bluuebunny/crossref_metadata_2025 huggingface dataset:
Origin identification of Chinese Maca using electronic nose coupled with GC-MS
Authors: Li Aimin , Duan Shenglin , Dang Yanting , Zhang Xi , Xia Kai , Liu Shiwei , Han Xiaofeng , Wen Jian , Li Zijie , Wang Xi , Liu Jia , Yuan Peng , Gao Xiao-Dong
Published: August 2019

Maca (Lepidium meyeniiWalp.), originated in the high Andes of Peru, is rich in nutrients and phytochemicals. As a new resource food in China, Maca suffers marketing disorders due to the limitation of basic research. Due to the close relationship of Maca quality and origin of place, it’s of scientific, economic and social importance to set up a rapid, reliable and efficient method to identify Maca origin. In the present study, 303 Maca samples were collected from 101 villages of the main producing area in China. Using electronic nose and BP neutral network algorithm, a Maca odor database was set up to trace the origin. GC-MS was then employed to analyze the characteristic components qualitatively and semi-quantitatively. As a result, very significant differences (p < 0.01) were detected in the volatile components of Maca from different areas. This study not only constructs a network model to forecast the Maca origin, but also reveals the relationship between Maca odor fingerprints and origins.
Simulation Analyses of tDCS Montages for the Investigation of Dorsal and Ventral Pathways
Authors: Bhattacharjee Sagarika , Kashyap Rajan , Rapp Brenda , Oishi Kenichi , Desmond John E. , Chen S. H. Annabel
Published: August 2019

Modulating higher cognitive functions like reading with transcranial direct current stimulation (tDCS) can be challenging as reading involves regions in the dorsal and ventral cortical areas that lie in close proximity. If the two pathways are stimulated simultaneously, the function of dorsal pathway (predominantly used for graphophonological conversion) might interfere with the function of the ventral pathway (used for semantics), and vice-versa. To achieve functional specificity in tDCS for investigating the two pathways of reading, it is important to stimulate each pathway per session such that the spread of current across the cortical areas due to the two montages has minimal overlap. The present study intends to achieve this by introducing a systematic approach for tDCS analysis. We employed the COMETS2 software to simulate 10 montage configurations (5 for each pathway) for three electrode sizes: 5 × 5, 3 × 3, and 5 × 7 cm2. This diversity in montage configuration is chosen since previous studies found the position and the size of anode and cathode to play an important role. The values of the magnitude of current density (MCD) obtained from the configuration were used to calculate: (i) average MCD in each cortical lobe, (ii) number of overlapping coordinates, and (iii) cortical areas with high MCD. The measures (i) and (iii) ascertained the current spread by each montage within a cortical lobe, and (ii) verified the overlap of the spread of current between a pair of montages. The analyses show that a montage using the electrode size of 5 × 5 cm2 with the anode at CP5 and cathode at CZ, and another with anode at TP7 and cathode at nape of the neck are optimal choices for dorsal and ventral pathways, respectively. To verify, we cross-validated the results with ROAST. This systematic approach was helpful in reducing the ambiguity of montage selection prior to conducting a tDCS study.
In vitro anti-HIV-1 activity of the bioactive compound extracted and purified from two different marine macroalgae (seaweeds) (Dictyota bartayesiana J.V.Lamouroux and Turbinaria decurrens Bory)
Authors: Sanniyasi Elumalai , Venkatasubramanian Gayathri , Anbalagan Madhu Mitra , Raj Preethy P. , Gopal Rajesh Kanna
Published: August 2019

Highly active antiretroviral therapy (HAART) is the only available remedial measure to treat HIV infected patients, as recognized by the WHO. However, it is associated with toxicity (nephrotoxicity), high cost and most preferably drug resistance in the first-line treatment. Wherefore, potential and novel natural source is the only option for the modern world to challenge this global issue. In recent years, sulfated polysaccharide from marine macroalgae shown to be biologically active as anti-inflammatory, anticoagulant, antitumor, immunomodulatory and antiviral agents. As a direct inhibitor of HIV including other retroviruses, it is considered as a “new generation antiretroviral drug”. In our present study, Fucoidan, a sulfated polysaccharide has been extracted from two different macroalgae Dictyota bartayesiana (DD) and Turbinaria decurrens (TD) based on hot water extraction method and further confirmed by FT-IR and RP-HPLC methods. Both the crude and purified fucoidan samples were evaluated for anti-HIV activity after ion exchange chromatography purification. The maximum inhibitory activity of crude and purified fucoidan samples are 90.5% and 89% in the fucoidan extracts of DD. Whereas, it was 89.7% and 92% in the fucoidan extracts of TD. Simultaneously, the IC50 values were determined and recorded as 1.56 µg/ml and 57.6 ng/ml in both the crude and purified fucoidan extracts of DD respectively. Similarly, for TD, it was 3 µg/ml and 131.7 ng/ml in the fucoidan extracts of TD. Therefore, further extensive research work is the most needful to fill the gaps to develop this sulfated polysaccharide as a potential drug for the treatment of HIV patients.
Differential fracture response to traumatic brain injury suggests dominance of neuroinflammatory response in polytrauma
Authors: Morioka Kazuhito , Marmor Yotvat , Sacramento Jeffrey A. , Lin Amity , Shao Tiffany , Miclau Katherine R. , Clark Daniel R. , Beattie Michael S. , Marcucio Ralph S. , Miclau Theodore , Ferguson Adam R. , Bresnahan Jacqueline C. , Bahney Chelsea S.
Published: August 2019

