is facilitated by along-fault low dynamic frictional resistance, which is controlled by a number of physico-chemical lubrication mechanisms. In particular, rotary shear experiments conducted at seismic slip rates (1 ms−1) show that phyllosilicates can facilitate co-seismic slip along faults during earthquakes. This evidence is crucial for hazard assessment along oceanic subduction zones, where pelagic clays participate in seismic slip propagation. Conversely, the reason why, in continental domains, co-seismic slip along faults can propagate up to the Earth’s surface is still poorly understood. We document the occurrence of micrometer-thick phyllosilicate-bearing layers along a carbonate-hosted seismogenic extensional fault in the central Apennines, Italy. Using friction experiments, we demonstrate that, at seismic slip rates (1 ms−1), similar calcite gouges with pre-existing phyllosilicate-bearing (clay content ≤3 wt.%) micro-layers weaken faster than calcite gouges or mixed calcite-phyllosilicate gouges. We thus propose that, within calcite gouge, ultra-low clay content (≤3 wt.%) localized along micrometer-thick layers can facilitate seismic slip propagation during earthquakes in continental domains, possibly enhancing surface displacement.
Lanthanum hexaboride for solar energy applications
Authors: Sani Elisa , Mercatelli Luca , Meucci Marco , Zoli Luca , Sciti Diletta 
Published: March 2017

AbstractWe investigate the optical properties of LaB6 – based materials, as possible candidates for solid absorbers in Concentrating Solar Power (CSP) systems. Bulk LaB6 materials were thermally consolidated by hot pressing starting from commercial powders. To assess the solar absorbance and spectral selectivity properties, room-temperature hemispherical reflectance spectra were measured from the ultraviolet to the mid-infrared, considering different compositions, porosities and surface roughnesses. Thermal emittance at around 1100 K has been measured. Experimental results showed that LaB6 can have a solar absorbance comparable to that of the most advanced solar absorber material in actual plants such as Silicon Carbide, with a higher spectral selectivity. Moreover, LaB6 has also the appealing characteristics to be a thermionic material, so that it could act at the same time both as direct high-temperature solar absorber and as electron source, significantly reducing system complexity in future concentrating solar thermionic systems and bringing a real innovation in this field.
Structural Insight into the Specific DNA Template Binding to DnaG primase in Bacteria
Authors: Zhou Yingqin , Luo Hao , Liu Zhongchuan , Yang Mu , Pang Xiaoyun , Sun Fei , Wang Ganggang 
Published: March 2017

AbstractBacterial primase initiates the repeated synthesis of short RNA primers that are extended by DNA polymerase to synthesize Okazaki fragments on the lagging strand at replication forks. It remains unclear how the enzyme recognizes specific initiation sites. In this study, the DnaG primase from Bacillus subtilis (BsuDnaG) was characterized and the crystal structure of the RNA polymerase domain (RPD) was determined. Structural comparisons revealed that the tethered zinc binding domain plays an important role in the interactions between primase and specific template sequence. Structural and biochemical data defined the ssDNA template binding surface as an L shape, and a model for the template ssDNA binding to primase is proposed. The flexibility of the DnaG primases from B. subtilis and G. stearothermophilus were compared, and the results implied that the intrinsic flexibility of the primase may facilitate the interactions between primase and various partners in the replisome. These results shed light on the mechanism by which DnaG recognizes the specific initiation site.
Intubation-free in vivo imaging of the tracheal mucosa using two-photon microscopy
Authors: Veres Tibor Z. , Kopcsányi Tamás , Tirri Marko , Braun Armin , Miyasaka Masayuki , Germain Ronald N. , Jalkanen Sirpa , Salmi Marko 
Published: March 2017

