bluuebunny/crossref_metadata_2025 huggingface dataset:
Non-glide effects and dislocation core fields in BCC metals
Authors: Kraych Antoine , Clouet Emmanuel , Dezerald Lucile , Ventelon Lisa , Willaime François , Rodney David
Published: November 2019

A hallmark of low-temperature plasticity in body-centered cubic (BCC) metals is its departure from Schmid’s law. One aspect is that non-glide stresses, which do not produce any driving force on the dislocations, may affect the yield stress. We show here that this effect is due to a variation of the relaxation volume of the $$1/2\langle 111\rangle$$1∕2⟨111⟩ screw dislocations during glide. We predict quantitatively non-glide effects by modeling the dislocation core as an Eshelby inclusion, which couples elastically to the applied stress. This model explains the physical origin of the generalized yield criterion classically used to include non-Schmid effects in constitutive models of BCC plasticity. We use first-principles calculations to properly account for dislocation cores and use tungsten as a reference BCC metal. However, the methodology developed here applies to other BCC metals, other energy models and other solids showing non-glide effects.
Quantum random number generation with uncharacterized laser and sunlight
Authors: Li Yu-Huai , Han Xuan , Cao Yuan , Yuan Xiao , Li Zheng-Ping , Guan Jian-Yu , Yin Juan , Zhang Qiang , Ma Xiongfeng , Peng Cheng-Zhi , Pan Jian-Wei
Published: November 2019

The entropy or randomness source is an essential ingredient in random number generation. Quantum random number generators generally require well modeled and calibrated light sources, such as a laser, to generate randomness. With uncharacterized light sources, such as sunlight or an uncharacterized laser, genuine randomness is practically hard to be quantified or extracted owing to its unknown or complicated structure. By exploiting a recently proposed source-independent randomness generation protocol, we theoretically modify it by considering practical issues and experimentally realize the modified scheme with an uncharacterized laser and a sunlight source. The extracted randomness is guaranteed to be secure independent of its source and the randomness generation speed reaches 1 Mbps, three orders of magnitude higher than the original realization. Our result signifies the power of quantum technology in randomness generation and paves the way to high-speed semi-self-testing quantum random number generators with practical light sources.
Autocrine Production of Interleukin-34 Promotes the Development of Endometriosis through CSF1R/JAK3/STAT6 signaling
Authors: Lin Kaiqing , Ma Junyan , Peng Yaomin , Sun Meina , Xu Kaihong , Wu Ruijin , Lin Jun
Published: November 2019

Interleukin (IL)-34 plays a critical role in cell proliferation, differentiation, apoptosis, angiogenesis, inflammation and immunoregulation. Numerous diseases can be attributed to the dysregulation of IL-34 signaling. This study was performed to investigate the function of IL-34 in the pathogenesis of endometriosis. Firstly, by enzyme linked immunoabsorbent assay, we found that IL-34, VEGF, MMP-2 and MMP-9 were increased in the sera of patients with endometriosis. Secondly, exposure to IL-34 promoted the proliferation, migration and invasion of eutopic endometrial stromal cells (ESCs). Additionally, stimulation with IL-34 up-regulated colony-stimulating factor 1 receptor (CSF1R), p-JAK3, p-STAT6, VEGF, MMP-2 and MMP-9 in these eutopic ESCs. Treatment with AS1517499, an inhibitor of STAT6, remarkably abrogated the alterations induced by IL-34. A Chromatin immunoprecipitation (ChIP) assay demonstrated binding of STAT6 to the IL-34 promoter, further implicating STAT6 in IL-34 signaling. Notably, reverse results were obtained in ectopic ESCs with the application of an IL-34 neutralizing antibody. In vivo, AS1517499 suppressed the maintenance of endometriosis lesions in rats. In summary, autocrine production of IL-34, mediated by STAT6, promoted the development of endometriosis in vitro and in vivo through the CSF1R/JAK3/STAT6 pathway. Our research reveals the function of IL-34 in endometriosis, which may provide insight into novel therapeutic strategies for endometriosis.
Mycobacterium tuberculosis CysA2 is a dual sulfurtransferase with activity against thiosulfate and 3-mercaptopyruvate and interacts with mammalian cells
Authors: Meza A. N. , Cambui C. C. N. , Moreno A. C. R. , Fessel M. R. , Balan A.
Published: November 2019

Cyanide is a toxic compound that is converted to the non-toxic thiocyanate by a rhodanese enzyme. Rhodaneses belong to the family of transferases (sulfurtransferases), which are largely studied. The sulfur donor defines the subfamily of these enzymes as thiosulfate:cyanide sulfurtransferases or rhodaneses (TSTs) or 3-mercaptopyruvate sulfurtransfeases (MSTs). InMycobacterium tuberculosis, the causative agent of tuberculosis, the gene Rv0815c encodes the protein CysA2, a putative uncharacterized thiosulfate:cyanide sulfurtransferase that belongs to the essential sulfur assimilation pathway in the bacillus and is secreted during infection. In this work, we characterized the functional and structural properties of CysA2 and its kinetic parameters. The recombinant CysA2 is a α/β protein with two rhodanese-like domains that maintains the functional motifs and a catalytic cysteine. Sulfurtransferase activity was determined using thiosulfate and 3-mercaptopyruvate as sulfur donors. The assays showed Kmvalues of 2.89 mM and 7.02 mM for thiosulfate and 3-mercaptopyruvate, respectively, indicating the protein has dual activity as TST and MST. Immunological assays revealed that CysA2 interacted with pulmonary cells, and it was capable to activate macrophages and dendritic cells, indicating the stimulation of the immune response, which is important for its use as an antigen for vaccine development and immunodiagnostic.
Understanding allosteric interactions in hMLKL protein that modulate necroptosis and its inhibition
Authors: Bansal Nupur , Sciabola Simone , Bhisetti Govinda
Published: November 2019

