bluuebunny/crossref_metadata_2025 huggingface dataset:
Modulation of gene transcription and epigenetics of colon carcinoma cells by bacterial membrane vesicles
Authors: Vdovikova Svitlana , Gilfillan Siv , Wang Shixiong , Dongre Mitesh , Wai Sun Nyunt , Hurtado Antoni
Published: May 2018

Interactions between bacteria and colon cancer cells influence the transcription of the host cell. Yet is it undetermined whether the bacteria itself or the communication between the host and bacteria is responsible for the genomic changes in the eukaryotic cell. Now, we have investigated the genomic and epigenetic consequences of co-culturing colorectal carcinoma cells with membrane vesicles from pathogenic bacteria Vibrio cholerae and non-pathogenic commensal bacteria Escherichia coli. Our study reveals that membrane vesicles from pathogenic and commensal bacteria have a global impact on the gene expression of colon-carcinoma cells. The changes in gene expression correlate positively with both epigenetic changes and chromatin accessibility of promoters at transcription start sites of genes induced by both types of membrane vesicles. Moreover, we have demonstrated that membrane vesicles obtained only from V. cholerae induced the expression of genes associated with epithelial cell differentiation. Altogether, our study suggests that the observed genomic changes in host cells might be due to specific components of membrane vesicles and do not require communication by direct contact with the bacteria.
Released Mitochondrial DNA Following Intestinal Ischemia Reperfusion Induces the Inflammatory Response and Gut Barrier Dysfunction
Authors: Hu Qiongyuan , Ren Huajian , Ren Jianan , Liu Qinjie , Wu Jie , Wu Xiuwen , Li Guanwei , Wang Gefei , Gu Guosheng , Guo Kun , Hong Zhiwu , Liu Song , Li Jieshou
Published: May 2018

Ischemia-reperfusion (I/R) injury is a challenging clinical problem, especially injuries involving the gastrointestinal tract. Mitochondrial DNA (mtDNA) is released upon cell death and stress, and can induce the inflammatory response. We aimed to investigate the role of mtDNA in the pathogenesis of intestinal I/R. Intestinal I/R model was established with clamping of the superior mesenteric artery, and IEC-6 cells were incubated under hypoxia/reoxygenation (H/R) conditions to simulate I/R injury. Using in vitro models, H/R up-regulated oxidative stress, disrupted mitochondrial activity and the mitochondrial membrane potential, induced apoptosis and elevated the mtDNA levels in the supernatant of intestinal epithelial cells, and the co-culture of mtDNA with human primary dendritic cells significantly elevated TLR9-MyD88 expression and enhanced the production of inflammatory cytokines and chemokines. MtDNA was also released in a mouse model of intestinal I/R and was associated with the increased secretion of inflammatory cytokines and increased gut barrier injury compared with that of the sham group. We concluded that mtDNA contributes to I/R injury and may serve as a biomarker of intestinal I/R. We further suggest that oxidized mtDNA originated from IECs during intestinal I/R exacerbates the acute proinflammatory process by eliciting the production of proinflammatory cytokines and chemokines.
Chronic stress of high dietary carbohydrate level causes inflammation and influences glucose transport through SOCS3 in Japanese flounder Paralichthys olivaceus
Authors: Deng Kangyu , Pan Mingzhu , Liu Jiahuan , Yang Mengxi , Gu Zhixiang , Zhang Yue , Liu Guangxia , Liu Dong , Zhang Wenbing , Mai Kangsen
Published: May 2018

Carnivorous fish is thought to be high-glucose intolerance. But the reasons were still unclear. The aim of the present study is to investigate the effects of high level of dietary carbohydrate on the survival, growth and immune responses of Paralichthys olivaceus, and the underlying molecular mechanism related to the immune and glucose metabolism. P. olivaceus were fed with 8%, 16% and 24% of dietary carbohydrate for 10 weeks, respectively. After that, a glucose tolerance test (GTT) was conducted. Results showed that excessive (24%) dietary carbohydrate significantly decreased the growth and glucose tolerance ability according to the GTT. It significantly increased hepatic NADPH oxidase activity and malondialdehyde content and serum contents of IL-6 and advanced glycation end products. The expressions of glucose transport-relevant genes in liver and the content of related hormones in serum were analyzed. In conclusion, it was confirmed that IL-6 increased the expression of suppressor of cytokine signaling 3 (SOCS3) and regulated the downstream targets of PI3K-AKT mediated signal transduction, and then downregulated the glucose transporter 2 activity in liver of P. olivaceus fed diet with excessive carbohydrate level. It was suggested that SOCS3 served as a bridge between immune response and glucose metabolism in P. olivaceus.
Identification and application of exogenous dsRNA confers plant protection against Sclerotinia sclerotiorum and Botrytis cinerea
Authors: McLoughlin Austein G. , Wytinck Nick , Walker Philip L. , Girard Ian J. , Rashid Khalid Y. , de Kievit Teresa , Fernando W. G. Dilantha , Whyard Steve , Belmonte Mark F.
Published: May 2018

