bluuebunny/crossref_metadata_2025 huggingface dataset:
Mutant KLF1 in Adult Anemic Nan Mice Leads to Profound Transcriptome Changes and Disordered Erythropoiesis
Authors: Nébor Danitza , Graber Joel H. , Ciciotte Steven L. , Robledo Raymond F. , Papoin Julien , Hartman Emily , Gillinder Kevin R. , Perkins Andrew C. , Bieker James J. , Blanc Lionel , Peters Luanne L.
Published: August 2018

Anemic Nan mice carry a mutation (E339D) in the second zinc finger of erythroid transcription factor KLF1. Nan-KLF1 fails to bind a subset of normal KLF1 targets and ectopically binds a large set of genes not normally engaged by KLF1, resulting in a corrupted fetal liver transcriptome. Here, we performed RNAseq using flow cytometric-sorted spleen erythroid precursors from adult Nan and WT littermates rendered anemic by phlebotomy to identify global transcriptome changes specific to the Nan Klf1 mutation as opposed to anemia generally. Mutant Nan-KLF1 leads to extensive and progressive transcriptome corruption in adult spleen erythroid precursors such that stress erythropoiesis is severely compromised. Terminal erythroid differentiation is defective in the bone marrow as well. Principle component analysis reveals two major patterns of differential gene expression predicting that defects in basic cellular processes including translation, cell cycle, and DNA repair could contribute to disordered erythropoiesis and anemia in Nan. Significant erythroid precursor stage specific changes were identified in some of these processes in Nan. Remarkably, however, despite expression changes in large numbers of associated genes, most basic cellular processes were intact in Nan indicating that developing red cells display significant physiological resiliency and establish new homeostatic set points in vivo.
K+ binding and proton redistribution in the E2P state of the H+, K+-ATPase
Authors: Dubey Vikas , Han Minwoo , Kopec Wojciech , Solov’yov Ilia A. , Abe Kazuhiro , Khandelia Himanshu
Published: August 2018

The H+, K+-ATPase (HKA) uses ATP to pump protons into the gastric lumen against a million-fold proton concentration gradient while counter-transporting K+ from the lumen. The mechanism of release of a proton into a highly acidic stomach environment, and the subsequent binding of a K+ ion necessitates a network of protonable residues and dynamically changing protonation states in the cation binding pocket dominated by five acidic amino acid residues E343, E795, E820, D824, and D942. We perform molecular dynamics simulations of spontaneous K+ binding to all possible protonation combinations of the acidic amino acids and carry out free energy calculations to determine the optimal protonation state of the luminal-open E2P state of the pump which is ready to bind luminal K+. A dynamic pKa correlation analysis reveals the likelihood of proton transfer events within the cation binding pocket. In agreement with in-vitro measurements, we find that E795 is likely to be protonated, and that E820 is at the center of the proton transfer network in the luminal-open E2P state. The acidic residues D942 and D824 are likely to remain protonated, and the proton redistribution occurs predominantly amongst the glutamate residues exposed to the lumen. The analysis also shows that a lower number of K+ ions bind at lower pH, modeled by a higher number of protons in the cation binding pocket, in agreement with the ‘transport stoichiometry variation’ hypothesis.
RNAm expression profile of cancer marker genes in HepG2 cells treated with different concentrations of a new indolin-3-one from Pseudomonas aeruginosa
Authors: Benicio Lucas Milanez , Simionato Ane Stefano , Novello Cláudio Roberto , Guimarães Jeconias Rocha , Felicidade Ingrid , de Oliveira Admilton Gonçalves , de Mello João Carlos Palazzo , Mantovani Mário Sérgio , Chryssafidis Andreas Lazaros , Andrade Galdino , de Syllos Colus Ilce Mara , de Oliveira Marcelo Tempesta
Published: August 2018

The present study tested the effects of a newly identified indolin-3-one compound (compound 1), produced by Pseudomonas aeruginosa, on HepG2 cells. The MTT assays demonstrated decreased metabolic activities in HepG2 cells treated with compound 1, with dose- and time-dependent intensifying effect, starting at a concentration of 40 µM. The IC50 after 24, 48, 72, and 96 h treatments were 41.35, 52.7, 92.79 and 66.65 μM of compound 1, respectively. Below 80 µM, no significative damage on erythrocytes membranes was observed by the hemolytic assays. The RT-qPCR revealed that the compound modulated key genes involved in carcinogenesis process, indicating possible indolin-3-one mechanisms of action. The data showed that gene expression alterations promoted by compound 1, in concentrations up to 60 μM after 48 h, led to a decrease in cellular progression and there was no direct cellular damage. In addition, non-cytotoxic concentrations of compound 1 halved the concentration of the chemotherapeutic doxorubicin, maintaining similar therapeutic effect against HepG2 cells. The novelty of the molecule and the biological activities observed in the present study emphasize the potential of the compound 1 in cancer therapy research.
PSD-95-nNOS Coupling Regulates Contextual Fear Extinction in the Dorsal CA3
Authors: Cai Cheng-Yun , Chen Chen , Zhou Ying , Han Zhou , Qin Cheng , Cao Bo , Tao Yan , Bian Xin-Lan , Lin Yu-Hui , Chang Lei , Wu Hai-Yin , Luo Chun-Xia , Zhu Dong-Ya
Published: August 2018

