bluuebunny/crossref_metadata_2025 huggingface dataset:
Commentary on: L-Methylfolate, Methylcobolamine, and N-Acetylcysteine in the Treatment of Alzheimer's Disease-Related Cognitive Decline
Authors: Cummings Jeffrey L
Published: February 2017

Drs. McCaddon and Hudson provide a thorough review of the multiple ways in which vitamin B12, vitamin B6, folate, and homocysteine (Hey) are implicated in the pathogenesis of Alzheimer's disease (AD). They noted that Hey is more often elevated in AD and in mild cognitive impairment (MCI) than in cognitively healthy elderly; phosphatases needed to limit tau hyperphosphoryalation and neurofibrillary tangle formation require methylation and are dependent on folate and methylation status; cerebrospinal fluid (CSF) tau levels correlated with markers of methylation status; reduced folate and B12 levels lead to increase β-secretase and pesenilin 1 (PS1) actions leading to greater amyloid-β production in in vitro models; elevated Hey levels in rates are associated with increased PS1 activity and spatial memory deficits that are reversed following treatment with B12 and folate; raised Hey levels in vitro increase amyloid-β protein neurotoxicity; methylation impacts transmitters and transmitter function relevant to AD; in cultured neurons, Hey induces injury in DNA and stimulates cell death pathways. B12 deficiency leads to accumulation of methyl malonic acid, which inhibits mitochondrial function and may compromise energy generation and impair maintenance of synaptic plasticity. Methylation abnormalities result in excessive generation of reactive oxygen species that contribute importantly to cell injury. Biomarkers of oxidative injury, such as isoprostanes, are elevated in AD and suggest excess oxidation. Thus, there are multiple pathways through which deficient methylation may contribute to AD. In some cases, the observations are derived from models with B12 or folate deficiency and some in vitro observations have not been tested in in vivo models. There are no biomarkers specific to some of the pathways implicated and the magnitude of the impact of the deficiency or its treatment has not been established for all the relationships. Two open-label experiments in early- and late-stage AD patients have suggested benefit.
Psychosocial Treatment for Bipolar Disorder
Authors: Reilly-Harrington Noreen
Published: February 2017

Medication is the mainstay of treatment for bipolar disorder. However, no medication will be effective if patients do not take it, and the rates of medication compliance in bipolar disorder are very low. Johnson and McFarland found that the modal length of compliance with a mood stabilizer was only 2 months. Keck and colleagues found that 50% to 66% of patients with bipolar disorder exhibit poor compliance within the first 12 months of treatment. In addition, even with adequate medication compliance, high rates of relapse persist.

Adjunctive psychosocial treatments can help reduce relapse and provide patients as well as their families with tools to manage bipolar disorder more effectively. Several forms of intensive psychotherapy have shown promise for the treatment of bipolar disorder. In the Systematic Treatment Enhancement Program for Bipolar Disorder, Miklowitz and colleagues compared three forms of intensive interventions: cognitive-behavioral therapy (CBT), interpersonal and social rhythm therapy, and family-focused treatment. These were compared to a brief, 3-session psychoeducational intervention known as collaborative care. A total of 293 depressed patients with bipolar type I or type II disorder were treated with protocol pharmacotherapy and were randomly assigned to either one of the three intensive interventions or the brief psychoeducational intervention.

The three intensive interventions provided up to 30 sessions of treatment over a 9-month period. The collaborative care intervention consisted of three sessions administered over a 6-week period. The authors found that patients who received one of the intensive interventions had a median time to recovery 110 days earlier than patients who had received the collaborative care conditions. Patients who received one of the three intensive psychotherapies also had significantly higher year-end recovery rates, and are more than 1 to 1.5 times more likely to be clinically well during any study month. No statistically significant differences were found between the 3 intensive treatments.
Penta-band linear tapered feed planar spiral antenna for vehicular communications
Authors: Ramya  , Rama Rao Thipparaju
Published: February 2017

Owing to dynamic nature of vehicular environments, it becomes essential to achieve effective communication via vehicle-to-vehicle and infrastructure-to-vehicle. This leads to the need for an antenna system that supports multiple frequency bands, high gain, broadside radiation pattern, and circular polarization. We propose single-arm penta-band-based spiral antenna with dimensions of 51 × 35 × 1.574 mm3resonating at navigational wireless frequencies 1.2 GHz for IRNSS and 1.5 GHz for GPS; wireless communication frequencies 2.45 and 3.3 GHz and dedicated short range communication frequency 5.8 GHz. Linear taper feed has been introduced to achieve good impedance matching and the outer edge feed of the spiral on the same plane helps to achieve circular polarization. The measurement result proves the betterment in impedance of the spiral antenna that varies from 50 –55 Ω across the desired operating frequencies.
A new compact and miniaturized multiband uniplanar CPW-fed Monopole antenna with T-slot inverted for multiple wireless applications
Authors: Dakir Rachid , Zbitou Jamal , Mouhsen Ahmed , Tribak Abdelwahed , Sanchez Angel Mediavilla , Latrach Mohamed
Published: February 2017