Sclerotinia sclerotiorum, the causal agent of white stem rot, is responsible for significant losses in crop yields around the globe. While our understanding of S. sclerotiorum infection is becoming clearer, genetic control of the pathogen has been elusive and effective control of pathogen colonization using traditional broad-spectrum agro-chemical protocols are less effective than desired. In the current study, we developed species-specific RNA interference-based control treatments capable of reducing fungal infection. Development of a target identification pipeline using global RNA sequencing data for selection and application of double stranded RNA (dsRNA) molecules identified single gene targets of the fungus. Using this approach, we demonstrate the utility of this technology through foliar applications of dsRNAs to the leaf surface that significantly decreased fungal infection and S. sclerotiorum disease symptoms. Select target gene homologs were also tested in the closely related species, Botrytis cinerea, reducing lesion size and providing compelling evidence of the adaptability and flexibility of this technology in protecting plants against devastating fungal pathogens.
Self-reference and random sampling approach for label-free identification of DNA composition using plasmonic nanomaterials
Authors: Freeman Lindsay M. , Pang Lin , Fainman Yeshaiahu
Published: May 2018

The analysis of DNA has led to revolutionary advancements in the fields of medical diagnostics, genomics, prenatal screening, and forensic science, with the global DNA testing market expected to reach revenues of USD 10.04 billion per year by 2020. However, the current methods for DNA analysis remain dependent on the necessity for fluorophores or conjugated proteins, leading to high costs associated with consumable materials and manual labor. Here, we demonstrate a potential label-free DNA composition detection method using surface-enhanced Raman spectroscopy (SERS) in which we identify the composition of cytosine and adenine within single strands of DNA. This approach depends on the fact that there is one phosphate backbone per nucleotide, which we use as a reference to compensate for systematic measurement variations. We utilize plasmonic nanomaterials with random Raman sampling to perform label-free detection of the nucleotide composition within DNA strands, generating a calibration curve from standard samples of DNA and demonstrating the capability of resolving the nucleotide composition. The work represents an innovative way for detection of the DNA composition within DNA strands without the necessity of attached labels, offering a highly sensitive and reproducible method that factors in random sampling to minimize error.
Complete mitochondrial and rDNA complex sequences of important vector species of Biomphalaria, obligatory hosts of the human-infecting blood fluke, Schistosoma mansoni
Authors: Zhang Si-Ming , Bu Lijing , Laidemitt Martina R. , Lu Lijun , Mutuku Martin W. , Mkoji Gerald M. , Loker Eric S.
Published: May 2018

Using high throughput Illumina sequencing technology, we determined complete sequences for the mitochondrial genome (mitogenome) and nuclear ribosomal DNA (rDNA) complex for three African freshwater snail taxa within the genusBiomphalaria,B. pfeifferi,B. sudanicaandB. choanomphala, and for two laboratory strains ofB. glabrataoriginating from the Neotropics.Biomphalariasnails are obligate vectors of the blood flukeSchistosoma mansoni, a major etiologic agent of human intestinal schistosomiasis. Our data show that mitogenomes from African and NeotropicalBiomphalariaare highly conserved. With respect to rDNA, the two internal transcribed spacers (ITS1 and 2) were found to be highly variable whereas the three ribosomal RNA genes (28S, 5.8S and 18S rRNA) exhibited no or very limited variation. Our analyses reveal that the two taxa inhabiting Lake Victoria,B. sudanicaandB. choanomphala, are very similar to one another relative to the similarity either shows toB. pfeifferiorB. glabrata. This new sequence information may prove useful for developing new markers for snail identification, environmental detection/monitoring purposes or for tracking epidemiology and snail dependencies ofS. mansoniin endemic areas. It also provides new information pertinent to still unresolved questions inBiomphalariasystematics and nomenclature.
Acquisition and dissemination of cephalosporin-resistant E. coli in migratory birds sampled at an Alaska landfill as inferred through genomic analysis
Authors: Ahlstrom Christina A. , Bonnedahl Jonas , Woksepp Hanna , Hernandez Jorge , Olsen Björn , Ramey Andrew M.
Published: May 2018

Antimicrobial resistance (AMR) in bacterial pathogens threatens global health, though the spread of AMR bacteria and AMR genes between humans, animals, and the environment is still largely unknown. Here, we investigated the role of wild birds in the epidemiology of AMR Escherichia coli. Using next-generation sequencing, we characterized cephalosporin-resistant E. coli cultured from sympatric gulls and bald eagles inhabiting a landfill habitat in Alaska to identify genetic determinants conferring AMR, explore potential transmission pathways of AMR bacteria and genes at this site, and investigate how their genetic diversity compares to isolates reported in other taxa. We found genetically diverse E. coli isolates with sequence types previously associated with human infections and resistance genes of clinical importance, including blaCTX-M and blaCMY. Identical resistance profiles were observed in genetically unrelated E. coli isolates from both gulls and bald eagles. Conversely, isolates with indistinguishable core-genomes were found to have different resistance profiles. Our findings support complex epidemiological interactions including bacterial strain sharing between gulls and bald eagles and horizontal gene transfer among E. coli harboured by birds. Results suggest that landfills may serve as a source for AMR acquisition and/or maintenance, including bacterial sequence types and AMR genes relevant to human health.
Delayed and progressive damages to juvenile mice after moderate traumatic brain injury
Authors: Zhao Shu , Wang Xiaoting , Gao Xiang , Chen Jinhui
Published: May 2018