Fear extinction depends on N-methyl-D-aspartate glutamate receptors (NMDARs) and brain-derived neurotrophic factor (BDNF) activation in the limbic system. However, postsynaptic density-95 (PSD-95) and neuronal nitric oxide synthase (nNOS) coupling, the downstream signaling of NMDARs activation, obstructs the BDNF signaling transduction. Thus, we wondered distinct roles of NMDAR activation and PSD-95-nNOS coupling on fear extinction. To explore the mechanisms, we detected protein-protein interaction using coimmunoprecipitation and measured protein expression by western blot. Contextual fear extinction induced a shift from PSD-95-nNOS to PSD-95-TrkB association in the dorsal hippocampus and c-Fos expression in the dorsal CA3. Disrupting PSD-95-nNOS coupling in the dorsal CA3 up-regulated phosphorylation of extracellular signal-regulates kinase (ERK) and BDNF, enhanced the association of BDNF-TrkB signaling with PSD-95, and promoted contextual fear extinction. Conversely, blocking NMDARs in the dorsal CA3 down-regulated BDNF expression and hindered contextual fear extinction. NMDARs activation and PSD-95-nNOS coupling play different roles in modulating contextual fear extinction in the hippocampus. Because inhibitors of PSD-95-nNOS interaction produce antidepressant and anxiolytic effect without NMDAR-induced side effects, PSD-95-nNOS could be a valuable target for PTSD treatment.
Author Correction: Chemosensitivity profiling of osteosarcoma tumour cell lines identifies a model of BRCAness
Authors: Holme Harriett , Gulati Aditi , Brough Rachel , Fleuren Emmy D. G. , Bajrami Ilirjana , Campbell James , Chong Irene Y. , Costa-Cabral Sara , Elliott Richard , Fenton Tim , Frankum Jessica , Jones Samuel E. , Menon Malini , Miller Rowan , Pemberton Helen N. , Postel-Vinay Sophie , Rafiq Rumana , Selfe Joanna L. , von Kriegsheim Alex , Munoz Amaya Garcia , Rodriguez Javier , Shipley Janet , van der Graaf Winette T. A. , Williamson Chris T. , Ryan Colm J. , Pettitt Stephen , Ashworth Alan , Strauss Sandra J. , Lord Christopher J.
Published: August 2018

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has been fixed in the paper.
Author Correction: Plasmodium APC3 mediates chromosome condensation and cytokinesis during atypical mitosis in male gametogenesis
Authors: Wall Richard J. , Ferguson David J. P. , Freville Aline , Franke-Fayard Blandine , Brady Declan , Zeeshan Mohammad , Bottrill Andrew R. , Wheatley Sally , Fry Andrew M. , Janse Chris J. , Yamano Hiroyuki , Holder Anthony A. , Guttery David S. , Tewari Rita
Published: August 2018

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has not been fixed in the paper.
Event-related potentials of automatic imitation are modulated by ethnicity during stimulus processing, but not during motor execution
Authors: Rauchbauer Birgit , Pfabigan Daniela M. , Lamm Claus
Published: August 2018

This study investigated neural processes underlying automatic imitation and its modulation by ethnically diverse hand stimuli (Black, White) using event-related brain potentials (ERPs). Automatic imitation relies on motor stimulus-response compatibility (SRC), i.e., response conflict caused by motoric (in)congruency between task-irrelevant hand stimuli and the required response. Our novel task aimed to separate two distinct neuro-cognitive processing stages of automatic imitation and its modulation by ethnicity: the stage of stimulus processing (i.e. perception), comprising presentation of stimulus ethnicity and SRC, and the stage of response execution (i.e. action). Effects of ethnicity were observed in ERPs of different stages of stimulus processing - during presentation of ethnicity (LPP) and SRC (N190, P3). ERPs at response execution, Pre-Motion Positivity (PMP) and Reafferent Potential (RAP), were only sensitive to congruency. The N190 results may index visual self-other distinction, while the neural timecourse of P3 and PMP variation could reflect a dynamical decision process linking perception to action, with motor initiation reflected in the PMP component. The PMP might further index motor-related self-other distinction regardless of ethnicity. Importantly, overt motor execution was not influenced by ethnically diverse stimuli, which suggests generalizability of the automatic imitation effect across ethnicities.
Characterization of bacterial microbiota compositions along the intestinal tract in pigs and their interactions and functions
Authors: Crespo-Piazuelo Daniel , Estellé Jordi , Revilla Manuel , Criado-Mesas Lourdes , Ramayo-Caldas Yuliaxis , Óvilo Cristina , Fernández Ana I. , Ballester Maria , Folch Josep M.
Published: August 2018

In addition to its value in meat production, the pig is an interesting animal model for human digestive tract studies due to its physiological similarities. The aim of this study was to describe the microbiome composition, distribution and interaction along the Iberian pig intestinal tract and its role in whole-body energy homeostasis. The V3-V4 region of the 16S rRNA gene was amplified and sequenced from the microbiomes of five gut sections (duodenum, jejunum, ileum, and proximal and distal colon) in thirteen castrated male pigs. A total of 1,669 operational taxonomic units distributed in 179 genera were found among all samples. The two most abundant genera in the small intestine wereLactobacillusandClostridium, whilePrevotellawas predominant in the colon. The colon samples were more similar among the pigs and richer in species than the small intestine samples were. In the small intestine, the metagenome prediction pointed to rapid internalization and conversion of the available simple carbohydrates for microbial proliferation and maintenance. In the colon, a competition among anaerobic bacteria for plant polysaccharide degradation to produce short chain fatty acids was found. This study confirms that the energy pathways of the gut microbiome differ along its sections and provides a description of the correlations between genera.
Targeted next-generation sequencing-based molecular diagnosis of congenital hand malformations in Chinese population
Authors: Qin Litao , Lou Guiyu , Guo Liangjie , Zhang Yuwei , Wang Hongdan , Wang Li , Hou Qiaofang , Liu Hongyan , Li Xichuan , Liao Shixiu
Published: August 2018

