bluuebunny/crossref_metadata_2025 huggingface dataset:
KCC2 downregulation facilitates epileptic seizures
Authors: Chen Lulan , Wan Li , Wu Zheng , Ren Wanting , Huang Yian , Qian Binbin , Wang Yun
Published: March 2017

GABAA receptor-mediated inhibition depends on the maintenance of low level intracellular [Cl−] concentration, which in adult depends on neuron specific K+-Cl− cotransporter-2 (KCC2). Previous studies have shown that KCC2 was downregulated in both epileptic patients and various epileptic animal models. However, the temporal relationship between KCC2 downregulation and seizure induction is unclear yet. In this study, we explored the temporal relationship and the influence of KCC2 downregulation on seizure induction. Significant downregulation of plasma membrane KCC2 was directly associated with severe (Racine Score III and above) behavioral seizures in vivo, and occurred before epileptiform bursting activities in vitro induced by convulsant. Overexpression of KCC2 using KCC2 plasmid effectively enhanced resistance to convulsant-induced epileptiform bursting activities in vitro. Furthermore, suppression of membrane KCC2 expression, using shRNAKCC2 plasmid in vitro and shRNAKCC2 containing lentivirus in vivo, induced spontaneous epileptiform bursting activities in vitro and Racine III seizure behaviors accompanied by epileptic EEG in vivo. Our findings novelly demonstrated that altered expression of KCC2 is not the consequence of seizure occurrence but likely is the contributing factor.
Atypical sensory sensitivity as a shared feature between synaesthesia and autism
Authors: Ward Jamie , Hoadley Claire , Hughes James E. A. , Smith Paula , Allison Carrie , Baron-Cohen Simon , Simner Julia
Published: March 2017

Several studies have suggested that there is a link between synaesthesia and autism but the nature of that link remains poorly characterised. The present study considers whether atypical sensory sensitivity may be a common link between the conditions. Sensory hypersensitivity (aversion to certain sounds, touch, etc., or increased ability to make sensory discriminations) and/or hyposensitivity (desire to stimulate the senses , or a reduced response to sensory stimuli are a recently introduced diagnostic feature of autism spectrum conditions (ASC). Synaesthesia is defined by unusual sensory experiences and has also been linked to a typical cortical hyper-excitability. The Glasgow Sensory Questionnaire (GSQ) was administered to synaesthetes and people with ASC. Both groups reported increased sensory sensitivity relative to controls with a large effect size. Both groups also reported a similar pattern of both increased hyper- and hypo-sensitivities across multiple senses. The AQ (Autism-Spectrum Quotient) scores were elevated in the synaesthetes, and one subscale of this measure (attention to detail) placed synaesthetes within the autistic range. A standard laboratory test of visual stress (the Pattern Glare Test), administered online, corroborated the findings of increased sensitivity to aversive visual stimuli in synaesthetes. We conclude that atypical sensory sensitivity is an important shared feature between autism and synaesthesia.
Correction: Corrigendum: Mechanism of Consistent Gyrus Formation: an Experimental and Computational Study
Authors: Zhang Tuo , Razavi Mir Jalil , Li Xiao , Chen Hanbo , Liu Tianming , Wang Xianqiao
Published: March 2017

Scientific Reports 6: Article number: 37272; published online: 17 November 2016; updated: 07 March 2017. In the methods section, under the subheading ‘Human Fetal Brain Atlas Dataset’ “Generally, this dataset includes T2 templates and tissue probability maps (for the brain mask, cortex, hemispheres,cerebrospinal fluid [CSF], and ventricles) for ages between 23–37 weeks of gestation.
Partial delignification of wood and membrane preparation using a quaternary ammonium ionic liquid
Authors: Miao Jiaojiao , Yu Yongqi , Jiang Zeming , Tang Lan , Zhang Liping
Published: March 2017

This work determined that southern yellow pine wood can almost be completely dissolved in the quaternary ammonium ionic liquid tetrabutylammonium acetate with dimethyl sulfoxide (in a 2:8 mass ratio), after minimal grinding, upon heating at 85 °C for three dissolution/reconstitution cycles, each 1.5 h. Approximately 34.6% of the native lignin and 67.4% of the native carbohydrates present in the original wood can subsequently be extracted, respectively, and were assessed. A gradual decrease in lignin with increased extraction cycles resulted in increased crystallinity index of the cellulose II in the cellulose-rich residue, as confirmed by X-ray diffraction. An increasingly homogeneous macrostructure in the cellulose-rich residue was also evident from scanning electron microscopy images. Membranes cast directly from either wood or cellulose-rich residue solutions in the same tetrabutylammonium acetate/dimethyl sulfoxide system, were prepared using a papermaking-like process. Morphological and mechanical studies indicated that lignin extraction made the membranes more uniform and flexible. Systematic increases in the fibril lengths and orientations of the recovered materials were also found with decreasing lignin contents on the basis of atomic force microscopy analysis. This work demonstrates that relatively efficient partial separation of pine wood and subsequent membrane preparation are possible using a quaternary ammonium ionic liquid.
Theta-alpha EEG phase distributions in the frontal area for dissociation of visual and auditory working memory
Authors: Akiyama Masakazu , Tero Atsushi , Kawasaki Masahiro , Nishiura Yasumasa , Yamaguchi Yoko
Published: March 2017