Symptoms are commonly more severe in pediatric traumatic brain injury (TBI) patients than in young adult TBI patients. To understand the mechanism, juvenile mice received a controlled cortical impact (CCI) injury at moderate level. Tissue lesion and cell death were measured and compared to our previous reports on brain injury in the young adult mice that received same level of impact using same injury device. Tissue lesion and cell death in the cortex was much less in the juvenile mouse brain in the first few hours after injury. However, once the injury occurred, it developed more rapidly, lasted much longer, and eventually led to exaggerated cell death and a 32.7% larger tissue lesion cavity in the cortex of juvenile mouse brain than of young adult mouse brain. Moreover, we found significant cell death in the thalamus of juvenile brains at 72 h, which was not commonly seen in the young adult mice. In summary, cell death in juvenile mice was delayed, lasted longer, and finally resulted in more severe brain injury than in the young adult mice. The results suggest that pediatric TBI patients may have a longer therapeutic window, but they also need longer intensive clinical care after injury.
Long-lived monolithic micro-optics for multispectral GRIN applications
Authors: Lepicard Antoine , Bondu Flavie , Kang Myungkoo , Sisken Laura , Yadav Anupama , Adamietz Frederic , Rodriguez Vincent , Richardson Kathleen , Dussauze Marc
Published: May 2018

The potential for realizing robust, monolithic, near-surface refractive micro-optic elements with long-lived stability is demonstrated in visible and infrared transmitting glasses capable of use in dual band applications. Employing an enhanced understanding of glass chemistry and geometric control of mobile ion migration made possible with electrode patterning, flat, permanent, thermally-poled micro-optic structures have been produced and characterized. Sub-surface (t~5–10 µm) compositional and structural modification during the poling process results in formation of spatially-varying refractive index profiles, exhibiting induced Δn changes up to 5 × 10−2which remain stable for >15 months. The universality of this approach applied to monolithic vis-near infrared [NIR] oxide and NIR-midwave infrared [MIR] chalcogenide glass materials is demonstrated for the first time. Element size, shape and gradient profile variation possible through pattern design and fabrication is shown to enable a variety of design options not possible using other GRIN process methodologies.
Reprogramming, oscillations and transdifferentiation in epigenetic landscapes
Authors: Kaity Bivash , Sarkar Ratan , Chakrabarti Buddhapriya , Mitra Mithun K.
Published: May 2018

Waddington’s epigenetic landscape provides a phenomenological understanding of the cell differentiation pathways from the pluripotent to mature lineage-committed cell lines. In light of recent successes in the reverse programming process there has been significant interest in quantifying the underlying landscape picture through the mathematics of gene regulatory networks. We investigate the role of time delays arising from multi-step chemical reactions and epigenetic rearrangement on the cell differentiation landscape for a realistic two-gene regulatory network, consisting of self-promoting and mutually inhibiting genes. Our work provides the first theoretical basis of the transdifferentiation process in the presence of delays, where one differentiated cell type can transition to another directly without passing through the undifferentiated state. Additionally, the interplay of time-delayed feedback and a time dependent chemical drive leads to long-lived oscillatory states in appropriate parameter regimes. This work emphasizes the important role played by time-delayed feedback loops in gene regulatory circuits and provides a framework for the characterization of epigenetic landscapes.
Classical and alternative complement activation on photoreceptor outer segments drives monocyte-dependent retinal atrophy
Authors: Katschke Kenneth J. , Xi Hongkang , Cox Christian , Truong Tom , Malato Yann , Lee Wyne P. , McKenzie Brent , Arceo Rommel , Tao Jianhua , Rangell Linda , Reichelt Mike , Diehl Lauri , Elstrott Justin , Weimer Robby M , van Lookeren Campagne Menno
Published: May 2018

Geographic atrophy (GA), the advanced form of dry age-related macular degeneration (AMD), is characterized by progressive loss of retinal pigment epithelium cells and photoreceptors in the setting of characteristic extracellular deposits and remains a serious unmet medical need. While genetic predisposition to AMD is dominated by polymorphisms in complement genes, it remains unclear how complement activation contributes to retinal atrophy. Here we demonstrate that complement is activated on photoreceptor outer segments (POS) in the retina peripheral to atrophic lesions associated with GA. When exposed to human serum following outer blood-retinal barrier breakdown, POS act as potent activators of the classical and alternative complement pathway. In mouse models of retinal degeneration, classical and alternative pathway complement activation on photoreceptors contributed to the loss of photoreceptor function. This was dependent on C5a-mediated recruitment of peripheral blood monocytes but independent of resident microglia. Genetic or pharmacologic inhibition of both classical and alternative complement C3 and C5 convertases was required to reduce progressive degeneration of photoreceptor rods and cones. Our study implicates systemic classical and alternative complement proteins and peripheral blood monocytes as critical effectors of localized retinal degeneration with potential relevance for the contribution of complement activation to GA.
Mesoscale eddies influence the movements of mature female white sharks in the Gulf Stream and Sargasso Sea
Authors: Gaube Peter , Braun Camrin D. , Lawson Gareth L. , McGillicuddy Dennis J. , Penna Alice Della , Skomal Gregory B. , Fischer Chris , Thorrold Simon R.
Published: May 2018