AbstractThe mucosal layer of conducting airways is the primary tissue exposed to inhaled microorganisms, allergens and pollutants. We developed an in vivo two-photon microscopic approach that allows performing dynamic imaging studies in the mouse trachea, which is a commonly used in vivo model of human small-diameter bronchi. By providing stabilized access to the tracheal mucosa without intubation, our setup uniquely allows dynamic in vivo imaging of mucociliary clearance and steady-state immune cell behavior within the complex airway mucosal tissue.
Amide hydrogens reveal a temperature-dependent structural transition that enhances site-II Ca2+-binding affinity in a C-domain mutant of cardiac troponin C
Authors: Veltri Tiago , de Oliveira Guilherme A. P. , Bienkiewicz Ewa A. , Palhano Fernando L. , Marques Mayra de A. , Moraes Adolfo H. , Silva Jerson L. , Sorenson Martha M. , Pinto Jose R. 
Published: March 2017

AbstractThe hypertrophic cardiomyopathy-associated mutant D145E, in cardiac troponin C (cTnC) C-domain, causes generalised instability at multiple sites in the isolated protein. As a result, structure and function of the mutant are more susceptible to higher temperatures. Above 25 °C there are large, progressive increases in N-domain Ca2+-binding affinity for D145E but only small changes for the wild-type protein. NMR-derived backbone amide temperature coefficients for many residues show a sharp transition above 30–40 °C, indicating a temperature-dependent conformational change that is most prominent around the mutated EF-hand IV, as well as throughout the C-domain. Smaller, isolated changes occur in the N-domain. Cardiac skinned fibres reconstituted with D145E are more sensitive to Ca2+ than fibres reconstituted with wild-type, and this defect is amplified near body-temperature. We speculate that the D145E mutation destabilises the native conformation of EF-hand IV, leading to a transient unfolding and dissociation of helix H that becomes more prominent at higher temperatures. This creates exposed hydrophobic surfaces that may be capable of binding unnaturally to a variety of targets, possibly including the N-domain of cTnC when it is in its open Ca2+-saturated state. This would constitute a potential route for propagating signals from one end of TnC to the other.
An Assay System for Point-of-Care Diagnosis of Tuberculosis using Commercially Manufactured PCB Technology
Authors: Evans Daniel , Papadimitriou Konstantinos I. , Greathead Louise , Vasilakis Nikolaos , Pantelidis Panagiotis , Kelleher Peter , Morgan Hywel , Prodromakis Themistoklis 
Published: March 2017

AbstractRapid advances in clinical technologies, detection sensitivity and analytical throughput have delivered a significant expansion in our knowledge of prognostic and diagnostic biomarkers in many common infectious diseases, such as Tuberculosis (TB). During the last decade, a significant number of approaches to TB diagnosis have been attempted at Point-of-Care (PoC), exploiting a large variation of techniques and materials. In this work, we describe an electronics-based Enzyme-Linked ImmunoSorbent Assay (eELISA), using a Lab-on-a-Printed Circuit Board (LoPCB) approach, for TB diagnosis based on cytokine detection. The test relies upon an electrochemical (amperometric) assay, comprising a high-precision bioinstrumentation board and amperometric sensors, produced exclusively using standard PCB manufacturing processes. Electrochemical detection uses standard Au and Ag electrodes together with a bespoke, low-power, multichannel, portable data-acquisition system. We demonstrate high-performance assay chemistry performed at microfluidic volumes on Au pads directly at the PCB surface with improved limit of detection (~10 pg/mL) over standard colorimetric ELISA methods. The assay has also been implemented in plasma, showing the utility of the system for medical applications. This work is a significant step towards the development of a low-cost, portable, high-precision diagnostic and monitoring technology, which once combined with appropriate PCB-based microfluidic networks will provide complete LoPCB platforms.
Sodium fluoride induces nephrotoxicity via oxidative stress-regulated mitochondrial SIRT3 signaling pathway
Authors: Song Chao , Fu Beibei , Zhang Jingcheng , Zhao Jiamin , Yuan Mengke , Peng Wei , Zhang Yong , Wu Haibo 
Published: March 2017