Polytraumatic injuries, specifically long bone fracture and traumatic brain injury (TBI), frequently occur together. Clinical observation has long held that TBI can accelerate fracture healing, yet the complexity and heterogeneity of these injuries has produced conflicting data with limited information on underlying mechanisms. We developed a murine polytrauma model with TBI and fracture to evaluate healing in a controlled system. Fractures were created both contralateral and ipsilateral to the TBI to test whether differential responses of humoral and/or neuronal systems drove altered healing patterns. Our results show increased bone formation after TBI when injuries occur contralateral to each other, rather than ipsilateral, suggesting a role of the nervous system based on the crossed neuroanatomy of motor and sensory systems. Analysis of the humoral system shows that blood cell counts and inflammatory markers are differentially modulated by polytrauma. A data-driven multivariate analysis integrating all outcome measures showed a distinct pathological state of polytrauma and co-variations between fracture, TBI and systemic markers. Taken together, our results suggest that a contralateral bone fracture and TBI alter the local neuroinflammatory state to accelerate early fracture healing. We believe applying a similar data-driven approach to clinical polytrauma may help to better understand the complicated pathophysiological mechanisms of healing.
Specimen Collection for Translational Studies in Hidradenitis Suppurativa
Authors: Byrd A. S. , Dina Y. , Okoh U. J. , Quartey Q. Q. , Carmona-Rivera C. , Williams D. W. , Kerns M. L. , Miller R. J. , Petukhova L. , Naik H. B. , Barnes L. A. , Shipman W. D. , Caffrey J. A. , Sacks J. M. , Milner S. M. , Aliu O. , Broderick K. P. , Kim D. , Liu H. , Dillen C. A. , Ahn R. , Frew J. W. , Kaplan M. J. , Kang S. , Garza L. A. , Miller L. S. , Alavi A. , Lowes M. A. , Okoye G. A.
Published: August 2019

Hidradenitis suppurativa (HS) is a chronic inflammatory disorder characterized by painful nodules, sinus tracts, and scars occurring predominantly in intertriginous regions. The prevalence of HS is currently 0.053–4%, with a predominance in African-American women and has been linked to low socioeconomic status. The majority of the reported literature is  retrospective, population based, epidemiologic studies. In this regard, there is a need to establish a repository of biospecimens, which represent appropriate gender and racial demographics amongst HS patients. These efforts will diminish knowledge gaps in understanding the disease pathophysiology. Hence, we sought to outline a step-by-step protocol detailing how we established our HS biobank to facilitate the formation of other HS tissue banks. Equipping researchers with carefully detailed processes for collection of HS specimens would accelerate the accumulation of well-organized human biological material. Over time, the scientific community will have access to a broad range of HS tissue biospecimens, ultimately leading to more rigorous basic and translational research. Moreover, an improved understanding of the pathophysiology is necessary for the discovery of novel therapies for this debilitating disease. We aim to provide high impact translational research methodology for cutaneous biology research and foster multidisciplinary collaboration and advancement of our understanding of cutaneous diseases.
High Density Genetic Maps of Seashore Paspalum Using Genotyping-By-Sequencing and Their Relationship to The Sorghum Bicolor Genome
Authors: Qi Peng , Eudy Douglas , Schnable James C. , Schmutz Jeremy , Raymer Paul L. , Devos Katrien M.
Published: August 2019

As a step towards trait mapping in the halophyte seashore paspalum (Paspalum vaginatum Sw.), we developed an F1 mapping population from a cross between two genetically diverse and heterozygous accessions, 509022 and HI33. Progeny were genotyped using a genotyping-by-sequencing (GBS) approach and sequence reads were analyzed for single nucleotide polymorphisms (SNPs) using the UGbS-Flex pipeline. More markers were identified that segregated in the maternal parent (HA maps) compared to the paternal parent (AH maps), suggesting that 509022 had overall higher levels of heterozygosity than HI33. We also generated maps that consisted of markers that were heterozygous in both parents (HH maps). The AH, HA and HH maps each comprised more than 1000 markers. Markers formed 10 linkage groups, corresponding to the ten seashore paspalum chromosomes. Comparative analyses showed that each seashore paspalum chromosome was syntenic to and highly colinear with a single sorghum chromosome. Four inversions were identified, two of which were sorghum-specific while the other two were likely specific to seashore paspalum. These high-density maps are the first available genetic maps for seashore paspalum. The maps will provide a valuable tool for plant breeders and others in the Paspalum community to identify traits of interest, including salt tolerance.
Spermatogenesis in haploid males of the jewel wasp Nasonia vitripennis
Authors: Ferree Patrick M. , Aldrich John C. , Jing Xueyuan A. , Norwood Christopher T. , Van Schaick Mary R. , Cheema Manjinder S. , Ausió Juan , Gowen Brent E.
Published: August 2019

Males of hymenopteran insects, which include ants, bees and wasps, develop as haploids from unfertilized eggs. In order to accommodate their lack of homologous chromosome pairs, some hymenopterans such as the honeybee have been shown to produce haploid sperm through an abortive meiosis. We employed microscopic approaches to visualize landmark aspects of spermatogenesis in the jewel wasp Nasonia vitripennis, a model for hymenopteran reproduction and development. Our work demonstrates that N. vitripennis, like other examined hymenopterans, exhibits characteristics indicative of an abortive meiosis, including slight enlargement of spermatocytes preceding meiotic initiation. However, we saw no evidence of cytoplasmic buds containing centrioles that are produced from the first abortive meiotic division, which occurs in the honeybee. In contrast to other previously studied hymenopterans, N. vitripennis males produce sperm in bundles that vary widely from 16 to over 200, thus reflecting a range of cellular divisions. Our results highlight interesting variations in spermatogenesis among the hymenopteran insects, and together with previous studies, they suggest a pattern of progression from meiosis to a more mitotic state in producing sperm.
Transient multimers modulate conformer abundances of prion protein monomer through conformational selection
Authors: Van der Rest Guillaume , Rezaei Human , Halgand Frédéric
Published: August 2019

