bluuebunny/crossref_metadata_2025 huggingface dataset:
Ratiometric Matryoshka biosensors from a nested cassette of green- and orange-emitting fluorescent proteins
Authors: Ast Cindy , Foret Jessica , Oltrogge Luke M. , De Michele Roberto , Kleist Thomas J. , Ho Cheng-Hsun , Frommer Wolf B.
Published: August 2017

Sensitivity, dynamic and detection range as well as exclusion of expression and instrumental artifacts are critical for the quantitation of data obtained with fluorescent protein (FP)-based biosensors in vivo. Current biosensors designs are, in general, unable to simultaneously meet all these criteria. Here, we describe a generalizable platform to create dual-FP biosensors with large dynamic ranges by employing a single FP-cassette, named GO-(Green-Orange) Matryoshka. The cassette nests a stable reference FP (large Stokes shift LSSmOrange) within a reporter FP (circularly permuted green FP). GO- Matryoshka yields green and orange fluorescence upon blue excitation. As proof of concept, we converted existing, single-emission biosensors into a series of ratiometric calcium sensors (MatryoshCaMP6s) and ammonium transport activity sensors (AmTryoshka1;3). We additionally identified the internal acid-base equilibrium as a key determinant of the GCaMP dynamic range. Matryoshka technology promises flexibility in the design of a wide spectrum of ratiometric biosensors and expanded in vivo applications.
Exact broadband excitation of two-level systems by mapping spins to springs
Authors: Li Jr-Shin , Ruths Justin , Glaser Steffen J.
Published: August 2017

Designing accurate and high-fidelity broadband pulses is an essential component in conducting quantum experiments across fields from protein spectroscopy to quantum optics. However, constructing exact and analytic broadband pulses remains unsolved due to the nonlinearity and complexity of the underlying spin system dynamics. Here, we present a nontrivial dynamic connection between nonlinear spin and linear spring systems and show the surprising result that such nonlinear and complex pulse design problems are equivalent to designing controls to steer linear harmonic oscillators under optimal forcing. We derive analytic broadband π/2 and π pulses that perform exact, or asymptotically exact, excitation and inversion over a defined bandwidth, and also with bounded amplitude. This development opens up avenues for pulse sequence design and lays a foundation for understanding the control of two-level systems.
Phenotype-driven precision oncology as a guide for clinical decisions one patient at a time
Authors: Chia Shumei , Low Joo-Leng , Zhang Xiaoqian , Kwang Xue-Lin , Chong Fui-Teen , Sharma Ankur , Bertrand Denis , Toh Shen Yon , Leong Hui-Sun , Thangavelu Matan T. , Hwang Jacqueline S. G. , Lim Kok-Hing , Skanthakumar Thakshayeni , Tan Hiang-Khoon , Su Yan , Hui Choo Siang , Hentze Hannes , Tan Iain B. H. , Lezhava Alexander , Tan Patrick , Tan Daniel S. W. , Periyasamy Giridharan , Koh Judice L. Y. , Gopalakrishna Iyer N. , DasGupta Ramanuj
Published: August 2017

Genomics-driven cancer therapeutics has gained prominence in personalized cancer treatment. However, its utility in indications lacking biomarker-driven treatment strategies remains limited. Here we present a “phenotype-driven precision-oncology” approach, based on the notion that biological response to perturbations, chemical or genetic, in ex vivo patient-individualized models can serve as predictive biomarkers for therapeutic response in the clinic. We generated a library of “screenable” patient-derived primary cultures (PDCs) for head and neck squamous cell carcinomas that reproducibly predicted treatment response in matched patient-derived-xenograft models. Importantly, PDCs could guide clinical practice and predict tumour progression in two n = 1 co-clinical trials. Comprehensive “-omics” interrogation of PDCs derived from one of these models revealed YAP1 as a putative biomarker for treatment response and survival in ~24% of oral squamous cell carcinoma. We envision that scaling of the proposed PDC approach could uncover biomarkers for therapeutic stratification and guide real-time therapeutic decisions in the future.
Endocytic sorting motif interactions involved in Nef-mediated downmodulation of CD4 and CD3
Authors: Manrique Santiago , Sauter Daniel , Horenkamp Florian A. , Lülf Sebastian , Yu Hangxing , Hotter Dominik , Anand Kanchan , Kirchhoff Frank , Geyer Matthias
Published: August 2017

Lentiviral Nefs recruit assembly polypeptide complexes and target sorting motifs in cellular receptors to induce their internalization. While Nef-mediated CD4 downmodulation is conserved, the ability to internalize CD3 was lost in HIV-1 and its precursors. Although both functions play key roles in lentiviral replication and pathogenicity, the underlying structural requirements are poorly defined. Here, we determine the structure of SIVmac239 Nef bound to the ExxxLM motif of another Nef molecule at 2.5 Å resolution. This provides a basis for a structural model, where a hydrophobic crevice in simian immunodeficiency virus (SIV) Nef targets a dileucine motif in CD4 and a tyrosine-based motif in CD3. Introducing key residues into this crevice of HIV-1 Nef enables CD3 binding but an additional N-terminal tyrosine motif is required for internalization. Our resolution of the CD4/Nef/AP2 complex and generation of HIV-1 Nefs capable of CD3 downregulation provide insights into sorting motif interactions and target discrimination of Nef.
pGlyco 2.0 enables precision N-glycoproteomics with comprehensive quality control and one-step mass spectrometry for intact glycopeptide identification
Authors: Liu Ming-Qi , Zeng Wen-Feng , Fang Pan , Cao Wei-Qian , Liu Chao , Yan Guo-Quan , Zhang Yang , Peng Chao , Wu Jian-Qiang , Zhang Xiao-Jin , Tu Hui-Jun , Chi Hao , Sun Rui-Xiang , Cao Yong , Dong Meng-Qiu , Jiang Bi-Yun , Huang Jiang-Ming , Shen Hua-Li , Wong Catherine C. L. , He Si-Min , Yang Peng-Yuan
Published: August 2017