Satellite-tracking of mature white sharks (Carcharodon carcharias) has revealed open-ocean movements spanning months and covering tens of thousands of kilometers. But how are the energetic demands of these active apex predators met as they leave coastal areas with relatively high prey abundance to swim across the open ocean through waters often characterized as biological deserts? Here we investigate mesoscale oceanographic variability encountered by two white sharks as they moved through the Gulf Stream region and Sargasso Sea in the North Atlantic Ocean. In the vicinity of the Gulf Stream, the two mature female white sharks exhibited extensive use of the interiors of clockwise-rotating anticyclonic eddies, characterized by positive (warm) temperature anomalies. One tagged white shark was also equipped with an archival tag that indicated this individual made frequent dives to nearly 1,000 m in anticyclones, where it was presumably foraging on mesopelagic prey. We propose that warm temperature anomalies in anticyclones make prey more accessible and energetically profitable to adult white sharks in the Gulf Stream region by reducing the physiological costs of thermoregulation in cold water. The results presented here provide valuable new insight into open ocean habitat use by mature, female white sharks that may be applicable to other large pelagic predators.
Magnetic Mesoporous Calcium Sillicate/Chitosan Porous Scaffolds for Enhanced Bone Regeneration and Photothermal-Chemotherapy of Osteosarcoma
Authors: Yang Fan , Lu Jiawei , Ke Qinfei , Peng Xiaoyuan , Guo Yaping , Xie Xuetao
Published: May 2018

The development of multifunctional biomaterials to repair bone defects after neoplasm removal and inhibit tumor recurrence remained huge clinical challenges. Here, we demonstrate a kind of innovative and multifunctional magnetic mesoporous calcium sillicate/chitosan (MCSC) porous scaffolds, made of M-type ferrite particles (SrFe12O19), mesoporous calcium silicate (CaSiO3) and chitosan (CS), which exert robust anti-tumor and bone regeneration properties. The mesopores in the CaSiO3 microspheres contributed to the drug delivery property, and the SrFe12O19 particles improved photothermal therapy (PTT) conversion efficacy. With the irradiation of NIR laser, doxorubicin (DOX) was rapidly released from the MCSC/DOX scaffolds. In vitro and in vivo tests demonstrated that the MCSC scaffolds possessed the excellent anti-tumor efficacy via the synergetic effect of DOX drug release and hyperthermia ablation. Moreover, BMP-2/Smad/Runx2 pathway was involved in the MCSC scaffolds promoted proliferation and osteogenic differentiation of human bone marrow stromal cells (hBMSCs). Taken together, the MCSC scaffolds have the ability to promote osteogenesis and enhance synergetic photothermal-chemotherapy against osteosarcoma, indicating MCSC scaffolds may have great application potential for bone tumor-related defects.
Contrasting roles for actin in the cellular uptake of cell penetrating peptide conjugates
Authors: He L. , Sayers E. J. , Watson P. , Jones A. T.
Published: May 2018

The increased need for macromolecular therapeutics, such as peptides, proteins and nucleotides, to reach intracellular targets necessitates more effective delivery vectors and a higher level of understanding of their mechanism of action. Cell penetrating peptides (CPPs) can transport a range of macromolecules into cells, either through direct plasma membrane translocation or endocytosis. All known endocytic pathways involve cell-cortex remodelling, a process shown to be regulated by reorganisation of the actin cytoskeleton. Here using flow cytometry, confocal microscopy and a variety of actin inhibitors we identify how actin disorganisation in different cell types differentially influences the cellular entry of three probes: the CPP octaarginine – Alexa488 conjugate (R8-Alexa488), octaarginine conjugated Enhanced Green Fluorescent Protein (EGFP-R8), and the fluid phase probe dextran. Disrupting actin organisation in A431 skin epithelial cells dramatically increases the uptake of EGFP-R8 and dextran, and contrasts strongly to inhibitory effects observed with transferrin and R8 attached to the fluorophore Alexa488. This demonstrates that uptake of the same CPP can occur via different endocytic processes depending on the conjugated fluorescent entity. Overall this study highlights how cargo influences cell uptake of this peptide and that the actin cytoskeleton may act as a gateway or barrier to endocytosis of drug delivery vectors.
Adeno-associated virus 2/9 delivery of Cre recombinase in mouse primary afferents
Authors: Abdallah Khaled , Nadeau Francis , Bergeron Francis , Blouin Sylvie , Blais Véronique , Bradbury Kelly M. , Lavoie Christine L. , Parent Jean-Luc , Gendron Louis
Published: May 2018

Genetically-modified animal models have significantly increased our understanding of the complex central nervous system circuits. Among these models, inducible transgenic mice whose specific gene expression can be modulated through a Cre recombinase/LoxP system are useful to study the role of specific peptides and proteins in a given population of cells. In the present study, we describe an efficient approach to selectively deliver a Cre-GFP to dorsal root ganglia (DRG) neurons. First, mice of different ages were injected in both hindpaws with a recombinant adeno-associated virus (rAAV2/9-CBA-Cre-GFP). Using this route of injection in mice at 5 days of age, we report that approximately 20% of all DRG neurons express GFP, 6 to 8 weeks after the infection. The level of infection was reduced by 50% when the virus was administered at 2 weeks of age. Additionally, the virus-mediated delivery of the Cre-GFP was also investigated via the intrathecal route. When injected intrathecally, the rAAV2/9-CBA-Cre-GFP virus infected a much higher proportion of DRG neurons than the intraplantar injection, with up to 51.6% of infected lumbar DRG neurons. Noteworthy, both routes of injection predominantly transduced DRG neurons over spinal and brain neurons.
Enhancement of magnetic properties through morphology control of SrFe12O19 nanocrystallites
Authors: Eikeland Anna Zink , Stingaciu Marian , Mamakhel Aref Hasen , Saura-Múzquiz Matilde , Christensen Mogens
Published: May 2018