Mixed Lineage Kinase domain-Like (MLKL), a key player in necroptosis, is a multi-domain protein with an N-terminal 4 helical bundle (4HB) and a pseudokinase domain (PsK) connected by brace helices. Phosphorylation of PsK domain of MLKL is a key step towards oligomerization of 4HB domain that causes cell death. Necrosulfonamide (NSA) binds to the 4HB domain of MLKL to inhibit necroptosis. To understand the molecular details of MLKL function and it’s inhibition, we have performed a molecular dynamic study on hMLKL protein in apo, phosphorylated and NSA-bound states for a total 3 μs simulation time. Our simulations show increased inter-domain flexibility, increased rigidification of the activation loop and increased alpha helical content in the brace helix region revealing a form of monomeric hMLKL necessary for oligomerization upon phosphorylation as compared to apo state. NSA binding disrupts this activated form and causes two main effects on hMLKL conformation: (1) locking of the relative orientation of 4HB and PsK domains by the formation of several new interactions and (2) prevention of key 4HB residues to participate in cross-linking for oligomer formation. This new understanding of the effect of hMLKL conformations on phosphorylation and NSA binding suggest new avenues for designing effective allosteric inhibitors of hMLKL.
Insufficient production of IL-10 from M2 macrophages impairs in vitro endothelial progenitor cell differentiation in patients with Moyamoya disease
Authors: Nagata Eiichiro , Masuda Haruchika , Nakayama Taira , Netsu Shizuka , Yuzawa Hiroko , Fujii Natsuko , Kohara Saori , Sorimachi Takatoshi , Osada Takahiro , Imazeki Ryoko , Matsumae Mitsunori , Asahara Takayuki , Takizawa Shunya
Published: November 2019

Moyamoya disease (MMD) is well known to be caused by insufficient cerebral vascular formation. However, the essential pathogenesis has not yet been identified. Using our recently developed technique of generating vasculogenic and anti-inflammatory cultures, we investigated endothelial progenitor cell (EPC) expansion and differentiation under the cytokine milieu generated by the peripheral blood mononuclear cells (PBMNCs) of the operated and non-operated MMD patients. EPC colony forming assay of the cultured PBMNCs disclosed the decline of the definitive EPC colony numbers in the both MMD patients. The level of interleukin-10 (IL-10) was lower in secretory cytokines from the cultured PBMNCs of MMD patients than that in that of controls using a cytometric bead array. The addition of human recombinant IL-10 to PBMNCs cultured from MMD patients restored the EPC colony forming potential of MMD PBMNCs. Following phorbol myristate acetate stimulation of the cultured PBMNCs, flow cytometry revealed a decrease in intracellular IL-10 storage in the main cell populations of the PBMNCs cultured from MMD patients relative to those cultured from controls. The present data provide the expected mechanism of vascular malformation in MMD pathogenesis originated from the insufficient production of IL-10 secreting cells from PBMNCs fostering EPC expansion and differentiation.
Additive manufacturing of laminar flow cells for single-molecule experiments
Authors: Ahmadi Arash , Till Katharina , Hafting Yngve , Schüttpelz Mark , Bjørås Magnar , Glette Kyrre , Tørresen Jim , Rowe Alexander D. , Dalhus Bjørn
Published: November 2019

A microfluidic laminar flow cell (LFC) forms an indispensable component in single-molecule experiments, enabling different substances to be delivered directly to the point under observation and thereby tightly controlling the biochemical environment immediately surrounding single molecules. Despite substantial progress in the production of such components, the process remains relatively inefficient, inaccurate and time-consuming. Here we address challenges and limitations in the routines, materials and the designs that have been commonly employed in the field, and introduce a new generation of LFCs designed for single-molecule experiments and assembled using additive manufacturing. We present single- and multi-channel, as well as reservoir-based LFCs produced by 3D printing to perform single-molecule experiments. Using these flow cells along with optical tweezers, we show compatibility with single-molecule experiments including the isolation and manipulation of single DNA molecules either attached to the surface of a coverslip or as freely movable DNA dumbbells, as well as direct observation of protein-DNA interactions. Using additive manufacturing to produce LFCs with versatility of design and ease of production allow experimentalists to optimize the flow cells to their biological experiments and provide considerable potential for performing multi-component single-molecule experiments.
Adsorption of indium by waste biomass of brown alga Ascophyllum nodosum
Authors: Pennesi Chiara , Amato Alessia , Occhialini Stefano , Critchley Alan T. , Totti Cecilia , Giorgini Elisabetta , Conti Carla , Beolchini Francesca
Published: November 2019

