bluuebunny/crossref_metadata_2025 huggingface dataset:
Emerging Concepts and Functions of Autophagy as a Regulator of Synaptic Components and Plasticity
Authors: Liang YongTian
Published: January 2019

Protein homeostasis (proteostasis) is crucial to the maintenance of neuronal integrity and function. As the contact sites between neurons, synapses rely heavily on precisely regulated protein-protein interactions to support synaptic transmission and plasticity processes. Autophagy is an effective degradative pathway that can digest cellular components and maintain cellular proteostasis. Perturbations of autophagy have been implicated in aging and neurodegeneration due to a failure to remove damaged proteins and defective organelles. Recent evidence has demonstrated that autophagosome formation is prominent at synaptic terminals and neuronal autophagy is regulated in a compartment-specific fashion. Moreover, synaptic components including synaptic proteins and vesicles, postsynaptic receptors and synaptic mitochondria are known to be degraded by autophagy, thereby contributing to the remodeling of synapses. Indeed, emerging studies indicate that modulation of autophagy may be required for different forms of synaptic plasticity and memory formation. In this review, I will discuss our current understanding of the important role of neuronal/synaptic autophagy in maintaining neuronal function by degrading synaptic components and try to propose a conceptual framework of how the degradation of synaptic components via autophagy might impact synaptic function and contribute to synaptic plasticity.
Generation and Transport of Magnetic Flux in Accretion–Ejection Flows
Authors: Contopoulos Ioannis
Published: January 2019

Astrophysical accretion flows are associated with energetic emission of radiation and outflows (winds and jets). Extensive observations of these two processes in X-ray binary outbursts are available. A convincing understanding of their dynamics remains, however, elusive. The main agent that controls the dynamics is believed to be a large scale magnetic field that threads the system. We propose that during the quiescent state, the field is held in place by a delicate balance between inward advection and outward diffusion through the accreting matter. We also propose that the source of the field is a growing toroidal electric current generated by the aberrated radiation pressure on the innermost plasma electrons in orbit around the central black hole. This is the astrophysical mechanism of the Cosmic Battery. When the return magnetic field outside the toroidal electric current diffuses through the surrounding disk, the disk magnetic field and its associated accretion rate gradually increase, thus leading the system to an outburst. After the central accretion flow approaches equipartition with radiation, it is disrupted, and the Cosmic Battery ceases to operate. The outward field diffusion is then reversed, magnetic flux reconnects with the flux accumulated around the central black hole and disappears. The magnetic field and the associated accretion rate slowly decrease, and the system is gradually driven back to quiescence. We conclude that the action (or inaction) of the Cosmic Battery may be the missing key that will allow us to understand the long-term evolution of astrophysical accretion–ejection flows.
Under-Recognition of Fractures as Osteoporosis Indicators
Authors: Lagari Violet S. , Al-Yatama Fatima , Rodriguez Gracielena , Berger Hara R. , Levis Silvina
Published: January 2019

After the first fracture, the risk of subsequent fractures increases significantly. Medical treatment can reduce the risk of a second fracture by about 50%, but many older adults do not receive osteoporosis medication following their first fracture. This observational study aimed to understand primary care management patterns of older adults after osteoporotic fractures at the Miami Veterans Affairs (VA) Healthcare System. A retrospective review of 219 fracture cases selected by International Classification of Disease (ICD-9) codes between October 2015 and September 2016 identified 114 individuals age ≥50 years who had a non-traumatic fracture code entered in their medical record for the first time. Among them, 72 (63%) did not undergo a bone mineral density (BMD) test or receive treatment in the 12 months following their fracture. Of the 40 individuals who had a BMD test post-fracture, 17 (100%) received or were considered for anti-osteoporosis treatment if their T-score indicated osteoporosis (T-score ≤−2.5), but only 8/23 (35%) if the T-score was >−2.5. Physicians are more likely to prescribe osteoporosis therapy based on a BMD T-score diagnosis of osteoporosis, rather than a clinical diagnosis of osteoporosis based on a low-trauma fracture. A change in practice patterns is necessary to decrease the incidence of fractures.
Acknowledgement to Reviewers of Healthcare in 2018
Authors:   Healthcare Editorial Office
Published: January 2019

Rigorous peer-review is the corner-stone of high-quality academic publishing [...]
Tapping into Synchrotron and Benchtop Circular Dichroism Spectroscopy for Expanding Studies of Complex Polysaccharides and their Interactions in Anoxic Archaeological Wood
Authors: Phillips-Jones Mary K. , Harding Stephen E.
Published: January 2019

Circular dichroism (CD) (and synchrotron circular dichroism (SCD)) spectroscopy is a rapid, highly sensitive technique used to investigate structural conformational changes in biomolecules in response to interactions with ligands in solution and in film. It is a chiroptical method and at least one of the interacting molecules must possess optical activity (or chirality). In this review, we compare the capabilities of CD and SCD in the characterisation of celluloses and lignin polymers in archaeological wood. Cellulose produces a range of spectral characteristics dependent on environment and form; many of the reported transitions occur in the vacuum-ultraviolet region (< 180 nm) most conveniently delivered using a synchrotron source. The use of induced CD in which achiral dyes are bound to celluloses to give shifted spectra in the visible region is also discussed, together with its employment to identify the handedness of the chiral twists in nanocrystalline cellulose. Lignin is one target for the design of future consolidants that interact with archaeological wood to preserve it. It is reportedly achiral, but here we review several studies in which CD spectroscopy has successfully revealed lignin interactions with chiral enzymes, highlighting the potential usefulness of the technique in future research to identify new generation consolidants.
Acknowledgement to Reviewers of Heritage in 2018
Authors:   Heritage Editorial Office
Published: January 2019