In this paper, the design of a new compact uniplanar coplanar waveguide-fed antenna for multiband wireless application is presented and investigated. This antenna has a compact size of 25 × 25 mm2 and consists of a three parallel stub optimized added on rectangular slot to the radiator patch and T-shaped which inverted in the ground plane. The final prototype antenna designing resonantes at frequency bands (2.4–2.9 GHz), (3.7–5.2 GHz), and (5.7–6 GHz) with a return loss less than −10 dB. Details of the antenna configuration, design, simulation, and experimental results are presented, investigated, and discussed. The compactness, simple feeding technique, and conception of the uniplanar design make it easy to be integrated within devices of multiples wireless applications.
Hysterectomy and incidence of depressive symptoms in midlife women: the Australian Longitudinal Study on Women's Health
Authors: Wilson L. , Pandeya N. , Byles J. , Mishra G.
Published: February 2017

Aims.

There is limited longitudinal research that has looked at the longer term incidence of depressive symptoms, comparing women with a hysterectomy to women without a hysterectomy. We aimed to investigate the association between hysterectomy status and the 12-year incidence of depressive symptoms in a mid-aged cohort of Australian women, and whether these relationships were modified by use of exogenous hormones.

Methods.

We used generalised estimating equation models for binary outcome data to assess the associations of the incidence of depressive symptoms (measured by the 10-item Centre for Epidemiologic Studies Depression Scale) across five surveys over a 12-year period, in women with a hysterectomy with ovarian conservation, or a hysterectomy with bilateral oophorectomy compared with women without a hysterectomy. We further stratified women with hysterectomy by their current use of menopausal hormone therapy (MHT). Women who reported prior treatment for depression were excluded from the analysis.

Results.

Compared with women without a hysterectomy (n = 4002), both women with a hysterectomy with ovarian conservation (n = 884) and women with a hysterectomy and bilateral oophorectomy (n = 450) had a higher risk of depressive symptoms (relative risk (RR) 1.20; 95% confidence interval (CI) 1.06–1.36 and RR 1.44; 95% CI 1.22–1.68, respectively). There were differences in the strength of the risk for women with a hysterectomy with ovarian conservation, compared with those without, when we stratified by current MHT use. Compared with women without a hysterectomy who did not use MHT, women with a hysterectomy with ovarian conservation who were also MHT users had a higher risk of depressive symptoms (RR 1.57; 95% CI 1.31–1.88) than women with a hysterectomy with ovarian conservation but did not use MHT (RR 1.17; 95% CI 1.02–1.35). For women with a hysterectomy and bilateral oophorectomy, MHT use did not attenuate the risk. We could not rule out, however, that the higher risk seen among MHT users may be due to confounding by indication, i.e. MHT was prescribed to treat depressive symptoms, but their depressive symptoms persisted.

Conclusions.

Women with a hysterectomy (with and without bilateral oophorectomy) have a higher risk of new incidence of depressive symptoms in the longer term that was not explained by lifestyle or socio-economic factors.
A Potential Role of the 5-HTTLPR Polymorphism in Self-Reported Executive Functioning
Authors: Alfimova Margarita V. , Golimbet Vera , Lezheiko Tatyana , Korovaitseva Galina
Published: February 2017