Congenital hand malformations is rare and characterized by hand deformities. It is highly heterogeneous, both clinically and genetically, which complicates the identification of causative genes and mutations. Recently, targeted next-generation (NGS) sequencing has been successfully used for the detection of heterogeneous diseases, and the use of NGS also has contributed significantly in evaluating the etiology of heterogeneous disease. Here, we employed targeted NGS to screen 248 genes involved in genetic skeletal disorders, including congenital hand malformations. Three pathogenic mutations located in the GJA1, ROR2 and TBX5 genes were detected in three large Chinese families with congenital hand malformations. Two novel mutations were reported, and a known causative mutation was verified in this Chinese population. This is also the first report that the same panel of targeted NGS was employed to perform molecular diagnosis of different subtypes of congenital hand malformations. Our study supported the application of a targeted NGS panel as an effective tool to detect the genetic cause for heterogeneous diseases in clinical diagnosis.
A versatile open-source analysis of the limiting efficiency of photo electrochemical water-splitting
Authors: Holmes-Gentle Isaac , Hellgardt Klaus
Published: August 2018

Understanding the fundamental thermodynamic limits of photo-electrochemical (PEC) water splitting is of great scientific and practical importance. In this work, a ‘detailed balance’ type model of solar quantum energy converters and non-linear circuit analysis is used to calculate the thermodynamic limiting efficiency of various configurations of PEC design. This model is released as freely accessible open-source (GNU GPL v3) code written in MATLAB with a graphical user interface (GUI). The capabilities of the model are demonstrated by simulating selected permutations of PEC design and results are validated against previous literature. This tool will enable solar fuel researchers to easily compare experimental results to theoretical limits to assess its realised performance using the GUI. Furthermore, the code itself is intended to be extendable and so can be modified to include non-ideal losses such as the over-potential required or complex optical phenomena.
Phase Modulators Based on High Mobility Ambipolar ReSe2 Field-Effect Transistors
Authors: Pradhan Nihar R. , Garcia Carlos , Isenberg Bridget , Rhodes Daniel , Feng Simin , Memaran Shahriar , Xin Yan , McCreary Amber , Walker Angela R. Hight , Raeliarijaona Aldo , Terrones Humberto , Terrones Mauricio , McGill Stephen , Balicas Luis
Published: August 2018

We fabricated ambipolar field-effect transistors (FETs) from multi-layered triclinic ReSe2, mechanically exfoliated onto a SiO2 layer grown on p-doped Si. In contrast to previous reports on thin layers (~2 to 3 layers), we extract field-effect carrier mobilities in excess of 102 cm2/Vs at room temperature in crystals with nearly ~10 atomic layers. These thicker FETs also show nearly zero threshold gate voltage for conduction and high ON to OFF current ratios when compared to the FETs built from thinner layers. We also demonstrate that it is possible to utilize this ambipolarity to fabricate logical elements or digital synthesizers. For instance, we demonstrate that one can produce simple, gate-voltage tunable phase modulators with the ability to shift the phase of the input signal by either 90° or nearly 180°. Given that it is possible to engineer these same elements with improved architectures, for example on h-BN in order to decrease the threshold gate voltage and increase the carrier mobilities, it is possible to improve their characteristics in order to engineer ultra-thin layered logic elements based on ReSe2.
Author Correction: Amplitude of travelling front as inferred from 14C predicts levels of genetic admixture among European early farmers
Authors: Silva Fabio , Vander Linden Marc
Published: August 2018

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has not been fixed in the paper.
Polyphenols (S3) Isolated from Cone Scales of Pinus koraiensis Alleviate Decreased Bone Formation in Rat under Simulated Microgravity
Authors: Diao Yan , Chen Bin , Wei Lijun , Wang Zhenyu
Published: August 2018

In order to screen out an effective bone loss protectant from natural plant polyphenol and to elucidate the mechanism of the plant polyphenols that alleviate bone loss under simulated microgravity, the proliferation activities of 9 total polyphenol extracts from natural product (TPENP) on osteoblasts were measured. Polyphenols (S3) was isolated from total polyphenols of cone scales from pinus koraiensis (Korean pine). ALP activity in osteoblasts and MDA level in femur were measured. Mechanical properties and microstructure of the distal cancellous region of the femur in rat were tested. Various bone metabolism markers, enzymes activity and genes expression were also analyzed. The results showed that S3 has the highest activity of osteoblast proliferation. S3 promoted ALP activity in osteoblasts, enhanced mechanical properties and microstructure of the distal cancellous region of femur in rat, decreased MDA level, elevated the serum concentration of BALP, PINP and activities of SOD, CAT, GSH-Px in femur under simulated microgravity. In addition, S3 enhanced the expression of NRF-2, β-catenin, p-GSK3-β, OSX, RUNX2, Osteonectin, Osteocalcin, ALP and collagen I. These results indicated that S3 can alleviated bone loss induced by simulated microgravity through abate the inhibition of the oxidative stress on Wnt/β-catenin signaling pathway.
Author Correction: Apparent diffusion coefficient histogram in breast cancer brain metastases may predict their biological subtype and progression
Authors: Ahn Sung Jun , Park Mijin , Bang Sungkyu , Cho Eunseo , Ahn Sung Gwe , Suh Sang Hyun , Lee Jong-Min
Published: August 2018

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has been fixed in the paper.
High-pressure Raman scattering in bulk HfS2: comparison of density functional theory methods in layered MS2 compounds (M = Hf, Mo) under compression
Authors: Ibáñez J. , Woźniak T. , Dybala F. , Oliva R. , Hernández S. , Kudrawiec R.
Published: August 2018