Rigorous peer-review is the corner-stone of high-quality academic publishing [...]
Analysis of Epidemiological Characteristics of Notifiable Diseases Reported in Children Aged 0–14 Years from 2008 to 2017 in Zhejiang Province, China
Authors: Lu Qinbao , Ding Zheyuan , Wu Chen , Wu Haocheng , Lin Junfen
Published: January 2019

This study aims to learn the characteristics of morbidity and mortality of notifiable diseases reported in children aged 0–14 years in Zhejiang Province in 2008–2017. We collated data from the China Information System for Disease Control and Prevention in Zhejiang province between 1 January 2008 and 31 December 2017 of children aged 0–14 years. From 2008 to 2017, a total of 32 types and 1,994,740 cases of notifiable diseases were reported in children aged 0–14 years, including 266 deaths in Zhejiang Province. The annual average morbidity was 2502.87/100,000, and the annual average mortality was 0.33/100,000. Male morbidity was 2886.98/100,000, and female morbidity was 2072.16/100,000, with the male morbidity rate higher than the female morbidity rate (χ2 = 54,033.12, p < 0.01). No Class A infectious diseases were reported. The morbidity of Class B infectious diseases showed a downward trend, but that of Class C infectious diseases showed an upward trend. There were 72,041 cases in 22 kinds of Class B infectious disease and 138 death cases, with a morbidity rate of 90.39/100,000, and a mortality rate of 0.17/100,000. There were 1,922,699 cases in 10 kinds of Class C infectious disease and 128 death cases, with a morbidity rate of 2412.47/100,000, and a mortality rate of 0.16/100,000. The main high-prevalence diseases included hand-foot-and-mouth disease (1430.38/100,000), other infectious diarrheal diseases (721.40/100,000), mumps (168.83/100,000), and influenza (47.40/100,000). We should focus on the prevention and control of hand-foot and mouth disease, other infectious diarrheal diseases, mumps and influenza in children aged 0–14 years in Zhejiang Province. It is recommended to strengthen epidemic surveillance and undertake early prevention and control measures in order to reduce the younger children incidence rate of infectious diseases. Immunization planning vaccines can help achieve a significant preventive decline of infectious diseases.
Assessing the Impact of Land-Use Planning on the Atmospheric Environment through Predicting the Spatial Variability of Airborne Pollutants
Authors: Chen Longgao , Li Long , Yang Xiaoyan , Zhang Yu , Chen Longqian , Ma Xiaodong
Published: January 2019

As an important contributor to pollutant emissions to the atmosphere, land use can degrade environmental quality. In order to assess the impact of land-use planning on the atmosphere, we propose a methodology combining the land-use-based emission inventories of airborne pollutants and the long-term air pollution multi-source dispersion (LAPMD) model in this study. Through a case study of the eastern Chinese city of Lianyungang, we conclude that (1) land-use-based emission inventorying is a more economical way to assess the overall pollutant emissions compared with the industry-based method, and the LAPMD model can map the spatial variability of airborne pollutant concentrations that directly reflects how the implementation of the land-use planning (LUP) scheme impacts on the atmosphere; (2) the environmental friendliness of the LUP scheme can be assessed by an overlay analysis based on the pollution concentration maps and land-use planning maps; (3) decreases in the emissions of SO2 and PM10 within Lianyungang indicate the overall positive impact of land-use planning implementation, while increases in these emissions from certain land-use types (i.e., urban residential and transportation lands) suggest the aggravation of airborne pollutants from these land parcels; and (4) the city center, where most urban population resides, and areas around key plots would be affected by high pollution concentrations. Our methodology is applicable to study areas for which meteorological data are accessible, and is, therefore, useful for decision making if land-use planning schemes specify the objects of airborne pollutant concentration.
Non-Medical Use of Novel Synthetic Opioids: A New Challenge to Public Health
Authors: Lovrecic Barbara , Lovrecic Mercedes , Gabrovec Branko , Carli Marco , Pacini Matteo , Maremmani Angelo G. I. , Maremmani Icro
Published: January 2019

Background: In the last decade there has been a progressive increase in the use of new psychoactive substances (NPSs) that are not yet under international control. In particular, novel synthetic opioids (NSOs) have reappeared on the recreational drug market in the last few years. As a result, the use of NSOs has increased rapidly. This poses an emerging and demanding challenge to public health. Aim: To raise awareness among clinicians and other professionals about NPSs, especially NSOs, to summarize current knowledge about pharmacological properties, forms of NSO on the market, pattern of use, effects and consequences of use. Methods: An electronic search was carried out on the Medline/PubMed and Google Scholar databases to find selected search terms. Results: Some NPSs are already controlled, while others can be legally sold directly on the drug market (mainly via internet, less so by drug dealers) or be used as precursors for the synthesis of other designer drugs that mimic the psychoactive effects of controlled substances. Potential side-effects of NSOs include miosis, sedation, respiratory depression, hypothermia, inhibition of gastrointestinal propulsion, death (from opioid overdose). Conclusions: The severity of the opioid crisis has intensified with the introduction of highly potent NSOs on the drug market. As long as addicts are dying from overdose or similar causes, there is something more constructive to do than waiting for addicts to overdose on heroin at a place located near a remedy, as if to say, within reach of naloxone.
Expression Analysis of PIN Genes in Root Tips and Nodules of Lotus japonicus
Authors: Sańko-Sawczenko Izabela , Dmitruk Dominika , Łotocka Barbara , Różańska Elżbieta , Czarnocka Weronika
Published: January 2019