Working memory (WM) is known to be associated with synchronization of the theta and alpha bands observed in electroencephalograms (EEGs). Although frontal-posterior global theta synchronization appears in modality-specific WM, local theta synchronization in frontal regions has been found in modality-independent WM. How frontal theta oscillations separately synchronize with task-relevant sensory brain areas remains an open question. Here, we focused on theta-alpha phase relationships in frontal areas using EEG, and then verified their functional roles with mathematical models. EEG data showed that the relationship between theta (6 Hz) and alpha (12 Hz) phases in the frontal areas was about 1:2 during both auditory and visual WM, and that the phase distributions between auditory and visual WM were different. Next, we used the differences in phase distributions to construct FitzHugh-Nagumo type mathematical models. The results replicated the modality-specific branching by orthogonally of the trigonometric functions for theta and alpha oscillations. Furthermore, mathematical and experimental results were consistent with regards to the phase relationships and amplitudes observed in frontal and sensory areas. These results indicate the important role that different phase distributions of theta and alpha oscillations have in modality-specific dissociation in the brain.
Altered Topological Properties of Brain Networks in Social Anxiety Disorder: A Resting-state Functional MRI Study
Authors: Zhu Hongru , Qiu Changjian , Meng Yajing , Yuan Minlan , Zhang Yan , Ren Zhengjia , Li Yuchen , Huang Xiaoqi , Gong Qiyong , Lui Su , Zhang Wei
Published: March 2017

Recent studies involving connectome analysis including graph theory have yielded potential biomarkers for mental disorders. In this study, we aimed to investigate the differences of resting-state network between patients with social anxiety disorder (SAD) and healthy controls (HCs), as well as to distinguish between individual subjects using topological properties. In total, 42 SAD patients and the same number of HCs underwent resting functional MRI, and the topological organization of the whole-brain functional network was calculated using graph theory. Compared with the controls, the patients showed a decrease in 49 positive connections. In the topological analysis, the patients showed an increase in the area under the curve (AUC) of the global shortest path length of the network (Lp) and a decrease in the AUC of the global clustering coefficient of the network (Cp). Furthermore, the AUCs of Lp and Cp were used to effectively discriminate the individual SAD patients from the HCs with high accuracy. This study revealed that the neural networks of the SAD patients showed changes in topological characteristics, and these changes were prominent not only in both groups but also at the individual level. This study provides a new perspective for the identification of patients with SAD.
A multi-component classifier for nonalcoholic fatty liver disease (NAFLD) based on genomic, proteomic, and phenomic data domains
Authors: Wood G. Craig , Chu Xin , Argyropoulos George , Benotti Peter , Rolston David , Mirshahi Tooraj , Petrick Anthony , Gabrielson John , Carey David J. , DiStefano Johanna K. , Still Christopher D. , Gerhard Glenn S.
Published: March 2017

Non-alcoholic fatty liver disease (NAFLD) represents a spectrum of conditions that include steatohepatitis and fibrosis that are thought to emanate from hepatic steatosis. Few robust biomarkers or diagnostic tests have been developed for hepatic steatosis in the setting of obesity. We have developed a multi-component classifier for hepatic steatosis comprised of phenotypic, genomic, and proteomic variables using data from 576 adults with extreme obesity who underwent bariatric surgery and intra-operative liver biopsy. Using a 443 patient training set, protein biomarker discovery was performed using the highly multiplexed SOMAscan® proteomic assay, a set of 19 clinical variables, and the steatosis predisposing PNPLA3 rs738409 single nucleotide polymorphism genotype status. The most stable markers were selected using a stability selection algorithm with a L1-regularized logistic regression kernel and were then fitted with logistic regression models to classify steatosis, that were then tested against a 133 sample blinded verification set. The highest area under the ROC curve (AUC) for steatosis of PNPLA3 rs738409 genotype, 8 proteins, or 19 phenotypic variables was 0.913, whereas the final classifier that included variables from all three domains had an AUC of 0.935. These data indicate that multi-domain modeling has better predictive power than comprehensive analysis of variables from a single domain.
ZYZ-168 alleviates cardiac fibrosis after myocardial infarction through inhibition of ERK1/2-dependent ROCK1 activation
Authors: Luo Shanshan , Hieu Tran Ba , Ma Fenfen , Yu Ying , Cao Zhonglian , Wang Minjun , Wu Weijun , Mao Yicheng , Rose Peter , Law Betty Yuen-Kwan , Zhu Yi Zhun
Published: March 2017

Selective treatments for myocardial infarction (MI) induced cardiac fibrosis are lacking. In this study, we focus on the therapeutic potential of a synthetic cardio-protective agent named ZYZ-168 towards MI-induced cardiac fibrosis and try to reveal the underlying mechanism. ZYZ-168 was administered to rats with coronary artery ligation over a period of six weeks. Ecocardiography and Masson staining showed that ZYZ-168 substantially improved cardiac function and reduced interstitial fibrosis. The expression of α–smooth muscle actin (α-SMA) and Collagen I were reduced as was the activity of matrix metalloproteinase 9 (MMP-9). These were related with decreased phosphorylation of ERK1/2 and expression of Rho-associated coiled-coil containing protein kinase 1 (ROCK1). In cardiac fibroblasts stimulated with TGF-β1, phenotypic switches of cardiac fibroblasts to myofibroblasts were observed. Inhibition of ERK1/2 phosphorylation or knockdown of ROCK1 expectedly reduced TGF-β1 induced fibrotic responses. ZYZ-168 appeared to inhibit the fibrotic responses in a concentration dependent manner, in part via a decrease in ROCK 1 expression through inhibition of the phosphorylation status of ERK1/2. For inhibition of ERK1/2 phosphorylation with a specific inhibitor reduced the activation of ROCK1. Considering its anti-apoptosis activity in MI, ZYZ-168 may be a potential drug candidate for treatment of MI-induced cardiac fibrosis.
Applying torque to the Escherichia coli flagellar motor using magnetic tweezers
Authors: van Oene Maarten M. , Dickinson Laura E. , Cross Bronwen , Pedaci Francesco , Lipfert Jan , Dekker Nynke H.
Published: March 2017