We report high-pressure Raman-scattering measurements on the transition-metal dichalcogenide (TMDC) compound HfS2. The aim of this work is twofold: (i) to investigate the high-pressure behavior of the zone-center optical phonon modes of HfS2 and experimentally determine the linear pressure coefficients and mode Grüneisen parameters of this material; (ii) to test the validity of different density functional theory (DFT) approaches in order to predict the lattice-dynamical properties of HfS2 under pressure. For this purpose, the experimental results are compared with the results of DFT calculations performed with different functionals, with and without Van der Waals (vdW) interaction. We find that DFT calculations within the generalized gradient approximation (GGA) properly describe the high-pressure lattice dynamics of HfS2 when vdW interactions are taken into account. In contrast, we show that DFT within the local density approximation (LDA), which is widely used to predict structural and vibrational properties at ambient conditions in 2D compounds, fails to reproduce the behavior of HfS2 under compression. Similar conclusions are reached in the case of MoS2. This suggests that large errors may be introduced if the compressibility and Grüneisen parameters of bulk TMDCs are calculated with bare DFT-LDA. Therefore, the validity of different approaches to calculate the structural and vibrational properties of bulk and few-layered vdW materials under compression should be carefully assessed.
No association between resistance mutations, empiric antibiotic, and mortality in ceftriaxone-resistant Escherichia coli and Klebsiella pneumoniae bacteremia
Authors: Heng Shi Thong , Chen Swaine L. , Wong Joshua G. X. , Lye David C. , Ng Tat Ming
Published: August 2018

The objective of this study was to correlate resistance mutations of extended spectrum beta-lactamases (ESBL) and AmpC beta-lactamases and virulence factors (VF) with 30-day mortality in patients treated with either piperacillin-tazobactam or carbapenems. A post-hoc analysis on 123 patients with ceftriaxone-resistantEscherichia coliandKlebsiella pneumoniaebacteremia treated empirically with piperacillin-tazobactam and carbapenems was performed. Beta-lactamase resistance mutations and VF were identified by whole genome sequencing (WGS). The primary endpoint was 30-day mortality. Multivariate analyses were performed using logistic regression. WGS showed diverse multilocus sequence types (MLST) in 43 K. pneumoniaestrains, while ST131 predominated inE. colistrains (57/80). CTX-M was most commonly detected (76/80 [95%] ofE. coli; 39/43 [91%] ofK pneumoniae.), followed by OXA (53/80 [66%] ofE. coli; 34/43 [79%] ofK. pneumoniae). A significant correlation was found between the number of genes encoding third-generation cephalosporin-resistant beta-lactamases and 30-day mortality (p = 0.045). The positive association was not significant after controlling for empiric carbapenem, Pitt score 3 andK. pneumoniae(OR 2.43, P = 0.073). None of the VF was associated with 30-day mortality. No association was found between 30-day mortality and any ESBL and AmpC beta-lactamases or VF when piperacillin-tazobactam or carbapenems were given. No significant association between 30-day mortality and active empiric therapy was found.
Presence of esterase and laccase in Bacillus subtilis facilitates biodegradation and detoxification of cypermethrin
Authors: Gangola Saurabh , Sharma Anita , Bhatt Pankaj , Khati Priyanka , Chaudhary Parul
Published: August 2018

Ubiquitous presence of cypermethrin as a contaminant in surface stream and soil necessitates to develop potential bioremediation methods to degrade and eliminate this pollutant from the environment. A cypermethrin utilizing bacterial strain (MIC, 450  ppm) was isolated from the soil of pesticide contaminated agriculture field and characterized by using polyphasic approach. On molecular basis bacterial isolate showed 98% homology with Bacillus subtilis strain 1D. Under optimized growth conditions, bacteria showed 95% degradation of cypermethrin after 15 days and the end products of cypermethrin biodegradation under aerobic conditions were cyclododecylamine, phenol, 3-(2,2-dichloroethenyl 2,2-dimethyl cyclopropane carboxylate,1-decanol,chloroacetic acid, acetic acid, cyclopentan palmitoleic acid, and decanoic acid. Amplification of esterase (700 bp) and laccase (1200 bp) genes was confirmed by PCR which showed a possible role of these enzymes in biodegradation of cypermethrin. In the presence of cypermethrin Km value(s) of both the enzymes was low than the control. A nobel cypermethrin degradation pathway followed by B. subtilis was proposed on the basis of characterization of biodegraded products of cypermethrin using GC-MS. Cypermethrin biodegradation ability of Bacillus subtilis strain 1D without producing any toxic end product reveals the potential of this organism in cleaning of pesticide contaminated soil and water.
Author Correction: Exploring the pathology of an epidermal disease affecting a circum-Antarctic sea star
Authors: Núñez-Pons Laura , Work Thierry M. , Angulo-Preckler Carlos , Moles Juan , Avila Conxita
Published: August 2018

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has been fixed in the paper.
Whole-genome sequencing and comparative analysis of two plant-associated strains of Rhodopseudomonas palustris (PS3 and YSC3)
Authors: Lo Kai-Jiun , Lin Shih-Shun , Lu Chia-Wei , Kuo Chih-Horng , Liu Chi-Te
Published: August 2018

Rhodopseudomonas palustris strains PS3 and YSC3 are purple non-sulfur phototrophic bacteria isolated from Taiwanese paddy soils. PS3 has beneficial effects on plant growth and enhances the uptake efficiency of applied fertilizer nutrients. In contrast, YSC3 has no significant effect on plant growth. The genomic structures of PS3 and YSC3 are similar; each contains one circular chromosome that is 5,269,926 or 5,371,816 bp in size, with 4,799 or 4,907 protein-coding genes, respectively. In this study, a large class of genes involved in chemotaxis and motility was identified in both strains, and genes associated with plant growth promotion, such as nitrogen fixation-, IAA synthesis- and ACC deamination-associated genes, were also identified. We noticed that the growth rate, the amount of biofilm formation, and the relative expression levels of several chemotaxis-associated genes were significantly higher for PS3 than for YSC3 upon treatment with root exudates. These results indicate that PS3 responds better to the presence of plant hosts, which may contribute to the successful interactions of PS3 with plant hosts. Moreover, these findings indicate that the existence of gene clusters associated with plant growth promotion is required but not sufficient for a bacterium to exhibit phenotypes associated with plant growth promotion.
Effect of Kinetic Degrees of Freedom on Multi-Finger Synergies and Task Performance during Force Production and Release Tasks
Authors: Kim Kitae , Xu Dayuan , Park Jaebum
Published: August 2018