The biosorption capacities of dried meal and a waste product from the processing for biostimulant extract of Ascophyllum nodosum were evaluated as candidates for low-cost, effective biomaterials for the recovery of indium(III). The use of indium has significantly grown in the last decade, because of its utilization in hi-tech. Two formats were evaluated as biosorbents: waste-biomass, a residue derived from the alkaline extraction of a commercial, biostimulant product, and natural-biomass which was harvested, dried and milled as a commercial, “kelp meal” product. Two systems have been evaluated: ideal system with indium only, and double metal-system with indium and iron, where two different levels of iron were investigated. For both systems, the indium biosorption by the brown algal biomass was found to be pH-dependent, with an optimum at pH3. In the ideal system, indium adsorption was higher (maximum adsorptions of 48 mg/g for the processed, waste biomass and 63 mg/g for the natural biomass), than in the double metal-system where the maximum adsorption was with iron at 0.07 g/L. Good values of indium adsorption were demonstrated in both the ideal and double systems: there was competition between the iron and indium ions for the binding sites available in the A. nodosum-derived materials. Data suggested that the processed, waste biomass of the algae, could be a good biosorbent for its indium absorption properties. This had the double advantages of both recovery of indium (high economic importance), and also definition of a virtuous circular economic innovative strategy, whereby a waste becomes a valuable resource.
Construction and characterization of a double mutant of Enterococcus faecalis that does not produce biogenic amines
Authors: Perez Marta , Calles-Enríquez Marina , del Rio Beatriz , Redruello Begoña , de Jong Anne , Kuipers Oscar P. , Kok Jan , Martin M. Cruz , Ladero Victor , Fernandez Maria , Alvarez Miguel A.
Published: November 2019

Enterococcus faecalis is a lactic acid bacterium characterized by its tolerance of very diverse environmental conditions, a property that allows it to colonize many different habitats. This species can be found in food products, especially in fermented foods where it plays an important role as a biopreservative and influences the development of organoleptic characteristics. However, E. faecalis also produces the biogenic amines tyramine and putrescine. The consumption of food with high concentrations of these compounds can cause health problems. The present work reports the construction, via homologous recombination, of a double mutant of E. faecalis in which the clusters involved in tyramine and putrescine synthesis (which are located in different regions of the chromosome) are no longer present. Analyses showed the double mutant to grow and adhere to intestinal cells normally, and that the elimination of genes involved in the production of tyramine and putrescine has no effect on the expression of other genes.
Human faecal collection methods demonstrate a bias in microbiome composition by cell wall structure
Authors: Watson Emma-Jane , Giles Jennifer , Scherer Benjamin L. , Blatchford Paul
Published: November 2019

Clinical trial faecal collections present challenges through geographical spread and inexperienced participants. Collection techniques have been developed and tested to overcome these challenges, but previous studies investigating these techniques have demonstrated a highly variable capacity for sample preservation. Furthermore, these studies typically only examine either preservation of genetic content or metabolites, not both. This study investigated the Stool Nucleic Acid Collection and Preservation Tube (Norgen BioTek Corp) for the preservation of both microbial DNA and microbial organic acid metabolites in human faecal samples when compared to frozen samples. Twenty six healthy adult participants were instructed to collect a bowel movement, subsample into collection tubes and immediately transfer the remaining bulk to −20 °C storage. Resulting organic acid concentrations remained comparable across methods when the preservation tubes were used correctly. The 16S rRNA gene sequencing data revealed twenty significantly different bacterial genera between the two collection methods. Ten Gram-negative genera were more abundant in the collection tubes, and ten Gram-positive genera were more abundant in the fresh frozen samples. This study has illustrated that faecal collection methods bias the microbial community profile according to Gram status and this should be considered when designing studies that collect and store human faecal samples.
The DOT1L inhibitor Pinometostat decreases the host-response against infections: Considerations about its use in human therapy
Authors: Marcos-Villar Laura , Nieto Amelia
Published: November 2019

Patients with acute myeloid leukemia frequently present translocations of MLL gene. Rearrangements of MLL protein (MLL-r) in complexes that contain the histone methyltransferase DOT1L are common, which elicit abnormal methylation of lysine 79 of histone H3 at MLL target genes. Phase 1 clinical studies with pinometostat (EPZ-5676), an inhibitor of DOT1L activity, demonstrated the therapeutic potential for targeting DOT1L in MLL-r leukemia patients. We previously reported that down-regulation of DOT1L increases influenza and vesicular stomatitis virus replication and decreases the antiviral response. Here we show that DOT1L inhibition also reduces Sendai virus-induced innate response and its overexpression decreases influenza virus multiplication, reinforcing the notion of DOT1L controlling viral replication. Accordingly, genes involved in the host innate response against pathogens (RUBICON, TRIM25, BCL3) are deregulated in human lung epithelial cells treated with pinometostat. Concomitantly, deregulation of some of these genes together with that of the MicroRNA let-7B, may account for the beneficial effects of pinometostat treatment in patients with MLL-r involving DOT1L. These results support a possible increased vulnerability to infection in MLL-r leukemia patients undergoing pinometostat treatment. Close follow up of infection should be considered in pinometostat therapy to reduce some severe side effects during the treatment.
Immunoproteomic analysis of Borrelia miyamotoi for the identification of serodiagnostic antigens
Authors: Harris Emma K. , Harton Marisa R. , de Mello Marques Maria Angela , Belisle John T. , Molins Claudia R. , Breuner Nicole , Wormser Gary P. , Gilmore Robert D.
Published: November 2019

The tick-borne spirochete,Borrelia miyamotoi, is an emerging pathogen of public health significance. CurrentB.miyamotoiserodiagnostic testing depends on reactivity against GlpQ which is not highly sensitive on acute phase serum samples. Additionally, anti-B.miyamotoiantibodies can cross-react with C6 antigen testing forB.burgdorferi, the causative agent of Lyme disease, underscoring the need for improved serological assays that produce accurate diagnostic results. We performed an immunoproteomics analysis ofB.miyamotoiproteins to identify novel serodiagnostic antigens. Sera from mice infected withB.miyamotoiby subcutaneous inoculation or tick bite were collected for immunoblotting againstB.miyamotoimembrane-associated proteins separated by 2-dimensional electrophoresis (2DE). In total, 88 proteins in 40 2DE immunoreactive spots were identified via mass spectrometry. Multiple variable large proteins (Vlps) and a putative lipoprotein were among those identified and analyzed. Reactivity of anti-B.miyamotoisera against recombinant Vlps and the putative lipoprotein confirmed their immunogenicity. Mouse anti-B.burgdorferiserum was cross-reactive to all recombinant Vlps, but not against the putative lipoprotein by IgG. Furthermore, antibodies against the recombinant putative lipoprotein were present in serum from aB.miyamotoi-infected human patient, but not a Lyme disease patient. Results presented here provide a comprehensive profile ofB.miyamotoiantigens that induce the host immune response and identify a putative lipoprotein as a potentially specific antigen forB.miyamotoiserodetection.
Design of highly efficient phosphor-converted white light-emitting diodes with color rendering indices (R1 − R15) ≥ 95 for artificial lighting
Authors: Ahn Yong Nam , Kim Kyu Do , Anoop Gopinathan , Kim Gab Soo , Yoo Jae Soo
Published: November 2019

