bluuebunny/crossref_metadata_2025 huggingface dataset:
Identification of a hybrid myocardial zone in the mammalian heart after birth
Authors: Tian Xueying , Li Yan , He Lingjuan , Zhang Hui , Huang Xiuzhen , Liu Qiaozhen , Pu Wenjuan , Zhang Libo , Li Yi , Zhao Huan , Wang Zhifu , Zhu Jianhong , Nie Yu , Hu Shengshou , Sedmera David , Zhong Tao P. , Yu Ying , Zhang Li , Yan Yan , Qiao Zengyong , Wang Qing-Dong , Wu Sean M. , Pu William T. , Anderson Robert H. , Zhou Bin
Published: July 2017

Noncompaction cardiomyopathy is characterized by the presence of extensive trabeculations, which could lead to heart failure and malignant arrhythmias. How trabeculations resolve to form compact myocardium is poorly understood. Elucidation of this process is critical to understanding the pathophysiology of noncompaction disease. Here we use genetic lineage tracing to mark the Nppa+or Hey2+cardiomyocytes as trabecular and compact components of the ventricular wall. We find that Nppa+and Hey2+cardiomyocytes, respectively, from the endocardial and epicardial zones of the ventricular wall postnatally. Interposed between these two postnatal layers is a hybrid zone, which is composed of cells derived from both the Nppa+and Hey2+populations. Inhibition of the fetal Hey2+cell contribution to the hybrid zone results in persistence of excessive trabeculations in postnatal heart. Our findings indicate that the expansion of Hey2+fetal compact component, and its contribution to the hybrid myocardial zone, are essential for normal formation of the ventricular walls.
Novel transcriptional signatures for sputum-independent diagnostics of tuberculosis in children
Authors: Gjøen John Espen , Jenum Synne , Sivakumaran Dhanasekaran , Mukherjee Aparna , Macaden Ragini , Kabra Sushil K. , Lodha Rakesh , Ottenhoff Tom H. M. , Haks Marielle C. , Doherty Timothy Mark , Ritz Christian , Grewal Harleen M. S.
Published: July 2017

Pediatric tuberculosis (TB) is challenging to diagnose, confirmed by growth of Mycobacterium tuberculosis at best in 40% of cases. The WHO has assigned high priority to the development of non-sputum diagnostic tools. We therefore sought to identify transcriptional signatures in whole blood of Indian children, capable of discriminating intra-thoracic TB disease from other symptomatic illnesses. We investigated the expression of 198 genes in a training set, comprising 47 TB cases (19 definite/28 probable) and 36 asymptomatic household controls, and identified a 7- and a 10-transcript signature, both including NOD2, GBP5, IFITM1/3, KIF1B and TNIP1. The discriminatory abilities of the signatures were evaluated in a test set comprising 24 TB cases (17 definite/7 probable) and 26 symptomatic non-TB cases. In separating TB-cases from symptomatic non-TB cases, both signatures provided an AUC of 0.94 (95%CI, 0.88–1.00), a sensitivity of 91.7% (95%CI, 71.5–98.5) regardless of culture status, and 100% sensitivity for definite TB. The 7-transcript signature provided a specificity of 80.8% (95%CI, 60.0–92.7), and the 10-transcript signature a specificity of 88.5% (95%CI, 68.7–96.9%). Although warranting exploration and validation in other populations, our findings are promising and potentially relevant for future non-sputum based POC diagnostic tools for pediatric TB.
AIM2 Inflammasome-Mediated Pyroptosis in Enterovirus A71-Infected Neuronal Cells Restricts Viral Replication
Authors: Yogarajah Thinesshwary , Ong Kien Chai , Perera David , Wong Kum Thong
Published: July 2017

Encephalomyelitis is a well-known complication of hand, foot, and mouth disease (HFMD) due to Enterovirus 71 (EV71) infection. Viral RNA/antigens could be detected in the central nervous system (CNS) neurons in fatal encephalomyelitis but the mechanisms of neuronal cell death is not clearly understood. We investigated the role of absent in melanoma 2 (AIM2) inflammasome in neuronal cell death, and its relationship to viral replication. Our transcriptomic analysis, RT-qPCR, Western blot, immunofluorescence and flow cytometry studies consistently showed AIM2 gene up-regulation and protein expression in EV-A71-infected SK-N-SH cells. Downstream AIM2-induced genes, CARD16, caspase-1 and IL-1β were also up-regulated and caspase-1 was activated to form cleaved caspase-1 p20 subunits. As evidenced by 7-AAD positivity, pyroptosis was confirmed in infected cells. Overall, these findings have a strong correlation with decreases in viral titers, copy numbers and proteins, and reduced proportions of infected cells. AIM2 and viral antigens were detected by immunohistochemistry in infected neurons in inflamed areas of the CNS in EV-A71 encephalomyelitis. In infected AIM2-knockdown cells, AIM2 and related downstream gene expressions, and pyroptosis were suppressed, resulting in significantly increased virus infection. These results support the notion that AIM2 inflammasome-mediated pyroptosis is an important mechanism of neuronal cell death and it could play an important role in limiting EV-A71 replication.
Involvement of the p62/NRF2 signal transduction pathway on erythrophagocytosis
Authors: Santarino Inês B. , Viegas Michelle S. , Domingues Neuza S. , Ribeiro Ana M. , Soares Miguel P. , Vieira Otília V.
Published: July 2017