The bacterial flagellar motor of Escherichia coli is a nanoscale rotary engine essential for bacterial propulsion. Studies on the power output of single motors rely on the measurement of motor torque and rotation under external load. Here, we investigate the use of magnetic tweezers, which in principle allow the application and active control of a calibrated load torque, to study single flagellar motors in Escherichia coli. We manipulate the external load on the motor by adjusting the magnetic field experienced by a magnetic bead linked to the motor, and we probe the motor’s response. A simple model describes the average motor speed over the entire range of applied fields. We extract the motor torque at stall and find it to be similar to the motor torque at drag-limited speed. In addition, use of the magnetic tweezers allows us to force motor rotation in both forward and backward directions. We monitor the motor’s performance before and after periods of forced rotation and observe no destructive effects on the motor. Our experiments show how magnetic tweezers can provide active and fast control of the external load while also exposing remaining challenges in calibration. Through their non-invasive character and straightforward parallelization, magnetic tweezers provide an attractive platform to study nanoscale rotary motors at the single-motor level.
Elucidation of terpenoid metabolism in Scoparia dulcis by RNA-seq analysis
Authors: Yamamura Yoshimi , Kurosaki Fumiya , Lee Jung-Bum
Published: March 2017

Scoparia dulcis biosynthesize bioactive diterpenes, such as scopadulcic acid B (SDB), which are known for their unique molecular skeleton. Although the biosynthesis of bioactive diterpenes is catalyzed by a sequence of class II and class I diterpene synthases (diTPSs), the mechanisms underlying this process are yet to be fully identified. To elucidate these biosynthetic machinery, we performed a high-throughput RNA-seq analysis, and de novo assembly of clean reads revealed 46,332 unique transcripts and 40,503 two unigenes. We found diTPSs genes including a putative syn-copalyl diphosphate synthase (SdCPS2) and two kaurene synthase-like (SdKSLs) genes. Besides them, total 79 full-length of cytochrome P450 (CYP450) genes were also discovered. The expression analyses showed selected CYP450s associated with their expression pattern of SdCPS2 and SdKSL1, suggesting that CYP450 candidates involved diterpene modification. SdCPS2 represents the first predicted gene to produce syn-copalyl diphosphate in dicots. In addition, SdKSL1 potentially contributes to the SDB biosynthetic pathway. Therefore, these identified genes associated with diterpene biosynthesis lead to the development of genetic engineering focus on diterpene metabolism in S. dulcis.
Ethylene-induced transcriptional and hormonal responses at the onset of sugarcane ripening
Authors: Cunha Camila P. , Roberto Guilherme G. , Vicentini Renato , Lembke Carolina G. , Souza Glaucia M. , Ribeiro Rafael V. , Machado Eduardo C. , Lagôa Ana M. M. A. , Menossi Marcelo
Published: March 2017

The effects of ethephon as a sugarcane ripener are attributed to ethylene. However, the role of this phytohormone at the molecular level is unknown. We performed a transcriptome analysis combined with the evaluation of sucrose metabolism and hormone profiling of sugarcane plants sprayed with ethephon or aminoethoxyvinylglycine (AVG), an ethylene inhibitor, at the onset of ripening. The differential response between ethephon and AVG on sucrose level and sucrose synthase activity in internodes indicates ethylene as a potential regulator of sink strength. The correlation between hormone levels and transcriptional changes suggests ethylene as a trigger of multiple hormone signal cascades, with approximately 18% of differentially expressed genes involved in hormone biosynthesis, metabolism, signalling, and response. A defence response elicited in leaves favoured salicylic acid over the ethylene/jasmonic acid pathway, while the upper internode was prone to respond to ethylene with strong stimuli on ethylene biosynthesis and signalling genes. Besides, ethylene acted synergistically with abscisic acid, another ripening factor, and antagonistically with gibberellin and auxin. We identified potential ethylene target genes and characterized the hormonal status during ripening, providing insights into the action of ethylene at the site of sucrose accumulation. A molecular model of ethylene interplay with other hormones is proposed.
Improved Bioavailability and Antitumor Effect of Docetaxel by TPGS Modified Proniosomes: In Vitro and In Vivo Evaluations
Authors: Liu Helong , Tu Liangxing , Zhou Yongxin , Dang Zefang , Wang Luting , Du Junfeng , Feng Jianfang , Hu Kaili
Published: March 2017

A novel oral drug delivery system, TPGS modified docetaxel proniosomes (DTX-TPGS-PNs), was designed to enhance the oral bioavailability and antitumor efficiency of the poorly water-soluble drug docetaxel. DTX-TPGS-PN niosomes were 93 ± 6.5 nm in size, −18.53 ± 1.65 mV in zeta potential and exhibited spherical morphology, with an encapsulation efficiency of 97.31 ± 0.60%. The system showed sustained release in both simulated gastric and intestinal fluid. The results of caco-2 monolayer, everted gut sac model and improved single-pass intestinal perfusion model transport studies showed that DTX-TPGS-PN niosomes could significantly improve the absorption of DTX. The pharmacokinetics study suggested the absolute bioavailability of DTX-TPGS-PN niosomes were 7.3 times that of DTX solution. In addition, a higher antitumor efficacy than DTX solution was demonstrated in MCF-7 and MDA-MB-231 cells in vitro and in MCF-7 tumor-bearing mice model in vivo. Our results demonstrated DTX-TPGS-PN is promising in enhancing the bioavailability and efficiency of poorly water-soluble drug DTX, and the potential of proniosomes as stable precursors for oral drug delivery.
Catch-and-Release of Target Cells Using Aptamer-Conjugated Electroactive Zwitterionic Oligopeptide SAM
Authors: Enomoto Junko , Kageyama Tatsuto , Osaki Tatsuya , Bonalumi Flavia , Marchese Francesca , Gautieri Alfonso , Bianchi Elena , Dubini Gabriele , Arrigoni Chiara , Moretti Matteo , Fukuda Junji
Published: March 2017