The precise and large-scale identification of intact glycopeptides is a critical step in glycoproteomics. Owing to the complexity of glycosylation, the current overall throughput, data quality and accessibility of intact glycopeptide identification lack behind those in routine proteomic analyses. Here, we propose a workflow for the precise high-throughput identification of intact N-glycopeptides at the proteome scale using stepped-energy fragmentation and a dedicated search engine. pGlyco 2.0 conducts comprehensive quality control including false discovery rate evaluation at all three levels of matches to glycans, peptides and glycopeptides, improving the current level of accuracy of intact glycopeptide identification. The N-glycoproteome of samples metabolically labeled with 15N/13C were analyzed quantitatively and utilized to validate the glycopeptide identification, which could be used as a novel benchmark pipeline to compare different search engines. Finally, we report a large-scale glycoproteome dataset consisting of 10,009 distinct site-specific N-glycans on 1988 glycosylation sites from 955 glycoproteins in five mouse tissues.
Significance of penile hypersensitivity in premature ejaculation
Authors: Guo Liqiang , Liu Yuqiang , Wang Xuesheng , Yuan Mingzhen , Yu Yang , Zhang Xiulin , Zhao Shengtian
Published: August 2017

To assess the correlation between penile hypersensitivity and premature ejaculation (PE), a total of 420 consecutive subjects attending our andrologic clinic for suspected PE were enrolled. The entire cohort was asked to complete the self-report intravaginal ejaculation latency time (IELT) by stopwatch. According to the IELT, the subjects were classified into 3 groups. Vibratory thresholds were recorded at the glans penis and penile shaft using a biothesiometer. We found that vibratory thresholds in the glans penis and penile shaft were significantly lower in both mild and severe PE group than in the control group (3.81 ± 0.57 and 3.54 ± 0.43 vs 4.73 ± 0.77 for glans penis p = 0.000; 3.64 ± 0.52 and 3.37 ± 0.50 vs 4.62 ± 0.69 for penile shaft p = 0.002). The vibratory threshold decreased as the disease aggravated. In the mild and severe PE groups, a significant positive correlation was detected between the mean values of IELT and the vibratory thresholds. Furthermore, in the receiver operating characteristics curve analysis, the area under the curve of the glans penis and penile shaft vibratory thresholds predicting severe PE were 0.852 and 0.893 respectively. Our study established a dose-dependent association between penile vibratory threshold and PE. Therefore, the vibratory threshold can serve as a potential marker for predicting the severity of PE.
Comparison of musculoskeletal networks of the primate forelimb
Authors: Molnar Julia , Esteve-Altava Borja , Rolian Campbell , Diogo Rui
Published: August 2017

Anatomical network analysis is a framework for quantitatively characterizing the topological organization of anatomical structures, thus providing a way to compare structural integration and modularity among species. Here we apply this approach to study the macroevolution of the forelimb in primates, a structure whose proportions and functions vary widely within this group. We analyzed musculoskeletal network models in 22 genera, including members of all major extant primate groups and three outgroup taxa, after an extensive literature survey and dissections. The modules of the proximal limb are largely similar among taxa, but those of the distal limb show substantial variation. Some network parameters are similar within phylogenetic groups (e.g., non-primates, strepsirrhines, New World monkeys, and hominoids). Reorganization of the modules in the hominoid hand compared to other primates may relate to functional changes such as coordination of individual digit movements, increased pronation/supination, and knuckle-walking. Surprisingly, humans are one of the few taxa we studied in which the thumb musculoskeletal structures do not form an independent anatomical module. This difference may be caused by the loss in humans of some intrinsic muscles associated with the digits or the acquisition of additional muscles that integrate the thumb more closely with surrounding structures.
Correcting for photodestruction in super-resolution optical fluctuation imaging
Authors: Peeters Yves , Vandenberg Wim , Duwé Sam , Bouwens Arno , Lukeš Tomáš , Ruckebusch Cyril , Lasser Theo , Dedecker Peter
Published: August 2017

Super-resolution optical fluctuation imaging overcomes the diffraction limit by analyzing fluctuations in the fluorophore emission. A key assumption of the imaging is that the fluorophores are independent, though this is invalidated in the presence of photodestruction. In this work, we evaluate the effect of photodestruction on SOFI imaging using theoretical considerations and computer simulations. We find that photodestruction gives rise to an additional signal that does not present an easily interpretable view of the sample structure. This additional signal is strong and the resulting images typically exhibit less noise. Accordingly, these images may be mis-interpreted as being more visually pleasing or more informative. To address this uncertainty, we develop a procedure that can robustly estimate to what extent any particular experiment is affected by photodestruction. We also develop a detailed assessment methodology and use it to evaluate the performance of several correction algorithms. We identify two approaches that can correct for the presence of even strong photodestruction, one of which can be implemented directly in the SOFI calculation software.
Linc-ing Circulating Long Non-coding RNAs to the Diagnosis and Malignant Prediction of Intraductal Papillary Mucinous Neoplasms of the Pancreas
Authors: Permuth Jennifer B. , Chen Dung-Tsa , Yoder Sean J. , Li Jiannong , Smith Andrew T. , Choi Jung W. , Kim Jongphil , Balagurunathan Yoganand , Jiang Kun , Coppola Domenico , Centeno Barbara A. , Klapman Jason , Hodul Pam , Karreth Florian A. , Trevino Jose G. , Merchant Nipun , Magliocco Anthony , Malafa Mokenge P. , Gillies Robert
Published: August 2017