Auxins are postulated to be one of the pivotal factors in nodulation. However, their transporters in Lotus japonicus, the model species for the study of the development of determinate-type root nodules, have been scarcely described so far, and thus their role in nodulation has remained unknown. Our research is the first focusing on polar auxin transporters in L. japonicus. We analyzed and compared expression of PINs in 20 days post rhizobial inoculation (dpi) and 54 dpi root nodules of L. japonicus by real-time quantitative polymerase chain reaction (qPCR) along with the histochemical β-glucuronidase (GUS) reporter gene assay in transgenic hairy roots. The results indicate that LjPINs are essential during root nodule development since they are predominantly expressed in the primordia and young, developing nodules. However, along with differentiation, expression levels of several PINs decreased and occurred particularly in the nodule vascular bundles, especially in connection with the root’s stele. Moreover, our study demonstrated the importance of both polar auxin transport and auxin intracellular homeostasis during L. japonicus root nodule development and differentiation.
Variation in the Promoter Region of the MC4R Gene Elucidates the Association of Body Measurement Traits in Hu Sheep
Authors: Shishay Girmay , Liu Guiqiong , Jiang Xunping , Yu Yun , Teketay Wassie , Du Dandan , Jing Huang , Liu Chenghui
Published: January 2019

The melanocortin 4 receptor (MC4R) gene is expressed in the appetite-regulating areas of the brain and is engaged in the leptin signaling pathway. Although previous studies have identified variants in the coding region of the sheep MC4R gene showing significant associations with birth weight, weaning weight, and backfat thickness, no such associations have been reported for the promoter region. Besides, the essential promoter region of the sheep MC4R has not been delineated. In this study, to better understand the transcriptional regulation of MC4R and to elucidate the association between regulatory variants and haplotypes with body measurement traits in sheep, we cloned and characterized the MC4R promoter. We found that the minimal promoter of the gene is located within the region −1207/−880 bp upstream of the first exon. Real-time quantitative PCR (RT-qPCR) data revealed the mRNA expression of the MC4R gene had a significant difference between sex and age. In the association analysis, eight single nucleotide polymorphisms (SNPs) had a significant association with one or more traits (p < 0.05); of these, two SNPs were novel. Notably, individuals with haplotype H1H2 (CT-GA-GT-GA-GT-GA-GA-CG) were heavier in body weight than other haplotypes. Altogether, variations in the MC4R gene promoter, most notably haplotype H1H2, may greatly benefit marker-assisted selection in sheep.
Analysis of the Influence of Fibers on the Formability of Metal Blanks in Manufacturing Processes for Fiber Metal Laminates
Authors: Mennecart Thomas , Gies Soeren , Ben Khalifa Noomane , Tekkaya A. Erman
Published: January 2019

In the one-step manufacturing process for fiber metal laminate parts, the so-called in situ hybridization process, the fabrics are interacting with metal blanks. During deep drawing, the liquid matrix is injected between the metal sheets through the woven fiber layers. The metal blanks can be in contact with dry or with infiltrated fibers. The formability of the blanks is influenced by the variation of the starting time of injection. The reason for that is that, due to high contact forces, the fibers are able to deform the metal surface locally, so that movement and the strain of the blanks is inhibited. To investigate the influence of different fibers on the formability of metals, Nakazima tests are performed. In these tests, two metal blanks are formed with an interlayer of fibers. The results are compared with the formability of two blanks without any interlayer. It is shown that in with fibers between sheets, the formability decreases compared to the formability of two metal blanks without interlayers. Based on a simplified numerical model for different types of fibers, the interactions of the fibers with the metal blank are analyzed. It could be shown that the friction due to contact has more influence than the friction due to the form fit caused by the imprints.
Acknowledgement to Reviewers of Journal of Marine Science and Engineering in 2018
Authors:   JMSE Editorial Office
Published: January 2019

Rigorous peer-review is the corner-stone of high-quality academic publishing [...]
The Transition from Static to Dynamic Boundary Friction of a Lubricated Spreading and a Non-Spreading Adhesive Contact by Macroscopic Oscillatory Tribometry
Authors: Koplin Christof , Abdel-Wahed Sherif Ahmed , Jaeger Raimund , Scherge Matthias
Published: January 2019