Prions are known to be involved in neurodegenerative pathologies such as Creutzfeld-Jakob disease. Current models point to a molecular event which rely on a transmissible structural change that leads to the production of β-sheet-rich prion conformer (PrPSc). PrPSc itself has the capability to trigger the structural rearrangement of the ubiquitously present prion (PrPc) substrate in a self-perpetuating cascade. In this article, we demonstrate that recombinant PrPc exists in a conformational equilibrium. The conformers’ abundances were shown to be dependent on PrPc concentration through the formation of transient multimers leading to conformational selection. The study of PrPc mutants that follow dedicated oligomerization pathways demonstrated that the conformers’ relative abundances are modified, thus reinforcing the assertion that the nature of conformers’ interactions orient the oligomerization pathways. Further this result can be viewed as the “signature” of an aborted oligomerization process. This discovery sheds a new light on the possible origin of prion protein diseases, namely that a change in prion protein structure could be transmitted through the formation of transient multimers having different conformer compositions. This could explain the selection of a transient multimeric type that could be viewed as the precursor of PrPSc responsible for structural information transmission, and strain apparition.
High temperature AlInP X-ray spectrometers
Authors: Zhao S. , Butera S. , Lioliou G. , Krysa A. B. , Barnett A. M.
Published: August 2019

Two custom-made Al0.52In0.48P p+-i-n+ mesa photodiodes with different diameters (217 µm ± 15 µm and 409 µm ± 28 µm) and i layer thicknesses of 6 µm have been electrically characterised over the temperature range 0 °C to 100 °C. Each photodiode was then investigated as a high-temperature-tolerant photon counting X-ray detector by connecting it to a custom-made low-noise charge-sensitive preamplifier and illuminating it with an 55Fe radioisotope X-ray source (Mn Kα = 5.9 keV; Mn Kβ = 6.49 keV). At 100 °C, the best energy resolutions (full width at half maximum at 5.9 keV) achieved using the 217 µm ± 15 µm diameter photodiode and the 409 µm ± 28 µm diameter photodiode were 1.31 keV ± 0.04 keV and 1.64 keV ± 0.08 keV, respectively. Noise analysis of the system is presented. The dielectric dissipation factor of Al0.52In0.48P was estimated as a function of temperature, up to 100 °C. The results show the performance of the thickest Al0.52In0.48P X-ray detectors so far reported at high temperature. The work has relevance for the development of novel space science instrumentation for use in hot space environments and extreme terrestrial applications.
Dynamics and diversity of bacteria associated with the disease vectors Aedes aegypti and Aedes albopictus
Authors: Bennett Kelly L. , Gómez-Martínez Carmelo , Chin Yamileth , Saltonstall Kristin , McMillan W. Owen , Rovira Jose R. , Loaiza Jose R.
Published: August 2019

Aedes aegypti and Aedes albopictus develop in the same aquatic sites where they encounter microorganisms that influence their life history and capacity to transmit human arboviruses. Some bacteria such as Wolbachia are currently being considered for the control of Dengue, Chikungunya and Zika. Yet little is known about the dynamics and diversity of Aedes-associated bacteria, including larval habitat features that shape their tempo-spatial distribution. We applied large-scale 16S rRNA amplicon sequencing to 960 adults and larvae of both Ae. aegypti and Ae. albopictus mosquitoes from 59 sampling sites widely distributed across nine provinces of Panama. We find both species share a limited, yet highly variable core microbiota, reflecting high stochasticity within their oviposition habitats. Despite sharing a large proportion of microbiota, Ae. aegypti harbours higher bacterial diversity than Ae. albopictus, primarily due to rarer bacterial groups at the larval stage. We find significant differences between the bacterial communities of larvae and adult mosquitoes, and among samples from metal and ceramic containers. However, we find little support for geography, water temperature and pH as predictors of bacterial associates. We report a low incidence of natural Wolbachia infection for both Aedes and its geographical distribution. This baseline information provides a foundation for studies on the functions and interactions of Aedes-associated bacteria with consequences for bio-control within Panama.
Differential expression of miRNAs and their targets in wax-deficient rapeseed
Authors: Liu Tingting , Tang Jingquan , Chen Li , Zeng Jiayue , Wen Jing , Yi Bin , Ma Chaozhi , Tu Jinxing , Fu Tingdong , Shen Jinxiong
Published: August 2019