Intense effort is directed toward searching for associations between genes and neuropsychological measures of executive functions. In contrast, the impact of genetic polymorphisms on self-rating of everyday executive functioning has not been investigated so far. This study was designed to test associations of self-reported executive functioning, measured with the Behavior Rating Inventory of Executive Function (BRIEF-A), with dopaminergic and serotoninergic genes in non-clinical population and to assess impact of neuropsychological and personality characteristics on these associations. One hundred healthy adults completed the BRIEF-A, personality inventories SPQ-74, STAI, MMPI, and neuropsychological tests for executive functions. Polymorphisms in theDRD4, COMT, DRD2, HTR2A, andSLC6A4genes were genotyped. We revealed a significant main effect of theSLC6A4’s 5-HTTLPR polymorphism on BRIEF-A scores (F= 2.21,P= .018, η2= .24). Among the BRIEF-A measures, the genotype effect was significant for the Plan/Organize (F= 7.34,P= .008, η2= .07) and Task Monitor scales (F= 4.33,P= .04, η2= .04), and the Metacognition index (F= 4.21,P= .043, η2= .04). Carriers of the short allele reported fewer problems than homozygotes for the long allele. Correlations of the BRIEF-A measures with neuropsychological variables were weak, while those with personality characteristics were strong, with trait anxiety being the most powerful predictor of the BRIEF-A scores. However, the relationship between the 5-HTTLPR and BRIEF-A scores remained significant when trait anxiety was controlled for. The results suggest a potential role of the 5-HTTLPR in self-reported everyday task planning and monitoring.
Potent single-domain antibodies that arrest respiratory syncytial virus fusion protein in its prefusion state
Authors: Rossey Iebe , Gilman Morgan S. A. , Kabeche Stephanie C. , Sedeyn Koen , Wrapp Daniel , Kanekiyo Masaru , Chen Man , Mas Vicente , Spitaels Jan , Melero José A. , Graham Barney S. , Schepens Bert , McLellan Jason S. , Saelens Xavier
Published: February 2017

Human respiratory syncytial virus (RSV) is the main cause of lower respiratory tract infections in young children. The RSV fusion protein (F) is highly conserved and is the only viral membrane protein that is essential for infection. The prefusion conformation of RSV F is considered the most relevant target for antiviral strategies because it is the fusion-competent form of the protein and the primary target of neutralizing activity present in human serum. Here, we describe two llama-derived single-domain antibodies (VHHs) that have potent RSV-neutralizing activity and bind selectively to prefusion RSV F with picomolar affinity. Crystal structures of these VHHs in complex with prefusion F show that they recognize a conserved cavity formed by two F protomers. In addition, the VHHs prevent RSV replication and lung infiltration of inflammatory monocytes and T cells in RSV-challenged mice. These prefusion F-specific VHHs represent promising antiviral agents against RSV.
Protective role of fructokinase blockade in the pathogenesis of acute kidney injury in mice
Authors: Andres-Hernando Ana , Li Nanxing , Cicerchi Christina , Inaba Shinichiro , Chen Wei , Roncal-Jimenez Carlos , Le Myphuong T. , Wempe Michael F. , Milagres Tamara , Ishimoto Takuji , Fini Mehdi , Nakagawa Takahiko , Johnson Richard J. , Lanaspa Miguel A.
Published: February 2017

Acute kidney injury is associated with high mortality, especially in intensive care unit patients. The polyol pathway is a metabolic route able to convert glucose into fructose. Here we show the detrimental role of endogenous fructose production by the polyol pathway and its metabolism through fructokinase in the pathogenesis of ischaemic acute kidney injury (iAKI). Consistent with elevated urinary fructose in AKI patients, mice undergoing iAKI show significant polyol pathway activation in the kidney cortex characterized by high levels of aldose reductase, sorbitol and endogenous fructose. Wild type but not fructokinase knockout animals demonstrate severe kidney injury associated with ATP depletion, elevated uric acid, oxidative stress and inflammation. Interestingly, both the renal injury and dysfunction in wild-type mice undergoing iAKI is significantly ameliorated when exposed to luteolin, a recently discovered fructokinase inhibitor. This study demonstrates a role for fructokinase and endogenous fructose as mediators of acute renal disease.
A metamorphic inorganic framework that can be switched between eight single-crystalline states
Authors: Zhan Caihong , Cameron Jamie M. , Gabb David , Boyd Thomas , Winter Ross S. , Vilà-Nadal Laia , Mitchell Scott G. , Glatzel Stefan , Breternitz Joachim , Gregory Duncan H. , Long De-Liang , Macdonell Andrew , Cronin Leroy
Published: February 2017

The design of highly flexible framework materials requires organic linkers, whereas inorganic materials are more robust but inflexible. Here, by using linkable inorganic rings made up of tungsten oxide (P8W48O184) building blocks, we synthesized an inorganic single crystal material that can undergo at least eight different crystal-to-crystal transformations, with gigantic crystal volume contraction and expansion changes ranging from −2,170 to +1,720 Å3 with no reduction in crystallinity. Not only does this material undergo the largest single crystal-to-single crystal volume transformation thus far reported (to the best of our knowledge), the system also shows conformational flexibility while maintaining robustness over several cycles in the reversible uptake and release of guest molecules switching the crystal between different metamorphic states. This material combines the robustness of inorganic materials with the flexibility of organic frameworks, thereby challenging the notion that flexible materials with robustness are mutually exclusive.
Modulating supramolecular binding of carbon dioxide in a redox-active porous metal-organic framework
Authors: Lu Zhenzhong , Godfrey Harry G. W. , da Silva Ivan , Cheng Yongqiang , Savage Mathew , Tuna Floriana , McInnes Eric J. L. , Teat Simon J. , Gagnon Kevin J. , Frogley Mark D. , Manuel Pascal , Rudić Svemir , Ramirez-Cuesta Anibal J. , Easun Timothy L. , Yang Sihai , Schröder Martin
Published: February 2017