Pancreatic ductal adenocarcinoma (PDAC) is an aggressive disease that lacks effective biomarkers for early detection. We hypothesized that circulating long non-coding RNAs (lncRNAs) may act as diagnostic markers of incidentally-detected cystic PDAC precursors known as intraductal papillary mucinous neoplasms (IPMNs) and predictors of their pathology/histological classification. Using NanoString nCounter® technology, we measured the abundance of 28 candidate lncRNAs in pre-operative plasma from a cohort of pathologically-confirmed IPMN cases of various grades of severity and non-diseased controls. Results showed that two lncRNAs (GAS5andSRA) aided in differentiating IPMNs from controls. An 8-lncRNA signature (includingADARB2-AS1,ANRIL,GLIS3-AS1,LINC00472,MEG3,PANDA,PVT1, andUCA1) had greater accuracy than standard clinical and radiologic features in distinguishing ‘aggressive/malignant’ IPMNs that warrant surgical removal from ‘indolent/benign’ IPMNs that can be observed. When the 8-lncRNA signature was combined with plasma miRNA data and quantitative ‘radiomic’ imaging features, the accuracy of predicting IPMN pathological classification improved. Our findings provide novel information on the ability to detect lncRNAs in plasma from patients with IPMNs and suggest that an lncRNA-based blood test may have utility as a diagnostic adjunct for identifying IPMNs and their pathology, especially when incorporated with biomarkers such as miRNAs, quantitative imaging features, and clinical data.
Prenatal noise stress impairs HPA axis and cognitive performance in mice
Authors: Jafari Zahra , Mehla Jogender , Kolb Bryan E. , Mohajerani Majid H.
Published: August 2017

Noise stress is a common environmental pollutant whose adverse effect on offspring performance has been less studied. This study was novel in terms of using “noise” as a prenatal stress compared with physical stress to explore the effect of stress during gestation on HPA axis activation, cognitive performance, and motor coordination, as well as in investigating the effect of behavioral assessments on the corticosterone (CORT) levels. Three groups of C57BL/6 mice with a gestational history of either noise stress (NS), physical stress (PS), or no stress were examined in several behavioral tests. Plasma CORT level was significantly higher before starting the behavioral tests in NS group than the two other groups. It was significantly increased after the behavioral tests in both prenatal stressed groups relative to the controls. Stress caused anxiety-like behavior and reduced learning and memory performance in both stressed groups compared to the controls, as well as decreased motor coordination in the NS group relative to the other groups. The findings suggested that: prenatal NS severely changes the HPA axis; both prenatal stressors, and particularly NS, negatively impair the offspring’s cognitive and motor performance; and, they also cause a strong susceptibility to interpret environmental experiences as stressful conditions.
Cell based assay identifies TLR2 and TLR4 stimulating impurities in Interferon beta
Authors: Haile Lydia Asrat , Polumuri Swamy Kumar , Rao Roshni , Kelley-Baker Logan , Kryndushkin Dimitri , Rajaiah Rajesh , Israely Tomer , Rao V. Ashutosh , Verthelyi Daniela
Published: August 2017

Immunogenicity can have devastating consequences on the safety and efficacy of therapeutic proteins. Therefore, evaluating and mitigating the risk of product immunogenicity is critical for the development these products. This study, showed that Betaseron and Extavia, which are reported to be more immunogenic among IFNβ products in clinical usage, contain residual innate immune response modulating impurities (IIRMIs) capable of activating NF-κB and induced expression of inflammatory mediators. These IIRMIs were undetectable in Rebif or Avonex. The stimulatory effect was attributed solely to IIRMIs because it was evident in murine cells lacking the interferon receptor (IFNAR). The IIRMIs in Betaseron and Extavia triggered NF-κB activation in HEK-293 cells bearing TLR2 and TLR4 in MyD88 dependent manner. Importantly, the IIRMIs in Betaseron induced up-regulation of IL-6, IL-1β, and ccl5 in the skin of IFNAR knock out mice following subcutaneous administration. This indicates that trace level IIRMIs in Betaseron could contribute to the higher immunogenicity rates seen in clinics. Together these data suggest that cell based assays can reveal subtle but clinically relevant differences in IIRMIs following manufacturing changes or between products with the same active ingredients but different manufacturing processes. Appreciating these differences may inform immunogenicity risk assessments.
Intermittence and connectivity of interactions in pigeon flock flights
Authors: Chen Duxin , Liu Xiaolu , Xu Bowen , Zhang Hai-Tao
Published: August 2017

Collective circular motion is a common yet spectacular behavior of pigeon flocks. Efficient and robust inter-individual communication is required for flock coordination during this widely-spreaded movement pattern. When a flock hovers near the home loft, the rotational direction undergoes regular spontaneous variations. Based on intensive analyses of high spatial-temporal resolution GPS data, we quantified the intensity of velocity alignment among different individuals in terms of their velocity fluctuations. It is found that pigeon flocks employ an intermittent interaction (alignment) mechanism, where intra-group information transmission is not required at every instant. However, the union of the topologies of several consecutive interaction networks always keeps connected. This biological observation strongly suggests the presence of a jointly connected topology in pigeon flocks, which helps substantially reduce the communication and/or information processing requirements while retaining the agility and stability of the group. Finally, we conducted extensive investigation on the interaction mechanism as well as the spontaneous changes in rotational direction of pigeon flocks. These results shed some light onto the coordination mechanism exploration of bird flocks’ collective motions.
Hydrogen peroxide dynamics in subcellular compartments of malaria parasites using genetically encoded redox probes
Authors: Rahbari Mahsa , Rahlfs Stefan , Przyborski Jude M. , Schuh Anna Katharina , Hunt Nicholas H. , Fidock David A. , Grau Georges E. , Becker Katja
Published: August 2017