Erythrophagocytosis, the phagocytic removal of damaged red blood cells (RBC), and subsequent phagolysosome biogenesis are important processes in iron/heme metabolism and homeostasis. Phagolysosome biogenesis implies the interaction of nascent phagosomes with endocytic compartments and also autophagy effectors. Here, we report that besides recruitment of microtubule-associated protein-1-light chain 3 (LC3), additional autophagy machinery such as sequestosome 1 (p62) is also acquired by single-membrane phagosomes at very early stages of the phagocytic process and that its acquisition is very important to the outcome of the process. In bone marrow-derived macrophages (BMDM) silenced for p62, RBC degradation is inhibited. P62, is also required for nuclear translocation and activation of the transcription factor Nuclear factor E2-related Factor 2 (NRF2) during erythrophagocytosis. Deletion of theNrf2allele reduces p62 expression and compromises RBC degradation. In conclusion, we reveal that erythrophagocytosis relies on an interplay between p62 and NRF2, potentially acting as protective mechanism to maintain reactive oxygen species at basal levels and preserve macrophage homeostasis.
Contrast enhancement of biological nanoporous materials with zinc oxide infiltration for electron and X-ray nanoscale microscopy
Authors: Ocola L. E. , Sampathkumar V. , Kasthuri N. , Winarski R. P.
Published: July 2017

We show that using infiltration of ZnO metal oxide can be useful for high resolution imaging of biological samples in electron and X-ray microscopy. The method is compatible with standard fixation techniques that leave the sample dry, such as finishing with super critical CO2 drying, or simple vacuum drying up to 95 °C. We demonstrate this technique can be applied on tooth and brain tissue samples. We also show that high resolution X-ray tomography can be performed on biological systems using Zn K edge (1s) absorption to enhance internal structures, and obtained the first nanoscale 10 KeV X-ray absorption images of the interior regions of a tooth.
Trivalent Y3+ ionic sensor development based on (E)-Methyl-N′-nitrobenzylidene-benzenesulfonohydrazide (MNBBSH) derivatives modified with nafion matrix
Authors: Hussain Mohammad Musarraf , Rahman Mohammed M. , Arshad Muhammad Nadeem , Asiri Abdullah M.
Published: July 2017

(E)-Methyl-N′-nitrobenzylidene-benzenesulfonohydrazide (MNBBSH) compounds were synthesized using a condensation procedure from the derivatives of nitrobenzaldehyde and 4-Methyl-benzenesulfonylhydrazine, which crystallized in ethanol and methanol as well as characterized by FTIR, UV-Vis, 1H-NMR, and 13C-NMR. MNBBSH structure was confirmed using a single crystal X-ray diffraction technique and used for the detection of selective yttrium ion (Y3+) by I-V system. A thin layer of MNBBSH was deposited onto a glassy carbon electrode (GCE) with 5% nafion for the sensitive and selective Y3+ sensor. The modified MNBBSH/GCE sensor is exhibited the better electrochemical performances such as sensitivity, limit of detection (LOD), linear dynamic range (LDR), limit of quantification (LOQ), short response time, and long term storage ability towards the selective metal ion (Y3+). The calibration curve of 2-MNBBSH/GCE sensor was plotted at +1.1 V over a broad range of Y3+ concentration. Sensitivity, LOD, LDR and LOQ of the fabricated sensor towards Y3+ were calculated from the calibration curve and found as 1.90 pAμM−1 cm−2, 10.0 pM, 1.0 nM~1.0 mM and 338.33 mM respectively. The 2-MNBBSH/Nafion/GCE sensor was applied to the selective determination of Y3+ in spiked samples such as industrial effluent and real water samples from different sources, and found acceptable and reasonable results.
Theoretical study of superionic phase transition in Li2S
Authors: Jand Sara Panahian , Zhang Qian , Kaghazchi Payam
Published: July 2017

We have studied temperature-induced superionic phase transition in Li2S, which is one of the most promising Li-S battery cathode material. Concentration of ionic carriers at low and high temperature was evaluated from thermodynamics of defects (using density functional theory) and detailed balance condition (using ab initio molecular dynamics (AIMD)), respectively. Diffusion coefficients were also obtained using AIMD simulations. Calculated ionic conductivity shows that superionic phase transition occurs at T = 900 K, which is in agreement with reported experimental values. The superionic behavior of Li2S is found to be due to thermodynamic reason (i.e. a large concentration of disordered defects).
Aptamer-mediated survivin RNAi enables 5-fluorouracil to eliminate colorectal cancer stem cells
Authors: AlShamaileh Hadi , Wang Tao , Xiang Dongxi , Yin Wang , Tran Phuong Ha-Lien , Barrero Roberto A. , Zhang Pei-Zhuo , Li Yong , Kong Lingxue , Liu Ke , Zhou Shu-Feng , Hou Yingchun , Shigdar Sarah , Duan Wei
Published: July 2017

The development of chemoresistance and inability in elimination of cancer stem cells are among the key limitations of cancer chemotherapy. Novel molecular therapeutic strategies able to overcome such limitations are urgently needed for future effective management of cancer. In this report, we show that EpCAM-aptamer-guided survivin RNAi effectively downregulated survivin both in colorectal cancer cells in vitro and in a mouse xenograft model for colorectal cancer. When combined with the conventional chemotherapeutic agents, the aptamer-guided survivin RNAi was able to enhance the sensitivity towards 5-FU or oxaliplatin in colorectal cancer stem cells, increase apoptosis, inhibit tumour growth and improve the overall survival of mice bearing xenograft colorectal cancer. Our results indicate that survivin is one of the key players responsible for the innate chemoresistance of colorectal cancer stem cells. Thus, aptamer-mediated targeting of survivin in cancer stem cells in combination with chemotherapeutic drugs constitutes a new avenue to improve treatment outcome in oncologic clinics.
Derivative Technology of DNA Barcoding (Nucleotide Signature and SNP Double Peak Methods) Detects Adulterants and Substitution in Chinese Patent Medicines
Authors: Gao Zitong , Liu Yang , Wang Xiaoyue , Song Jingyuan , Chen Shilin , Ragupathy Subramanyam , Han Jianping , Newmaster Steven G.
Published: July 2017