Nanocrystallites of the permanent magnetic material SrFe12O19 were synthesised using a conventional sol-gel (CSG) and a modified sol-gel (MSG) synthesis route. In the MSG synthesis, crystallite growth takes place in a solid NaCl matrix, resulting in freestanding nanocrystallites, as opposed to the CSG synthesis, where the produced nanocrystals are strongly intergrown. The resulting nanocrystallites from both methods exhibit similar intrinsic magnetic properties, but significantly different morphology and degree of aggregation. The nanocrystallites were compacted into dense pellets using a Spark Plasma Sintering (SPS) press, this allows investigating the influence of crystallite morphology and the alignment of the nanocrystallites on the magnetic performance. A remarkable correlation was observed between the crystallites morphology and their ability to align in the compaction process. Consequently, a significant enhancement of the maximum energy product was obtained after SPS for the MSG prepared sample (22.0 kJ/m3), compared to CSG sample, which achieved an energy product of 11.6 kJ/m3.
A double helical motif in OCIAD2 is essential for its localization, interactions and STAT3 activation
Authors: Sinha Saloni , Bheemsetty Venkata Anudeep , Inamdar Maneesha S.
Published: May 2018

The Ovarian Carcinoma Immunoreactive Antigen domain (OCIAD) - containing proteins OCIAD1/Asrij and OCIAD2, are implicated in several cancers and neurodegenerative diseases. While Asrij has a conserved role in facilitating STAT3 activation for JAK/STAT signaling, the expression and function of OCIAD2 in non-cancerous contexts remains unknown. Here, we report thatociad2neighborsociad1/asrijin most vertebrate genomes, and the two genes likely arose by tandem gene duplication, probably somewhere between the Ordovician and Silurian eras. We show thatociad2expression is higher in the mouse kidney, liver and brain relative to other tissues. OCIAD2 localizes to early endosomes and mitochondria, and interacts with Asrij and STAT3. Knockdown and overexpression studies showed that OCIAD2 is essential for STAT3 activation and cell migration, which could contribute to its role in tumor metastasis. Structure prediction programs, protein disruption studies, biochemical and functional assays revealed a double helical motif in the OCIA domain that is necessary and sufficient for its localization, interactions and STAT3 activation. Given the importance of JAK/STAT signaling in development and disease, our studies shed light on the evolution and conserved function of the OCIA domain in regulating this pathway and will be critical for understanding this clinically important protein family.
Morphoregulatory functions of the RNA-binding motif protein 3 in cell spreading, polarity and migration
Authors: Pilotte J. , Kiosses W. , Chan S. W. , Makarenkova H. P. , Dupont-Versteegden E. , Vanderklish P. W.
Published: May 2018

RNA-binding proteins are emerging as key regulators of transitions in cell morphology. The RNA-binding motif protein 3 (RBM3) is a cold-inducible RNA-binding protein with broadly relevant roles in cellular protection, and putative functions in cancer and development. Several findings suggest that RBM3 has morphoregulatory functions germane to its roles in these contexts. For example, RBM3 helps maintain the morphological integrity of cell protrusions during cell stress and disease. Moreover, it is highly expressed in migrating neurons of the developing brain and in cancer invadopodia, suggesting roles in migration. We here show that RBM3 regulates cell polarity, spreading and migration. RBM3 was present in spreading initiation centers, filopodia and blebs that formed during cell spreading in cell lines and primary myoblasts. Reducing RBM3 triggered exaggerated spreading, increased RhoA expression, and a loss of polarity that was rescued by Rho kinase inhibition and overexpression of CRMP2. High RBM3 expression enhanced the motility of cells migrating by a mesenchymal mode involving extension of long protrusions, whereas RBM3 knockdown slowed migration, greatly reducing the ability of cells to extend protrusions and impairing multiple processes that require directional migration. These data establish novel functions of RBM3 of potential significance to tissue repair, metastasis and development.
Influences of climate change on area variation of Qinghai Lake on Qinghai-Tibetan Plateau since 1980s
Authors: Tang Lingyi , Duan Xiaofang , Kong Fanjin , Zhang Fan , Zheng Yangfan , Li Zhen , Mei Yi , Zhao Yanwen , Hu Shuijin
Published: May 2018

Qinghai-Tibetan Plateau is the most sensitive region to global warming on Earth. Qinghai Lake, the largest lake on the plateau, has experienced evident area variation during the past several decades. To quantify the area changes of Qinghai Lake, a satellite-based survey based on Landsat images from the 1980s to 2010s has been performed. In addition, meteorological data from all the seven available stations on Qinghai-Tibetan Plateau has been analyzed. Area of Qinghai Lake shrank ~2% during 1987–2005, and then increased ~3% from 2005–2016. Meanwhile, the average annual temperature increased 0.319 °C/10 y in the past 50 years, where the value is 0.415 °C/10 y from 2005–2016. The structural equation modeling (SEM) shows that precipitation is the primary factor influencing the area of Qinghai Lake. Moreover, temperature might be tightly correlated with precipitation, snow line, and evaporation, thereby indirectly causes alternations of the lake area. This study elucidated the significant area variation of water body on the Qinghai-Tibetan Plateau under global warming since 1980s.
Unravelling the secret of seed-based gels in water: the nanoscale 3D network formation
Authors: Samateh Malick , Pottackal Neethu , Manafirasi Setareh , Vidyasagar Adiyala , Maldarelli Charles , John George
Published: May 2018