Lubricated poly(ether ether ketone) (PEEK) and polyamide (PA46)–steel tribosystems were investigated. They show a complex but systematic transition behavior from static to boundary friction, to dynamic friction or to mixed-lubrication. Nonstandard macroscopic oscillatory tribometry as well as gliding experiments were carried out. A previous study showed that the surface and interfacial energies of PEEK, lubricant and steel can indicate trends in the tribological behavior. In the current study, these findings are confirmed for PA46 and a wider range of lubricants. It was shown that a reversal of the order of the work of spreading of two lubricants by switching from PEEK to PA46 as polymer component in the tribological system also resulted in a reversal of the coefficient of friction (COF) at low gliding velocities for these systems. The adhesion threshold of PA46 with the non-spreading lubricants water, glycerine, a water–glycerine mixture, ethylene glycol and poly-1-decene decreased with increasing solving tendency of the lubricants in contrast to the previous results for spreading lubricants for PEEK. Furthermore, the onset of forced wetting was studied for lubricants with different surface and interfacial energies and viscosities η. In general, a 1/η dependency was observed for the velocity which marks the onset of forced wetting. This agrees with theoretical models.
Liquid-Phase Exfoliated Silicon Nanosheets: Saturable Absorber for Solid-State Lasers
Authors: Wang Mengxia , Zhang Fang , Wang Zhengping , Xu Xinguang
Published: January 2019

As a newly-developed two-dimensional (2D) material of group-IVA, few-layer silicon (Si) nanosheets were prepared by the liquid phase exfoliation (LPE) method. Its non-linear saturable adsorption property was investigated by 532 and 1064 nm nanosecond lasers. Using Si nanosheets as the saturable absorber (SA), passive Q-switched all-solid-state lasers were demonstrated for the first time. For different laser emissions of Nd3+ at 0.9, 1.06, and 1.34 µm, the narrowest Q-switched pulse widths were 200.2, 103.7, and 110.4 ns, corresponding to the highest peak powers of 2.76, 2.15, and 1.26 W. The results provide a promising SA for solid-state pulsed lasers and broaden the potential application range of Si nanosheets in ultrafast photonics and optoelectronics.
Explicit Solutions and Bifurcations for a System of Rational Difference Equations
Authors: Al-Hdaibat Bashir , Al-Ashhab Saleem , Sabra Ramadan
Published: January 2019

In this paper, we consider the explicit solution of the following system of nonlinear rational difference equations: x n + 1 = x n − 1 / x n − 1 + r , y n + 1 = x n − 1 y n / x n − 1 y n + r , with initial conditions x − 1 , x 0 and y 0 , which are arbitrary positive real numbers. By doing this, we encounter the hypergeometric function. We also investigate global dynamics of this system. The global dynamics of this system consists of two kind of bifurcations.
Fabrication and Characterization of Core-Shell Electrospun Fibrous Mats Containing Medicinal Herbs for Wound Healing and Skin Tissue Engineering
Authors: Zahedi Elahe , Esmaeili Akbar , Eslahi Niloofar , Shokrgozar Mohammad Ali , Simchi Abdolreza
Published: January 2019

Nanofibrous structures mimicking the native extracellular matrix have attracted considerable attention for biomedical applications. The present study aims to design and produce drug-eluting core-shell fibrous scaffolds for wound healing and skin tissue engineering. Aloe vera extracts were encapsulated inside polymer fibers containing chitosan, polycaprolactone, and keratin using the co-axial electrospinning technique. Electron microscopic studies show that continuous and uniform fibers with an average diameter of 209 ± 47 nm were successfully fabricated. The fibers have a core-shell structure with a shell thickness of about 90 nm, as confirmed by transmission electron microscopy. By employing Fourier-transform infrared spectroscopy, the characteristic peaks of Aloe vera were detected, which indicate successful incorporation of this natural herb into the polymeric fibers. Tensile testing and hydrophilicity measurements indicated an ultimate strength of 5.3 MPa (elongation of 0.63%) and water contact angle of 89°. In-vitro biological assay revealed increased cellular growth and adhesion with the presence of Aloe vera without any cytotoxic effects. The prepared core-shell fibrous mats containing medical herbs have a great potential for wound healing applications.
Polymorphisms of ABCG2 and SLC22A12 Genes Associated with Gout Risk in Vietnamese Population
Authors: Thuy Duong Nguyen , Thy Ngoc Nguyen , Tran Minh Thang Nguyen , Thi Hoai Phuong Bach , Thanh Nga Nguyen , Doan Tinh Nguyen , Hai Quynh Do , Dang Ton Nguyen , Van Hai Nong
Published: January 2019

Background and objective: Gout is a common form of inflammatory arthritis caused by the crystallization of uric acid. Previous studies have demonstrated that the genetic predisposition of gout varies in different ethnic populations. However the association study of genetic variants with gout remains unknown in the Vietnamese population. Our study aimed to assess the relationship between polymorphisms in ABCG2 and SLC22A12 and gout susceptibility in Vietnamese. Materials and methods: Genomic DNA was extracted from blood of a total of 170 patients with gout and 351 healthy controls. We genotyped single nucleotide polymorphisms (SNPs): rs72552713, rs12505410 of the ABCG2 gene and rs11231825, rs7932775 of the SLC22A12 gene using polymerase chain reaction–restriction fragment length polymorphism (PCR–RFLP) and then confirmed 10% of randomly selected subjects by Sanger sequencing. Results: Three SNPs (rs72552713 and rs12505410 and rs11231825) were in accordance with Hardy–Weinberg Equilibrium (HWE) (p > 0.05) while rs7932775 was not (p < 0.05). For rs72552713, CT genotype was significantly different between gout patient and control groups (p < 0.001) and the T allele was associated with an increased risk of gout (OR = 21.19; 95% CI: 3.00–918.96; p < 0.001). Serum uric acid and hyperuricemia differed significantly between CC and CT genotype groups (p = 0.004 and 0.008, respectively). For rs11231825, a protective effect against gout risk was identified in the presence of the C allele when compared with the T allele (OR = 0.712; 95% CI: 0.526–0.964 p = 0.0302). In contrast, no significant difference of allele frequencies between gout patients and controls was detected for rs12505410 (p > 0.05). However, significant differences in serum uric acid and systolic blood pressure were obtained among gout patients. Conclusion: Our results suggest that ABCG2 rs72552713 and SLC22A12 rs11231825 are likely associated with gout in the Vietnamese population in which T allele may be a risk factor for gout susceptibility.
Influence of Heat Treatment in the Microstructure of a Joint of Nodular Graphite Cast Iron when Using the Tungsten Inert Gas Welding Process with Perlitic Grey Cast Iron Rods as Filler Material
Authors: Cárcel-Carrasco Francisco-Javier , Pascual-Guillamón Manuel , Salas-Vicente Fidel , Donderis-Quiles Vicente
Published: January 2019