Lonicerae japonicae Flos has been used to produce hundred kinds of Chinese patent medicines (CPMs) in China. Economically motivated adulterants have been documented, leading to market instability and a decline in consumer confidence. ITS2 has been used to identify raw medicinal materials, but it’s not suitable for the identification of botanical extracts and complex CPMs. Therefore, a short barcode for the identification of processed CPMs would be profitable. A 34 bp nucleotide signature (5′ CTAGCGGTGGTCGTACGATAGCCAATGCATGAGT 3′) was developed derived from ITS2 region of Eucommiae Folium based on unique motifs. Mixtures of powdered Lonicerae japonicae Flos and Lonicerae Flos resulted in double peaks at the expected SNP (Single Nucleotide Polymorphisms) positions, of which the height of the peaks were roughly indicative of the species’ ratio in the mixed powder. Subsequently we tested 20 extracts and 47 CPMs labelled as containing some species of Lonicera. The results revealed only 17% of the extracts and 22% of the CPMs were authentic, others exist substitution or adulterant; 7% were shown to contain both of two adulterants Eucommiae Folium and Lonicerae Flos. The methods developed in this study will widely broaden the application of DNA barcode in quality assurance of natural health products.
Design and discovery of novel monastrol-1,3,5-triazines as potent anti-breast cancer agent via attenuating Epidermal Growth Factor Receptor tyrosine kinase
Authors: Srivastava Jitendra Kumar , Pillai Girinath G. , Bhat Hans Raj , Verma Amita , Singh Udaya Pratap
Published: July 2017

A novel series of hybrid analogues of monastrol-1,3,5-triazine were designed and developed via one-pot synthesis using Bi(NO3)3 as a catalyst. Entire compounds were evaluated for their anticancer activity against HeLa (cervical cancer), MCF-7 (breast cancer), HL-60 (Human promyelocytic leukemia), HepG2 (Hepatocellular carcinoma) and MCF 12A (normal epithelial breast cell line) using MTT assay, where they showed highest inhibitory activity against MCF-7. The molecules were also found to be non-toxic to MCF 12A cells. These molecules showed considerable inhibitory percentage against Epidermal Growth Factor Receptor tyrosine kinase (EGFR-TK), in in-vitro assay. Molecular docking study was carried out on the analogs and reference compound (Erlotinib) into the ATP binding site of EGFR-TK domain (PDB ID:1M17) to elucidate vital structural residues necessary for bioactivity. The effect of most active compound 7l was also estimated in-vivo in DMBA induced mammary tumor in female Sprague-Dawley rats. The effect of anti-breast cancer effect of 7l was quantified on the basis of tumour incidence, body weight and tumor volume in DMBA-induced rats. Its effect on biochemical parameters, such as antioxidant status (SOD, CAT, GPX and GSH) and lipid peroxidation was also studied. The compound 7l showed inhibition of EGFR downstream signalling in the western blot analysis.
CrossCheck: an open-source web tool for high-throughput screen data analysis
Authors: Najafov Jamil , Najafov Ayaz
Published: July 2017

Modern high-throughput screening methods allow researchers to generate large datasets that potentially contain important biological information. However, oftentimes, picking relevant hits from such screens and generating testable hypotheses requires training in bioinformatics and the skills to efficiently perform database mining. There are currently no tools available to general public that allow users to cross-reference their screen datasets with published screen datasets. To this end, we developed CrossCheck, an online platform for high-throughput screen data analysis. CrossCheck is a centralized database that allows effortless comparison of the user-entered list of gene symbols with 16,231 published datasets. These datasets include published data from genome-wide RNAi and CRISPR screens, interactome proteomics and phosphoproteomics screens, cancer mutation databases, low-throughput studies of major cell signaling mediators, such as kinases, E3 ubiquitin ligases and phosphatases, and gene ontological information. Moreover, CrossCheck includes a novel database of predicted protein kinase substrates, which was developed using proteome-wide consensus motif searches. CrossCheck dramatically simplifies high-throughput screen data analysis and enables researchers to dig deep into the published literature and streamline data-driven hypothesis generation. CrossCheck is freely accessible as a web-based application at http://proteinguru.com/crosscheck.
Mapping resistance responses to Sclerotinia infestation in introgression lines of Brassica juncea carrying genomic segments from wild Brassicaceae B. fruticulosa
Authors: Rana Kusum , Atri Chhaya , Gupta Mehak , Akhatar Javed , Sandhu Prabhjodh S. , Kumar Nitin , Jaswal Ravinder , Barbetti Martin J. , Banga Surinder S.
Published: July 2017

Sclerotinia stem rot (Sclerotinia sclerotiorum) is a major disease of Brassica oilseeds. As suitable donors to develop resistant cultivars are not available in crop Brassicas, we introgressed resistance from a wild Brassicaceae species, B. fruticulosa. We produced 206 B. juncea-B. fruticulosa introgression lines (ILs). These were assessed for pollen grain fertility, genome size variations and resistance responses to Sclerotinia following stem inoculations under disease-conducive conditions. Of these, 115 ILs showing normal fertility and genome size were selected for cytogenetic characterization using florescent genomic in situ hybridization (Fl-GISH). B. fruticulosa segment substitutions were indicated in 28 ILs. These were predominantly terminal and located on B-genome chromosomes. A final set of 93 highly fertile and euploid (2n = 36) ILs were repeat-evaluated for their resistance responses during 2014–15. They were also genotyped with 202 transferable and 60 candidate gene SSRs. Association mapping allowed detection of ten significant marker trait associations (MTAs) after Bonferroni correction. These were: CNU-m157-2, RA2G05, CNU-m353-3, CNU-m442-5, ACMP00454-2, ACMP00454-3, EIN2-3-1, M641-1, Na10D09-1 and Na10D11-1. This is the first time such a molecular mapping technique has been deployed with introgression lines carrying genomic segments from B. fruticulosa, and the first to show that they possess high levels of resistance against S. sclerotiorum.
Benchmarking selected computational gene network growing tools in context of virus-host interactions
Authors: Taye Biruhalem , Vaz Candida , Tanavde Vivek , Kuznetsov Vladimir A. , Eisenhaber Frank , Sugrue Richard J. , Maurer-Stroh Sebastian
Published: July 2017