Phosphor-converted white light-emitting diodes (pc-WLEDs) are excellent energy-efficient light sources for artificial lighting applications. One goal of artificial lighting is to make objects/images look natural – as they look under the sunlight. The ability of a light source to accurately render the natural color of an object is gauged by the parameter – color rendering index (CRI). A conventional pc-WLED has an average CRI ~ 80, which is very low for accurate color reproduction. To utilize the pc-WLEDs for artificial lighting applications, all the CRI points (R1 – R15) should be above 95. However, there is a trade-off between CRI and luminous efficacy (LER), and it is challenging to increase both CRI and LER. Herein we propose a novel LED package (PKG) design to achieve CRI points ≥95 and efficiency ~100 lm/W by introducing two blue LEDs and a UV LED in combination with green and red phosphors. The silicone encapsulant, the current through the LEDs, and the green/red phosphor ratio were optimized for achieving high CRI and LER. Our re-designed LED PKG will find applications in stadium lighting as well as for ultra-high-definition television production where high CRI points are required for the artificial light source.
Absence of the neutrophil serine protease cathepsin G decreases neutrophil granulocyte infiltration but does not change the severity of acute pancreatitis
Authors: Aghdassi Ali A. , John Daniel S. , Sendler Matthias , Storck Christian , van den Brandt Cindy , Krüger Burkhard , Weiss Frank Ulrich , Mayerle Julia , Lerch Markus M.
Published: November 2019

Acute pancreatitis is characterized by an early intracellular protease activation and invasion of leukocytes into the pancreas. Cathepsins constitute a large group of lysosomal enzymes, that have been shown to modulate trypsinogen activation and neutrophil infiltration. Cathepsin G (CTSG) is a neutrophil serine protease of the chymotrypsin C family known to degrade extracellular matrix components and to have regulatory functions in inflammatory disorders. The aim of this study was to investigate the role of CTSG in pancreatitis. Isolated acinar cells were exposed to recombinant CTSG and supramaximal cholezystokinin stimulation. In CTSG−/− mice and corresponding controls acute experimental pancreatitis was induced by serial caerulein injections. Severity was assessed by histology, serum enzyme levels and zymogen activation. Neutrophil infiltration was quantified by chloro-acetate ersterase staining and myeloperoxidase measurement. CTSG was expessed in inflammatory cells but not in pancreatic acinar cells. CTSG had no effect on intra-acinar-cell trypsinogen activation. In CTSG−/− mice a transient decrease of neutrophil infiltration into the pancreas and lungs was found during acute pancreatitis while the disease severity remained largely unchanged. CTSG is involved in pancreatic neutrophil infiltration during pancreatitis, albeit to a lesser degree than the related neutrophil (PMN) elastase. Its absence therefore leaves pancreatitis severity essentially unaffected.
Efficacy of rodenticide baits with decreased concentrations of brodifacoum: Validation of the impact of the new EU anticoagulant regulation
Authors: Frankova Marcela , Stejskal Vaclav , Aulicky Radek
Published: November 2019

Anticoagulants are the most frequently used rodenticides at the global scale. Because of their persistency, bioaccumulation and potential for secondary intoxication, they have faced increasing legislative regulations. Recently, the European Union Regulation (EU) 2016/1179 resulted in the production and application of rodenticides with nearly half dose (<30 ppm) of anticoagulants. However, published data on the biological efficacy of rodenticides with decreased doses are scarce in the EU. Therefore, this work compared the efficacy of the original high-dose (50 ppm) and new low-dose (25 ppm) brodifacoum-based baits in the offspring of wild-caught house mice (Mus musculus L.). In the no-choice laboratory feeding tests, 100% animals died in all treated groups and 0% died in the control groups. The achieved time to death did not differ between the original and low-dose baits across both types of feeding trials/regimes. The low-dose baits (25 ppm) were consequently tested under field conditions in two populations showing 95.7% and 99.8% efficacy. The obtained results highlighted the good efficacy of the new baits based on low-dose brodifacoum in non-resistant mouse populations. However, further validation is required regarding the remaining anticoagulant compounds and resistant rodent populations.
Serotonin is the main tryptophan metabolite associated with psychiatric comorbidity in abstinent cocaine-addicted patients
Authors: Araos Pedro , Vidal Rebeca , O’Shea Esther , Pedraz María , García-Marchena Nuria , Serrano Antonia , Suárez Juan , Castilla-Ortega Estela , Ruiz Juan Jesús , Campos-Cloute Rafael , Santín Luis J. , Rodríguez de Fonseca Fernando , Pavón Francisco Javier , Colado María Isabel
Published: November 2019