The present article analyses the influence of preheating and a postweld heat treatment in the microstructure, mechanical properties and wear behaviour of a joint of nodular graphite cast iron when using the tungsten inert gas (TIG) welding process with perlitic grey cast iron rods as filler material. Data obtained from the tests and the microstructural study of the samples show that the absence of a postweld heat treatment and of preheating leads to the apparition of hard structures and a notable reduction in elongation. Preheating or annealing the weld avoid the presence of these hard structures and increase the ductile behaviour of the joint although at the cost of a further loss of mechanical strength. Wear rate was found to be higher at the weld bead than at the base metal, even when the hardness of both areas is the same.
Fatigue Crack Growth Rate of the Long Term Operated Puddle Iron from the Eiffel Bridge
Authors: Lesiuk Grzegorz , Correia José A. F. O. , Smolnicki Michał , De Jesus Abílio M. P. , Duda Monika , Montenegro Pedro A. , Calcada Rui A. B.
Published: January 2019

The paper summarises an experimental study on the fatigue crack propagation and cracks paths in ancient steel—19th-century puddle iron from the Eiffel bridge. The tests were performed with the load R-ratio equal to 0.05 and 0.5. All tests were performed under different notch inclinations (mode I + II). The fatigue crack growth rate in the tested material is significantly higher than its “modern” equivalent—low carbon mild steel. The crack closure phenomenon occurs in specimens during the process of crack growth. Understanding this aspect is crucial for the examination of a stress R-ratio influence on kinetic fatigue fracture diagram (KFFD) description. Both the experimental and numerical approach, using the HP VEE environment, has been applied to the crack closure as well as the crack opening forces’ estimation. These analyses are based on the deformation of the hysteresis loop. The algorithm that was implemented in the numerical environment is promising when it comes to describing the kinetics of fatigue crack growth (taking into consideration the crack closure effect) in old metallic materials.
Acoustic Emissions during Structural Changes in Shape Memory Alloys
Authors: Beke Dezső László , Daróczi Lajos , Tóth László Zoltán , Bolgár Melinda Kalmárné , Samy Nora Mohareb , Hudák Anikó
Published: January 2019

Structural changes (martensitic transformation, rearrangements of martensitic variants) in shape memory alloys have an intermittent character that is accompanied by the emission of different (thermal, acoustic, and magnetic) noises, which are fingerprints of the driven criticality, resulting in a damped power-law behaviour. We will illustrate what kinds of important information can be obtained on the structural changes in shape memory alloys. It was established that the power exponents of distributions of acoustic emission (AE) parameters (energy, amplitude, etc.), belonging to martensitic transformations, show quite a universal character and depend only on the symmetry of the martensite. However, we have shown that the asymmetry of the transformation (the exponents are different for the forward and reverse transformations) results in as large differences as those due to the martensite symmetry. We will also demonstrate how the recently introduced AE clustering method can help to identify the different contributions responsible for the asymmetry. The usefulness of the investigations of time correlations between the subsequent events and correlations between acoustic and magnetic noise events in ferromagnetic shape memory alloys will be demonstrated too. Finally, examples of acoustic and magnetic emissions during variant rearrangements (superplastic or superelastic behaviour) in the martensitic state will be described.
Microfluidic Device for Screening for Target Cell-Specific Binding Molecules by Using Adherent Cells
Authors: Kaminaga Maho , Ishida Tadashi , Kadonosono Tetsuya , Kizaka-Kondoh Shinae , Omata Toru
Published: January 2019

This paper proposes a microfluidic device for screening molecules such as aptamers, antibodies, proteins, etc. for target cell-specific binding molecules. The discovery of cancer cell-specific binding molecules was the goal of this study. Its functions include filtering non-target cell-binding molecules, trapping molecules on the surface of target cells, washing away unbound molecules, and collecting target cell-specific binding molecules from target cells. These functions were effectively implemented by using our previously developed micro pillar arrays for cell homogeneous dispersion and pneumatic microvalves for tall microchannels. The device was also equipped with serially connected filter chambers in which non-target cells were cultured to reduce the molecules binding to non-target cells as much as possible. We evaluated the performance of the device using cancer cell lines (N87 cells as target cells and HeLa cells as non-target cells) and two fluorescent dye-labeled antibodies: Anti-human epidermal growth factor receptor 2 (anti-HER2) antibody that binds to target cells and anti-integrin antibody that binds to non-target cells. The results showed that the device could reduce anti-integrin antibodies to the detection limit of fluorescent measurement and collect anti-HER2 antibodies from the target cells.
An Alternative Platform for Protein Expression Using an Innate Whole Expression Module from Metagenomic DNA
Authors: Cheong Dae-Eun , Park So-Youn , Lim Ho-Dong , Kim Geun-Joong
Published: January 2019