Several available online tools provide network growing functions where an algorithm utilizing different data sources suggests additional genes/proteins that should connect an input gene set into functionally meaningful networks. Using the well-studied system of influenza host interactions, we compare the network growing function of two free tools GeneMANIA and STRING and the commercial IPA for their performance of recovering known influenza A virus host factors previously identified from siRNA screens. The result showed that given small (~30 genes) or medium (~150 genes) input sets all three network growing tools detect significantly more known host factors than random human genes with STRING overall performing strongest. Extending the networks with all the three tools significantly improved the detection of GO biological processes of known host factors compared to not growing networks. Interestingly, the rate of identification of true host factors using computational network growing is equal or better to doing another experimental siRNA screening study which could also be true and applied to other biological pathways/processes.
Investigating glycemic potential of rice by unraveling compositional variations in mature grain and starch mobilization patterns during seed germination
Authors: Guzman Maria Krishna de , Parween Sabiha , Butardo Vito M. , Alhambra Crisline Mae , Anacleto Roslen , Seiler Christiane , Bird Anthony R. , Chow Chung-Ping , Sreenivasulu Nese
Published: July 2017

Rice lines with slower starch digestibility provide opportunities in mitigating the global rise in type II diabetes and related non-communicable diseases. However, screening for low glycemic index (GI) in rice breeding programs is not possible due to time and cost constraints. This study evaluated the feasibility of using in vitro cooked grain amylolysis, starch mobilization patterns during seed germination, and variation in starch structure and composition in the mature seed to differentiate patterns of starch digestibility. Mobilization patterns of total starch, resistant starch, amylose and amylopectin chains, and free sugars during seed germination revealed that the process is analogous to digestion in the human gastrointestinal tract. The combination of these biochemical markers can be used as an alternative measure to predict GI. Additionally, transcriptome analysis of stored mRNA transcripts in high and low GI lines detected differences in starch metabolism and confirmed the importance of seed storage pathways in influencing digestibility. Pathway analyses supported by metabolomics data revealed that resistant starch, cell wall non-starch polysaccharides and flavonoids potentially contribute to slower digestibility. These new insights can guide precision breeding programs to produce low GI rice with acceptable cooking quality to help mitigate the burden of diet-associated lifestyle diseases.
Classification of skin phenotypes caused by diabetes mellitus using complex scattering parameters in the millimeter-wave frequency range
Authors: Dornuf Fabian , Martín-Mateos Pedro , Duarte Blanca , Hils Bernhard , Bonilla-Manrique Oscar Elias , Larcher Fernando , Acedo Pablo , Krozer Viktor
Published: July 2017

The pathological skin phenotype caused by hyperglycemia is an important indicator for the progress of diabetes mellitus. An early detection of diabetes assures an early intervention to regulate the carbohydrate metabolism. In this publication a non-invasive detection principle based on the measurement of complex scattering parameters in the millimeter-wave frequency range is presented. The measurement principle provides evidence of the applicability for the identification of different glycemic states in animal models. The method proposed here can be used to predict diabetes status in animal models and is interesting for application on humans in view of safeness of millimeter-wave radiation. Furthermore the complex scattering parameters give important information about the anatomic varieties between the analyzed skin samples of the different mice strains. In contrast to other methods, our approach is less sensitive to skin variations between animals.
Monolithically-Integrated TE-mode 1D Silicon-on-Insulator Isolators using Seedlayer-Free Garnet
Authors: Zhang Cui , Dulal Prabesh , Stadler Bethanie J. H. , Hutchings David C.
Published: July 2017

The first experimental TE-mode silicon-on-insulator (SOI) isolators using Faraday Rotation are here realized to fill the ‘missing link’ in source-integrated near infrared photonic circuits. The isolators are simple 1D 2-element waveguides, where garnet claddings and longitudinal magnetic fields produce nonreciprocal mode conversion, the waveguide equivalent of Faraday Rotation (FR). Quasi-phase matched claddings are used to overcome the limitations of birefringence. Current experimental SOI isolators use nonreciprocal phase shift (NRPS) in interferometers or ring resonators, but to date NRPS requires TM-modes, so the TE-modes normally produced by integrated lasers cannot be isolated without many ancillary polarisation controls. The presented FR isolators are made via lithography and sputter deposition, which allows facile upscaling compared to the pulsed laser deposition or wafer bonding used in the fabrication of NRPS devices. Here, isolation ratios and losses of 11 dB and 4 dB were obtained, and future designs are identified capable of isolation ratios >30 dB with losses <6 dB.
Opposite, bidirectional shifts in excitation and inhibition in specific types of dorsal horn interneurons are associated with spasticity and pain post-SCI
Authors: Kopach Olga , Medvediev Volodymyr , Krotov Volodymyr , Borisyuk Anya , Tsymbaliuk Vitaliy , Voitenko Nana
Published: July 2017