The cuticle of a plant, composed of cutin and wax, is the outermost hydrophobic layer covering the epidermis of all its aerial organs, protecting it from many abiotic and biotic stresses. The biosynthesis and regulation pathways of wax components have been well studied, whereas there are fewer reports on the small RNA-involved post-transcriptional regulation of wax biosynthesis in plants, particularly in Brassica napus. Previously, we conducted a study on a glossy mutant of rapeseed, and we assumed that there was a dominant repressor to inhibit the expression of wax-related genes. To verify this hypothesis and investigate the function of small RNAs in wax biosynthesis in B. napus, we constructed four small RNA libraries from the stem epidermis of wax-deficient mutant and wild-type plants for sequencing. Subsequently, 43,840,451 clean reads were generated and 24 nt sequences represented the dominant percentage. In total, 300 unique known miRNAs were identified and eight of them showed differential expression. In addition, the expression levels of six novel miRNAs were altered. Surprisingly, we found that four up-regulated miRNAs in the wax-deficient plants, bna-miR408b-5p, bna-miR165b-5p, bna-miR160a-3p, and bna-miR398-5p, were all complementary strands of their corresponding mature strands. Stem-loop qRT-PCR verified that the expression of bna-miR165a-5p was increased in the mutant stems, while its putative target, BnaA06g40560D (CYP96A2), was down-regulated. In addition, the expression of bna-miR827a was detected to be down-regulated in glossy mutant. 5′ RACE experimental data showed that bna-miR827a cleaves three NITROGEN LIMITATION ADAPTATION (NLA) genes (BnaC08g45940D, BnaA10g01450D and BnaC05g01480D). The down-regulation of bna-miR827a resulted in decreased cleavage on its targets, and led to the up-regulation of its targets, especially BnaA10g01450D gene. These results showed that bna-miR165a-5p might participate in wax biosynthesis process by regulating its putative target BnaA06g40560D (CYP96A2). The expression levels of a phosphate (Pi)-related miRNA, bna-miR827a, and its target genes were affected in wax-deficient rapeseeds. These results will promote the study of post-transcriptional regulation mechanisms of wax biosynthesis in B. napus and provide new directions for further research.
Catalytically Impaired TYK2 Variants are Protective Against Childhood- and Adult-Onset Systemic Lupus Erythematosus in Mexicans
Authors: Contreras-Cubas Cecilia , García-Ortiz Humberto , Velázquez-Cruz Rafael , Barajas-Olmos Francisco , Baca Paulina , Martínez-Hernández Angélica , Barbosa-Cobos Rosa Elda , Ramírez-Bello Julian , López-Hernández Maria A. , Svyryd Yevgeniya , Mutchinick Osvaldo M. , Baca Vicente , Orozco Lorena
Published: August 2019

Type I interferon (IFN-I) pathway plays a central role in the systemic lupus erythematosus (SLE) pathogenesis. Recent data suggest that SLE is associated with variants in IFN-I genes, such as tyrosine kinase 2 (TYK2), which is crucial in anti-viral immunity. Here, five TYK2 single nucleotide polymorphisms (SNPs) were genotyped in 368 childhood-onset SLE Mexican patients and 516 sex-matched healthy controls. Allele frequencies were also estimated in four indigenous groups. SLE protection was associated with TYK2 risk infection variants affecting residually its catalytic domain, rs12720356 (OR = 0.308; p = 0.041) and rs34536443 (OR = 0.370; p = 0.034), but not with rs2304256, rs12720270, and rs280500. This association was replicated in a 506 adult-onset SLE patients sample (OR = 0.250; p = 0.005, and OR = 0.277; p = 0.008, respectively). The minor alleles of both associated SNPs had a lower frequency in Mestizos than in Spaniards and were absent or rare in indigenous, suggesting that the presence of these alleles in the Mexican Mestizo population was derived from the Spaniards. For the first time, we report genetic variants with a protective effect in childhood- and adult-onset SLE Mexican population. Our results suggest that the frequency of IFN-I alleles associated with SLE, may have been shaped in populations exposed to infectious diseases for long periods, and this could be an explanation why Native American ancestry is associated with a higher SLE prevalence and an earlier onset.
Lyssavirus matrix protein cooperates with phosphoprotein to modulate the Jak-Stat pathway
Authors: Sonthonnax Florian , Besson Benoit , Bonnaud Emilie , Jouvion Grégory , Merino David , Larrous Florence , Bourhy Hervé
Published: August 2019

Phosphoprotein (P) and matrix protein (M) cooperate to undermine the immune response to rabies virus (RABV) infections. While P is involved in the modulation of the Jak-Stat pathway through the cytoplasmic retention of interferon (IFN)-activated STAT1 (pSTAT1), M interacts with the RelAp43-p105-ABIN2-TPL2 complex, to efficiently inhibit the nuclear factor-κB (NF-κB) pathway. Using transfections, protein-complementation assays, reverse genetics and DNA ChIP, we identified a role of M protein in the control of Jak-Stat signaling pathway, in synergy with the P protein. In unstimulated cells, both M and P proteins were found to interact with JAK1. Upon type-I IFN stimulation, the M switches toward pSTAT1 interaction, which results in an enhanced capacity of P protein to interact with pSTAT1 and restrain it in the cytoplasm. Furthermore, the role for M-protein positions 77, 100, 104 and 110 was also demonstrated in interaction with both JAK1 and pY-STAT1, and confirmed in vivo. Together, these data indicate that M protein cooperates with P protein to restrain in parallel, and sequentially, NF-κB and Jak-Stat pathways.
Robust Microfabrication of Highly Parallelized Three-Dimensional Microfluidics on Silicon
Authors: Yadavali Sagar , Lee Daeyeon , Issadore David
Published: August 2019