Many integrated gene clusters beyond a single genetic element are commonly trapped as the result of promoter traps in (meta)genomic DNA libraries. Generally, a single element, which is mainly the promoter, is deduced from the resulting gene clusters and employed to construct a new expression vector. However, expression patterns of target proteins under the incorporated promoter are often inconsistent with those shown in clones harboring plasmids with gene clusters. These results suggest that the integrated set of gene clusters with diverse cis- and trans-acting elements is evolutionarily tuned as a complete set for gene expression, and is an expression module with all the components for the expression of a nested open reading frame (ORF). This possibility is further supported by truncation and/or serial deletion analysis of this module in which the expression of the nested ORF is highly fluctuated or reduced frequently, despite being supported by plentiful cis-acting elements in the spanning regions around the ORF such as the promoter, ribosome binding site (RBS), terminator, and 3′-/5′-UTRs for gene expression. Here, we examined whether an innate module with a naturally overexpressed gene could be considered as a scaffold for an expression system. For a proof-of-principle study, we mined a complete expression module with an innately overexpressed ORF in E. coli from a metagenomics DNA library, and incorporated it into a vector that had no regulatory element for expressing the insert. We obtained successful expression of several inserts such as MBP, GFPuv, β-glucosidase, and esterase using this simple construct without tuning and codon optimization of the target insert.
The Tocantinzinho Paleoproterozoic Porphyry-Style Gold Deposit, Tapajós Mineral Province (Brazil): Geology, Petrology and Fluid Inclusion Evidence for Ore-Forming Processes
Authors: Lopes Adriana Araújo Castro , Moura Márcia Abrahão
Published: January 2019

The Tocantinzinho gold deposit, located in the Tapajós Mineral Province, Amazonia, Brazil, is considered the largest gold deposit in the region. It is a stockwork-disseminated gold deposit, hosted in a 1982 ± 8 Ma hydrothermalized monzogranite of the Creporizão Intrusive Suite, with petrographic and geochemical characteristics of volcanic arc to post-collisional granites. Gold is mainly associated with phyllic alteration. Primary fluid inclusions trapped in the mineralization stages are H2O–NaCl and unsaturated and homogenize either to the vapor or to the liquid with Th(t) of 300–430 °C, salinity of 2–16 wt % NaCl eq. and density from 0.43 to 0.94 g/cm3. At these conditions, Au is expected to be transported as Au(HS)2− complexes and ore is deposited as the result of boiling in the first mineralizing stages and of mixing between magmatic fluid and meteoric water during the phyllic alteration. Compared with other deposits, Tocantinzinho has similarities with magmatic-hydrothermal oxidized calc-alkaline granite-related gold deposits classified as porphyry gold deposits but we classify as a porphyry-style gold deposit, as it lacks some characteristics of the Phanerozoic porphyry-type deposits. The results from this study can be used to elaborate and guide prospection models in Amazonia and in similar Proterozoic terrains.
Simultaneous Detection of Carnosine and Anserine by UHPLC-MS/MS and Its Application on Biomarker Analysis for Differentiation of Meat and Bone Meal
Authors: Han Yahong , Gao Bing , Zhao Shengnan , Wang Mengyan , Jian Lin , Han Lujia , Liu Xian
Published: January 2019

A novel ultra-high performance liquid chromatography (UHPLC) procedure, coupled with tandem mass spectrometry (MS/MS), was established for the analysis of anserine (ANS) and carnosine (CAR) in meat and bone meal (MBM) (bovine, ovine, porcine, and poultry origins). The pretreatment strategies were optimized for four types of MBM samples prior to UHPLC-MS/MS analysis. This method allowed determining CAR and ANS in short analysis time (18 min per sample). The limits of detection (LODs) and limits of quantification (LOQs) of two analytes in four types of MBM samples were in the ranges of 0.41–3.07 ng/g and 0.83–5.71 ng/g, respectively. The recovery rates spiked with low, intermediate, and high levels of two analytes in four types of MBM samples were 48.53–98.93%, 60.12–98.94%, and 67.90–98.92%, respectively. Acceptable inter-day reproducibility (RSD < 12.63%) supported the application of this proposed method for determining CAR and ANS in MBM samples. Overall, this rapid, effective, and robust method was successfully applied for quantitative detection of CAR and ANS in MBM samples. Furthermore, The CAR/ANS ratio was found to be in the decreasing order: porcine > bovine > ovine > poultry MBM. This proposed methodology was novelly applied to identify the biomarker (CAR/ANS ratio) for species-specific identification of MBM.
Ent-homocyclopiamine B, a Prenylated Indole Alkaloid of Biogenetic Interest from the Endophytic Fungus Penicillium concentricum
Authors: Ali Tehane , Pham Tiffany M. , Ju Kou-San , Rakotondraibe Harinantenaina L.
Published: January 2019