AbstractAccumulation of mitochondrial reactive oxygen species (mROS) has been implicated in the pathogenesis of fluorosis. As the main mitochondrial deacetylase, SIRT3 is closely associated with oxidative stress. To investigate the role of SIRT3 in response to sodium fluoride (NaF)-induced nephrotoxicity. Our results showed that NaF treatment impaired mitochondrial ultrastructure, decreased cell viability and increased apoptosis in TCMK-1 cells. Oxidative stress, detected by mROS and 8-Hydroxy-2’-deoxyguanosine (8-OHdG) were higher in NaF-treated cells, accompanied by decreased level of reduced glutathione (GSH). NaF reduces manganese superoxide dismutase (SOD2) expression through SIRT3-mediated DNA-binding activity of FoxO3a and decrease SOD2 activity by inhibiting SIRT3-mediated deacetylation. These effects were ameliorated by overexpression of SIRT3. Peroxisome proliferator-activated receptor-coactivator 1a (PGC-1α) interacted with nuclear factor erythroid 2 (NF-E2)-related factor 2 (NRF2) that bound to SIRT3 promoter to regulate SIRT3 expression. The study provides new insights into a critical NRF2/PGC-1α-SIRT3 pathway in response to NaF-induced nephritic oxidative injury. In vivo treatment of SIRT3-expressing adenovirus protects against NaF-induced nephritic injury in mice. Moreover, mechanistic study revealed that ERK1/2 activation was associated with increased apoptosis induced by NaF. In conclusion, these data shedding light on new approaches for treatment of NaF-induced nephrotoxicity.
Genetic diversity and population structure of the Bacillus cereus group bacteria from diverse marine environments
Authors: Liu Yang , Lai Qiliang , Du Juan , Shao Zongze 
Published: March 2017

AbstractThe phylogenetic diversity of marine bacteria belonged to the Bacillus cereus group has not been well investigated. Here, we present the genetic diversity and population structure of 71 bacteria from diverse marine environments, using a multilocus sequence typing (MLST) approach and the analyses of digital DNA-DNA hybridization (dDDH) and average nucleotide identity (ANI) based on some representative genomic sequences. The MLST analysis demonstrated that these isolates were highly diverse and a wide distribution in marine environments and some of them showed niche specificity to some extent. They were assigned to 27 sequence types (STs) with 23 novel STs. Phylogenetic analysis of 82 bacteria containing 11 type strains based on MLST discriminated them as 20 clusters including 10 new ones. Both the dDDH and ANI results supported the proposition that each of 20 clusters represented one independent species, including 10 putative novel species. Values of 98.3% of MLST similarity and 96.2% of ANI were proposed as the standard for the species definition of this group. In summary, the first insight into the phylogenetic diversity of the group bacteria from marine environments will contribute to better understanding of their ecological role and evolution in contrast with terrestrial environments.
Engaging in a tone-detection task differentially modulates neural activity in the auditory cortex, amygdala, and striatum
Authors: Zhong Renjia , Ma Lanlan , Qin Ling 
Published: March 2017

AbstractThe relationship between attention and sensory coding is an area of active investigation. Previous studies have revealed that an animal’s behavioral state can play a crucial role in shaping the characteristics of neural responses in the auditory cortex (AC). However, behavioral modulation of auditory response in brain areas outside the AC is not well studied. In this study, we used the same experimental paradigm to examine the effects of attention on neural activity in multiple brain regions including the primary auditory cortex (A1), posterior auditory field (PAF), amygdala (AMY), and striatum (STR). Single-unit spike activity was recorded while cats were actively performing a tone-detection task or passively listening to the same tones. We found that tone-evoked neural responses in A1 were not significantly affected by task-engagement; however, those in PAF and AMY were enhanced, and those in STR were suppressed. The enhanced effect was associated with an improvement of accuracy of tone detection, which was estimated from the spike activity. Additionally, the firing rates of A1 and PAF neurons decreased upon motor response (licking) during the detection task. Our results suggest that attention may have different effects on auditory responsive brain areas depending on their physiological functions.
A recent deep earthquake doublet in light of long-term evolution of Nazca subduction
Authors: Zahradník J. , Čížková H. , Bina C. R. , Sokos E. , Janský J. , Tavera H. , Carvalho J. 
Published: March 2017