Spasticity, a common complication after spinal cord injury (SCI), is frequently accompanied by chronic pain. The physiological origin of this pain (critical to its treatment) remains unknown, although spastic motor dysfunction has been related to the hyperexcitability of motoneurons and to changes in spinal sensory processing. Here we show that the pain mechanism involves changes in sensory circuits of the dorsal horn (DH) where nociceptive inputs integrate for pain processing. Spasticity is associated with the DH hyperexcitability resulting from an increase in excitation and disinhibition occurring in two respective types of sensory interneurons. In the tonic-firing inhibitory lamina II interneurons, glutamatergic drive was reduced while glycinergic inhibition was potentiated. In contrast, excitatory drive was boosted to the adapting-firing excitatory lamina II interneurons while GABAergic and glycinergic inhibition were reduced. Thus, increased activity of excitatory DH interneurons coupled with the reduced excitability of inhibitory DH interneurons post-SCI could provide a neurophysiological mechanism of central sensitization and chronic pain associated with spasticity.
Neuronal imaging with ultrahigh dynamic range multiphoton microscopy
Authors: Yang Ruohui , Weber Timothy D. , Witkowski Ellen D. , Davison Ian G. , Mertz Jerome
Published: July 2017

Multiphoton microscopes are hampered by limited dynamic range, preventing weak sample features from being detected in the presence of strong features, or preventing the capture of unpredictable bursts in sample strength. We present a digital electronic add-on technique that vastly improves the dynamic range of a multiphoton microscope while limiting potential photodamage. The add-on provides real-time negative feedback to regulate the laser power delivered to the sample, and a log representation of the sample strength to accommodate ultrahigh dynamic range without loss of information. No microscope hardware modifications are required, making the technique readily compatible with commercial instruments. Benefits are shown in both structural and in-vivo functional mouse brain imaging applications.
Diastolic Augmentation Index Improves Radial Augmentation Index in Assessing Arterial Stiffness
Authors: Yao Yang , Hao Liling , Xu Lisheng , Zhang Yahui , Qi Lin , Sun Yingxian , Yang Benqiang , van de Vosse Frans N. , Yao Yudong
Published: July 2017

Arterial stiffness is an important risk factor for cardiovascular events. Radial augmentation index (AI
r
) can be more conveniently measured compared with carotid-femoral pulse wave velocity (cfPWV). However, the performance of AI
r
in assessing arterial stiffness is limited. This study proposes a novel index AI
rd
, a combination of AI
r
and diastolic augmentation index (AI
d
) with a weight α, to achieve better performance over AI
r
in assessing arterial stiffness. 120 subjects (43 ± 21 years old) were enrolled. The best-fit α is determined by the best correlation coefficient between AI
rd
and cfPWV. The performance of the method was tested using the 12-fold cross validation method. AI
rd
(r = 0.68, P < 0.001) shows a stronger correlation with cfPWV and a narrower prediction interval than AI
r
(r = 0.61, P < 0.001), AI
d
(r = −0.17, P = 0.06), the central augmentation index (AI
c
) (r = 0.61, P < 0.001) or AI
c
normalized for heart rate of 75 bpm (r = 0.65, P < 0.001). Compared with AI
r
(age, P < 0.001; gender, P < 0.001; heart rate, P < 0.001; diastolic blood pressure, P < 0.001; weight, P = 0.001), AI
rd
has fewer confounding factors (age, P < 0.001; gender, P < 0.001). In conclusion, AI
rd
derives performance improvement in assessing arterial stiffness, with a stronger correlation with cfPWV and fewer confounding factors.
Increased neural noise and impaired brain synchronization in fibromyalgia patients during cognitive interference
Authors: González-Villar A. J. , Samartin-Veiga N. , Arias M. , Carrillo-de-la-Peña M. T.
Published: July 2017

Fibromyalgia (FM) and other chronic pain syndromes are associated with cognitive dysfunction and attentional deficits, but the neural basis of such alterations is poorly understood. Dyscognition may be related to high levels of neural noise, understood as increased random electrical fluctuations that impair neural communication; however, this hypothesis has not yet been tested in any chronic pain condition. Here we compared electroencephalographic activity (EEG) in 18 FM patients -with high self-reported levels of cognitive dysfunction- and 22 controls during a cognitive control task. We considered the slope of the Power Spectrum Density (PSD) as an indicator of neural noise. As the PSD slope is flatter in noisier systems, we expected to see shallower slopes in the EEG of FM patients. Higher levels of neural noise should be accompanied by reduced power modulation and reduced synchronization between distant brain locations after stimulus presentation. As expected, FM patients showed flatter PSD slopes. After applying a Laplacian spatial filter, we found reduced theta and alpha power modulation and reduced midfrontal-posterior theta phase synchronization. Results suggest higher neural noise and impaired local and distant neural coordination in the patients and support the neural noise hypothesis to explain dyscognition in FM.
Highly selective tungstate transporter protein TupA from Desulfovibrio alaskensis G20
Authors: Otrelo-Cardoso Ana Rita , Nair Rashmi R. , Correia Márcia A. S. , Cordeiro Raquel S. Correia , Panjkovich Alejandro , Svergun Dmitri I. , Santos-Silva Teresa , Rivas Maria G.
Published: July 2017

Molybdenum and tungsten are taken up by bacteria and archaea as their soluble oxyanions through high affinity transport systems belonging to the ATP-binding cassette (ABC) transporters. The component A (ModA/TupA) of these transporters is the first selection gate from which the cell differentiates between MoO42−, WO42− and other similar oxyanions. We report the biochemical characterization and the crystal structure of the apo-TupA from Desulfovibrio desulfuricans G20, at 1.4 Å resolution. Small Angle X-ray Scattering data suggests that the protein adopts a closed and more stable conformation upon ion binding. The role of the arginine 118 in the selectivity of the oxyanion was also investigated and three mutants were constructed: R118K, R118E and R118Q. Isothermal titration calorimetry clearly shows the relevance of this residue for metal discrimination and oxyanion binding. In this sense, the three variants lost the ability to coordinate molybdate and the R118K mutant keeps an extremely high affinity for tungstate. These results contribute to an understanding of the metal-protein interaction, making it a suitable candidate for a recognition element of a biosensor for tungsten detection.
Genetic differentiation of the Schizothorax species complex (Cyprinidae) in the Nujiang River (upper Salween)
Authors: Chen Weitao , Yue Xingjian , He Shunping
Published: July 2017