Complex structures present in a human body has relatively large degrees-of-freedom (DOFs) as compared to the requirement of a particular task. This phenomenon called motor redundancy initially deemed as a computational problem rather can be understood as having the flexibility to perform the certain task successfully. Hence, the purpose of our study was to examine the positive impact of extra DOFs (redundant DOFs) during force production tasks. For this purpose, an experimental setup was designed to simulate archery-like shooting, and purposeful organization of a redundant set of finger forces determined the stability of important performance variables as well as accurate and precise performance. DOFs were adjusted by changing the number of fingers explicitly involved in the task. The concept of motor synergy and computational framework of uncontrolled manifold (UCM) approach was used to quantify stability indices during finger force production. As a result, accuracy and precision of the task improved with an increase in DOFs. Also, the stability indices of net finger forces and moment increased with active DOFs of fingers. We concluded that the controller actively utilizes extra DOFs to increase the stability of the performance, which is associated with the improved accuracy and precision of the task.
Adipokines and inflammatory markers in elderly subjects with high risk of type 2 diabetes and cardiovascular disease
Authors: Saukkonen Tuula , Mutt Shivaprakash Jagalur , Jokelainen Jari , Saukkonen Anna-Maria , Raza Ghulam Shere , Karhu Toni , Härkönen Pirjo , Eckel Jürgen , Herzig Karl-Heinz , Rajala Ulla , Keinänen-Kiukaanniemi Sirkka
Published: August 2018

Inflammation plays a significant role in pathogenesis of diabetes and atherosclerosis. Increased adiposity with an upregulation of cytokines in prediabetes has been associated with vascular inflammation and considered a leading causal factor for type 2 diabetes (T2D). Information on adipokines and inflammatory markers in prediabetes, defined by hemoglobin A1C (HbA1c) 5.7–6.4% in addition to impaired fasting glucose (IFG) and impaired glucose tolerance (IGT), are sparse. We conducted a population–based cross-sectional study (part of a follow-up study) of inhabitants of Oulu, Finland, born in 1935. Inflammatory markers and traditional risk markers of 367 subjects were measured. The glucose status was determined by an oral glucose tolerance test (OGTT) and HbA1c. Inflammatory markers and glycemic levels were analysed using analysis of covariance (ANCOVA). Of the participants, 193 were normoglycemic, 82 had prediabetes and 40 T2D. Inflammatory cytokines were significantly higher in subjects with prediabetes as compared to normoglycemic subjects: IL-4 (14.9 vs 5.9 pg/ml, p = 0.041), IP-10 (251 vs 209 pg/ml, p = 0.05), TNF-α (10.4 vs 6.9 pg/ml, p = 0.027), RANTES (43.3 vs 33.1 pg/ml, p = 0.009), CD40L (3708 vs 1671 pg/ml, p = 0.010) and VEGF (269 vs 174 pg/ml, p = 0.013). These inflammatory cytokines remained significant even after adjustment for waist circumference. The differences in inflammatory markers in prediabetic and T2D subjects were not statistically significant. Prediabetes was associated with low-grade inflammation with increased inflammatory cytokine levels, while the levels in prediabetic subjects were comparable to those in T2D subjects. The associations were independent of visceral adiposity.
Optimizing tissue-clearing conditions based on analysis of the critical factors affecting tissue-clearing procedures
Authors: Kim June Hoan , Jang Min Jee , Choi Jungyoon , Lee Eunsoo , Song Kyung–Deok , Cho Jaeho , Kim Keun-Tae , Cha Hyuk-Jin , Sun Woong
Published: August 2018

Tissue-clearing techniques have received great attention for volume imaging and for the potential to be applied in optical diagnosis. In principle, tissue clearing is achieved by reducing light scattering through a combination of lipid removal, size change, and matching of the refractive index (RI) between the imaging solution and the tissue. However, the contributions of these major factors in tissue clearing have not been systematically evaluated yet. In this study, we experimentally measured and mathematically calculated the contribution of these factors to the clearing of four organs (brain, liver, kidney, and lung). We found that these factors differentially influence the maximal clearing efficacy of tissues and the diffusivity of materials inside the tissue. We propose that these physical properties of organs can be utilized for the quality control (Q/C) process during tissue clearing, as well as for the monitoring of the pathological changes of tissues.
Multiuse of Bar-HRM for Ophiocordyceps sinensis identification and authentication
Authors: Osathanunkul Maslin , Osathanunkul Khukrit , Wongwanakul Sutthipan , Osathanunkul Rossarin , Madesis Panagiotis
Published: August 2018

Bar-HRM is a hybrid method which combines DNA barcoding and High Resolution Melting analysis. It has proven to be a fast, cost-effective and reliable molecular approach for species identification and authentication. Here, three aspects of the use of Bar-HRM are focused on. First, Bar-HRM is used to discriminate between closely related Ophiocordyceps species. Second, identification of an unknown powder that is claimed to be Ophiocordyceps species using Bar-HRM. Third, authenticating the O. sinensis products sold on the market by the Bar-HRM. Results from HRM analyses with ITS primers shows that the two Ophiocordyceps species (Ophiocordyceps sinensis and Ophiocordyceps militaris) were easily differentiated. Also, an unknown sample was able to be identified in less time compared with using DNA barcoding alone. In addition, the substitution or adulteration of O. sinensis products sold on market was detected via Bar-HRM. The substitution or adulteration of inferior Ophiocordyceps species, particularly O. militaris in high price O. sinensis products has been a concern throughout Asia. Based on our results, the Bar-HRM was again proved to be a promising tool for species identification and authentication.
Protein stabilization with retained function of monellin using a split GFP system
Authors: Weiffert Tanja , Linse Sara
Published: August 2018