Redox balance is essential for the survival, growth and multiplication of malaria parasites and oxidative stress is involved in the mechanism of action of many antimalarial drugs. Hydrogen peroxide (H2O2) plays an important role in redox signalling and pathogen-host cell interactions. For monitoring intra- and subcellular redox events, highly sensitive and specific probes are required. Here, we stably expressed the ratiometric H2O2redox sensor roGFP2-Orp1 in the cytosol and the mitochondria ofPlasmodium falciparum (P. falciparum)NF54-attBblood-stage parasites and evaluated its sensitivity towards oxidative stress, selected antimalarial drugs, and novel lead compounds. In both compartments, the sensor showed reproducible sensitivity towards H2O2in the low micromolar range and towards antimalarial compounds at pharmacologically relevant concentrations. Upon short-term exposure (4 h), artemisinin derivatives, quinine and mefloquine impacted H2O2levels in mitochondria, whereas chloroquine and a glucose-6-phosphate dehydrogenase (G6PD) inhibitor affected the cytosol; 24 h exposure to arylmethylamino steroids and G6PD inhibitors revealed oxidation of mitochondria and cytosol, respectively. Genomic integration of an H2O2sensor expressed in subcellular compartments ofP. falciparumprovides the basis for studying complex parasite-host cell interactions or drug effects with spatio-temporal resolution while preserving cell integrity, and sets the stage for high-throughput approaches to identify antimalarial agents perturbing redox equilibrium.
Comprehensive transcriptome profiling of Salvia miltiorrhiza for discovery of genes associated with the biosynthesis of tanshinones and phenolic acids
Authors: Zhou Wei , Huang Qiang , Wu Xiao , Zhou Zewen , Ding Mingquan , Shi Min , Huang Fenfen , Li Shen , Wang Yao , Kai Guoyin
Published: August 2017

Tanshinones and phenolic acids are crucial bioactive compounds biosynthesized in Salvia miltiorrhiza. Methyl jasmonate (MeJA) is an effective elicitor to enhance the production of phenolic acids and tanshinones simultaneously, while yeast extract (YE) is used as a biotic elicitor that only induce tanshinones accumulation. However, little was known about the different molecular mechanism. To identify the downstream and regulatory genes involved in tanshinone and phenolic acid biosynthesis, we conducted comprehensive transcriptome profiling of S. miltiorrhiza hairy roots treated with either MeJA or YE. Total 55588 unigenes were assembled from about 1.72 billion clean reads, of which 42458 unigenes (76.4%) were successfully annotated. The expression patterns of 19 selected genes in the significantly upregulated unigenes were verified by quantitative real-time PCR. The candidate downstream genes and other cytochrome P450s involved in the late steps of tanshinone and phenolic acid biosynthesis pathways were screened from the RNA-seq dataset based on co-expression pattern analysis with specific biosynthetic genes. Additionally, 375 transcription factors were identified to exhibit a significant up-regulated expression pattern in response to induction. This study can provide us a valuable gene resource for elucidating the molecular mechanism of tanshinones and phenolic acids biosynthesis in hairy roots of S. miltiorrhiza.
Blue Laser Diode Based Free-space Optical Data Transmission elevated to 18 Gbps over 16 m
Authors: Huang Yu-Fang , Chi Yu-Chieh , Kao Hsuan-Yun , Tsai Chen-Ting , Wang Huai-Yung , Kuo Hao-Chung , Nakamura Shuji , Huang Ding-Wei , Lin Gong-Ru
Published: August 2017

Up to 18-Gbps direct encoding of blue laser diode (BLD) is demonstrated for free-space data transmission. By reshaping the orthogonal frequency multiplexed (16-QAM OFDM) stream with sidelobe filtering, the raw data rate expedites from 17.2 to 18.4 Gbps. Employing an ultrafast p-i-n photodiode with smaller active area diameter and lower noise equivalent power significantly enlarges the data rate by 1.6 Gbps or upgrades the signal-to-noise ratio (SNR) by 0.2 dB. Replacing the 80-mW BLD with the 120-mW one essentially increases the received SNR by 0.4 dB under enhanced modulation throughput. Reinforcing the beam collimation and collection by increasing the numerical aperture with a plano-convex hyper-hemispherical lens further improves the SNR by 0.6 dB. After optimization, the 16-QAM OFDM data with and without sidelobe filtering are respectively delivered at raw data rates of 16.4 and 18 Gbps with spectral-density usage efficiency as high as 4 bit/s/Hz over 16 m in free space, wherein the BLD carried QAM-OFDM data stream remains its capacity after reformation with sidelobe filtering as the superior inter-carrier-interference immunity reinforces.
Identification of neuromedin U precursor-related peptide and its possible role in the regulation of prolactin release
Authors: Mori Kenji , Ida Takanori , Fudetani Mami , Mori Miwa , Kaiya Hiroyuki , Hino Jun , Nakahara Keiko , Murakami Noboru , Miyazato Mikiya , Kangawa Kenji
Published: August 2017