Hydrogen bonds dominate many chemical and biological processes, and chemical modification enables control and modulation of host–guest systems. Here we report a targeted modification of hydrogen bonding and its effect on guest binding in redox-active materials. MFM-300(VIII) {[VIII2(OH)2(L)], LH4=biphenyl-3,3′,5,5′-tetracarboxylic acid} can be oxidized to isostructural MFM-300(VIV), [VIV2O2(L)], in which deprotonation of the bridging hydroxyl groups occurs. MFM-300(VIII) shows the second highest CO2 uptake capacity in metal-organic framework materials at 298 K and 1 bar (6.0 mmol g−1) and involves hydrogen bonding between the OH group of the host and the O-donor of CO2, which binds in an end-on manner, "Equation missing"=1.863(1) Å. In contrast, CO2-loaded MFM-300(VIV) shows CO2 bound side-on to the oxy group and sandwiched between two phenyl groups involving a unique "Equation missing"···c.g.phenyl interaction [3.069(2), 3.146(3) Å]. The macroscopic packing of CO2 in the pores is directly influenced by these primary binding sites.
Advanced rechargeable aluminium ion battery with a high-quality natural graphite cathode
Authors: Wang Di-Yan , Wei Chuan-Yu , Lin Meng-Chang , Pan Chun-Jern , Chou Hung-Lung , Chen Hsin-An , Gong Ming , Wu Yingpeng , Yuan Chunze , Angell Michael , Hsieh Yu-Ju , Chen Yu-Hsun , Wen Cheng-Yen , Chen Chun-Wei , Hwang Bing-Joe , Chen Chia-Chun , Dai Hongjie
Published: February 2017

Recently, interest in aluminium ion batteries with aluminium anodes, graphite cathodes and ionic liquid electrolytes has increased; however, much remains to be done to increase the cathode capacity and to understand details of the anion–graphite intercalation mechanism. Here, an aluminium ion battery cell made using pristine natural graphite flakes achieves a specific capacity of ∼110 mAh g−1 with Coulombic efficiency ∼98%, at a current density of 99 mA g−1 (0.9 C) with clear discharge voltage plateaus (2.25–2.0 V and 1.9–1.5 V). The cell has a capacity of 60 mAh g−1 at 6 C, over 6,000 cycles with Coulombic efficiency ∼ 99%. Raman spectroscopy shows two different intercalation processes involving chloroaluminate anions at the two discharging plateaus, while C–Cl bonding on the surface, or edges of natural graphite, is found using X-ray absorption spectroscopy. Finally, theoretical calculations are employed to investigate the intercalation behaviour of choloraluminate anions in the graphite electrode.
Intratumoral modulation of the inducible co-stimulator ICOS by recombinant oncolytic virus promotes systemic anti-tumour immunity
Authors: Zamarin Dmitriy , Holmgaard Rikke B. , Ricca Jacob , Plitt Tamar , Palese Peter , Sharma Padmanee , Merghoub Taha , Wolchok Jedd D. , Allison James P.
Published: February 2017

Emerging data suggest that locoregional cancer therapeutic approaches with oncolytic viruses can lead to systemic anti-tumour immunity, although the appropriate targets for intratumoral immunomodulation using this strategy are not known. Here we find that intratumoral therapy with Newcastle disease virus (NDV), in addition to the activation of innate immunity, upregulates the expression of T-cell co-stimulatory receptors, with the inducible co-stimulator (ICOS) being most notable. To explore ICOS as a direct target in the tumour, we engineered a recombinant NDV-expressing ICOS ligand (NDV-ICOSL). In the bilateral flank tumour models, intratumoral administration of NDV-ICOSL results in enhanced infiltration with activated T cells in both virus-injected and distant tumours, and leads to effective rejection of both tumours when used in combination with systemic CTLA-4 blockade. These findings highlight that intratumoral immunomodulation with an oncolytic virus expressing a rationally selected ligand can be an effective strategy to drive systemic efficacy of immune checkpoint blockade.
Self-organizing actin patterns shape membrane architecture but not cell mechanics
Authors: Fritzsche M. , Li D. , Colin-York H. , Chang V. T. , Moeendarbary E. , Felce J. H. , Sezgin E. , Charras G. , Betzig E. , Eggeling C.
Published: February 2017