Phenotypically diverse species from recently evolved groups always share allele/haplotype due to insufficient differentiation in the early process. In this study, we performed population genetics analyses using sequences from the mitochondrial cytochromebgene, and two nuclear genes to investigate the genetic differentiation of the closely relatedSchizothoraxspecies complex, comprising a group of alpine fish living in the Nujiang River. The results from both mtDNA and nDNA markers revealed relatively low but pronounced genetic differentiation among the threeSchizothoraxspecies, i.e.,Schizothorax gongshanensis,S.lissolabiatus, andS.nukiangensis. However, haplotype sharing was frequently occurred among the three species. Divergence time estimation suggested the last glaciation on the Tibetan Plateau (0.075–0.01 Ma) might drive the divergence of the species complex. Gene flow might contribute to the haplotype sharing betweenS.gongshanensisandS.lissolabiatus, and betweenS.gongshanensisandS.nukiangensis, whereas retention of ancestral polymorphisms seemed to be a better explanation of the haplotype sharing betweenS.lissolabiatusandS.nukiangensis. In addition,S.lissolabiatuspopulations should obtain more protection in the future because of their low genetic diversity and habitat fragmentation. In summary, our study assesses genetic differentiation among the three closely relatedSchizothoraxspecies and explores the possible driving forces for their differentiation.
Prediction of presynaptic and postsynaptic neurotoxins by combining various Chou’s pseudo components
Authors: Huo Haiyan , Li Tao , Wang Shiyuan , Lv Yingli , Zuo Yongchun , Yang Lei
Published: July 2017

Presynaptic and postsynaptic neurotoxins are two groups of neurotoxins. Identification of presynaptic and postsynaptic neurotoxins is an important work for numerous newly found toxins. It is both costly and time consuming to determine these two neurotoxins by experimental methods. As a complement, using computational methods for predicting presynaptic and postsynaptic neurotoxins could provide some useful information in a timely manner. In this study, we described four algorithms for predicting presynaptic and postsynaptic neurotoxins from sequence driven features by using Increment of Diversity (ID), Multinomial Naive Bayes Classifier (MNBC), Random Forest (RF), and K-nearest Neighbours Classifier (IBK). Each protein sequence was encoded by pseudo amino acid (PseAA) compositions and three biological motif features, including MEME, Prosite and InterPro motif features. The Maximum Relevance Minimum Redundancy (MRMR) feature selection method was used to rank the PseAA compositions and the 50 top ranked features were selected to improve the prediction accuracy. The PseAA compositions and three kinds of biological motif features were combined and 12 different parameters that defined as P1-P12 were selected as the input parameters of ID, MNBC, RF, and IBK. The prediction results obtained in this study were significantly better than those of previously developed methods.
Interferometric rotating point spread function
Authors: Wang Wei , Situ Guohai
Published: July 2017

Rotating point spread functions (PSF), such as the double helix (DH) PSF, are widely used in localization-based super-resolution imaging because of their large working depth range. In this article, we propose an interferometric DH PSF (iDH PSF) using two opposed objective lenses as in the 4Pi microscope. In the proposed iDH PSF, the super-resolution in the axial PSF is transferred to the azimuthal rotation. Moreover, we design an iDH PSF whose imaging range reaches 3 μm, which is roughly 3 times as much as that which can be obtained by using other interferometric localization-based super-resolution imaging methods.
Therapeutic targeting of HMGB1 during experimental sepsis modulates the inflammatory cytokine profile to one associated with improved clinical outcomes
Authors: Stevens Natalie E. , Chapman Marianne J. , Fraser Cara K. , Kuchel Tim R. , Hayball John D. , Diener Kerrilyn R.
Published: July 2017

Sepsis remains a significant health burden and a major clinical need exists for therapeutics to dampen the excessive and uncontrolled immune activation. Nuclear protein high mobility group box protein 1 (HMGB1) is released following cell death and is a late mediator in sepsis pathogenesis. While approaches targeting HMGB1 have demonstrated reduced mortality in pre-clinical models of sepsis, the impact of HMGB1 blockade on the complex septic inflammatory milieu and the development of subsequent immunosuppression remain enigmatic. Analysis of plasma samples obtained from septic shock patients established an association between increased HMGB1 and non-survival, higher APACHE II scores, and increased pro-inflammatory cytokine responses. Pre-clinically, administration of neutralising ovine anti-HMGB1 polyclonal antibodies improved survival in murine endotoxaemia and caecal ligation and puncture-induced sepsis models, and altered early cytokine profiles to one which corresponded to patterns observed in the surviving patient cohort. Additionally, anti-HMGB1 treated murine sepsis survivors were significantly more resistant to secondary bacterial infection and exhibited altered innate immune cell phenotypes and cytokine responses. These findings demonstrate that anti-HMGB1 antibodies alter inflammation in murine sepsis models and reduce sepsis mortality without potentiating immunosuppression.
SgRNA Expression of CRIPSR-Cas9 System Based on MiRNA Polycistrons as a Versatile Tool to Manipulate Multiple and Tissue-Specific Genome Editing
Authors: Xie Chen , Chen Yan-Lian , Wang Dong-Fang , Wang Yi-Lin , Zhang Tian-Peng , Li Hui , Liang Fu , Zhao Yong , Zhang Guang-Ya
Published: July 2017