The discovery of neuropeptides provides insights into the regulation of physiological processes. The precursor for the neuropeptide neuromedin U contains multiple consensus sequences for proteolytic processing, suggesting that this precursor might generate additional peptides. We performed immunoaffinity chromatography of rat brain extracts and consequently identified such a product, which we designated neuromedin U precursor-related peptide (NURP). In rat brain, NURP was present as two mature peptides of 33 and 36 residues. Radioimmunoassays revealed NURP immunoreactivity in the pituitary, small intestine, and brain of rats, with the most intense reactivity in the pituitary. Intracerebroventricular administration of NURP to both male and female rats robustly increased plasma concentrations of prolactin but not of other anterior pituitary hormones. In contrast, NURP failed to stimulate prolactin release from dispersed anterior pituitary cells. Pretreatment of rats with bromocriptine, a dopamine receptor agonist, blocked the prolactin-releasing activity of NURP. In rats pretreated with the antagonist sulpiride, intracerebroventricular administration of NURP did not increase plasma prolactin concentrations more than administration of saline. These data suggest that NURP induces prolactin release by acting indirectly on the pituitary; dopamine from the hypothalamus, which inhibits prolactin release, may be involved in this activity of NURP.
Hyperactive TGF-β Signaling in Smooth Muscle Cells Exposed to HIV-protein(s) and Cocaine: Role in Pulmonary Vasculopathy
Authors: Dalvi Pranjali , Sharma Himanshu , Konstantinova Tomara , Sanderson Miles , Brien-Ladner Amy O’ , Dhillon Navneet K.
Published: August 2017

We earlier demonstrated synergistic increase in the proliferation of pulmonary smooth muscle cells on exposure to HIV-proteins and/or cocaine due to severe down-modulation of bone morphogenetic protein receptor (BMPR) axis: the anti-proliferative arm of TGF-β super family of receptors. Here, now we demonstrate the effect of HIV-Tat and cocaine on the proliferative TGF-β signaling cascade. We observed a significant increase in the secretion of TGF-β1 ligand along with enhanced protein expression of TGFβ Receptor (TGFβR)-1, TGFβR-2 and phosphorylated SMAD2/3 in human pulmonary arterial smooth muscle cells on treatment with cocaine and Tat. Further, we noticed an increase in the levels of p-TAK1 complexed with TGFβR-2. Concomitant to this a significant increase in the activation of TAK1-mediated, SMAD-independent downstream signaling molecules: p-MKK4 and p-JNK was observed. However, activation of MKK3/6-p38MAPK, another axis downstream of TAK1 was found to be reduced due to attenuation in the protein levels of BMPR2. Both SMAD and non-SMAD dependent TGFβR cascades were found to contribute to hyper-proliferation. Finally the increase in the levels of phosphorylated TGFβR1 and TGFβR2 on exposure to HIV-proteins and cocaine was confirmed in pulmonary smooth muscle cells from cocaine injected HIV-transgenic rats and in total lung extracts from HIV infected cocaine and/or opioid users.
Restless legs syndrome in Parkinson disease: Clinical characteristics, abnormal iron metabolism and altered neurotransmitters
Authors: Piao Ying-Shan , Lian Teng-Hong , Hu Yang , Zuo Li-Jun , Guo Peng , Yu Shu-Yang , Liu Li , Jin Zhao , Zhao Hui , Li Li-Xia , yu Qiu-Jin , Wang Rui-Dan , Chen Sheng-Di , Chan Piu , Wang Xiao-Min , Zhang Wei
Published: August 2017

Relationships among clinical characteristics, iron metabolism and neurotransmitters in Parkinson disease (PD) patients with restless legs syndrome (RLS) remains unclear. We divided 218 patients into PD with and with no RLS (PD-RLS and PD-NRLS) groups by RLS-rating scale (RLS-RS) score. Motor and non-motor symptoms were rated by related scales. Iron and related proteins, and neurotransmitters in cerebrospinal fluid (CSF) and serum were measured. PD-RLS frequency was 40.37%. PD-RLS group had longer duration, higher stage and scores of motor symptoms, depression, anxiety, sleep disorders, fatigue and apathy, and increased transferrin and decreased iron, ferritin, dopamine (DA) and 5-hydroxytryptamine (5-HT) in CSF. In CSF of PD-RLS group, RLS-RS score was positively correlated with transferrin level and negatively correlated with iron and ferritin levels; RLS-RS score was negatively correlated with DA and 5-HT levels; transferrin level was negatively correlated with DA and 5-HT levels, and ferritin level was positively correlated with DA level. In serum, PD-RLS group had decreased iron and transferrin levels, which were negatively correlated with RLS-RS score. PD-RLS was common and severer in motor and some non-motor symptoms. Iron deficiency induced by its metabolism dysfunctions in peripheral and central systems might cause PD-RLS through decreasing brain DA and 5-HT.
Non-random transmission of parental alleles into crop-wild and crop-weed hybrid lineages separated by a transgene and neutral identifiers in rice
Authors: Wang Zhe , Wang Lei , Wang Zhi , Lu Bao-Rong
Published: August 2017