Nucleic acid aptamers possess attractive features such as specific molecular recognition, high-affinity binding, and rapid acquisition and replication, which could be feasible components for separating specific cells from other cell types. This study demonstrates that aptamers conjugated to an oligopeptide self-assembled monolayer (SAM) can be used to selectively trap human hepatic cancer cells from cell mixtures containing normal human hepatocytes or human fibroblasts. Molecular dynamics calculations have been performed to understand how the configurations of the aptamers are related to the experimental results of selective cell capture. We further demonstrate that the captured hepatic cancer cells can be detached and collected along with electrochemical desorption of the oligopeptide SAM, and by repeating these catch-and-release processes, target cells can be enriched. This combination of capture with aptamers and detachment with electrochemical reactions is a promising tool in various research fields ranging from basic cancer research to tissue engineering applications.
Profiling analysis of long non-coding RNAs in early postnatal mouse hearts
Authors: Sun Xiongshan , Han Qi , Luo Hongqin , Pan Xiaodong , Ji Yan , Yang Yao , Chen Hanying , Wang Fangjie , Lai Wenjing , Guan Xiao , Zhang Qi , Tang Yuan , Chu Jianhong , Yu Jianhua , Shou Weinian , Deng Youcai , Li Xiaohui
Published: March 2017

Mammalian cardiomyocytes undergo a critical hyperplastic-to-hypertrophic growth transition at early postnatal age, which is important in establishing normal physiological function of postnatal hearts. In the current study, we intended to explore the role of long non-coding (lnc) RNAs in this transitional stage. We analyzed lncRNA expression profiles in mouse hearts at postnatal day (P) 1, P7 and P28 via microarray. We identified 1,146 differentially expressed lncRNAs with more than 2.0-fold change when compared the expression profiles of P1 to P7, P1 to P28, and P7 to P28. The neighboring genes of these differentially expressed lncRNAs were mainly involved in DNA replication-associated biological processes. We were particularly interested in one novel cardiac-enriched lncRNA, ENSMUST00000117266, whose expression was dramatically down-regulated from P1 to P28 and was also sensitive to hypoxia, paraquat, and myocardial infarction. Knockdown ENSMUST00000117266 led to a significant increase of neonatal mouse cardiomyocytes in G0/G1 phase and reduction in G2/M phase, suggesting that ENSMUST00000117266 is involved in regulating cardiomyocyte proliferative activity and is likely associated with hyperplastic-to-hypertrophic growth transition. In conclusion, our data have identified a large group of lncRNAs presented in the early postnatal mouse heart. Some of these lncRNAs may have important functions in cardiac hyperplastic-to-hypertrophic growth transition.
Complexation of Manganese with Glutarimidedioxime: Implication for Extraction Uranium from Seawater
Authors: Xie Xiang , Tian Yin , Qin Zhen , Yu Qianhong , Wei Hongyuan , Wang Dongqi , Li Xingliang , Wang Xiaolin
Published: March 2017

The molecule of glutaroimidedioxime, a cyclic imidedioxime moiety that can form during the synthesis of the poly(amidoxime)sorbent and is reputedly responsible for the extraction of uranium from seawater. Complexation of manganese (II) with glutarimidedioxime in aqueous solutions was investigated with potentiometry, calorimetry, ESI-mass spectrometry, electrochemical measurements and quantum chemical calculations. Results show that complexation reactions of manganese with glutarimidedioxime are both enthalpy and entropy driven processes, implying that the sorption of manganese on the glutarimidedioxime-functionalized sorbent would be enhanced at higher temperatures. Complex formation of manganese with glutarimidedioxime can assist redox of Mn(II/III). There are about ~15% of equilibrium manganese complex with the ligand in seawater pH(8.3), indicating that manganese could compete to some degree with uranium for sorption sites.
Evaluation of dynamic changes in interstitial fluid proteome following microdialysis probe insertion trauma in trapezius muscle of healthy women
Authors: Turkina Maria V. , Ghafouri Nazdar , Gerdle Björn , Ghafouri Bijar
Published: March 2017

Microdialysis (MD) has been shown to be a promising technique for sampling of biomarkers. Implantation of MD probe causes an acute tissue trauma and provokes innate response cascades. In order to normalize tissue a two hours equilibration period for analysis of small molecules has been reported previously. However, how the proteome profile changes due to this acute trauma has yet to be fully understood. To characterize the early proteome events induced by this trauma we compared proteome in muscle dialysate collected during the equilibration period with two hours later in “post-trauma”. Samples were collected from healthy females using a 100 kDa MW cut off membrane and analyzed by high sensitive liquid chromatography tandem mass spectrometry. Proteins involved in stress response, immune system processes, inflammatory responses and nociception from extracellular and intracellular fluid spaces were identified. Sixteen proteins were found to be differentially abundant in samples collected during first two hours in comparison to “post-trauma”. Our data suggests that microdialysis in combination with mass spectrometry may provide potentially new insights into the interstitial proteome of trapezius muscle, yet should be further adjusted for biomarker discovery and diagnostics. Moreover, MD proteome alterations in response to catheter injury may reflect individual innate reactivity.
Body mass index trajectory patterns and changes in visceral fat and glucose metabolism before the onset of type 2 diabetes
Authors: Kuwahara Keisuke , Honda Toru , Nakagawa Tohru , Yamamoto Shuichiro , Hayashi Takeshi , Mizoue Tetsuya
Published: March 2017