CRISPR/Cas9-mediated genome editing is a next-generation strategy for genetic modifications. Typically, sgRNA is constitutively expressed relying on RNA polymerase III promoters. Polymerase II promoters initiate transcription in a flexible manner, but sgRNAs generated by RNA polymerase II promoter lost their nuclease activity. To express sgRNAs in a tissue-specific fashion and endow CRISPR with more versatile function, a novel system was established in a polycistron, where miRNAs (or shRNAs) and sgRNAs alternately emerged and co-expressed under the control of a single polymerase II promoter. Effective expression and further processing of functional miRNAs and sgRNAs were achieved. The redundant nucleotides adjacent to sgRNA were degraded, and 5′- cap structure was responsible for the compromised nuclease capacity of sgRNA: Cas9 complex. Furthermore, this strategy fulfilled conducting multiplex genome editing, as well as executing neural- specific genome editing and enhancing the proportion of homologous recombination via inhibiting NHEJ pathway by shRNA. In summary, we designed a new construction for efficient expression of sgRNAs with miRNAs (shRNAs) by virtue of RNA polymerase II promoters, which will spur the development of safer, more controllable/regulable and powerful CRISPR/Cas9 system-mediated genome editing in a wide variety of further biomedical applications.
Sexual and non-sexual social preferences in male and female white-eyed bulbuls
Authors: Kabasakal Bekir , Poláček Miroslav , Aslan Aziz , Hoi Herbert , Erdoğan Ali , Griggio Matteo
Published: July 2017

While the function of ornaments shaped by sexual selection is to attract mates or drive off rivals, these signals may also evolve through social selection, in which the social context affects the fitness of signallers and receivers. Classical ‘mate choice’ experiments often reveal preferences for ornaments, but few studies have considered whether these are strictly sexual or reflect general social preferences. Indeed, an alternative possibility is that ornaments evolve through ‘non-sexual social selection’ (hereafter ‘social selection’). We examined the role of ornamentation (yellow ventral patch) and familiarity (individuals recognize group mates with which they have had previous interactions) on mate choice (opposite-sex stimuli preference) and social choice (same-sex stimuli preference) in both male and female white-eyed bulbuls (Pycnonotus xanthopygos). In the mate choice test, females preferred unfamiliar males with increased yellow. There were no biologically important differences in male preferences based on familiarity or intensity of patch colour. In the social choice test, females preferred to associate with familiar females. Males preferred to associate with familiar males but also preferred to associate with less ornamented males. Our results suggest that ornamentation and familiarity are important features, playing different roles in males and females, in both social and sexual selection processes.
Observed trends in the magnitude and persistence of monthly temperature variability
Authors: Lenton Timothy M. , Dakos Vasilis , Bathiany Sebastian , Scheffer Marten
Published: July 2017

Climate variability is critically important for nature and society, especially if it increases in amplitude and/or fluctuations become more persistent. However, the issues of whether climate variability is changing, and if so, whether this is due to anthropogenic forcing, are subjects of ongoing debate. Increases in the amplitude and persistence of temperature fluctuations have been detected in some regions, e.g. the North Pacific, but there is no agreed global signal. Here we systematically scan monthly surface temperature indices and spatial datasets to look for trends in variance and autocorrelation (persistence). We show that monthly temperature variability and autocorrelation increased over 1957–2002 across large parts of the North Pacific, North Atlantic, North America and the Mediterranean. Furthermore, (multi)decadal internal climate variability appears to influence trends in monthly temperature variability and autocorrelation. Historically-forced climate models do not reproduce the observed trends in temperature variance and autocorrelation, consistent with the models poorly capturing (multi)decadal internal climate variability. Based on a review of established spatial correlations and corresponding mechanistic ‘teleconnections’ we hypothesise that observed slowing down of sea surface temperature variability contributed to observed increases in land temperature variability and autocorrelation, which in turn contributed to persistent droughts in North America and the Mediterranean.
CD300f:IL-5 cross-talk inhibits adipose tissue eosinophil homing and subsequent IL-4 production
Authors: Rozenberg Perri , Reichman Hadar , Zab-Bar Israel , Itan Michal , Pasmanik-Chor Metsada , Bouffi Carine , Qimron Udi , Bachelet Ido , Fulkerson Patricia C. , Rothenberg Marc E. , Munitz Ariel
Published: July 2017

Eosinophils and their associated cytokines IL-4 and IL-5 are emerging as central orchestrators of the immune-metabolic axis. Herein, we demonstrate that cross-talk between the Ig-superfamily receptor CD300f and IL-5 is a key checkpoint that modifies the ability of eosinophils to regulate metabolic outcomes. Generation ofIl5Tg/Cd300f−/−mice revealed marked and distinct increases in eosinophil levels and their production of IL-4 in the white and brown adipose tissues. Consequently,Il5Tg/Cd300f−/−mice had increased alternatively activated macrophage accumulation in the adipose tissue.Cd300f−/−mice displayed age-related accumulation of eosinophils and macrophages in the adipose tissue and decreased adipose tissue weight, which was associated with decreased diet-induced weight gain and insulin resistance. Notably,Il5Tg/CD300f−/−were protected from diet-induced weight gain and glucose intolerance. These findings highlight the cross-talk between IL-5 receptor and CD300f as a novel pathway regulating adipose tissue eosinophils and offer new entry points for therapeutic intervention for obesity and its complications.
Bottom-up hydrogen deuterium exchange mass spectrometry: data analysis and interpretation
Authors: Brown Kerene A. , Wilson Derek J.
Published: July 2017