It is essential to assess environmental impact of transgene flow from genetically engineered crops to their wild or weedy relatives before commercialization. Measuring comparative trials of fitness in the transgene-flow-resulted hybrids plays the key role in the assessment, where the segregated isogenic hybrid lineages/subpopulations with or without a transgene of the same genomic background are involved. Here, we report substantial genomic differentiation between transgene-present and -absent lineages (F2-F3) divided by a glyphosate-resistance transgene from a crop-wild/weed hybrid population in rice. We further confirmed that such differentiation is attributed to increased frequencies of crop-parent alleles in transgenic hybrid lineages at multiple loci across the genome, as estimated by SSR (simple sequence repeat) markers. Such preferential transmission of parental alleles was also found in equally divided crop-wild/weed hybrid lineages with or without a particular neutral SSR identifier. We conclude that selecting either a transgene or neutral marker as an identifier to create hybrid lineages will result in different genomic background of the lineages due to non-random transmission of parental alleles. Non-random allele transmission may misrepresent the outcomes of fitness effects. We therefore propose seeking other means to evaluate fitness effects of transgenes for assessing environmental impact caused by crop-to-wild/weed gene flow.
Riparian plant litter quality increases with latitude
Authors: Boyero Luz , Graça Manuel A. S. , Tonin Alan M. , Pérez Javier , J. Swafford Andrew , Ferreira Verónica , Landeira-Dabarca Andrea , A. Alexandrou Markos , Gessner Mark O. , McKie Brendan G. , Albariño Ricardo J. , Barmuta Leon A. , Callisto Marcos , Chará Julián , Chauvet Eric , Colón-Gaud Checo , Dudgeon David , Encalada Andrea C. , Figueroa Ricardo , Flecker Alexander S. , Fleituch Tadeusz , Frainer André , Gonçalves José F. , Helson Julie E. , Iwata Tomoya , Mathooko Jude , M’Erimba Charles , Pringle Catherine M. , Ramírez Alonso , Swan Christopher M. , Yule Catherine M. , Pearson Richard G.
Published: August 2017

Plant litter represents a major basal resource in streams, where its decomposition is partly regulated by litter traits. Litter-trait variation may determine the latitudinal gradient in decomposition in streams, which is mainly microbial in the tropics and detritivore-mediated at high latitudes. However, this hypothesis remains untested, as we lack information on large-scale trait variation for riparian litter. Variation cannot easily be inferred from existing leaf-trait databases, since nutrient resorption can cause traits of litter and green leaves to diverge. Here we present the first global-scale assessment of riparian litter quality by determining latitudinal variation (spanning 107°) in litter traits (nutrient concentrations; physical and chemical defences) of 151 species from 24 regions and their relationships with environmental factors and phylogeny. We hypothesized that litter quality would increase with latitude (despite variation within regions) and traits would be correlated to produce ‘syndromes’ resulting from phylogeny and environmental variation. We found lower litter quality and higher nitrogen:phosphorus ratios in the tropics. Traits were linked but showed no phylogenetic signal, suggesting that syndromes were environmentally determined. Poorer litter quality and greater phosphorus limitation towards the equator may restrict detritivore-mediated decomposition, contributing to the predominance of microbial decomposers in tropical streams.
Serum lysophospholipid levels are altered in dyslipidemic hamsters
Authors: Suárez-García Susana , Caimari Antoni , del Bas Josep Maria , Suárez Manuel , Arola Lluís
Published: August 2017

Dyslipidemias are common disorders that predispose individuals to severe diseases. It is known that healthy living habits can prevent dyslipidemias if they are diagnosed properly. Therefore, biomarkers that assist in diagnosis are essential. The aim of this study was to identify biomarkers of dyslipidemia progression, which in turn disclose its etiology. These findings will pave the way for examinations of the regulatory mechanisms involved in dyslipidemias. Hamsters were fed either a normal-fat diet (NFD) or a high-fat diet. Some of the NFD-fed animals were further treated with the hyperlipidemic agent Poloxamer 407. Non-targeted metabolomics was used to investigate progressive changes in unknown serum metabolites. The hepatic expression of putative biomarker-related genes was also analyzed. The serum levels of lysophospholipids (Lyso-PLs) and their related enzymes lecithin-cholesterol acyltransferase (LCAT), secreted phospholipase A2(sPLA2) and paraoxonase-1 were altered in dyslipidemic hamsters. Lysophosphatidylcholine levels were increased in diet-induced dyslipidemic groups, whereas lysophosphatidylethanolamine levels increased in response to the chemical treatment. The liver was significantly involved in regulating the levels of these molecules, based on the modified expression of endothelial lipase (Lipg), sPLA2(Pla2g2a) and acyltransferases (LcatandLpcat3). We concluded that Lyso-PL evaluation could aid in the comprehensive diagnosis and management of lipid disorders.
Whole Transcriptome Analysis of Notochord-Derived Cells during Embryonic Formation of the Nucleus Pulposus
Authors: Peck Sun H. , McKee Kendra K. , Tobias John W. , Malhotra Neil R. , Harfe Brian D. , Smith Lachlan J.
Published: August 2017

Recapitulation of developmental signals represents a promising strategy for treating intervertebral disc degeneration. During development, embryonic notochord-derived cells (NDCs) are the direct progenitors of cells that populate the adult nucleus pulposus (NP) and are an important source of secreted signaling molecules. The objective of this study was to define global gene expression profiles of NDCs at key stages of embryonic disc formation. NDCs were isolated from Shh-cre;ROSA:YFP mice at embryonic day 12.5 and postnatal day 0, representing opposite ends of the notochord to NP transformation. Differences in global mRNA abundance across this developmental window were established using RNA-Seq. Protein expression of selected molecules was confirmed using immunohistochemistry. Principal component analysis revealed clustering of gene expression at each developmental stage with more than 5000 genes significantly differentially expressed between E12.5 and P0. There was significantly lower mRNA abundance of sonic hedgehog pathway elements at P0 vs E12.5, while abundance of elements of the transforming growth factor-beta and insulin-like growth factors pathways, and extracellular matrix components including collagen 6 and aggrecan, were significantly higher at P0. This study represents the first transcriptome-wide analysis of embryonic NDCs. Results suggest signaling and biosynthesis of NDCs change dramatically as a function of developmental stage.
Manipulating of Different-Polarized Reflected Waves with Graphene-based Plasmonic Metasurfaces in Terahertz Regime
Authors: Deng Li , Wu Yongle , Zhang Chen , Hong Weijun , Peng Biao , Zhu Jianfeng , Li Shufang
Published: August 2017