Sweet proteins are an unexploited resource in the search for non-carbohydrate sweeteners mainly due to their low stability towards heating. Variants of the sweet protein monellin, with increased stability, were derived by anin vivoscreening method based on the thermodynamic linkage between fragment complementation and protein stability. This approach depends on the correlation between mutational effects on the affinity between protein fragments and the stability of the intact protein. By linking the two fragments of monellin to the split GFP (green fluorescent protein) system, reconstitution of GFP was promoted and moderately fluorescent colonies were obtained. Two separate random libraries were produced for the monellin chains and the mutant clones were ranked based on fluorescence intensity. Mutants with increased affinity between the fragments, and subsequently increased stability, caused increased fluorescence intensity of split GFP. Single chain monellin variants of the top-ranked mutants for each chain, S76Y in the A-chain and W3C + R39G in the B-chain and all combinations thereof, were expressed and the increase in stability was verified by temperature denaturation studies using circular dichroism spectroscopy. Functionality studies showed that mutant S76Y has retained sweetness and has potential use within the food industry.
Bovine telomere dynamics and the association between telomere length and productive lifespan
Authors: Seeker Luise A. , Ilska Joanna J. , Psifidi Androniki , Wilbourn Rachael V. , Underwood Sarah L. , Fairlie Jennifer , Holland Rebecca , Froy Hannah , Salvo-Chirnside Eliane , Bagnall Ainsley , Whitelaw Bruce , Coffey Mike P. , Nussey Daniel H. , Banos Georgios
Published: August 2018

Average telomere length (TL) in blood cells has been shown to decline with age in a range of vertebrate species, and there is evidence that TL is a heritable trait associated with late-life health and mortality in humans. In non-human mammals, few studies to date have examined lifelong telomere dynamics and no study has estimated the heritability of TL, despite these being important steps towards assessing the potential of TL as a biomarker of productive lifespan and health in livestock species. Here we measured relative leukocyte TL (RLTL) in 1,328 samples from 308 Holstein Friesian dairy cows and in 284 samples from 38 female calves. We found that RLTL declines after birth but remains relatively stable in adult life. We also calculated the first heritability estimates of RLTL in a livestock species which were 0.38 (SE = 0.03) and 0.32 (SE = 0.08) for the cow and the calf dataset, respectively. RLTL measured at the ages of one and five years were positively correlated with productive lifespan (p < 0.05). We conclude that bovine RLTL is a heritable trait, and its association with productive lifespan may be used in breeding programmes aiming to enhance cow longevity.
The osteoprogenitor-specific loss of ephrinB1 results in an osteoporotic phenotype affecting the balance between bone formation and resorption
Authors: Arthur Agnieszka , Nguyen Thao M. , Paton Sharon , Klisuric Ana , Zannettino Andrew C. W. , Gronthos Stan
Published: August 2018

The present study investigated the effects of conditional deletion of ephrinB1 in osteoprogenitor cells driven by the Osterix (Osx) promoter, on skeletal integrity in a murine model of ovariectomy-induced (OVX) osteoporosis. Histomorphometric and μCT analyses revealed that loss of ephrinB1 in sham Osx:cre-ephrinB1fl/fl mice caused a reduction in trabecular bone comparable to OVX Osx:Cre mice, which was associated with a significant reduction in bone formation rates and decrease in osteoblast numbers. Interestingly, these observations were not exacerbated in OVX Osx:cre-ephrinB1fl/fl mice. Furthermore, sham Osx:cre-ephrinB1fl/fl mice displayed significantly higher osteoclast numbers and circulating degraded collagen type 1 compared to OVX Osx:Cre mice. Confirmation studies found that cultured monocytes expressing EphB2 formed fewer TRAP+ multinucleated osteoclasts and exhibited lower resorption activity in the presence of soluble ephrinB1-Fc compared to IgG control. This inhibition of osteoclast formation and function induced by ephrinB1-Fc was reversed in the presence of an EphB2 chemical inhibitor. Collectively, these observations suggest that ephrinB1, expressed by osteoprogenitors, influences bone loss during the development of osteoporosis, by regulating both osteoblast and osteoclast formation and function, leading to a loss of skeletal integrity.
Animal infection studies of two recently discovered African bat paramyxoviruses, Achimota 1 and Achimota 2
Authors: Barr Jennifer , Todd Shawn , Crameri Gary , Foord Adam , Marsh Glenn , Frazer Leah , Payne Jean , Harper Jenni , Baker Kate S. , Cunningham Andrew A. , Wood James L. N. , Middleton Deborah , Wang Lin-Fa
Published: August 2018