Chia (Salvia hispanica) and basil (Ocimum basilicum) seeds have the intrinsic ability to form a hydrogel concomitant with moisture-retention, slow releasing capability and proposed health benefits such as curbing diabetes and obesity by delaying digestion process. However, the underlying mode of gelation at nanoscopic level is not clearly explained or explored. The present study elucidates and corroborates the hypothesis that the gelling behavior of such seeds is due to their nanoscale 3D-network formation. The preliminary study revealed the influence of several conditions like polarity, pH and hydrophilicity/hydrophobicity on fiber extrusion from the seeds which leads to gelation. Optical microscopic analysis clearly demonstrated bundles of fibers emanating from the seed coat while in contact with water, and live growth of fibers to form 3D network. Scanning electron microscope (SEM) and transmission electron microscope (TEM) studies confirmed 3D network formation with fiber diameters ranging from 20 to 50 nm.
The impacts of the quantum-dot confining potential on the spin-orbit effect
Authors: Li Rui , Liu Zhi-Hai , Wu Yidong , Liu C. S.
Published: May 2018

For a nanowire quantum dot with the confining potential modeled by both the infinite and the finite square wells, we obtain exactly the energy spectrum and the wave functions in the strong spin-orbit coupling regime. We find that regardless of how small the well height is, there are at least two bound states in the finite square well: one has the σ
x
$${\mathscr{P}}$$
P
 = −1 symmetry and the other has the σ
x
$${\mathscr{P}}$$
P
 = 1 symmetry. When the well height is slowly tuned from large to small, the position of the maximal probability density of the first excited state moves from the center to x ≠ 0, while the position of the maximal probability density of the ground state is always at the center. A strong enhancement of the spin-orbit effect is demonstrated by tuning the well height. In particular, there exists a critical height $${V}_{0}^{c}$$

V

0

c

, at which the spin-orbit effect is enhanced to maximal.
Detection of Recent Myocardial Infarction Using Native T1 Mapping in a Swine Model: A Validation Study
Authors: Cui Chen , Wang Shuli , Lu Minjie , Duan Xuejing , Wang Hongyue , Jia Liujun , Tang Yue , Sirajuddin Arlene , Prasad Sanjay K. , Kellman Peter , Arai Andrew E. , Zhao Shihua
Published: May 2018

Late gadolinium enhancement (LGE) imaging is the currently the gold standard for in-vivo detection of myocardial infarction. However, gadolinium contrast administration is contraindicated in patients with renal insufficiency. We aim to evaluate the diagnostic sensitivity and specificity of this contrast-free MRI technique, native T1 mapping, in detecting recent myocardial infarction versus a reference histological gold standard. Ten pigs underwent CMR at 2 weeks after induced MI. The infarct size and transmural extent of MI was calculated using native T1 maps and LGE images. Histological validation was performed using triphenyl tetrazolium chloride (TTC) staining in the corresponding ex-vivo slices. The infarct size and transmural extent of myocardial infarction assessed by T1 mapping correlated well with that assessed by LGE and TTC images. Using TTC staining as the reference, T1 mapping demonstrated underestimation of infarct size and transmural extent of infarction. Additionally, there was a slight but not significant difference found in the diagnostic performance between the native T1 maps and LGE images for the location of MI. Our study shows that native T1 mapping is feasible alternative method to the LGE technique for the assessment of the size, transmural extent, and location of MI in patients who cannot receive gadolinium contrast.
Disruption of neonatal cardiomyocyte physiology following exposure to bisphenol-a
Authors: Ramadan Manelle , Sherman Meredith , Jaimes Rafael , Chaluvadi Ashika , Swift Luther , Posnack Nikki Gillum
Published: May 2018

Bisphenol chemicals are commonly used in the manufacturing of polycarbonate plastics, polyvinyl chloride plastics, resins, and thermal printing applications. Humans are inadvertently exposed to bisphenols through contact with consumer products and/or medical devices. Recent reports have shown a link between bisphenol-a (BPA) exposure and adverse cardiovascular outcomes; although these studies have been limited to adult subjects and models. Since cardiac physiology differs significantly between the developing and adult heart, we aimed to assess the impact of BPA exposure on cardiac function, using a neonatal cardiomyocyte model. Neonatal rat ventricular myocytes were monitored to assess cell viability, spontaneous beating rate, beat rate variability, and calcium-handling parameters in the presence of control or bisphenol-supplemented media. A range of doses were tested to mimic environmental exposure (10−9–10−8M), maximum clinical exposure (10−5M), and supraphysiological exposure levels (10−4M). Acute BPA exposure altered cardiomyocyte functionality, resulting in a slowed spontaneous beating rate and increased beat rate variability. BPA exposure also impaired intracellular calcium handling, resulting in diminished calcium transient amplitudes, prolonged calcium transient upstroke and duration time. Alterations in calcium handling also increased the propensity for alternans and skipped beats. Notably, the effect of BPA-treatment on calcium handling was partially reversible. Our data suggest that acute BPA exposure could precipitate secondary adverse effects on contractile performance and/or electrical alternans, both of which are dependent on intracellular calcium homeostasis.
The Protease Activated Receptor2 Promotes Rab5a Mediated Generation of Pro-metastatic Microvesicles
Authors: Das Kaushik , Prasad Ramesh , Roy Sreetama , Mukherjee Ashis , Sen Prosenjit
Published: May 2018