The lack of effective treatments and a high rate of relapse in cocaine addiction constitute a major health problem. The present study was conducted to examine the expression of tryptophan-derived metabolites in the context of cocaine addiction and psychiatric comorbidity, which is common in addicted subjects. Abstinent patients with cocaine use disorder (CUD) and control subjects were recruited for a cross-sectional study. Participants were assessed with a semi-structured diagnostic interview (PRISM) based on DSM-IV-TR for substance and mental disorders. Plasma concentrations of tryptophan metabolites and their association with relevant CUD-related variables and psychiatric comorbidity were explored. We observed decreased plasma kynurenic acid concentrations in the cocaine group, however no associations between CUD-related variables and tryptophan-derived metabolites were found. In contrast, 5-HT concentrations were increased in CUD-patients and the diagnosis of different psychiatric disorders in the cocaine group was related to higher plasma 5-HT concentrations compared with non-comorbid patients. Therefore, while changes in plasma kynurenic acid concentrations appear to be directly associated with lifetime CUD, changes in 5-HT concentrations are associated with psychiatric comorbidity. These results emphasize the need to find potential biomarkers for a better stratification of cocaine-addicted patients in order to develop therapeutic approaches to prevent cocaine relapse.
Heading choices of flying Drosophila under changing angles of polarized light
Authors: Mathejczyk Thomas F. , Wernet Mathias F.
Published: November 2019

Many navigating insects include the celestial polarization pattern as an additional visual cue to orient their travels. Spontaneous orientation responses of both walking and flying fruit flies (Drosophila melanogaster) to linearly polarized light have previously been demonstrated. Using newly designed modular flight arenas consisting entirely of off-the-shelf parts and 3D-printed components we present individual flying flies with a slow and continuous rotational change in the incident angle of linear polarization. Under such open-loop conditions, single flies choose arbitrary headings with respect to the angle of polarized light and show a clear tendency to maintain those chosen headings for several minutes, thereby adjusting their course to the slow rotation of the incident stimulus. Importantly, flies show the tendency to maintain a chosen heading even when two individual test periods under a linearly polarized stimulus are interrupted by an epoch of unpolarized light lasting several minutes. Finally, we show that these behavioral responses are wavelength-specific, existing under polarized UV stimulus while being absent under polarized green light. Taken together, these findings provide further evidence supporting Drosophila’s abilities to use celestial cues for visually guided navigation and course correction.
Role of precursors mixing sequence on the properties of CoMn2O4 cathode materials and their application in pseudocapacitor
Authors: Pattanayak Bhaskar , Simanjuntak Firman Mangasa , Panda Debashis , Yang Chih - Chieh , Kumar Amit , Le Phuoc – Anh , Wei Kung – Hwa , Tseng Tseung –Yuen
Published: November 2019

In this study, the effect of oxygen vacancy in the CoMn2O4 on pseudocapacitive characteristics was examined, and two tetragonal CoMn2O4 spinel compounds with different oxygen vacancy concentrations and morphologies were synthesized by controlling the mixing sequence of the Co and Mn precursors. The mixing sequence was changed; thus, morphologies were changed from spherical nanoparticles to nanoflakes and oxygen vacancies were increased. Electrochemical studies have revealed that tetragonal CoMn2O4 spinels with a higher number of oxygen vacancies exhibit a higher specific capacitance of 1709 F g−1 than those with a lower number of oxygen vacancies, which have a higher specific capacitance of 990 F g−1. Oxygen vacancies create an active site for oxygen ion intercalation. Therefore, oxidation–reduction reactions occur because of the diffusion of oxygen ions at octahedral/tetrahedral crystal edges. The solid-state asymmetric pseudocapacitor exhibits a maximum energy density of 32 Wh-kg−1 and an excellent cyclic stability of nearly 100%.
A human expression system based on HEK293 for the stable production of recombinant erythropoietin
Authors: Chin Christine Lin , Goh Justin Bryan , Srinivasan Harini , Liu Kaiwen Ivy , Gowher Ali , Shanmugam Raghuvaran , Lim Hsueh Lee , Choo Matthew , Tang Wen Qin , Tan Andy Hee-Meng , Nguyen-Khuong Terry , Tan Meng How , Ng Say Kong
Published: November 2019

Mammalian host cell lines are the preferred expression systems for the manufacture of complex therapeutics and recombinant proteins. However, the most utilized mammalian host systems, namely Chinese hamster ovary (CHO), Sp2/0 and NS0 mouse myeloma cells, can produce glycoproteins with non-human glycans that may potentially illicit immunogenic responses. Hence, we developed a fully human expression system based on HEK293 cells for the stable and high titer production of recombinant proteins by first knocking out GLUL (encoding glutamine synthetase) using CRISPR-Cas9 system. Expression vectors using human GLUL as selection marker were then generated, with recombinant human erythropoietin (EPO) as our model protein. Selection was performed using methionine sulfoximine (MSX) to select for high EPO expression cells. EPO production of up to 92700 U/mL of EPO as analyzed by ELISA or 696 mg/L by densitometry was demonstrated in a 2 L stirred-tank fed batch bioreactor. Mass spectrometry analysis revealed that N-glycosylation of the produced EPO was similar to endogenous human proteins and non-human glycan epitopes were not detected. Collectively, our results highlight the use of a human cellular expression system for the high titer and xenogeneic-free production of EPO and possibly other complex recombinant proteins.
Discovery of a potent small molecule inhibiting Huntington’s disease (HD) pathogenesis via targeting CAG repeats RNA and Poly Q protein
Authors: Khan Eshan , Mishra Subodh Kumar , Mishra Ribhav , Mishra Amit , Kumar Amit
Published: November 2019