A graphene-based plasmonic metasurface which can independently control different polarized electromagnetic waves with reasonably small losses in terahertz regime is proposed and demonstrated in this paper. This metasurface is composed of graphene based elements. Owing to anisotropic plasmonic resonance of the graphene-based elements, the reflected phases and magnitudes of orthogonally polarized waves can be independently controlled by varying dimensions of the element. Four types of graphene-based plasmonic metasurfaces with different reflected phases distributions are synthesized and simulated, exhibiting diverse functions such as polarized beam splitting, beam deflection, and linear-to-circular polarization conversion. The simulation results demonstrate excellent performances as theoretical expectation. The proposed graphene-based plasmonic metasurface can be applied to realize extremely light-weight, ultra-compact, and high-performances electromagnetic structures for diverse terahertz applications.
Forensic age prediction for saliva samples using methylation-sensitive high resolution melting: exploratory application for cigarette butts
Authors: Hamano Yuya , Manabe Sho , Morimoto Chie , Fujimoto Shuntaro , Tamaki Keiji
Published: August 2017

There is high demand for forensic age prediction in actual crime investigations. In this study, a novel age prediction model for saliva samples using methylation-sensitive high resolution melting (MS-HRM) was developed. The methylation profiles of ELOVL2 and EDARADD showed high correlations with age and were used to predict age with support vector regression. ELOVL2 was first reported as an age predictive marker for saliva samples. The prediction model showed high accuracy with a mean absolute deviation (MAD) from chronological age of 5.96 years among 197 training samples. The model was further validated with an additional 50 test samples (MAD = 6.25). In addition, the age prediction model was applied to saliva extracted from seven cigarette butts, as in an actual crime scene. The MAD (7.65 years) for these samples was slightly higher than that of intact saliva samples. A smoking habit or the ingredients of cigarettes themselves did not significantly affect the prediction model and could be ignored. MS-HRM provides a quick (2 hours) and cost-effective (95% decreased compared to that of DNA chips) method of analysis. Thus, this study may provide a novel strategy for predicting the age of a person of interest in actual crime scene investigations.
Divergent Evolution of Carbonaceous Aerosols during Dispersal of East Asian Haze
Authors: Fang Wenzheng , Andersson August , Zheng Mei , Lee Meehye , Holmstrand Henry , Kim Sang-Woo , Du Ke , Gustafsson Örjan
Published: August 2017

Wintertime East Asia is plagued by severe haze episodes, characterized by large contributions of carbonaceous aerosols. However, the sources and atmospheric transformations of these major components are poorly constrained, hindering development of efficient mitigation strategies and detailed modelling of effects. Here we present dual carbon isotope (δ13C and Δ14C) signatures for black carbon (BC), organic carbon (OC) and water-soluble organic carbon (WSOC) aerosols collected in urban (Beijing and BC for Shanghai) and regional receptors (e.g., Korea Climate Observatory at Gosan) during January 2014. Fossil sources (>50%) dominate BC at all sites with most stemming from coal combustion, except for Shanghai, where liquid fossil source is largest. During source-to-receptor transport, the δ13C fingerprint becomes enriched for WSOC but depleted for water-insoluble OC (WIOC). This reveals that the atmospheric processing of these two major pools are fundamentally different. The photochemical aging (e.g., photodissociation, photooxidation) during formation and transport can release CO2/CO or short-chain VOCs with lighter carbon, whereas the remaining WSOC becomes increasingly enriched in δ13C. On the other hand, several processes, e.g., secondary formation, rearrangement reaction in the particle phase, and photooxidation can influence WIOC. Taken together, this study highlights high fossil contributions for all carbonaceous aerosol sub-compartments in East Asia, and suggests different transformation pathways for different classes of carbonaceous aerosols.
Mechanism of splenic cell death and host mortality in a Plasmodium yoelii malaria model
Authors: Lacerda-Queiroz Norinne , Riteau Nicolas , Eastman Richard T. , Bock Kevin W. , Orandle Marlene S. , Moore Ian N. , Sher Alan , Long Carole A. , Jankovic Dragana , Su Xin-zhuan
Published: August 2017

Malaria is a fatal disease that displays a spectrum of symptoms and severity, which are determined by complex host-parasite interactions. It has been difficult to study the effects of parasite strains on disease severity in human infections, but the mechanisms leading to specific disease phenotypes can be investigated using strains of rodent malaria parasites that cause different disease symptoms in inbred mice. Using a unique mouse malaria model, here we investigated the mechanisms of splenic cell death and their relationship to control of parasitemia and host mortality. C57BL/6 mice infected with Plasmodium yoelii nigeriensis N67C display high levels of pro-inflammatory cytokines and chemokines (IL-6, IFN-γ, TNF-α, CXCL1, and CCL2) and extensive splenic damage with dramatic reduction of splenic cell populations. These disease phenotypes were rescued in RAG2−/−, IFN-γ−/−, or T cell depleted mice, suggesting IFN-γ and T cell mediated disease mechanisms. Additionally, apoptosis was one of the major pathways involved in splenic cell death, which coincides with the peaks of pro-inflammatory cytokines. Our results demonstrate the critical roles of T cells and IFN-γ in mediating splenic cell apoptosis, parasitemia control, and host lethality and thus may provide important insights for preventing/reducing morbidity associated with severe malaria in humans.
Microscale Liquid Transport in Polycrystalline Inverse Opals across Grain Boundaries
Authors: Pham Q. N. , Barako M. T. , Tice J. , Won Y.
Published: August 2017