Metastasis, the hallmark of cancer propagation is attributed by the modification of phenotypic/functional behavior of cells to break attachment and migrate to distant body parts. Cancer cell-secreted microvesicles (MVs) contribute immensely in disease propagation. These nano-vesicles, generated from plasma membrane outward budding are taken up by nearby healthy cells thereby inducing phenotypic alterations in those recipient cells. Protease activated receptor 2 (PAR2), activated by trypsin, also contributes to cancer progression by increasing metastasis, angiogenesis etc. Here, we report that PAR2 activation promotes pro-metastatic MVs generation from human breast cancer cell line, MDA-MB-231. Rab5a, located at the plasma membrane plays vital roles in MVs biogenesis. We show that PAR2 stimulation promotes AKT phosphorylation which activates Rab5a by converting inactive Rab5a-GDP to active Rab5a-GTP. Active Rab5a polymerizes actin which critically regulates MVs shedding. Not only MVs generation, has this Rab5a activation also promoted cell migration and invasion. We reveal that Rab5a is over-expressed in human breast tumor specimen and contributes MVs generation in those patients. The involvement of p38 MAPK in MVs-induced cell metastasis has also been highlighted in the present study. Blockade of Rab5a activation can be a potential therapeutic approach to restrict MVs shedding and associated breast cancer metastasis.
The protein kinase CK2 catalytic domain from Plasmodium falciparum: crystal structure, tyrosine kinase activity and inhibition
Authors: Ruiz-Carrillo David , Lin Jianqing , El Sahili Abbas , Wei Meng , Sze Siu Kwan , Cheung Peter C. F. , Doerig Christian , Lescar Julien
Published: May 2018

Malaria causes every year over half-a-million deaths. The emergence of parasites resistant to available treatments makes the identification of new targets and their inhibitors an urgent task for the development of novel anti-malaria drugs. Protein kinase CK2 is an evolutionary-conserved eukaryotic serine/threonine protein kinase that in Plasmodium falciparum (PfCK2) has been characterized as a promising target for chemotherapeutic intervention against malaria. Here we report a crystallographic structure of the catalytic domain of PfCK2α (D179S inactive single mutant) in complex with ATP at a resolution of 3.0 Å. Compared to the human enzyme, the structure reveals a subtly altered ATP binding pocket comprising five substitutions in the vicinity of the adenine base, that together with potential allosteric sites, could be exploited to design novel inhibitors specifically targeting the Plasmodium enzyme. We provide evidence for the dual autophosphorylation of residues Thr63 and Tyr30 of PfCK2. We also show that CX4945, a human CK2 inhibitor in clinical trials against solid tumor cancers, is effective against PfCK2 with an IC50 of 13.2 nM.
Heart rate variability is associated with social value orientation in males but not females
Authors: Lischke Alexander , Mau-Moeller Anett , Jacksteit Robert , Pahnke Rike , Hamm Alfons O. , Weippert Matthias
Published: May 2018

Phylogenetic and neurobiological theories suggest that inter-individual differences in high frequency heart rate variability (HF-HRV) are associated with inter-individual differences in social behavior and social cognition. To test these theories, we investigated whether individuals with high and low HF-HRV would show different preferences for cooperative behavior in social contexts. We recorded resting state HF-HRV in 84 healthy individuals before they completed the Social Value Orientation task, a well-established measure of cooperative preferences. HF-HRV was derived from short-term (300 s) and ultra-short-term (60 s, 120 s) recordings of participants’ heart rate to determine the robustness of possible findings. Irrespective of recording length, we found a sex-dependent association between inter-individual differences in HF-HRV and inter-individual differences in social value orientation: The preference for cooperation was more pronounced among individuals with high as compared low HF-HRV, albeit only in male and not in female participants. These findings suggest that males with high HF-HRV are more inclined to engage in cooperative behavior than males with low HF-HRV.
Synchronisation of parental behaviours reduces the risk of nest predation in a socially monogamous passerine bird
Authors: Leniowski K. , Węgrzyn E.
Published: May 2018

Social monogamy with bi-parental care is the most common breeding pattern in birds, yet cooperation between mates has not been intensively studied to date. In this study we investigate synchronisation of parental behaviours in the blackcap Sylvia atricapilla, a species characterized by bi-parental care and high nest predation. We test the hypothesis that mates synchronize their behaviours to decrease total activity at the nest, which is known to affect predation rate in birds. We examine if blackcap parents synchronise their feeding trips more when nestlings are at the poikilothermic stage, and they may be more vulnerable to nest predation due to their inability to escape and survive outside the nest without parental brooding. We also investigate the alternation of feeding trips by parents. We show that blackcap parents synchronise the majority of their feeding trips during the whole nestling period, and the level of parental synchrony is higher before nestlings develop endothermy. The alternation of male and female feeding trips was much higher than would be expected by chance and was positively related to parental synchrony. We have demonstrated that synchronisation of parental feeding trips significantly decreased parental activity at the nest, and nest survival time increased with the synchrony of parental feeding trips.
A TPMS-based method for modeling porous scaffolds for bionic bone tissue engineering
Authors: Shi Jianping , Zhu Liya , Li Lan , Li Zongan , Yang Jiquan , Wang Xingsong
Published: May 2018