CAG repeats RNA causes various fatal neurodegenerative diseases exemplified by Huntington’s disease (HD) and several spinocerebellar ataxias (SCAs). Although there are differences in the pathogenic mechanisms, these diseases share the common cause, i.e., expansion of CAG repeats. The shared cause of these diseases raises the possibility for the exploiting the common target as a potential therapeutic approach. Oligonucleotide-based therapeutics are designed earlier with the help of the base pairing rule but are not very promiscuous, considering the nonspecific stimulation of the immune system and the poor cellular delivery. Therefore, small molecules-based therapeutics are preferred for targeting the repeats expansion disorders. Here, we have used the chemical similarity search approach to discern the small molecules that selectively target toxic CAG RNA. The lead compounds showed the specificity towards AA mismatch in biophysical studies including CD, ITC, and NMR spectroscopy and thus aided to forestall the polyQ mediated pathogenicity. Furthermore, the lead compounds also explicitly alleviate the polyQ mediated toxicity in HD cell models and patient-derived cells. These findings suggest that the lead compound could act as a chemical probe for AA mismatch containing RNA as well as plays a neuroprotective role in fatal neurodegenerative diseases like HD and SCAs.
Asymmetric supercapacitor of functionalised electrospun carbon fibers/poly(3,4-ethylenedioxythiophene)/manganese oxide//activated carbon with superior electrochemical performance
Authors: Mohd Abdah Muhammad Amirul Aizat , Azman Nur Hawa Nabilah , Kulandaivalu Shalini , Sulaiman Yusran
Published: November 2019

Asymmetric supercapacitors (ASC) have shown a great potential candidate for high-performance supercapacitor due to their wide operating potential which can remarkably enhance the capacitive behaviour. In present work, a novel positive electrode derived from functionalised carbon nanofibers/poly(3,4-ethylenedioxythiophene)/manganese oxide (f-CNFs/PEDOT/MnO2) was prepared using a multi-step route and activated carbon (AC) was fabricated as a negative electrode for ASC. A uniform distribution of PEDOT and MnO2 on f-CNFs as well as porous granular of AC are well-observed in FESEM. The assembled f-CNFs/PEDOT/MnO2//AC with an operating potential of 1.6 V can achieve a maximum specific capacitance of 537 F/g at a scan rate of 5 mV/s and good cycling stability (81.06% after cycling 8000 times). Furthermore, the as-prepared ASC exhibited reasonably high specific energy of 49.4 Wh/kg and low charge transfer resistance (Rct) of 2.27 Ω, thus, confirming f-CNFs/PEDOT/MnO2//AC as a promising electrode material for the future energy storage system.
Investigation of the curative effects of palm vitamin E tocotrienols on autoimmune arthritis disease in vivo
Authors: Zainal Zaida , Rahim Afiqah Abdul , Radhakrishnan Ammu Kutty , Chang Sui Kiat , Khaza’ai Huzwah
Published: November 2019

The tocotrienol-rich fraction (TRF) from palm oil contains vitamin E, which possesses potent antioxidant and anti-inflammatory activities. Rheumatoid arthritis (RA) is a chronic joint inflammatory disease characterised by severe joint pain, cartilage destruction, and bone erosion owing to the effects of various pro-inflammatory mediators and cytokines. Here, we investigated the therapeutic effects of TRF in a rat model of collagen-induced arthritis (CIA). Arthritis was induced by a single intradermal injection of collagen type II in Dark Agouti (DA) rats. Rats were then treated with or without TRF by oral gavage from day 28 after the first collagen injection. Arthritic rats supplemented with TRF showed decreased articular index scores, ankle circumferences, paw volumes, and radiographic scores when compared with untreated rats. The untreated arthritic rats showed higher plasma C-reactive protein levels (p < 0.05) and production of pro-inflammatory cytokines than arthritic rats fed TRF. Moreover, there was a marked reduction in the severity of histopathological changes observed in arthritic rats treated with TRF compared with that in untreated arthritic rats. Overall, the results show that TRF had beneficial effects in this rat model of RA.
A novel mouse model for septic arthritis induced by Pseudomonas aeruginosa
Authors: Jin Tao , Mohammad Majd , Hu Zhicheng , Fei Ying , Moore Edward R. B. , Pullerits Rille , Ali Abukar
Published: November 2019

Septic arthritis is one of the most aggressive joint diseases. Although caused predominantly byS. aureus, Gram-negative bacteria,Pseudomonas aeruginosaamong them, account for a significant percentage of the causal agents of septic arthritis. However, septic arthritis caused byP. aeruginosahas not been studied thus far, due to lack of an animal model. NMRI mice were inoculated with different doses ofP. aeruginosa. The clinical course of septic arthritis and radiological changes of joints were examined. Furthermore, the host molecular and cellular mechanisms involved inP. aeruginosa-induced septic arthritis were investigated. Inoculation of mice withP. aeruginosacaused septic arthritis in a dose-dependent manner. Neutrophil depletion led to higher mortality and more severe joint destruction (p < 0.01). In contrast, monocyte depletion resulted in higher mortality (p < 0.05) but similar arthritis severity compared to controls. Mice depleted of CD4+ T-cells inoculated withP. aeruginosadisplayed less severe bone damage (p < 0.05). For the first time, a mouse model forP. aeruginosaseptic arthritis is presented. Our data demonstrate that neutrophils play a protective role inP. aeruginosaseptic arthritis. Monocytes/macrophages, on the other hand, are only essential in preventingP. aeruginosa-induced mortality. Finally, CD4+ T-cells are pathogenic inP. aeruginosaseptic arthritis.
Higher Order Architecture of Designer Peptides Forms Bioinspired 10 nm siRNA Delivery System
Authors: Gamboa Alicia , Urfano Selina F. , Hernandez Katrina , Fraser Deborah A. , Ayalew Luladey , Slowinska Katarzyna
Published: November 2019