A tutorial review on the fundamentals of HDX-MS with an emphasis on data analysis and interpretation.
Monitoring of “on-demand” drug release using dual tumor marker mediated DNA-capped versatile mesoporous silica nanoparticles
Authors: Wang Song , Liu Fei , Li Xiang-Ling
Published: July 2017

We constructed a versatile drug delivery system using dual internal stimulus, achieving controllable release and monitoring simultaneously.
Evaluation of DFO-HOPO as an octadentate chelator for zirconium-89
Authors: Allott L. , Da Pieve C. , Meyers J. , Spinks T. , Ciobota D. M. , Kramer-Marek G. , Smith G.
Published: July 2017

The future of 89Zr-based immuno-PET is reliant upon the development of new chelators with improved stability compared to the currently used deferoxamine (DFO).
New mechanistic insights into intramolecular aromatic ligand hydroxylation and benzyl alcohol oxidation initiated by the well-defined (μ-peroxo)diiron(iii) complex
Authors: Sekino Mio , Furutachi Hideki , Tojo Rina , Hishi Ayumi , Kajikawa Hanako , Suzuki Takatoshi , Suzuki Kaito , Fujinami Shuhei , Akine Shigehisa , Sakata Yoko , Ohta Takehiro , Hayami Shinya , Suzuki Masatatsu
Published: July 2017

A diiron(iv)-oxo species (1-oxo) is an essential intermediate in the oxidation reaction initiated by1-O2.
Synthesis of rare-earth-metal-in-cryptand dications, [Ln(2.2.2-cryptand)]2+, from Sm2+, Eu2+, and Yb2+ silyl metallocenes (C5H4SiMe3)2Ln(THF)2
Authors: Huh Daniel N. , Kotyk Christopher M. , Gembicky Milan , Rheingold Arnold L. , Ziller Joseph W. , Evans William J.
Published: July 2017

Ln2+-in-cryptand complexes (Ln = Sm, Eu, Yb) containing +2 ions surrounded only by neutral ligands are readily formed from silyl metallocenes.
Poly(amino acid)-polyester graft copolymer nanoparticles for the acid-mediated release of doxorubicin
Authors: Price Daniel J. , Khuphe Mthulisi , Davies Robert P. W. , McLaughlan James R. , Ingram Nicola , Thornton Paul D.
Published: July 2017

OCA and NCA ring-opening polymerisations are combined to yield pH-responsive nanoparticles ideally suited for controlled doxorubicin release.
Rapid and ultrasensitive detection of endocrine disrupting chemicals using a nanosensor-enabled cell-based platform
Authors: Le Ngoc D. B. , Wang Xian , Geng Yingying , Tang Rui , Tonga Gulen Yesilbag , Jiang Ziwen , Rotello Vincent M.
Published: July 2017

A high-throughput cell-based nanosensor provides highly sensitive identification of estrogenic agents.
Organic selenocyanates as strong and directional chalcogen bond donors for crystal engineering
Authors: Huynh Huu-Tri , Jeannin Olivier , Fourmigué Marc
Published: July 2017

Organic selenocyanates can act as powerful chalcogen bond donors, with themselves or with Lewis bases.
Molybdenum and tungsten doped SnO2 transparent conductive thin films with broadband high transmittance between the visible and near-infrared regions
Authors: Huo Xinxin , Jiang Shenglin , Liu Pin , Shen Meng , Qiu Shiyong , Li Ming-Yu
Published: July 2017

We demonstrate an approach for the synthesis of SnO2 transparent conductive films with low square resistance and high transmittance over the visible and NIR regions via doping of molybdenum and tungsten.
Ultrafast dynamics and solvent-dependent deactivation kinetics of BODIPY molecular rotors
Authors: Suhina Tomislav , Amirjalayer Saeed , Woutersen Sander , Bonn Daniel , Brouwer Albert M.
Published: July 2017

The fluorescent excited state of a molecular rotor based on the meso-substituted boron-dipyrromethane (BODIPY) core decays rapidly to the ground state via a conical intersection. The fluorescence is strongly increased in viscous solvents, but solvent polarity has only a small effect.
Accurate determination of the charge transfer efficiency of photoanodes for solar water splitting
Authors: Klotz Dino , Grave Daniel A. , Rothschild Avner
Published: July 2017

The charge transfer efficiency,ηt, is important to distinguish between bulk and surface recombination losses, but it is difficult to determine it accurately. We provide a comparison of methods and give recommendations, how to obtain reliable values forηt.
Ultrafast X-ray measurements of the glass-like, high-frequency stiffness of aqueous solutions
Authors: Jiao Yishuo , Adams Bernhard , Rose-Petruck Christoph
Published: July 2017

The ultrafast dynamics of the domains surrounding solutes in aqueous solution were measured using laser-generating GHz phonons in 30 mM ferrocyanide solutions and the resulting molecular motions of the solutes and their hydrogen-bonded solvation shells were detected using ultrafast X-ray absorption spectroscopy (UXAS).
Evaporation–condensation effects on the thermoelectric performance of PbTe-based couples
Authors: Sadia Yatir , Ben-Ayoun Dana , Gelbstein Yaniv
Published: July 2017

In thermoelectric (TE) generators, Carnot efficiency maximization, by increasing the hot side temperature, is required for maximizing the heat to electricity energy conversion.
A comparative VUV absorption mass-spectroscopy study on protonated peptides of different size
Authors: Egorov D. , Hoekstra R. , Schlathölter T.
Published: July 2017

The response of gas-phase peptides upon vacuum ultraviolet absorption depends strongly on the peptide size.
Accurate prediction of energetic properties of ionic liquid clusters using a fragment-based quantum mechanical method
Authors: Liu Jinfeng , He Xiao
Published: July 2017

Accurate prediction of physicochemical properties of ionic liquids (ILs) is of great significance to understand and design novel ILs with unique properties.