We present a new, robust three dimensional microfabrication method for highly parallel microfluidics, to improve the throughput of on-chip material synthesis by allowing parallel and simultaneous operation of many replicate devices on a single chip. Recently, parallelized microfluidic chips fabricated in Silicon and glass have been developed to increase the throughput of microfluidic materials synthesis to an industrially relevant scale. These parallelized microfluidic chips require large arrays (>10,000) of Through Silicon Vias (TSVs) to deliver fluid from delivery channels to the parallelized devices. Ideally, these TSVs should have a small footprint to allow a high density of features to be packed into a single chip, have channels on both sides of the wafer, and at the same time minimize debris generation and wafer warping to enable permanent bonding of the device to glass. Because of these requirements and challenges, previous approaches cannot be easily applied to produce three dimensional microfluidic chips with a large array of TSVs. To address these issues, in this paper we report a fabrication strategy for the robust fabrication of three-dimensional Silicon microfluidic chips consisting of a dense array of TSVs, designed specifically for highly parallelized microfluidics. In particular, we have developed a two-layer TSV design that allows small diameter vias (d < 20 µm) without sacrificing the mechanical stability of the chip and a patterned SiO2 etch-stop layer to replace the use of carrier wafers in Deep Reactive Ion Etching (DRIE). Our microfabrication strategy allows >50,000 (d = 15 µm) TSVs to be fabricated on a single 4” wafer, using only conventional semiconductor fabrication equipment, with 100% yield (M = 16 chips) compared to 30% using previous approaches. We demonstrated the utility of these fabrication strategies by developing a chip that incorporates 20,160 flow focusing droplet generators onto a single 4” Silicon wafer, representing a 100% increase in the total number of droplet generators than previously reported. To demonstrate the utility of this chip for generating pharmaceutical microparticle formulations, we generated 5–9 µm polycaprolactone particles with a CV < 5% at a rate as high as 60 g/hr (>1 trillion particles/hour).
Disease-specific and glucocorticoid-responsive serum biomarkers for Duchenne Muscular Dystrophy
Authors: Hathout Yetrib , Liang Chen , Ogundele Michael , Xu Ganggang , Tawalbeh Shefa M. , Dang Utkarsh J , Hoffman Eric P. , Gordish-Dressman Heather , Conklin Laurie S. , van den Anker John N. , Clemens Paula R. , Mah Jean K. , Henricson Erik , McDonald Craig
Published: August 2019

Extensive biomarker discoveries for DMD have occurred in the past 7 years, and a vast array of these biomarkers were confirmed in independent cohorts and across different laboratories. In these previous studies, glucocorticoids and age were two major confounding variables. In this new study, using SomaScan technology and focusing on a subset of young DMD patients who were not yet treated with glucocorticoids, we identified 108 elevated and 70 decreased proteins in DMD relative to age matched healthy controls (p value < 0.05 after adjusting for multiple testing). The majority of the elevated proteins were muscle centric followed by cell adhesion, extracellular matrix proteins and a few pro-inflammatory proteins. The majority of decreased proteins were of cell adhesion, however, some had to do with cell differentiation and growth factors. Subsequent treatment of this group of DMD patients with glucocorticoids affected two major groups of pharmacodynamic biomarkers. The first group consisted of 80 serum proteins that were not associated with DMD and either decreased or increased following treatment with glucocorticoids, and therefore were reflective of a broader effect of glucocorticoids. The second group consisted of 17 serum proteins that were associated with DMD and these tended to normalize under treatment, thus reflecting physiologic effects of glucocorticoid treatment in DMD. In summary, we have identified a variety of circulating protein biomarkers that reflect the complex nature of DMD pathogenesis and response to glucocorticoids.
Inhibition of GATA2 restrains cell proliferation and enhances apoptosis and chemotherapy mediated apoptosis in human GATA2 overexpressing AML cells
Authors: Menendez-Gonzalez Juan Bautista , Sinnadurai Samantha , Gibbs Alex , Thomas Leigh-anne , Konstantinou Maria , Garcia-Valverde Alfonso , Boyer Magali , Wang Zhengke , Boyd Ashleigh S. , Blair Allison , Morgan Rhys G. , Rodrigues Neil P.
Published: August 2019

GATA2, a zinc finger transcription factor predominantly expressed in hematopoietic cells, acts as an essential regulator of hematopoietic stem cell generation, survival and functionality. Loss and gain of GATA2 expression has been implicated in myelodysplastic syndrome and acute myeloid leukemia (AML) yet the precise biological impact of GATA2 expression on human AML cell fate decisions remains ambiguous. Herein, we performed large-scale bioinformatics that demonstrated relatively frequent GATA2 overexpression in AML patients as well as select human AML (or AML-like) cell lines. By using shRNAi to target GATA2 in these AML cell lines, and an AML cell line expressing normal levels of GATA2, we found that inhibition of GATA2 caused attenuated cell proliferation and enhanced apoptosis exclusively in AML cell lines that overexpress GATA2. We proceeded to pharmacologically inhibit GATA2 in concert with AML chemotherapeutics and found this augmented cell killing in AML cell lines that overexpress GATA2, but not in an AML cell line expressing normal levels of GATA2. These data indicate that inhibition of GATA2 enhances chemotherapy-mediated apoptosis in human AML cells overexpressing GATA2. Thus, we define novel insights into the oncogenic role of GATA2 in human AML cells and suggest the potential utilization of transient GATA2 therapeutic targeting in AML.
Advancement through epidermis using tape stripping technique and Reflectance Confocal Microscopy
Authors: Olesen Caroline Meyer , Fuchs Christine Sofie Krohn , Philipsen Peter Alshede , Hædersdal Merete , Agner Tove , Clausen Maja-Lisa
Published: August 2019

The tape stripping technique is increasingly used in research regarding skin barrier function. However, number of tape strips varies between studies, and literature considering advancement into stratum corneum/epidermis in relation to number of tape strips is scarce. The aim of this pilot study was to assess the advancement through epidermis using tape stripping technique in healthy volunteers. A total of ten healthy volunteers were included. From all volunteers 0, 5, 15 and 35 consecutive tape strips (D-squame) were taken from four adjacent skin areas on the middle volar forearm, followed by Reflectance Confocal Microscopy (RCM) of the four areas to assess epidermal thickness. Squame Scan was used to determine amount of protein removed. Stratum corneum was completely removed in all volunteers after 35 tape strips. Advancement into epidermis was predominantly achieved by the first 15 tape strips, removing 25% of the total epidermis, whereas 35 tape strips removed 33% of epidermis. Protein removal per tape decreased with increasing depth. Information on advancement into the epidermis according to number of tape strips taken, is a significant step forward. The possibility to obtain samples from different layers of epidermis may lead to an improved understanding of skin barrier properties.
Pessimistic outcome expectancy does not explain ambiguity aversion in decision-making under uncertainty
Authors: Ahrends C. , Bravo F. , Kringelbach M. L. , Vuust P. , Rohrmeier M. A.
Published: August 2019