Cell-free studies have demonstrated how collective action of actin-associated proteins can organize actin filaments into dynamic patterns, such as vortices, asters and stars. Using complementary microscopic techniques, we here show evidence of such self-organization of the actin cortex in living HeLa cells. During cell adhesion, an active multistage process naturally leads to pattern transitions from actin vortices over stars into asters. This process is primarily driven by Arp2/3 complex nucleation, but not by myosin motors, which is in contrast to what has been theoretically predicted and observed in vitro. Concomitant measurements of mechanics and plasma membrane fluidity demonstrate that changes in actin patterning alter membrane architecture but occur functionally independent of macroscopic cortex elasticity. Consequently, tuning the activity of the Arp2/3 complex to alter filament assembly may thus be a mechanism allowing cells to adjust their membrane architecture without affecting their macroscopic mechanical properties.
Recurrently deregulated lncRNAs in hepatocellular carcinoma
Authors: Yang Yang , Chen Lei , Gu Jin , Zhang Hanshuo , Yuan Jiapei , Lian Qiuyu , Lv Guishuai , Wang Siqi , Wu Yang , Yang Yu-Cheng T. , Wang Dongfang , Liu Yang , Tang Jing , Luo Guijuan , Li Yang , Hu Long , Sun Xinbao , Wang Dong , Guo Mingzhou , Xi Qiaoran , Xi Jianzhong , Wang Hongyang , Zhang Michael Q. , Lu Zhi John
Published: February 2017

Hepatocellular carcinoma (HCC) cells often invade the portal venous system and subsequently develop into portal vein tumour thrombosis (PVTT). Long noncoding RNAs (lncRNAs) have been associated with HCC, but a comprehensive analysis of their specific association with HCC metastasis has not been conducted. Here, by analysing 60 clinical samples’ RNA-seq data from 20 HCC patients, we have identified and characterized 8,603 candidate lncRNAs. The expression patterns of 917 recurrently deregulated lncRNAs are correlated with clinical data in a TCGA cohort and published liver cancer data. Matched array data from the 60 samples show that copy number variations (CNVs) and alterations in DNA methylation contribute to the observed recurrent deregulation of 235 lncRNAs. Many recurrently deregulated lncRNAs are enriched in co-expressed clusters of genes related to cell adhesion, immune response and metabolic processes. Candidate lncRNAs related to metastasis, such as HAND2-AS1, were further validated using RNAi-based loss-of-function assays. Thus, we provide a valuable resource of functional lncRNAs and biomarkers associated with HCC tumorigenesis and metastasis.
CLK-dependent exon recognition and conjoined gene formation revealed with a novel small molecule inhibitor
Authors: Funnell Tyler , Tasaki Shinya , Oloumi Arusha , Araki Shinsuke , Kong Esther , Yap Damian , Nakayama Yusuke , Hughes Christopher S. , Cheng S.-W. Grace , Tozaki Hirokazu , Iwatani Misa , Sasaki Satoshi , Ohashi Tomohiro , Miyazaki Tohru , Morishita Nao , Morishita Daisuke , Ogasawara-Shimizu Mari , Ohori Momoko , Nakao Shoichi , Karashima Masatoshi , Sano Masaya , Murai Aiko , Nomura Toshiyuki , Uchiyama Noriko , Kawamoto Tomohiro , Hara Ryujiro , Nakanishi Osamu , Shumansky Karey , Rosner Jamie , Wan Adrian , McKinney Steven , Morin Gregg B. , Nakanishi Atsushi , Shah Sohrab , Toyoshiba Hiroyoshi , Aparicio Samuel
Published: February 2017