We investigated BMI trajectory patterns before diabetes diagnosis and examined associated changes in visceral adiposity and glucose metabolism. 23,978 non-diabetic Japanese participants (2,789 women) aged 30–64 years were assessed with a mean follow-up of 7.6 years. Diabetes was diagnosed via fasting glucose, HbA1c, and self-report. Latent-class trajectory analyses were performed to identify BMI trajectories. Longitudinal changes in BMI, visceral adiposity, and glucose metabolism were estimated using mixed models. 1,892 individuals developed diabetes. Three distinct BMI trajectories were identified in adults developing and not developing diabetes, respectively. Among adults developing diabetes, 47.3% were classified as “medium BMI” (n = 895), and had increased mean BMI within the obesity category before diagnosis. The “low BMI” group (38.4%, n = 726) had an initial mean BMI of 21.9 kg/m2, and demonstrated small weight gain. The “high BMI” group (n = 271) were severely obese and showed greater increase in BMI until diagnosis. All groups which developed diabetes showed absolute and/or relative increase in visceral fat and impaired β-cell compensation for insulin resistance. All groups not developing diabetes showed measured variables were relatively stable during observation. These data suggest that visceral fat gain may induce β-cell failure in compensation for insulin resistance, resulting in diabetes regardless of obesity level.
Increasing temperature reduces the coupling between available nitrogen and phosphorus in soils of Chinese grasslands
Authors: Geng Yan , Baumann Frank , Song Chao , Zhang Mi , Shi Yue , Kühn Peter , Scholten Thomas , He Jin-Sheng
Published: March 2017

Changes in climatic conditions along geographical gradients greatly affect soil nutrient cycling processes. Yet how climate regimes such as changes in temperature influence soil nitrogen (N) and phosphorus (P) concentrations and their stoichiometry is not well understood. This study investigated the spatial pattern and variability of soil N and P availability as well as their coupling relationships at two soil layers (0–10 and 10–20 cm) along a 4000-km climate transect in two grassland biomes of China, the Inner Mongolian temperate grasslands and the Tibetan alpine grasslands. Our results found that in both grasslands, from cold to warm sites the amounts of soil total N, total P and available P all decreased. By contrast, the amount of available N was positively related to mean annual temperature in the Tibetan grasslands. Meanwhile, with increasing temperature ratio of available N to P significantly increased but the linear relationship between them was considerably reduced. Thus, increasing temperature may not only induce a stoichiometric shift but also loose the coupling between available N and P. This N-P decoupling under warmer conditions was more evident in the Tibetan alpine grasslands where P limitation might become more widespread relative to N as temperatures continue to rise.
Ecological interactions among Saccharomyces cerevisiae strains: insight into the dominance phenomenon
Authors: Pérez-Torrado Roberto , Rantsiou Kalliopi , Perrone Benedeta , Navarro-Tapia Elisabeth , Querol Amparo , Cocolin Luca
Published: March 2017

This study investigates the behaviour of Saccharomyces cerevisiae strains, in order to obtain insight into the intraspecies competition taking place in mixed populations of this species. Two strains of S. cerevisiae, one dominant and one non-dominant, were labelled and mixed, and individual fermentations were set up to study the transcriptomes of the strains by means of RNA-seq. The results obtained suggest that cell-to-cell contact and aggregation, which are driven by the expression of genes that are associated with the cell surface, are indispensable conditions for the achievement of dominance. Observations on mixed aggregates, made up of cells of both strains, which were detected by means of flow cytometry, have confirmed the transcriptomic data. Furthermore, overexpression of the SSU1 gene, which encodes for a transporter that confers resistance to sulphites, provides an ecological advantage to the dominant strain. A mechanistic model is proposed that sheds light on the dominance phenomenon between different strains of the S. cerevisiae species. The collected data suggest that cell-to-cell contact, together with differential sulphite production and resistance is important in determining the dominance of one strain over another.
The molecular motor Myosin Va interacts with the cilia-centrosomal protein RPGRIP1L
Authors: Assis L. H. P. , Silva-Junior R. M. P. , Dolce L. G. , Alborghetti M. R. , Honorato R. V. , Nascimento A. F. Z. , Melo-Hanchuk T. D. , Trindade D. M. , Tonoli C. C. C. , Santos C. T. , Oliveira P. S. L. , Larson R. E. , Kobarg J. , Espreafico E. M. , Giuseppe P. O. , Murakami M. T.
Published: March 2017

Myosin Va (MyoVa) is an actin-based molecular motor abundantly found at the centrosome. However, the role of MyoVa at this organelle has been elusive due to the lack of evidence on interacting partners or functional data. Herein, we combined yeast two-hybrid screen, biochemical studies and cellular assays to demonstrate that MyoVa interacts with RPGRIP1L, a cilia-centrosomal protein that controls ciliary signaling and positioning. MyoVa binds to the C2 domains of RPGRIP1L via residues located near or in the Rab11a-binding site, a conserved site in the globular tail domain (GTD) from class V myosins. According to proximity ligation assays, MyoVa and RPGRIP1L can interact near the cilium base in ciliated RPE cells. Furthermore, we showed that RPE cells expressing dominant-negative constructs of MyoVa are mostly unciliated, providing the first experimental evidence about a possible link between this molecular motor and cilia-related processes.
Heterozygous mutation of eEF1A1b resulted in spermatogenesis arrest and infertility in male tilapia, Oreochromis niloticus
Authors: Chen Jinlin , Jiang Dongneng , Tan Dejie , Fan Zheng , Wei Yingying , Li Minghui , Wang Deshou
Published: March 2017