Bats are implicated as the natural reservoirs for several highly pathogenic viruses that can infect other animal species, including man. Here, we investigate the potential for two recently discovered bat rubulaviruses, Achimota virus 1 (AchPV1) and Achimota virus 2 (AchPV2), isolated from urine collected under urban bat (Eidolon helvum) roosts in Ghana, West Africa, to infect small laboratory animals. AchPV1 and AchPV2 are classified in the family Paramyxoviridae and cluster with other bat derived zoonotic rubulaviruses (i.e. Sosuga, Menangle and Tioman viruses). To assess the susceptibility of AchPV1 and AchPV2 in animals, infection studies were conducted in ferrets, guinea pigs and mice. Seroconversion, immunohistological evidence of infection, and viral shedding were identified in ferrets and guinea pigs, but not in mice. Infection was associated with respiratory disease in ferrets. Viral genome was detected in a range of tissues from ferrets and guinea pigs, however virus isolation was only achieved from ferret tissues. The results from this study indicate Achimota viruses (AchPVs) are able to cross the species barrier. Consequently, vigilance for infection with and disease caused by these viruses in people and domesticated animals is warranted in sub-Saharan Africa and the Arabian Peninsula where the reservoir hosts are present.
Electrophilic nitroalkene-tocopherol derivatives: synthesis, physicochemical characterization and evaluation of anti-inflammatory signaling responses
Authors: Rodriguez-Duarte Jorge , Dapueto Rosina , Galliussi Germán , Turell Lucía , Kamaid Andrés , Khoo Nicholas K. H. , Schopfer Francisco J. , Freeman Bruce A. , Escande Carlos , Batthyány Carlos , Ferrer-Sueta Gerardo , López Gloria V.
Published: August 2018

Inflammation plays a major role in the onset and development of chronic non-communicable diseases like obesity, cardiovascular diseases and cancer. Combined, these diseases represent the most common causes of death worldwide, thus development of novel pharmacological approaches is crucial. Electrophilic nitroalkenes derived from fatty acids are formed endogenously and exert anti-inflammatory actions by the modification of proteins involved in inflammation signaling cascades. We have developed novel nitroalkenes derived from α-tocopherol aiming to increase its salutary actions by adding anti-inflammatory properties to a well-known nutraceutical. We synthesized and characterized an α-tocopherol-nitroalkene (NATOH) and two hydrosoluble analogues derived from Trolox (NATxME and NATx0). We analyzed the kinetics of the Michael addition reaction of these compounds with thiols in micellar systems aiming to understand the effect of hydrophobic partition on the reactivity of nitroalkenes. We studied NATxME in vitro showing it exerts non-conventional anti-inflammatory responses by inducing Nrf2-Keap1-dependent gene expression and inhibiting the secretion of NF-κB dependent pro-inflammatory cytokines. NATxME was also effective in vivo, inhibiting neutrophil recruitment in a zebrafish model of inflammation. This work lays the foundation for the rational design of a new therapeutic strategy for the prevention and treatment of metabolic and inflammation-related diseases.
Diatom bloom-derived biotoxins cause aberrant development and gene expression in the appendicularian chordate Oikopleura dioica
Authors: Torres-Águila Nuria P. , Martí-Solans Josep , Ferrández-Roldán Alfonso , Almazán Alba , Roncalli Vittoria , D’Aniello Salvatore , Romano Giovanna , Palumbo Anna , Albalat Ricard , Cañestro Cristian
Published: August 2018

Investigating environmental hazards than could affect appendicularians is of prime ecological interest because they are among the most abundant components of the mesozooplankton. This work shows that embryo development of the appendicularianOikopleura dioicais compromised by diatom bloom-derived biotoxins, even at concentrations in the same range as those measured after blooms. Developmental gene expression analysis of biotoxin-treated embryos uncovers an aberrant golf ball-like phenotype affecting morphogenesis, midline convergence, and tail elongation. Biotoxins induce a rapid upregulation of defensome genes, and considerable delay and silencing of zygotic transcription of developmental genes. Upon a possible future intensification of blooms associated with ocean warming and acidification, our work puts an alert on the potential impact that an increase of biotoxins may have on marine food webs, and points to defensome genes as molecular biosensors that marine ecologists could use to monitor the genetic stress of natural populations exposed to microalgal blooms.
Spin crossover in discrete polynuclear iron(ii) complexes
Authors: Hogue Ross W. , Singh Sandhya , Brooker Sally
Published: August 2018

A comprehensive review of 127 dinuclear to octanuclear complexes, mostly 2012-present, reveals key design features and future directions for spin crossover active supramolecular assemblies.
Increased extracellular matrix density disrupts E-cadherin/β-catenin complex in gastric cancer cells
Authors: Jang Minjeong , Koh Ilkyoo , Lee Jae Eun , Lim Ju Yeon , Cheong Jae-Ho , Kim Pilnam
Published: August 2018

We studied the effect of ECM density on both intercellular- and ECM-interactions according to alterations of ECM-mediated signaling in gastric cancer cell lines.
Recent advances in radical transformations of internal alkynes
Authors: Huang Min-Hua , Hao Wen-Juan , Li Guigen , Tu Shu-Jiang , Jiang Bo
Published: August 2018

This review highlights the recent progress in the radical transformation of internal alkynes and focuses on the reaction mechanisms by carbon/heteroatom-centered triggered additions, and offers a comprehensive overview on the existing procedures and employed methodologies.
Transport properties and intermolecular interactions in binary mixtures based on the protic ionic liquid ethylimidazolium triflate and ethylene glycol
Authors: Yaghini Negin , Abdurrokhman Iqbaal , Hasani Mohammad , Martinelli Anna
Published: August 2018

The binary mixture based on the protic ionic liquid (PIL) ethylimidazolium triflate (C2HImTfO) and the diol compound ethylene glycol (EG) has been investigated in the whole composition range from pure PIL to pure EG.
Theoretical study of the bandgap regulation of a two-dimensional GeSn alloy under biaxial strain and uniaxial strain along the armchair direction
Authors: Huang Wenqi , Yang Hong , Cheng Buwen , Xue Chunlai
Published: August 2018

The combination of alloying Sn and applying an external strain is an efficient way to tune the bandgap of a two-dimensional GeSn alloy.
How abasic sites impact hole transfer dynamics in GC-rich DNA sequences
Authors: Corbella Marina , Voityuk Alexander A. , Curutchet Carles
Published: August 2018