Delivering liquid through the void spaces in porous metals is a daunting challenge for a variety of emerging interface technologies ranging from battery electrodes to evaporation surfaces. Hydraulic transport characteristics of well-ordered porous media are governed by the pore distribution, porosity, and morphology. Much like energy transport in polycrystalline solids, hydraulic transport in semi-ordered porous media is predominantly limited by defects and grain boundaries. Here, we report the wicking performances for porous copper inverse opals having pore diameters from 300 to 1000 nm by measuring the capillary-driven liquid rise. The capillary performance parameter within single crystal domain (K
ij
/R
eff
 = 10−3 to 10−2 µm) is an order of magnitude greater than the collective polycrystal (K
eff
/R
eff
 = ~10−5 to 10−3 µm) due to the hydraulic resistances (i.e. grain boundaries between individual grains). Inspired by the heterogeneity found in biological systems, we report that the capillary performance parameter of gradient porous copper (K
eff
/R
eff
 = ~10−3 µm), comparable to that of single crystals, overcomes hydraulic resistances through providing additional hydraulic routes in three dimensions. The understanding of microscopic liquid transport physics through porous crystals and across grain boundaries will help to pave the way for the spatial design of next-generation heterogeneous porous media.
Black P/graphene hybrid: A fast response humidity sensor with good reversibility and stability
Authors: Phan Duy-Thach , Park Inyong , Park Ah-Ram , Park Cheol-Min , Jeon Ki-Joon
Published: August 2017

Black phosphorus (BP) materials have attracted considerable attention owing to their ultra-sensitive humidity sensing characteristics because of the natural absorption of water (H2O) molecules on the BP surface caused by the specific 2D layer-crystalline structure. On the other hand, the BP-based humidity sensor is less repeatable due to the instability of BP with water molecules and the stability of the sensor is reduced. In this study, this limitation of the BP-based humidity sensor was overcome by preparing a BP/graphene hybrid as a novel humidity sensing nanostructure. The BP/graphene interface improved the stability of the humidity sensor after a few weeks with a linear response within the relative humidity (RH) range of 15–70%. The sensor’s response/recovery speed of the humidity sensor was extremely fast within few seconds. The response (S) of the humidity sensor based on the BP/graphene hybrid is 43.4% at RH = 70%. The estimated response and recovery time of the sensor is only 9 and 30 seconds at RH = 70% at room temperature. The experimental investigation reveals that the BP/graphene hybrid not only improves the reversibility and hysteresis factors but also enhances the stability of the humidity sensor.
Prior Exposure to Zika Virus Significantly Enhances Peak Dengue-2 Viremia in Rhesus Macaques
Authors: George Jeffy , Valiant William G. , Mattapallil Mary J. , Walker Michelle , Huang Yan-Jang S. , Vanlandingham Dana L. , Misamore John , Greenhouse Jack , Weiss Deborah E. , Verthelyi Daniela , Higgs Stephen , Andersen Hanne , Lewis Mark G. , Mattapallil Joseph J.
Published: August 2017

Structural and functional homologies between the Zika and Dengue viruses’ envelope proteins raise the possibility that cross-reactive antibodies induced following Zika virus infection might enhance subsequent Dengue infection. Using the rhesus macaque model we show that prior infection with Zika virus leads to a significant enhancement of Dengue-2 viremia that is accompanied by neutropenia, lympocytosis, hyperglycemia, and higher reticulocyte counts, along with the activation of pro-inflammatory monocyte subsets and release of inflammatory mediators. Zika virus infection induced detectable Dengue cross-reactive serum IgG responses that significantly amplified after Dengue-2 virus infection. Serum from Zika virus immune animals collected prior to Dengue-2 infection showed significant capacity for in vitro antibody dependent enhancement of Dengue-1, 2, 3 and 4 serotypes suggesting that pre-existing immunity to Zika virus could potentially enhance infection by heterologous Dengue serotypes. Our results provide first in vivo evidence that prior exposure to Zika virus infection can enhance Dengue infection, which has implications for understanding pathogenesis and the development of vaccines.
Comprehensive transcriptome mining of the direct conversion of mesodermal cells
Authors: Akbari Bijan , Wee Ping , Yaqubi Moein , Mohammadnia Abdulshakour
Published: August 2017

The direct reprogramming of somatic cells is a promising approach for regenerative medicine, especially in the production of mesoderm layer-derived cells. Meta-analysis studies provide precise insight into the undergoing processes and help increase the efficiency of reprogramming. Here, using 27 high-throughput expression data sets, we analyzed the direct reprogramming of mesodermal cells in humans and mice. Fibroblast-derived cells showed a common expression pattern of up- and down-regulated genes that were mainly involved in the suppression of the fibroblast-specific gene expression program, and may be used as markers of the initiation of reprogramming. Furthermore, we found a specific gene expression profile for each fibroblast-derived cell studied, and each gene set appeared to play specific functional roles in its cell type, suggesting their use as markers for their mature state. Furthermore, using data from protein-DNA interactions, we identified the main transcription factors (TFs) involved in the conversion process and ranked them based on their importance in their gene regulatory networks. In summary, our meta-analysis approach provides new insights on the direct conversion of mesodermal somatic cells, introduces a list of genes as markers for initiation and maturation, and identifies TFs for which manipulating their expression may increase the efficiency of direct conversion.