Ent-homocyclopiamine B (1), a new prenylated indole alkaloid bearing an alicyclic nitro group along with 2-methylbutane-1,2,4-triol (2) were isolated from an endophytic fungus Penicillium concentricum of the liverwort Trichocolea tomentella (Trichocoleaceae). The structure of 1 was elucidated through extensive spectroscopic analyses and comparison with data reported for a structurally related nitro-bearing Penicillium metabolite, clopiamine C (3), which contain an indolizidine ring instead of the quinolizine ring in 1. The new compound, ent-homocyclopiamine B, exhibited slight growth inhibition against Gram-positive bacteria. Based on the reported biosynthesis of related compounds and the isolation of the mevalonic acid derived compound 2-methyl-1,2,4-butanetriol (2), we proposed that ent-homocylopiamine B (1) was biosynthesized from lysine and prenyl group-producing mevalonic pathway.
Cross-Linking Chitosan into Hydroxypropylmethylcellulose for the Preparation of Neem Oil Coating for Postharvest Storage of Pitaya (Stenocereus pruinosus)
Authors: Hernández-Valencia Carmen G. , Román-Guerrero Angélica , Aguilar-Santamaría Ángeles , Cira Luis , Shirai Keiko
Published: January 2019

The market trend for pitaya is increasing, although the preservation of the quality of this fruit after the harvest is challenging due to microbial decay, dehydration, and oxidation. In this work, the application of antimicrobial chitosan-based coatings achieved successful postharvest preservation of pitaya (Stenocereus pruinosus) during storage at 10 ± 2 °C with a relative humidity of 80 ± 5%. The solution of cross-linked chitosan with hydroxypropylmethylcellulose with entrapped Neem oil (16 g·L−1) displayed the best postharvest fruit characteristics. The reduction of physiological weight loss and fungal contamination, with an increased redness index and release of azadirachtin from the microencapsulated oil, resulted in up to a 15 day shelf life for this fruit. This postharvest procedure has the potential to increase commercial exploitation of fresh pitaya, owing to its good taste and high content of antioxidants.
9-Norlignans: Occurrence, Properties and Their Semisynthetic Preparation from Hydroxymatairesinol
Authors: Eklund Patrik , Raitanen Jan-Erik
Published: January 2019

Lignans, neolignans, norlignans and norneolignans constitute a large class of phenolic natural compounds. 9-Norlignans, here defined to contain a β–β’ bond between the two phenylpropanoid units and to lack carbon number 9 from the parent lignan structure, are the most rarely occurring compounds within this class of natural compounds. We present here an overview of the structure, occurrence and biological activity of thirty-five 9-norlignans reported in the literature to date. In addition, we report the semisynthetic preparation of sixteen 9-norlignans using the natural lignan hydroxymatairesinol obtained from spruce knots, as starting material. 9-Norlignans are shown to exist in different species and to have various biological activities, and they may therefore serve as lead compounds for example for the development of anticancer agents. Hydroxymatairesinol is shown to be a readily available starting material for the preparation of norlignans of the imperanene, vitrofolal and noralashinol family.
Asymmetric Electrophilic Difluoromethylthiolation of Indanone-Based β-Keto Esters Using Difluoromethanesulfonyl Hypervalent Iodonium Ylides
Authors: Gondo Satoshi , Matsubara Okiya , Chachignon Hélène , Sumii Yuji , Cahard Dominique , Shibata Norio
Published: January 2019

The first electrophilic diastereoselective direct introduction of the difluoromethylthio group is described. We used a chiral auxiliary-based approach to illustrate the versatility of our recently developed difluoromethanesulfonyl hypervalent iodonium ylide reagents for the difluoromethylthiolation of indanone-based β-keto esters. Chiral SCF2H-featuring compounds were obtained in up to 93% ee value.
Production of Added-Value Chemical Compounds through Bioconversions of Olive-Mill Wastewaters Blended with Crude Glycerol by a Yarrowia lipolytica Strain
Authors: Sarris Dimitris , Rapti Anna , Papafotis Nikolaos , Koutinas Apostolis A. , Papanikolaou Seraphim
Published: January 2019

Olive mill wastewaters (OMW) are the major effluent deriving from olive oil production and are considered as one of the most challenging agro-industrial wastes to treat. Crude glycerol is the main by-product of alcoholic beverage and oleochemical production activities including biodiesel production. The tremendous quantities of glycerol produced worldwide represent a serious environmental challenge. The aim of this study was to assess the ability of Yarrowia lipolytica strain ACA-DC 5029 to grow on nitrogen-limited submerged shake-flask cultures, in crude glycerol and OMW blends as well as in media with high initial glycerol concentration and produce biomass, cellular lipids, citric acid and polyols. The rationale of using such blends was the dilution of concentrated glycerol by OMW to (partially or fully) replace process tap water with a wastewater stream. The strain presented satisfactory growth in blends; citric acid production was not affected by OMW addition (Citmax~37.0 g/L, YCit/Glol~0.55 g/g) and microbial oil accumulation raised proportionally to OMW addition (Lmax~2.0 g/L, YL/X~20% w/w). Partial removal of color (~30%) and phenolic compounds (~10% w/w) of the blended media occurred. In media with high glycerol concentration, a shift towards erythritol production was noted (Erymax~66.0 g/L, YEry/Glol~0.39 g/g) simultaneously with high amounts of produced citric acid (Citmax~79.0 g/L, YCit/Glol~0.46 g/g). Fatty acid analysis of microbial lipids demonstrated that OMW addition in blended media and in excess carbon media with high glycerol concentration favored oleic acid production.
S-Acyl-2-Thioethyl: A Convenient Base-Labile Protecting Group for the Synthesis of siRNAs Containing 5′-Vinylphosphonate
Authors: Nikan Mehran , Li Wenyu , Kinberger Garth A. , Seth Punit P. , Swayze Eric E. , Prakash Thazha P.
Published: January 2019