CDC-like kinase phosphorylation of serine/arginine-rich proteins is central to RNA splicing reactions. Yet, the genomic network of CDC-like kinase-dependent RNA processing events remains poorly defined. Here, we explore the connectivity of genomic CDC-like kinase splicing functions by applying graduated, short-exposure, pharmacological CDC-like kinase inhibition using a novel small molecule (T3) with very high potency, selectivity, and cell-based stability. Using RNA-Seq, we define CDC-like kinase-responsive alternative splicing events, the large majority of which monotonically increase or decrease with increasing CDC-like kinase inhibition. We show that distinct RNA-binding motifs are associated with T3 response in skipped exons. Unexpectedly, we observe dose-dependent conjoined gene transcription, which is associated with motif enrichment in the last and second exons of upstream and downstream partners, respectively. siRNA knockdown of CLK2-associated genes significantly increases conjoined gene formation. Collectively, our results reveal an unexpected role for CDC-like kinase in conjoined gene formation, via regulation of 3′-end processing and associated splicing factors.
Longitudinal test-retest neuroimaging data from healthy young adults in southwest China
Authors: Liu Wei , Wei Dongtao , Chen Qunlin , Yang Wenjing , Meng Jie , Wu Guorong , Bi Taiyong , Zhang Qinglin , Zuo Xi-Nian , Qiu Jiang
Published: February 2017

Multimodal magnetic resonance imaging (mMRI) has been widely used to map the structure and function of the human brain, as well as its behavioral associations. However, to date, a large sample with a long-term longitudinal design and a narrow age-span has been lacking for the assessment of test-retest reliability and reproducibility of brain-behavior correlations, as well as the development of novel causal insights into these correlational findings. Here we describe the SLIM dataset, which includes brain and behavioral data across a long-term retest-duration within three and a half years, mMRI scans provided a set of structural, diffusion and resting-state functional MRI images, along with rich samples of behavioral assessments addressed—demographic, cognitive and emotional information. Together with the Consortium for Reliability and Reproducibility (CoRR), the SLIM is expected to accelerate the reproducible sciences of the human brain by providing an open resource for brain-behavior discovery sciences with big-data approaches.
Inhibitory effects of cholinesterase inhibitor donepezil on the Kv1.5 potassium channel
Authors: Li Kai , Cheng Neng , Li Xian-Tao
Published: February 2017

Kv1.5 channels carry ultra-rapid delayed rectifier K+ currents in excitable cells, including neurons and cardiac myocytes. In the current study, the effects of cholinesterase inhibitor donepezil on cloned Kv1.5 channels expressed in HEK29 cells were explored using whole-cell recording technique. Exposure to donepezil resulted in a rapid and reversible block of Kv1.5 currents, with an IC50 value of 72.5 μM. The mutant R476V significantly reduced the binding affinity of donepezil to Kv1.5 channels, showing the target site in the outer mouth region. Donepezil produced a significant delay in the duration of activation and deactivation, and mutant R476V potentiated these effects without altering activation curves. In response to slowed deactivation time course, a typical crossover of Kv1.5 tail currents was clearly evident after bath application of donepezil. In addition, both this chemical and mutant R476V accelerated current decay during channel inactivation in a voltage-dependent way, but barely changed the inactivation and recovery curves. The presence of donepezil exhibited the use-dependent block of Kv1.5 currents in response to a series of depolarizing pulses. Our data indicate that donepezil can directly block Kv1.5 channels in its open and closed states.
Arrays of Individual DNA Molecules on Nanopatterned Substrates
Authors: Hager Roland , Halilovic Alma , Burns Jonathan R. , Schäffler Friedrich , Howorka Stefan
Published: February 2017

Arrays of individual molecules can combine the advantages of microarrays and single-molecule studies. They miniaturize assays to reduce sample and reagent consumption and increase throughput, and additionally uncover static and dynamic heterogeneity usually masked in molecular ensembles. However, realizing single-DNA arrays must tackle the challenge of capturing structurally highly dynamic strands onto defined substrate positions. Here, we create single-molecule arrays by electrostatically adhering single-stranded DNA of gene-like length onto positively charged carbon nanoislands. The nanosites are so small that only one molecule can bind per island. Undesired adsorption of DNA to the surrounding non-target areas is prevented via a surface-passivating film. Of further relevance, the DNA arrays are of tunable dimensions, and fabricated on optically transparent substrates that enable singe-molecule detection with fluorescence microscopy. The arrays are hence compatible with a wide range of bioanalytical, biophysical, and cell biological studies where individual DNA strands are either examined in isolation, or interact with other molecules or cells.
Investigating carrier localization and transfer in InGaN/GaN quantum wells with V-pits using near-field scanning optical microscopy and correlation analysis
Authors: Kim MinKwan , Choi Sunghan , Lee Joo-Hyung , Park ChungHyun , Chung Tae-Hoon , Baek Jong Hyeob , Cho Yong-Hoon
Published: February 2017