The higher-order architecture observed in biological systems, like viruses, is very effective in nucleic acid transport. The replications of this system has been attempted with both synthetic and naturally occurring polymers with mixed results. Here we describe a peptide/siRNA quaternary complex that functions as an siRNA delivery system. The rational design of a peptide assembly is inspired by the viral capsids, but not derived from them. We selected the collagen peptide (COL) to provide the structural stability and the folding framework, and hybridize it with the cell penetrating peptide (CPP) that allows for effective penetration of biological barriers. The peptide/siRNA quaternary complex forms stoichiometric, 10 nm nanoparticles, that show fast cellular uptake (<30 min), effective siRNA release, and gene silencing. The complex provides capsid-like protection for siRNA against nucleases without being immunostimulatory, or cytotoxic. Our data suggests that delivery vehicles based on synthetic quaternary structures that exhibit higher-order architecture may be effective in improving delivery and release of nucleic acid cargo.
Metabolic gene alterations impact the clinical aggressiveness and drug responses of 32 human cancers
Authors: Sinkala Musalula , Mulder Nicola , Patrick Martin Darren
Published: November 2019

Malignant cells reconfigure their metabolism to support oncogenic processes such as accelerated growth and proliferation. The mechanisms by which this occurs likely involve alterations to genes that encode metabolic enzymes. Here, using genomics data for 10,528 tumours of 32 different cancer types, we characterise the alterations of genes involved in various metabolic pathways. We find that mutations and copy number variations of metabolic genes are pervasive across all human cancers. Based on the frequencies of metabolic gene alterations, we further find that there are two distinct cancer supertypes that tend to be associated with different clinical outcomes. By utilising the known dose-response profiles of 825 cancer cell lines, we infer that cancers belonging to these supertypes are likely to respond differently to various anticancer drugs. Collectively our analyses define the foundational metabolic features of different cancer supertypes and subtypes upon which discriminatory strategies for treating particular tumours could be constructed.
Identifying fates of cancer cells exposed to mitotic inhibitors by quantitative phase imaging
Authors: Huang Dian , Roy Irena J. , Murray Graeme F. , Reed Jason , Zangle Thomas A. , Teitell Michael A.
Published: November 2019

A novel analysis method for cell fate responses to mitotic inhibitors using biophysical attributes obtained through quantitative phase imaging.
Sensitive photoelectrochemical immunoassay ofStaphylococcus aureusbased on one-pot electrodeposited ZnS/CdS heterojunction nanoparticles
Authors: Yang Hui , Zhao Xiao , Wang Hui , Deng Wenfang , Tan Yueming , Ma Ming , Xie Qingji
Published: November 2019

Sensitive photoelectrochemical immunoassay ofStaphylococcus aureusis described using one-pot electrodeposited ZnS/CdS heterojunction nanoparticles as an optoelectronic material.
PdZn alloy nanoparticles encapsulated within a few layers of graphene for efficient semi-hydrogenation of acetylene
Authors: Yang Lini , Guo Yushu , Long Jun , Xia Lixin , Li Dan , Xiao Jianping , Liu Hongyang
Published: November 2019

PdZn alloy NPs encapsulated within a few layers of graphene exhibit enhanced acetylene selectivity and robust long-term stability in selective hydrogenation of acetylene, compared with that of traditional supported Pd and PdZn alloy catalysts.
Silver-promoted cascade radical cyclization of γ,δ-unsaturated oxime esters with P(O)H compounds: synthesis of phosphorylated pyrrolines
Authors: Chen Chen , Bao Yinwei , Zhao Jinghui , Zhu Bolin
Published: November 2019

We report the first silver-promoted imino-phosphorylation of γ,δ-unsaturated oxime esters with P(O)H compounds to synthesize various phosphorylated pyrrolines.
Morphology of ammonium perchlorate in the presence of ethylene glycol as an additive: a first principle study
Authors: Khan Md Abdul Shafeeuulla , Vijayalakshmi R. , Singh Avtar , Nandi Amiya Kumar , Talawar M. B.
Published: November 2019

Surface energy is an important parameter to predict the morphology of ammonium perchlorate (AP) crystals in the presence and absence of ethylene glycol as a linear correlation is found between the interaction energies and the surface energies.
The axial/equatorial conformational landscape and intramolecular dispersion: new insights from the rotational spectra of monoterpenoids
Authors: Loru Donatella , Vigorito Annalisa , Santos Andreia F. M. , Tang Jackson , Sanz M. Eugenia
Published: November 2019

Using rotational spectroscopy and quantum chemistry calculations, we show that intramolecular dispersion stabilises the axial conformers of monoterpenoids, and that an accurate account of these interactions is challenging for theoretical methods.
Ultrathin nanosheet-anchored hexahedral prismatic Bi2MoO6 arrays: one-step constructed and crystal facet-based homojunctions boosting photocatalytic CO2 reduction and N2 fixation
Authors: Wang Lu , Gao Wa , Zhao Zongyan , Li Ping , He Huichao , Alsaedi Ahmed , Hayat Tasawar , Wang Xiaoyong , Zhou Yong , Zou Zhigang
Published: November 2019

A fascinating Bi2MoO6 homojunction (HJ) array vertically grown on an FTO substrate was built up through a convenient one-step route; the array consisted of ultrathin nanosheet (NS)-anchored hexahedral prismatic nanorods (NR).
The surface hybridization of diamond with vertical graphene: a new route to diamond electronics
Authors: Hembram K. P. S. S. , Lee Sohyung , Im Hyunsik , Ju Hyunsu , Jeong Sang-Hun , Lee Jae-Kap
Published: November 2019