When faced with a decision, most people like to know the odds and prefer to avoid ambiguity. It has been suggested that this aversion to ambiguity is linked to people’s assumption of worst possible outcomes. We used two closely linked behavioural tasks in 78 healthy participants to investigate whether such pessimistic prior beliefs can explain ambiguity aversion. In the risk-taking task, participants had to decide whether or not they place a bet, while in the beliefs task, participants were asked what they believed would be the outcome. Unexpectedly, we found that in the beliefs task, participants were not overly pessimistic about the outcome in the ambiguity condition and in fact closer to optimal levels of decision-making than in the risk conditions. While individual differences in pessimism could explain outcome expectancy, they had no effect on ambiguity aversion. Consequently, ambiguity aversion is more likely caused by general caution than by expectation of negative outcomes despite pessimism-dependent subjective weighting of probabilities.
Neuromuscular and biomechanical functions subserving finger dexterity in musicians
Authors: Kimoto Yudai , Oku Takanori , Furuya Shinichi
Published: August 2019

Exceptional finger dexterity enables skillful motor actions such as those required for musical performance. However, it has been not known whether and in what manner neuromuscular or biomechanical features of the fingers subserve the dexterity. We aimed to identify the features firstly differentiating the finger dexterity between trained and untrained individuals and secondly accounting for the individual differences in the dexterity across trained individuals. To this aim, two studies were conducted. The first study compared the finger dexterity and several neuromuscular and biomechanical characteristics of the fingers between pianists and non-musicians. As a measure of the dexterity, we used the maximum rate of repetitive finger movements. The results showed no differences in any biomechanical constraints of the fingers between the two groups (i.e. anatomical connectivity between the fingers and range of motion). However, the pianists exhibited faster finger movements and more independent control of movements between the fingers. These observations indicate expertise-dependent enhancement of the finger dexterity and reduction of neuromuscular constraints on movement independence between the fingers. The second study assessed individual differences in the finger dexterity between trained pianists. A penalized regression determined an association of the maximum movement speed of the fingers with both muscular strength and biomechanical characteristics of the fingers, but not with neuromuscular constraints of the fingers. None of these features covaried with measures of early and deliberate piano practice. These findings indicate that distinct biological factors of finger motor dexterity differentiate between the effects of piano practicing and individual differences across skilled pianists.
Human metallo-β-lactamase enzymes degrade penicillin
Authors: Diene Seydina M. , Pinault Lucile , Keshri Vivek , Armstrong Nicholas , Khelaifia Saber , Chabrière Eric , Caetano-Anolles Gustavo , Colson Philippe , La Scola Bernard , Rolain Jean-Marc , Pontarotti Pierre , Raoult Didier
Published: August 2019

Nonribosomal peptides are assemblages, including antibiotics, of canonical amino acids and other molecules. β-lactam antibiotics act on bacterial cell walls and can be cleaved by β-lactamases. β-lactamase activity in humans has been neglected, even though eighteen enzymes have already been annotated such in human genome. Their hydrolysis activities on antibiotics have not been previously investigated. Here, we report that human cells were able to digest penicillin and this activity was inhibited by β-lactamase inhibitor, i.e. sulbactam. Penicillin degradation in human cells was microbiologically demonstrated on Pneumococcus. We expressed a MBLAC2 human β-lactamase, known as an exosome biogenesis enzyme. It cleaved penicillin and was inhibited by sulbactam. Finally, β-lactamases are widely distributed, archaic, and have wide spectrum, including digesting anticancer and β-lactams, that can be then used as nutriments. The evidence of the other MBLAC2 role as a bona fide β-lactamase allows for reassessment of β-lactams and β-lactamases role in humans.
RTMS parameters in tinnitus trials: a systematic review
Authors: Schoisswohl Stefan , Agrawal Kushal , Simoes Jorge , Neff Patrick , Schlee Winfried , Langguth Berthold , Schecklmann Martin
Published: August 2019

Over the past few years extensive body of research was produced investigating the effects of repetitive transcranial magnetic stimulation (rTMS) for the treatment of chronic tinnitus with heterogeneous results. This heterogeneity is exemplified by two recently published large-scale clinical trials reporting different outcomes. Technical aspects of rTMS were suspected as a potential source for this incongruency. The aim of this systematic review is to examine the overall efficacy as well as to identify possible technical factors relevant for the effectiveness of rTMS tinnitus trials. Via a literature search appropriate original research papers were identified and rTMS parameters were extracted from each study arm for subsequent statistical analysis with respect to observed effects (significant vs. not significant pre-post rTMS effects). Our findings indicate that verum rTMS is superior to sham rTMS as demonstrated by the proportion of significant pre-post contrasts. Some relevant rTMS parameters (e.g., pulse waveform) are not reported. Lower rTMS stimulation intensity was associated with significant effects in verum rTMS arms. An additional stimulation of the DLPFC to the temporal cortex was not found to promote efficacy. Future research should consider differential effects of rTMS induced by technical parameters and strive for an exhaustive reporting of relevant rTMS parameters.
Graphene–ferroelectric transistors as complementary synapses for supervised learning in spiking neural network
Authors: Chen Yangyang , Zhou Yue , Zhuge Fuwei , Tian Bobo , Yan Mengge , Li Yi , He Yuhui , Miao Xiang Shui
Published: August 2019