The V-pits and potential fluctuations in InGaN/GaN multiple quantum wells (MQWs) are key factors for understanding the performance of InGaN/GaN-based light-emitting diodes (LEDs). However, photoluminescence (PL) measurements using conventional optical microscopy only provide ensemble information due to the spatial resolution limit, known as the diffraction barrier, which hinders the analysis of dislocations and potential fluctuations. Here, in order to investigate the influence of the V-pits and potential fluctuations on local optical properties, we performed nanoscopic luminescence mapping for standard and V-pit InGaN/GaN MQWs samples with different sized V-pits using near-field scanning optical microscopy (NSOM) with illumination mode (I-mode) at various laser excitation powers. From the nanoscopic PL mapping data, we could clearly observe luminescence features associated with dislocations and potential fluctuations in the InGaN/GaN MQWs. We also employed correlation analysis to quantitatively analyze the nanoscopic PL mapping data for the different MQWs samples. Based on the results of NSOM PL with I-mode and correlation analysis, we could demonstrate that carrier transfer in the MQWs sample with large sized V-pits is suppressed by deeper potential fluctuations and higher energy barriers compared to the standard sample.
Geometric tuning of self-propulsion for Janus catalytic particles
Authors: Michelin Sébastien , Lauga Eric
Published: February 2017

Catalytic swimmers have attracted much attention as alternatives to biological systems for examining collective microscopic dynamics and the response to physico-chemical signals. Yet, understanding and predicting even the most fundamental characteristics of their individual propulsion still raises important challenges. While chemical asymmetry is widely recognized as the cornerstone of catalytic propulsion, different experimental studies have reported that particles with identical chemical properties may propel in opposite directions. Here, we show that, beyond its chemical properties, the detailed shape of a catalytic swimmer plays an essential role in determining its direction of motion, demonstrating the compatibility of the classical theoretical framework with experimental observations.
AlkB homolog 3-mediated tRNA demethylation promotes protein synthesis in cancer cells
Authors: Ueda Yuko , Ooshio Ikumi , Fusamae Yasuyuki , Kitae Kaori , Kawaguchi Megumi , Jingushi Kentaro , Hase Hiroaki , Harada Kazuo , Hirata Kazumasa , Tsujikawa Kazutake
Published: February 2017

The mammalian AlkB homolog (ALKBH) family of proteins possess a 2-oxoglutarate- and Fe(II)-dependent oxygenase domain. A similar domain in the Escherichia coli AlkB protein catalyzes the oxidative demethylation of 1-methyladenine (1-meA) and 3-methylcytosine (3-meC) in both DNA and RNA. AlkB homolog 3 (ALKBH3) was also shown to demethylate 1-meA and 3-meC (induced in single-stranded DNA and RNA by a methylating agent) to reverse the methylation damage and retain the integrity of the DNA/RNA. We previously reported the high expression of ALKBH3 in clinical tumor specimens and its involvement in tumor progression. In this study, we found that ALKBH3 effectively demethylated 1-meA and 3-meC within endogenously methylated RNA. Moreover, using highly purified recombinant ALKBH3, we identified N6-methyladenine (N6-meA) in mammalian transfer RNA (tRNA) as a novel ALKBH3 substrate. An in vitro translation assay showed that ALKBH3-demethylated tRNA significantly enhanced protein translation efficiency. In addition, ALKBH3 knockdown in human cancer cells impaired cellular proliferation and suppressed the nascent protein synthesis that is usually accompanied by accumulation of the methylated RNAs. Thus, our data highlight a novel role for ALKBH3 in tumor progression via RNA demethylation and subsequent protein synthesis promotion.
Crystalline Structure, Defect Chemistry and Room Temperature Colossal Permittivity of Nd-doped Barium Titanate
Authors: Sun Qiaomei , Gu Qilin , Zhu Kongjun , Jin Rongying , Liu Jinsong , Wang Jing , Qiu Jinhao
Published: February 2017

Dielectric materials with high permittivity are strongly demanded for various technological applications. While polarization inherently exists in ferroelectric barium titanate (BaTiO3), its high permittivity can only be achieved by chemical and/or structural modification. Here, we report the room-temperature colossal permittivity (~760,000) obtained in xNd: BaTiO3 (x = 0.5 mol%) ceramics derived from the counterpart nanoparticles followed by conventional pressureless sintering process. Through the systematic analysis of chemical composition, crystalline structure and defect chemistry, the substitution mechanism involving the occupation of Nd3+ in Ba2+ -site associated with the generation of Ba vacancies and oxygen vacancies for charge compensation has been firstly demonstrated. The present study serves as a precedent and fundamental step toward further improvement of the permittivity of BaTiO3-based ceramics.
Predicting antimicrobial peptides with improved accuracy by incorporating the compositional, physico-chemical and structural features into Chou’s general PseAAC
Authors: Meher Prabina Kumar , Sahu Tanmaya Kumar , Saini Varsha , Rao Atmakuri Ramakrishna
Published: February 2017