Herein a method is proposed for engineering the electronic properties of diamond via surface hybridization with graphene.
Double C–N bond cleavages of N-alkyl 4-oxopiperidinium salts: access to unsymmetrical tertiary sulfonamides
Authors: Fu Ying , Li Ming-Peng , Shi Chun-Zhao , Li Fang-Rong , Du Zhengyin , Huo Congde
Published: November 2019

In this paper, regiospecific, double intraannular C–N bond cleavages of N-alkyl 4-oxopiperidinium salts are presented.
Hemin-catalyzed biomimetic oxidative phenol–indole [3 + 2] reactions in aqueous media
Authors: Fu Yu , Yu Qile , Zhang Yulong , Gao Zhonghong , Wu Yuzhou , Zhong Fangrui
Published: November 2019

A hemin/H2O2 catalytic system for oxidative phenol–indole [3 + 2] coupling in aqueous solution has been developed, enabling benign synthesis of valuable benzofuroindolines under sustainable conditions.
High responsivity ultraviolet detector based on novel SnO2 nanoarrays
Authors: Pan Xinhua , Zhang Tao , Lu Qiaoqi , Wang Weihao , Ye Zhizhen
Published: November 2019

In this work, tin oxide (SnO2) nanoarrays (NAs) with a novel morphology were fabricated by a hydrothermal method.
Metabolomics biotechnology, applications, and future trends: a systematic review
Authors: Yang Qiang , Zhang Ai-hua , Miao Jian-hua , Sun Hui , Han Ying , Yan Guang-li , Wu Fang-fang , Wang Xi-jun
Published: November 2019

Given the highly increased incidence of human diseases, a better understanding of the related mechanisms regarding endogenous metabolism is urgently needed.
The direct electrochemistry and bioelectrocatalysis of nitrate reductase at a gold nanoparticles/aminated graphene sheets modified glassy carbon electrode
Authors: Zhang Ke , Zhou Hao , Hu Ping , Lu Qing
Published: November 2019

The aminated graphene sheets could immobilize nitrate reductase stably and control its orientation through electrostatic attractions, achieving its direct electrochemistry.
The use of surfactant-filled mesoporous silica as an immobilising medium for a fluorescence lifetime pH indicator, providing long-term calibration stability
Authors: Totland C. , Thomas P. J. , Holst B. , Akhtar N. , Hovdenes J. , Skodvin T.
Published: November 2019

A material support is proposed which grants long-term stability for fluorescence lifetime pH measurements due to a homogeneous chemical microenvironment.
Confinement and activity regulate bacterial motion in porous media
Authors: Bhattacharjee Tapomoy , Datta Sujit S.
Published: November 2019

Direct visualization reveals how bacterial motility in a porous medium is regulated by pore-scale confinement and cellular activity, yielding fundamental insights into the behavior of active matter under confinement.
Multicolor luminescent supramolecular hydrogels based on cucurbit[8]uril and OPV derivative
Authors: Chang Yong-Zhen , Chen Yong , Liu Yu
Published: November 2019

Luminescent supramolecular hydrogels were constructed using photopolymerization, which emitted various tones of blue light.
An ultra-large deformation bidirectional actuator based on a carbon nanotube/PDMS composite and a chitosan film
Authors: Xu Hang , Xu Xiuzhu , Xu Jiawei , Dai Shengping , Dong Xu , Han Feng , Yuan Ningyi , Ding Jianning
Published: November 2019

Actuating materials can convert external stimuli (humidity, light, electricity, etc.) into mechanical energy, and realize multiple forms of movements.
A non-enzymatic electrochemical biosensor based on Au@PBA(Ni–Fe):MoS2 nanocubes for stable and sensitive detection of hydrogen peroxide released from living cells
Authors: Zhang Wang , Wang Chao , Guan Lihao , Peng Meihong , Li Kai , Lin Yuqing
Published: November 2019

Hydrogen peroxide (H2O2) is the main product of enzymatic reactions and plays an important role in biological processes.
Sacrificial additive-assisted film growth endows self-powered CsPbBr3 photodetectors with ultra-low dark current and high sensitivity
Authors: Zhu Weidong , Deng Minyu , Chen Dandan , Chen Dazheng , Xi He , Chang Jingjing , Zhang Jincheng , Zhang Chunfu , Hao Yue
Published: November 2019

A CsPbBr3 film is achieved by a PEAI sacrificial additive-based strategy, endowing a self-powered PD with ultra-low dark current and high sensitivity.
DNA methylation in disease: Immunodeficiency, Centromeric instability, Facial anomalies syndrome
Authors: Vukic Maja , Daxinger Lucia
Published: November 2019

DNA methylation is an epigenetic modification essential for normal mammalian development. Initially associated with gene silencing, more diverse roles for DNA methylation in the regulation of gene expression patterns are increasingly being recognized. Some of these insights come from studying the function of genes that are mutated in human diseases characterized by abnormal DNA methylation landscapes. The first disorder to be associated with congenital defects in DNA methylation was Immunodeficiency, Centromeric instability, Facial anomalies syndrome (ICF). The hallmark of this syndrome is hypomethylation of pericentromeric satellite repeats, with mutations in four genes: DNMT3B, ZBTB24, CDCA7 and HELLS, being linked to the disease. Here, we discuss recent progress in understanding the molecular interactions between these genes and consider current evidence for how aberrant DNA methylation may contribute to the abnormal phenotype present in ICF syndrome patients.