The hardware design of supervised learning (SL) in spiking neural network (SNN) prefers 3-terminal memristive synapses, where the third terminal is used to impose supervise signals. In this work we address this demand by fabricating graphene transistor gated through organic ferroelectrics of polyvinylidene fluoride. Through gate tuning not only is the nonvolatile and continuous change of graphene channel conductance demonstrated, but also the transition between electron-dominated and hole-dominated transport. By exploiting the adjustable bipolar characteristic, the graphene–ferroelectric transistor can be electrically reconfigured as potentiative or depressive synapse and in this way complementary synapses are realized. The complementary synapse and neuron circuit is then constructed to execute remote supervise method (ReSuMe) of SNN, and quick convergence to successful learning is found through network-level simulation when applying to a SL task of classifying 3 × 3-pixel images. The presented design of graphene–ferroelectric transistor-based complementary synapses and quantitative simulation may indicate a potential approach to hardware implementation of SL in SNN.
High-speed low-crosstalk detection of a 171Yb+ qubit using superconducting nanowire single photon detectors
Authors: Crain Stephen , Cahall Clinton , Vrijsen Geert , Wollman Emma E. , Shaw Matthew D. , Verma Varun B. , Nam Sae Woo , Kim Jungsang
Published: August 2019

Qubits used in quantum computing suffer from errors, either from the qubit interacting with the environment, or from imperfect quantum logic gates. Effective quantum error correcting codes require a high fidelity readout of ancilla qubits from which the error syndrome can be determined without affecting data qubits. Here, we present a detection scheme for 171Yb+ qubits, where we use superconducting nanowire single photon detectors and utilize photon time-of-arrival statistics to improve the fidelity and speed. Qubit shuttling allows for creating a separate detection region where an ancilla qubit can be measured without disrupting a data qubit. We achieve an average qubit state detection time of 11 μs with a fidelity of 99.931(6). The detection crosstalk error, defined as the probability that the data qubit coherence is lost due to the process of detecting an ancilla qubit, is reduced to ~2 × 10−5 by creating a separation of 370 μm between them.
Structure, Function, Orientation, Characterization and Immobilization of Antibodies for Immunosensor Development
Authors: Bhand Sunil , Singh Aruna Chandra
Published: August 2019

Immunosensors are a class of biosensing devices that use different bioreceptors such as antibodies, adhirons and aptamers. Antibodies are widely used key molecules for the detection of various analytes as they have a specific analyte binding site. According to recent research, the disulfide linkage located at the hinge region of an antibody can be used for generating half-antibody fragments. Other than this, the generated free-SH group can be used to offer oriented immobilization with the freely available antigen binding site that leads to an increase in accessibility for antigens and a decrease in variable interaction kinetics. Immunosensor capabilities i.e. selectivity and specificity, depend upon the orientation of antibodies and can be categorized based on the appropriate detection principle. These include surface modification with self-assembled monolayers, three-dimensional substrates and molecular imprinting, covalent binding (including targeting amine, carboxyl group, thiol coupling and carbodiimide linkage). Stability depends on bio affinity towards biotin–streptavidin interaction, material binding peptides, directed immobilization through DNA, protein binding peptides, metal affinity, and aptamers. Different transducing mechanisms are employed in the immunological development of biosensors; the preferred developments are based on optical and electrochemical immunosensing principles. In distinction to immunoassay, recent transducer technology allows the label-free quantification and detection of immune systems.
Electrochemical Magneto-immunosensors as Fast and Efficient Tools for Point-of-care Diagnostics
Authors: Ruiz-Vega Gisela , Lopez-Marzo Adaris , de-la-Serna Erica , Sanchez-Cano Ana , Baldrich Eva
Published: August 2019

Electrochemical magneto-immunosensors employ magnetic particles (MP) for analyte specific binding and pre-concentration, before the electrochemical detection (ED) of the assay takes place. This provides faster and more efficient analyte immunocapture than binding on two-dimensional structures and higher signals than classical immunosensing. In this context, electrochemical detection supplies high sensitivity and fast signal generation using robust and potentially miniaturised measurement equipment and transducers. However, MP handling is slightly more complex for end-users and more difficult to integrate in inexpensive point-of-care (POC) devices than manipulation of classical biosensors. In this chapter, we discuss some of the clues for the successful optimisation of electrochemical magneto-immunosensors and we review the attempts made to automate immuno-magnetic binding and operate electrochemical magneto-immunosensors using low-cost POC devices.
Immunosensors Using Screen-printed Electrodes
Authors: Cheeveewattanagul N. , Buppasirakul S. , Surareungchai W.
Published: August 2019

Immunosensors are prospective tools to transform analytical methods by providing a highly specific, rapid, and inexpensive detection for use in various fields of monitoring. In this chapter, screen printing technology is used to combine different strategies with recognition molecules modified on screen-printed based electrodes for immunocomplex detection. To develop innovative immunosensors, modification of the antibody or the electrode surface by nanomaterials is often used, and these strategies are discussed. These emerging hybrid technologies have led to miniaturisation and to a greater utilisation of immunosensors available for current applications, such as point-of-care diagnostics.
Gold nanoparticle etching induced by an enzymatic-like reaction for the colorimetric detection of hydrogen peroxide and glucose
Authors: Lu Manman , Su Linjing , Luo Yanghe , Ma Xionghui , Duan Zhenhua , Zhu Dongjian , Xiong Yuhao
Published: August 2019