Eukaryotic elongation factor 1 alpha (eEF1A) is an essential component of the translational apparatus. In the present study, eEF1A1b was isolated from the Nile tilapia. Real-time PCR and Western blot revealed that eEF1A1b was expressed highly in the testis from 90 dah (days after hatching) onwards. In situ hybridization and immunohistochemistry analyses showed that eEF1A1b was highly expressed in the spermatogonia of the testis. CRISPR/Cas9 mediated mutation of eEF1A1b resulted in spermatogenesis arrest and infertility in the F0 XY fish. Consistently, heterozygous mutation of eEF1A1b (eEF1A1b+/−) resulted in an absence of spermatocytes at 90 dah, very few spermatocytes, spermatids and spermatozoa at 180 dah, and decreased Cyp11b2 and serum 11-ketotestosterone level at both stages. Further examination of the fertilization capacity of the sperm indicated that the eEF1A1b+/− XY fish were infertile due to abnormal spermiogenesis. Transcriptomic analyses of the eEF1A1b+/− testis from 180 dah XY fish revealed that key elements involved in spermatogenesis, steroidogenesis and sperm motility were significantly down-regulated compared with the control XY. Transgenic overexpression of eEF1A1b rescued the spermatogenesis arrest phenotype of the eEF1A1b+/− testis. Taken together, our data suggested that eEF1A1b is crucial for spermatogenesis and male fertility in the Nile tilapia.
The trisaccharide raffinose modulates epidermal differentiation through activation of liver X receptor
Authors: Na Tae-Young , Kim Gyeong-Hwan , Oh Hyeon-Jeong , Lee Min-Ho , Han Yong-Hyun , Kim Ki Taek , Kim Ji-Su , Kim Dae-Duk , Lee Mi-Ock
Published: March 2017

The epidermal barrier function requires optimal keratinocyte differentiation and epidermal lipid synthesis. Liver X receptor (LXR) α and β, are important transcriptional regulators of the epidermal gene expression. Here, we show that raffinose, a ubiquitously present trisaccharide in plants, activated the transcriptional activity of LXRα/β, which led to the induction of genes required for keratinocyte differentiation such as involucrin and filaggrin, and genes involved in lipid metabolism and transport including SCD1 and ABCA1 in both HaCaT and normal human epidermal keratinocytes. Raffinose induced the expression of JunD and Fra1, and their DNA binding in the AP1 motif in the promoters of involucrin and loricrin. Interestingly, LXR bound the AP1 motif upon raffinose treatment, and conversely, JunD and Fra1 bound the LXR response element in promoters of LXR target genes, which indicates the presence of a postive cross-talk between LXR and AP1 in the regualtion of these genes. Finally, the effect of raffinose in epidermal barrier function was confirmed by applying raffinose in an ointment formulation to the skin of hairless mice. These findings suggest that raffinose could be examined as an ingredient in functional cosmetics and therapeutic agents for the treatment of cutaneous disorders associated with abnormal epidermal barrier function.
Intact sensory-motor network structure and function in far from onset premanifest Huntington’s disease
Authors: Gorges Martin , Müller Hans-Peter , Mayer Isabella Maria Sophie , Grupe Gesa Sophie , Kammer Thomas , Grön Georg , Kassubek Jan , Landwehrmeyer G. Bernhard , Wolf Robert Christian , Orth Michael
Published: March 2017

Structural and functional changes attributable to the neurodegenerative process in Huntington’s disease (HD) may be evident in HTT CAG repeat expansion carriers before the clinical manifestations of HD. It remains unclear, though, how far from motor onset a consistent signature of the neurodegenerative process in HD can be detected. Twelve far from onset preHD and 22 age-matched healthy control participants underwent volumetric structural magnetic resonance imaging (MRI), diffusion tensor imaging (DTI), and resting-state functional MRI (11 preHD, 22 controls) as well as electrophysiological measurements (12 preHD, 13 controls). There were no significant differences in white matter macro- and microstructure between far from onset preHD participants and controls. Functional connectivity in a basal ganglia-thalamic and motor networks, all measures of the motor efferent and sensory afferent pathways as well as sensory-motor integration were also similar in far from onset preHD and controls. With the methods used in far from onset preHD sensory-motor neural macro- or micro-structure and brain function were similar to healthy controls. This suggests that any observable structural and functional change in preHD nearer to onset, or in manifest HD, at least using comparable techniques such as in this study, most likely reflects an ongoing neurodegenerative process.
Screening with an NMNAT2-MSD platform identifies small molecules that modulate NMNAT2 levels in cortical neurons
Authors: Ali Yousuf O. , Bradley Gillian , Lu Hui-Chen
Published: March 2017