In the field of bone defect repair, gradient porous scaffolds have received increased attention because they provide a better environment for promoting tissue regeneration. In this study, we propose an effective method to generate bionic porous scaffolds based on the TPMS (triply periodic minimal surface) and SF (sigmoid function) methods. First, cortical bone morphological features (e.g., pore size and distribution) were determined for several regions of a rabbit femoral bone by analyzing CT-scans. A finite element method was used to evaluate the mechanical properties of the bone at these respective areas. These results were used to place different TPMS substructures into one scaffold domain with smooth transitions. The geometrical parameters of the scaffolds were optimized to match the elastic properties of a human bone. With this proposed method, a functional gradient porous scaffold could be designed and produced by an additive manufacturing method.
Synergistic effect of renalase and chronic kidney disease on endothelin-1 in patients with coronary artery disease ‒ a cross-sectional study
Authors: Li Yu-Hsuan , Sheu Wayne Huey-Herng , Lee Wen-Jane , Wang Jun -Sing , Fu Chia-Po , Liang Kae-Woei , Lee I-Te
Published: May 2018

Endothelin-1 (ET-1) is associated with endothelial dysfunction and vasoconstriction. Increased circulating ET-1 levels are associated with long-term cardiovascular mortality. Renalase, released from kidney, metabolizes catecholamines and regulates blood pressure. An increase in circulating renalase levels has been reported in patients with chronic kidney disease (CKD) and is associated with coronary artery disease (CAD). We hypothesized the existence of a synergistic effect of serum renalase levels and CKD on ET-1 levels in patients with CAD. We evaluated 342 non-diabetic patients with established CAD. ET-1 and renalase levels were measured in all patients after an overnight fast. Patients with CKD had higher ET-1 (1.95 ± 0.77 vs. 1.62 ± 0.76 pg/ml, P < 0.001) and renalase levels (46.8 ± 17.1 vs. 33.9 ± 9.9 ng/ml, P < 0.001) than patients without CKD. Patients with both CKD and high renalase levels (>the median of 36.2 ng/ml) exhibited the highest serum ET-1 (P value for the trend <0.001). According to multivariate linear regression analysis, the combination of high serum renalase levels with CKD was a significant risk factor for increased serum ET-1 levels (regression coefficient = 0.297, 95% confidence interval = 0.063‒0.531, P = 0.013). In conclusion, our data suggest a synergistic effect of high serum renalase levels and CKD on increases in ET-1 levels in patients with established CAD.
Identifying Suicide Ideation and Suicidal Attempts in a Psychiatric Clinical Research Database using Natural Language Processing
Authors: Fernandes Andrea C. , Dutta Rina , Velupillai Sumithra , Sanyal Jyoti , Stewart Robert , Chandran David
Published: May 2018

Research into suicide prevention has been hampered by methodological limitations such as low sample size and recall bias. Recently, Natural Language Processing (NLP) strategies have been used with Electronic Health Records to increase information extraction from free text notes as well as structured fields concerning suicidality and this allows access to much larger cohorts than previously possible. This paper presents two novel NLP approaches – a rule-based approach to classify the presence of suicide ideation and a hybrid machine learning and rule-based approach to identify suicide attempts in a psychiatric clinical database. Good performance of the two classifiers in the evaluation study suggest they can be used to accurately detect mentions of suicide ideation and attempt within free-text documents in this psychiatric database. The novelty of the two approaches lies in the malleability of each classifier if a need to refine performance, or meet alternate classification requirements arises. The algorithms can also be adapted to fit infrastructures of other clinical datasets given sufficient clinical recording practice knowledge, without dependency on medical codes or additional data extraction of known risk factors to predict suicidal behaviour.
Growth of ‘W’ doped molybdenum disulfide on graphene transferred molybdenum substrate
Authors: Asokan Vijayshankar , Zhu Dancheng , Huang Wei , Wang Hulian , Gao Wandong , Zhang Ze , Jin Chuanhong
Published: May 2018

In the present study, a novel method has been carried out to grow tungsten (W) doped molybdenum disulfide (MoS2) on the graphene transferred TEM grid in a chemical vapor deposition (CVD) setup. Tungsten trioxide (WO3) has been used as a source for ‘W’ while ‘Mo’ has been derived from Mo based substrate. Different experimental parameters were used in this experiment. Higher gas flow rate decreases the size of the sample flake and on other side increases the dopant concentrations. The interaction mechanism between Mo, S, W and oxygen (O) have been explored. The influence of oxygen seems to be not avoidable completely which also imposes effective growth condition for the reaction of Mo with incoming sulfur atoms. The difference in the migration energies of Mo, WO3, S clusters on the graphene and the higher reactivity of Mo clusters over other possibly formed atomic clusters on the graphene leads to the growth of W doped MoS2 monolayers. Formation of MoS2 monolayer and the nature of edge doping of ‘W’ is explained well with the crystal model using underlying nucleation principles. We believe our result provide a special route to prepare W doped MoS2 on graphene substrate in the future.