A rapid colorimetric method for the sensitive and selective detection of H2O2 and glucose was developed based on the etching of AuNPs.
Noninvasive monitoring of the development and treatment response of ischemic hindlimb by targeting matrix metalloproteinase-2 (MMP-2)
Authors: Sun Zhongchan , Ma Nan , Fan Wensi , Guo Lanyan , Chen Jiangwei , Zhu Lei , Tong Guang
Published: August 2019

An ultrafast MMP activatable probe monitoring the development of angiogenesis in ischemic hindlimb through fluorescence imaging in real-time.
Efficient photocaging of a tight-binding bisubstrate inhibitor of cAMP-dependent protein kinase
Authors: Sõrmus Tanel , Lavogina Darja , Enkvist Erki , Uri Asko , Viht Kaido
Published: August 2019

PKA bisubstrate inhibitor photocaging resulted in an over 5 orders of magnitude affinity difference between the photocaged and the active inhibitor.
Highly stable performance of lithium-sulfurized polyacrylonitrile batteries using a lean ether-based electrolyte
Authors: Shuai Yi , Wang Dudan , Chen Kanghua , Zhang Zeping , Wang Yu , Lou Jin
Published: August 2019

An ether-based electrolyte highly stable performance of Li–SPAN battery.
Sensitive and sustained imaging of intracellular microRNA in living cells by a high biocompatible liposomal vehicle introduced isothermal symmetric exponential amplification reaction
Authors: Yin Wen , Chen Jun , Yang Huihui , Zhang Yanfei , Dai Zong , Zou Xiaoyong
Published: August 2019

A biocompatible liposome was fabricated to introduce highly efficient oligonucleotide amplification in living cells for the sensitive and sustained imaging of microRNA.
Hysteretic four-step spin-crossover in a 3D Hofmann-type metal–organic framework with aromatic guest
Authors: Zhang Cui-Juan , Lian Kai-Ting , Huang Guo-Zhang , Bala Sukhen , Ni Zhao-Ping , Tong Ming-Liang
Published: August 2019

Hysteretic four-step spin crossover behaviour with the sequence of LS ↔ HS0.25LS0.75 ↔ HS0.5LS0.5 ↔ HS0.67LS0.33 ↔ HS is observed for the first time.
Unusual rearrangement of modified PNP ligand based Ru complexes relevant to alcohol dehydrogenation catalysis
Authors: Deolka Shubham , Tarannam Naziha , Fayzullin Robert R. , Kozuch Sebastian , Khaskin Eugene
Published: August 2019

Hangman PNP pincer Ru complexes undergo an unusual sp2–sp3 C–C bond cleavage and formation via a spyrocyclopropane transition state.
Metamorphic meta isomer: carbon dioxide and ketenes are formed via retro-Diels–Alder reactions in the decomposition of meta-benzenediol
Authors: Gerlach Marius , Bodi Andras , Hemberger Patrick
Published: August 2019

Deoxygenation of the lignin model compound resorcinol was investigated using VUV synchrotron radiation: Formation of two reactive ketenes and decarboxylation are the dominating pathways, much different from the other two benzenediol isomers.
Enhancement mechanism of sulfur dopants on the catalytic activity of N and P co-doped three-dimensional hierarchically porous carbon as a metal-free oxygen reduction electrocatalyst
Authors: Zan Yongxi , Zhang Zhengping , Dou Meiling , Wang Feng
Published: August 2019

A sulfur, nitrogen and phosphorus ternary-doped cattle-bone-derived hierarchically porous carbon metal-free electrocatalyst was synthesized, exhibiting superior oxygen reduction performance compared to Pt/C.
Catalytic resonance theory: superVolcanoes, catalytic molecular pumps, and oscillatory steady state
Authors: Ardagh M. Alexander , Birol Turan , Zhang Qi , Abdelrahman Omar A. , Dauenhauer Paul J.
Published: August 2019

Catalytic reactions on surfaces with forced oscillations in physical or electronic properties undergo controlled acceleration consistent with the selected parameters of frequency, amplitude, and external stimulus waveform.
Synthesis, characterization and biological evaluation of cationic organoruthenium(ii) fluorene complexes: influence of the nature of the counteranion
Authors: Haghdoost Mohammad Mehdi , Golbaghi Golara , Guard Juliette , Sielanczyk Sarah , Patten Shunmoogum A. , Castonguay Annie
Published: August 2019

In this study, the in vitro antiproliferative activity and the in vivo toxicity of ruthenium arene complexes bearing fluorene bidentate ligands was assessed in human breast cancer cells and on the development of zebrafish embryos, respectively.
Probing through-space and through-bond magnetic exchange couplings in a new benzotriazinyl radical and its metal complexes
Authors: Nasani Rajendar , Sidharth Thulaseedharan Nair Sailaja , Roy Subhadip , Mondal Arpan , Rawson Jeremy M. , Konar Sanjit
Published: August 2019

A new Blatter radical and its Zn(ii) (1), Ni(ii) (2) and Co(ii) (3) complexes were isolated. Complex 1 exhibited radical⋯radical antiferromagnetic exchange coupling, whereas complexes 2 and 3 showed ferromagnetic metal–radical coupling.
Biological evaluation of optically pure chiral binuclear copper(ii) complexes based on a rosin derivative as highly potential anticancer agents
Authors: Fei Bao-Li , Tu Shuangyan , Wei Zuzhuang , Wang Pingping , Long Jian-Ying , Qiao Chunhua , Chen Zhen-Feng
Published: August 2019

An optically pure binuclear copper(ii) complex was prepared based on a rosin derivative, which is a DNA/BSA binder and a potential drug with multifunctional anticancer effects.