Nicotinamide mononucleotide adenylyl transferase 2 (NMNAT2) is a key neuronal maintenance factor and provides potent neuroprotection in numerous preclinical models of neurological disorders. NMNAT2 is significantly reduced in Alzheimer’s, Huntington’s, Parkinson’s diseases. Here we developed a Meso Scale Discovery (MSD)-based screening platform to quantify endogenous NMNAT2 in cortical neurons. The high sensitivity and large dynamic range of this NMNAT2-MSD platform allowed us to screen the Sigma LOPAC library consisting of 1280 compounds. This library had a 2.89% hit rate, with 24 NMNAT2 positive and 13 negative modulators identified. Western analysis was conducted to validate and determine the dose-dependency of identified modulators. Caffeine, one identified NMNAT2 positive-modulator, when systemically administered restored NMNAT2 expression in rTg4510 tauopathy mice to normal levels. We confirmed in a cell culture model that four selected positive-modulators exerted NMNAT2-specific neuroprotection against vincristine-induced cell death while four selected NMNAT2 negative modulators reduced neuronal viability in an NMNAT2-dependent manner. Many of the identified NMNAT2 positive modulators are predicted to increase cAMP concentration, suggesting that neuronal NMNAT2 levels are tightly regulated by cAMP signaling. Taken together, our findings indicate that the NMNAT2-MSD platform provides a sensitive phenotypic screen to detect NMNAT2 in neurons.
Fluorescent reporters for markerless genomic integration in Staphylococcus aureus
Authors: de Jong Nienke W. M. , van der Horst Thijs , van Strijp Jos A. G. , Nijland Reindert
Published: March 2017

We present integration vectors for Staphylococcus aureus encoding the fluorescent reporters mAmetrine, CFP, sGFP, YFP, mCherry and mKate. The expression is driven either from the sarA-P1 promoter or from any other promoter of choice. The reporter can be inserted markerless in the chromosome of a wide range of S. aureus strains. The integration site chosen does not disrupt any open reading frame, provides good expression, and has no detectable effect on the strains physiology. As an intermediate construct, we present a set of replicating plasmids containing the same fluorescent reporters. Also in these reporter plasmids the sarA-P1 promoter can be replaced by any other promoter of interest for expression studies. Cassettes from the replication plasmids can be readily swapped with the integration vector. With these constructs it becomes possible to monitor reporters of separate fluorescent wavelengths simultaneously.
Gradual collapse of nuclear wave functions regulated by frequency tuned X-ray scattering
Authors: Ignatova Nina , Cruz Vinícius V. , Couto Rafael C. , Ertan Emelie , Zimin Andrey , Guimarães Freddy F. , Polyutov Sergey , Ågren Hans , Kimberg Victor , Odelius Michael , Gel’mukhanov Faris
Published: March 2017

As is well established, the symmetry breaking by isotope substitution in the water molecule results in localisation of the vibrations along one of the two bonds in the ground state. In this study we find that this localisation may be broken in excited electronic states. Contrary to the ground state, the stretching vibrations of HDO are delocalised in the bound "Equation missing" core-excited state in spite of the mass difference between hydrogen and deuterium. The reason for this effect can be traced to the narrow “canyon-like” shape of the potential of the "Equation missing" state along the symmetric stretching mode, which dominates over the localisation mass-difference effect. In contrast, the localisation of nuclear motion to one of the HDO bonds is preserved in the dissociative core-excited state "Equation missing". The dynamics of the delocalisation of nuclear motion in these core-excited states is studied using resonant inelastic X-ray scattering of the vibrationally excited HDO molecule. The results shed light on the process of a wave function collapse. After core-excitation into the "Equation missing" state of HDO the initial wave packet collapses gradually, rather than instantaneously, to a single vibrational eigenstate.
Cordycepin disrupts leukemia association with mesenchymal stromal cells and eliminates leukemia stem cell activity
Authors: Liang Shu-Man , Lu Yi-Jhu , Ko Bor-Sheng , Jan Yee-Jee , Shyue Song-Kun , Yet Shaw-Fang , Liou Jun-Yang
Published: March 2017

Maintaining stemness of leukemic stem cells (LSCs) and reciprocal interactions between leukemia and stromal cells support leukemic progression and resistance to chemotherapy. Targeting the niche-based microenvironment is thus a new approach for leukemia therapy. Cordycepin is an analogue of adenosine and has been suggested to possess anti-leukemia properties. However, whether cordycepin influences association of leukemia and mesenchymal stromal cells has never been investigated. Here we show that cordycepin reduces CD34+CD38− cells in U937 and K562 cells and induces Dkk1 expression via autocrine and paracrine regulation in leukemia and mesenchymal stromal/stem cells (MSCs). Cordycepin suppresses cell attachment of leukemia with MSCs and downregulates N-cadherin in leukemia and VCAM-1 in MSCs. Moreover, incubation with leukemic conditioned media (CM) significantly induces IL-8 and IL-6 expression in MSCs, which is abrogated by cordycepin. Suppression of leukemic CM-induced VCAM-1 and IL-8 by cordycepin in MSCs is mediated by impairing NFκB signaling. Finally, cordycepin combined with an adenosine deaminase inhibitor prolongs survival in a leukemic mouse model. Our results indicate that cordycepin is a potential anti-leukemia therapeutic adjuvant via eliminating LSCs and disrupting leukemia-stromal association.
Implications of the cattle trade network in Cameroon for regional disease prevention and control
Authors: Motta Paolo , Porphyre Thibaud , Handel Ian , Hamman Saidou M. , Ngu Ngwa Victor , Tanya Vincent , Morgan Kenton , Christley Rob , Bronsvoort Barend M. deC.
Published: March 2017