We recently reported that (E)-5′-vinylphosphonate (5′-VP) is a metabolically-stable phosphate mimic for siRNA and demonstrated that 5′-VP improves the potency of the fully modified siRNAs in vivo. Here, we report an alternative synthesis of 5′-VP modified guide strand using S-pivaloyl-2-thioethyl (tBu-SATE) protecting group. The tBu-SATE group is readily removed during the final cleavage of the oligonucleotide from the solid support and providing a more convenient route for the synthesis of siRNA guide strand carrying a 5′-vinylphosphonate.
Differential Binding of Tetrel-Bonding Bipodal Receptors to Monatomic and Polyatomic Anions
Authors: Scheiner Steve
Published: January 2019

Previous work has demonstrated that a bidentate receptor containing a pair of Sn atoms can engage in very strong interactions with halide ions via tetrel bonds. The question that is addressed here concerns the possibility that a receptor of this type might be designed that would preferentially bind a polyatomic over a monatomic anion since the former might better span the distance between the two Sn atoms. The binding of Cl− was thus compared to that of HCOO−, HSO4−, and H2PO4− with a wide variety of bidentate receptors. A pair of SnFH2 groups, as strong tetrel-binding agents, were first added to a phenyl ring in ortho, meta, and para arrangements. These same groups were also added in 1,3 and 1,4 positions of an aliphatic cyclohexyl ring. The tetrel-bonding groups were placed at the termini of (-C≡C-)n (n = 1,2) extending arms so as to further separate the two Sn atoms. Finally, the Sn atoms were incorporated directly into an eight-membered ring, rather than as appendages. The ordering of the binding energetics follows the HCO2− > Cl− > H2PO4− > HSO4− general pattern, with some variations in selected systems. The tetrel bonding is strong enough that in most cases, it engenders internal deformations within the receptors that allow them to engage in bidentate bonding, even for the monatomic chloride, which mutes any effects of a long Sn···Sn distance within the receptor.
Aptamer Efficacies for In Vitro and In Vivo Modulation of αC-Conotoxin PrXA Pharmacology
Authors: Taiwe Germain Sotoing , Montnach Jérôme , Nicolas Sébastien , De Waard Stéphan , Fiore Emmanuelle , Peyrin Eric , El-Aziz Tarek Mohamed Abd , Amar Muriel , Molgó Jordi , Ronjat Michel , Servent Denis , Ravelet Corinne , De Waard Michel
Published: January 2019

The medical staff is often powerless to treat patients affected by drug abuse or misuse and poisoning. In the case of envenomation, the treatment of choice remains horse sera administration that poses a wealth of other medical conditions and threats. Previously, we have demonstrated that DNA-based aptamers represent powerful neutralizing tools for lethal animal toxins of venomous origin. Herein, we further pursued our investigations in order to understand whether all toxin-interacting aptamers possessed equivalent potencies to neutralize αC-conotoxin PrXA in vitro and in vivo. We confirmed the high lethality in mice produced by αC-conotoxin PrXA regardless of the mode of injection and further characterized myoclonus produced by the toxin. We used high-throughput patch-clamp technology to assess the effect of αC-conotoxin PrXA on ACh-mediated responses in TE671 cells, responses that are carried by muscle-type nicotinic receptors. We show that 2 out of 4 aptamers reduce the affinity of the toxin for its receptor, most likely by interfering with the pharmacophore. In vivo, more complex responses on myoclonus and mice lethality are observed depending on the type of aptamer and mode of administration (concomitant or differed). Concomitant administration always works better than differed administration indicating the stability of the complex in vivo. The most remarkable conclusion is that an aptamer that has no or a limited efficacy in vitro may nevertheless be functional in vivo probably owing to an impact on the biodistribution or pharmacokinetics of the toxin in vivo. Overall, the results highlight that a blind selection of aptamers against toxins leads to efficient neutralizing compounds in vivo regardless of the mode of action. This opens the door to the use of aptamer mixtures as substitutes to horse sera for the neutralization of life-threatening animal venoms, an important WHO concern in tropical areas.
A Novelty System for Biotization of Plant Microshoots and Collection of Natural Compounds
Authors: Castro Mário Rui da Costa Basílio e , Ragonezi Carla , Oliveira Paulo Guilherme Leandro de , Zavattieri Maria Amely
Published: January 2019

An in vitro plant microshoot culture system composed of two phases; a liquid phase overlaid by a floating solid phase, which is described in detail herein. This system is designed to enable the extraction of natural compounds released/disseminated into the liquid phase during root growth, thus facilitating their processing and biochemical characterization. The solid phase holds the plant afloat and enables the simultaneous culture of a microorganism, yet avoiding its penetration into the liquid phase, where the roots are submerged. Both phases can be independently formulated as required for growth optimization of both organisms. Considering the closed system and known variables described in this patent, applications of the described method include testing with pesticides, herbicides, and other similar products.
Acknowledgement to Reviewers of MTI in 2018
Authors:   MTI Editorial Office
Published: January 2019

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