AbstractEarthquake faulting at ~600 km depth remains puzzling. Here we present a new kinematic interpretation of two Mw7.6 earthquakes of November 24, 2015. In contrast to teleseismic analysis of this doublet, we use regional seismic data providing robust two-point source models, further validated by regional back-projection and rupture-stop analysis. The doublet represents segmented rupture of a ∼30-year gap in a narrow, deep fault zone, fully consistent with the stress field derived from neighbouring 1976–2015 earthquakes. Seismic observations are interpreted using a geodynamic model of regional subduction, incorporating realistic rheology and major phase transitions, yielding a model slab that is nearly vertical in the deep-earthquake zone but stagnant below 660 km, consistent with tomographic imaging. Geodynamically modelled stresses match the seismically inferred stress field, where the steeply down-dip orientation of compressive stress axes at ∼600 km arises from combined viscous and buoyant forces resisting slab penetration into the lower mantle and deformation associated with slab buckling and stagnation. Observed fault-rupture geometry, demonstrated likelihood of seismic triggering, and high model temperatures in young subducted lithosphere, together favour nanometric crystallisation (and associated grain-boundary sliding) attending high-pressure dehydration as a likely seismogenic mechanism, unless a segment of much older lithosphere is present at depth.
Structural mechanisms for α-conotoxin activity at the human α3β4 nicotinic acetylcholine receptor
Authors: Abraham Nikita , Healy Michael , Ragnarsson Lotten , Brust Andreas , Alewood Paul F. , Lewis Richard J. 
Published: March 2017

AbstractNicotinic acetylcholine receptors (nAChR) are therapeutic targets for a range of human diseases. α-Conotoxins are naturally occurring peptide antagonists of nAChRs that have been used as pharmacological probes and investigated as drug leads for nAChR related disorders. However, α-conotoxin interactions have been mostly characterised at the α7 and α3β2 nAChRs, with interactions at other subtypes poorly understood. This study provides novel structural insights into the molecular basis for α-conotoxin activity at α3β4 nAChR, a therapeutic target where subtype specific antagonists have potential to treat nicotine addiction and lung cancer. A co-crystal structure of α-conotoxin LsIA with Lymnaea stagnalis acetylcholine binding protein guided the design and functional characterisations of LsIA analogues that identified the minimum pharmacophore regulating α3β4 antagonism. Interactions of the LsIA R10F with β4 K57 and the conserved –NN– α-conotoxin motif with β4 I77 and I109 conferred α3β4 activity to the otherwise inactive LsIA. Using these structural insights, we designed LsIA analogues with α3β4 activity. This new understanding of the structural basis of protein-protein interactions between α-conotoxins and α3β4 may help rationally guide the development of α3β4 selective antagonists with therapeutic potential.
Exposure to paternal tobacco smoking increased child hospitalization for lower respiratory infections but not for other diseases in Vietnam
Authors: Miyahara Reiko , Takahashi Kensuke , Anh Nguyen Thi Hien , Thiem Vu Dinh , Suzuki Motoi , Yoshino Hiroshi , Tho Le Huu , Moriuchi Hiroyuki , Cox Sharon E. , Yoshida Lay Myint , Anh Dang Duc , Ariyoshi Koya , Yasunami Michio 
Published: March 2017

AbstractExposure to environmental tobacco smoke (ETS) is an important modifiable risk factor for child hospitalization, although its contribution is not well documented in countries where ETS due to maternal tobacco smoking is negligible. We conducted a birth cohort study of 1999 neonates between May 2009 and May 2010 in Nha Trang, Vietnam, to evaluate paternal tobacco smoking as a risk factor for infectious and non-infectious diseases. Hospitalizations during a 24-month observation period were identified using hospital records. The effect of paternal exposure during pregnancy and infancy on infectious disease incidence was evaluated using Poisson regression models. In total, 35.6% of 1624 children who attended follow-up visits required at least one hospitalization by 2 years of age, and the most common reason for hospitalization was lower respiratory tract infection (LRTI). Paternal tobacco smoking independently increased the risk of LRTI 1.76-fold (95% CI: 1.24–2.51) after adjusting for possible confounders but was not associated with any other cause of hospitalization. The population attributable fraction indicated that effective interventions to prevent paternal smoking in the presence of children would reduce LRTI-related hospitalizations by 14.8% in this epidemiological setting.