Movement of live animals is a major risk factor for the spread of livestock diseases and zoonotic infections. Understanding contact patterns is key to informing cost-effective surveillance and control strategies. In West and Central Africa some of the most rapid urbanization globally is expected to increase the demand for animal-source foods and the need for safer and more efficient animal production. Livestock trading points represent a strategic contact node in the dissemination of multiple pathogens. From October 2014 to May 2015 official transaction records were collected and a questionnaire-based survey was carried out in cattle markets throughout Western and Central-Northern Cameroon. The data were used to analyse the cattle trade network including a total of 127 livestock markets within Cameroon and five neighboring countries. This study explores for the first time the influence of animal trade on infectious disease spread in the region. The investigations showed that national borders do not present a barrier against pathogen dissemination and that non-neighbouring countries are epidemiologically connected, highlighting the importance of a regional approach to disease surveillance, prevention and control. Furthermore, these findings provide evidence for the benefit of strategic risk-based approaches for disease monitoring, surveillance and control, as well as for communication and training purposes through targeting key regions, highly connected livestock markets and central trading links.
Inhibition of PHD3 by salidroside promotes neovascularization through cell–cell communications mediated by muscle-secreted angiogenic factors
Authors: Zhang Jing , Kasim Vivi , Xie Yu-Dan , Huang Can , Sisjayawan Julita , Dwi Ariyanti Agnes , Yan Xue-Song , Wu Xiao-Yan , Liu Cai-Ping , Yang Li , Miyagishi Makoto , Wu Shou-Rong
Published: March 2017

Therapeutic angiogenesis has been considered as a potential strategy for treating peripheral artery diseases including hind-limb ischemia (HLI); however, no effective drug-based treatment is currently available. Here we showed that intramuscular administration of salidroside, an active compound of Chinese herb Rhodiola, could robustly enhance blood perfusion recovery by promoting neovascularization in HLI mice. We revealed that salidroside promoted skeletal muscle cell migration and paracrine function through inhibiting the transcriptional level of prolyl-hydroxylase domain 3 (PHD3) without affecting PHD1 and PHD2. Paracrine signals from salidroside-treated skeletal muscle cells enhanced endothelial and smooth muscle cells migration, while inhibition of FGF2/FGF2R and PDGF-BB/PDGFR-β pathways abolished this effect, as well as neovascularization in HLI mice. Furthermore, we elucidated that salidroside inhibition on PHD3 might occur through estrogen receptor alpha (ERα). Together, our findings highlights the potential application of salidroside as a novel pharmalogical inhibitor of ERα/PHD3 axis for therapeutic angiogenesis in HLI diseases.
Diverse origin of mitochondrial lineages in Iron Age Black Sea Scythians
Authors: Juras Anna , Krzewińska Maja , Nikitin Alexey G. , Ehler Edvard , Chyleński Maciej , Łukasik Sylwia , Krenz-Niedbała Marta , Sinika Vitaly , Piontek Janusz , Ivanova Svetlana , Dabert Miroslawa , Götherström Anders
Published: March 2017

Scythians were nomadic and semi-nomadic people that ruled the Eurasian steppe during much of the first millennium BCE. While having been extensively studied by archaeology, very little is known about their genetic identity. To fill this gap, we analyzed ancient mitochondrial DNA (mtDNA) from Scythians of the North Pontic Region (NPR) and successfully retrieved 19 whole mtDNA genomes. We have identified three potential mtDNA lineage ancestries of the NPR Scythians tracing back to hunter-gatherer and nomadic populations of east and west Eurasia as well as the Neolithic farming expansion into Europe. One third of all mt lineages in our dataset belonged to subdivisions of mt haplogroup U5. A comparison of NPR Scythian mtDNA linages with other contemporaneous Scythian groups, the Saka and the Pazyryks, reveals a common mtDNA package comprised of haplogroups H/H5, U5a, A, D/D4, and F1/F2. Of these, west Eurasian lineages show a downward cline in the west-east direction while east Eurasian haplogroups display the opposite trajectory. An overall similarity in mtDNA lineages of the NPR Scythians was found with the late Bronze Age Srubnaya population of the Northern Black Sea region which supports the archaeological hypothesis suggesting Srubnaya people as ancestors of the NPR Scythians.
An optimized microfabricated platform for the optical generation and detection of hyperpolarized 129Xe
Authors: Kennedy Daniel J. , Seltzer Scott J. , Jiménez-Martínez Ricardo , Ring Hattie L. , Malecek Nicolas S. , Knappe Svenja , Donley Elizabeth A. , Kitching John , Bajaj Vikram S. , Pines Alexander
Published: March 2017

Low thermal-equilibrium nuclear spin polarizations and the need for sophisticated instrumentation render conventional nuclear magnetic resonance (NMR) spectroscopy and imaging (MRI) incompatible with small-scale microfluidic devices. Hyperpolarized 129Xe gas has found use in the study of many materials but has required very large and expensive instrumentation. Recently a microfabricated device with modest instrumentation demonstrated all-optical hyperpolarization and detection of 129Xe gas. This device was limited by 129Xe polarizations less than 1%, 129Xe NMR signals smaller than 20 nT, and transport of hyperpolarized 129Xe over millimeter lengths. Higher polarizations, versatile detection schemes, and flow of 129Xe over larger distances are desirable for wider applications. Here we demonstrate an ultra-sensitive microfabricated platform that achieves 129Xe polarizations reaching 7%, NMR signals exceeding 1 μT, lifetimes up to 6 s, and simultaneous two-mode detection, consisting of a high-sensitivity in situ channel with signal-to-noise of 105 and a lower-sensitivity ex situ detection channel which may be useful in a wider variety of conditions. 129Xe is hyperpolarized and detected in locations more than 1 cm apart. Our versatile device is an optimal platform for microfluidic magnetic resonance in particular, but equally attractive for wider nuclear spin applications benefitting from ultra-sensitive detection, long coherences, and simple instrumentation.