Hole transfer dynamics through GC-rich DNA duplexes containing abasic sites is strongly modulated by the nature of the unpaired nucleobase.
The influence of nanoparticles on the polarizabilities and hyperpolarizabilities of photochromic molecules
Authors: Boye Ida Marie Ingmer , Hansen Mia Harring , Mikkelsen Kurt V.
Published: August 2018

We consider how nanoparticles affect molecular photoswitches and our focus is on how the polarizabilities and hyperpolarizabilities of the dihydroazulene/vinylheptafulvene system changes, when the compounds interact with gold nanoparticles.
Interactions between azines and alcohols: a rotational study of pyridine–tert-butyl alcohol
Authors: Spada Lorenzo , Uriarte Iciar , Li Weixing , Evangelisti Luca , Cocinero Emilio J. , Caminati Walther
Published: August 2018

The observed spectrum identifies aCssymmetry σ-type complex, with the two subunits held together by coplanar “classical” O–H⋯N and weak C–H⋯π intermolecular hydrogen bonds. The O⋯N distance decreases by 4 mÅ upon deuteration of the hydroxyl group (reverse Ubbelohde effect).
Toward sustainable and systematic recycling of spent rechargeable batteries
Authors: Zhang Xiaoxiao , Li Li , Fan Ersha , Xue Qing , Bian Yifan , Wu Feng , Chen Renjie
Published: August 2018

A comprehensive and novel view on battery recycling is provided in terms of the science and technology, engineering, and policy.
Metamorphosis of cycloalkenes for the divergent total synthesis of polycyclic indole alkaloids
Authors: Xu Zhengren , Wang Qian , Zhu Jieping
Published: August 2018

This review summarizes the divergent synthesis of monoterpene indole alkaloids using cycloalkene as the turning point of structural diversity.
Macroscopic heat release in a molecular solar thermal energy storage system
Authors: Wang Zhihang , Roffey Anna , Losantos Raul , Lennartson Anders , Jevric Martyn , Petersen Anne U. , Quant Maria , Dreos Ambra , Wen Xin , Sampedro Diego , Börjesson Karl , Moth-Poulsen Kasper
Published: August 2018

The development of solar energy can potentially meet the growing requirements for a global energy system beyond fossil fuels, but necessitates new scalable technologies for solar energy storage.
Integrated diesel production from lignocellulosic sugarsviaoleaginous yeast
Authors: Sànchez i Nogué Violeta , Black Brenna A. , Kruger Jacob S. , Singer Christine A. , Ramirez Kelsey J. , Reed Michelle L. , Cleveland Nicholas S. , Singer Emily R. , Yi Xiunan , Yeap Rou Yi , Linger Jeffrey G. , Beckham Gregg T.
Published: August 2018

Oleaginous microbes are promising platform strains for the production of renewable diesel and fatty-acid derived chemicals given their capacity to produce high lipid yields.
Microfluidic auto-alignment of protein patterns for dissecting multi-receptor crosstalk in platelets
Authors: Zhou F. , Chen Y. , Felner E. I. , Zhu C. , Lu H.
Published: August 2018

We present a microfluidic system with precisely aligned ligand and antibody patterns to assay multi-ligand-receptor systems in cell adhension, using well controlled sequential cell-surface contacts.
In-droplet microparticle washing and enrichment using surface acoustic wave-driven acoustic radiation force
Authors: Park Jinsoo , Destgeer Ghulam , Kim Hyoungsoo , Cho Yeunwoo , Sung Hyung Jin
Published: August 2018

An acoustofluidic device for in-droplet microparticle washing and enrichment.
Probing charge transfer dynamics in a single iron tetraphenylporphyrin dyad adsorbed on an insulating surface
Authors: Ramos Pablo , Mankarious Marc , Pavanello Michele , Riedel Damien
Published: August 2018

Charge transfer is investigated in a planar dyad adsorbed on an insulting layer via local electronic excitations.
A strategy for realizing tunable luminescence and full-color emission in Sr3Gd2(Si3O9)2:Eu phosphors by introducing dual functional Mn2+
Authors: Zhu Yingli , Liang Yujun , Liu Shiqi , Li Haoran , Chen Jiahui , Lei Wen
Published: August 2018

The introduced Mn2+ ion can act as both an activator and a structure regulator in the SGSO:Eu system to achieve full-color emission and tunable luminescence of SGSO:0.03Eu,Mn phosphors.
A triple-functionalised metal centre-catalyzed enantioselective multicomponent reaction
Authors: Wei Qinghua , Ma Xiaochu , Chen Jianghui , Niu Li , Yang Xi , Xia Fei , Liu Shunying
Published: August 2018

A model of a triple-functionalised metal centre for the discovery of unprecedented enantioselective reactions was exquisitely developed by using a RhI/(DHQ)2PHAL catalyst system via multiple coordination interactions with different ligands and substrates.
Current advances of carbene-mediated photoaffinity labeling in medicinal chemistry
Authors: Ge Sha-Sha , Chen Biao , Wu Yuan-Yuan , Long Qing-Su , Zhao Yong-Liang , Wang Pei-Yi , Yang Song
Published: August 2018

Photoaffinity labeling (PAL) in combination with a chemical probe to covalently bind its target upon UV irradiation has demonstrated considerable promise in drug discovery for identifying new drug targets and binding sites.
Investigation of the occupancy ratio dependence for microlens arrays on diamond
Authors: Zhu Tian-Fei , Fu Jiao , Liu Zongchen , Liang Yan , Wang Wei , Wen Feng , Zhang Jingwen , Wang Hong-Xing
Published: August 2018

Diamond microlens arrays with a high occupancy ratio were fabricated by an improved thermal reflow method.