Antimicrobial peptides (AMPs) are important components of the innate immune system that have been found to be effective against disease causing pathogens. Identification of AMPs through wet-lab experiment is expensive. Therefore, development of efficient computational tool is essential to identify the best candidate AMP prior to the in vitro experimentation. In this study, we made an attempt to develop a support vector machine (SVM) based computational approach for prediction of AMPs with improved accuracy. Initially, compositional, physico-chemical and structural features of the peptides were generated that were subsequently used as input in SVM for prediction of AMPs. The proposed approach achieved higher accuracy than several existing approaches, while compared using benchmark dataset. Based on the proposed approach, an online prediction server iAMPpred has also been developed to help the scientific community in predicting AMPs, which is freely accessible at http://cabgrid.res.in:8080/amppred/. The proposed approach is believed to supplement the tools and techniques that have been developed in the past for prediction of AMPs.
Extracellular protonation modulates cell-cell interaction mechanics and tissue invasion in human melanoma cells
Authors: Hofschröer Verena , Koch Alexander , Ludwig Florian Timo , Friedl Peter , Oberleithner Hans , Stock Christian , Schwab Albrecht
Published: February 2017

Detachment of cells from the primary tumour precedes metastatic progression by facilitating cell release into the tissue. Solid tumours exhibit altered pH homeostasis with extracellular acidification. In human melanoma, the Na+/H+ exchanger NHE1 is an important modifier of the tumour nanoenvironment. Here we tested the modulation of cell-cell-adhesion by extracellular pH and NHE1. MV3 tumour spheroids embedded in a collagen matrix unravelled the efficacy of cell-cell contact loosening and 3D emigration into an environment mimicking physiological confinement. Adhesive interaction strength between individual MV3 cells was quantified using atomic force microscopy and validated by multicellular aggregation assays. Extracellular acidification from pHe7.4 to 6.4 decreases cell migration and invasion but increases single cell detachment from the spheroids. Acidification and NHE1 overexpression both reduce cell-cell adhesion strength, indicated by reduced maximum pulling forces and adhesion energies. Multicellular aggregation and spheroid formation are strongly impaired under acidification or NHE1 overexpression. We show a clear dependence of melanoma cell-cell adhesion on pHe and NHE1 as a modulator. These effects are opposite to cell-matrix interactions that are strengthened by protons extruded via NHE1. We conclude that these opposite effects of NHE1 act synergistically during the metastatic cascade.
Heteroaryldihydropyrimidine (HAP) and Sulfamoylbenzamide (SBA) Inhibit Hepatitis B Virus Replication by Different Molecular Mechanisms
Authors: Zhou Zheng , Hu Taishan , Zhou Xue , Wildum Steffen , Garcia-Alcalde Fernando , Xu Zhiheng , Wu Daitze , Mao Yi , Tian Xiaojun , Zhou Yuan , Shen Fang , Zhang Zhisen , Tang Guozhi , Najera Isabel , Yang Guang , Shen Hong C. , Young John A. T. , Qin Ning
Published: February 2017

Heteroaryldihydropyrimidine (HAP) and sulfamoylbenzamide (SBA) are promising non-nucleos(t)ide HBV replication inhibitors. HAPs are known to promote core protein mis-assembly, but the molecular mechanism of abnormal assembly is still elusive. Likewise, the assembly status of core protein induced by SBA remains unknown. Here we show that SBA, unlike HAP, does not promote core protein mis-assembly. Interestingly, two reference compounds HAP_R01 and SBA_R01 bind to the same pocket at the dimer-dimer interface in the crystal structures of core protein Y132A hexamer. The striking difference lies in a unique hydrophobic subpocket that is occupied by the thiazole group of HAP_R01, but is unperturbed by SBA_R01. Photoaffinity labeling confirms the HAP_R01 binding pose at the dimer-dimer interface on capsid and suggests a new mechanism of HAP-induced mis-assembly. Based on the common features in crystal structures we predict that T33 mutations generate similar susceptibility changes to both compounds. In contrast, mutations at positions in close contact with HAP-specific groups (P25A, P25S, or V124F) only reduce susceptibility to HAP_R01, but not to SBA_R01. Thus, HAP and SBA are likely to have distinctive resistance profiles. Notably, P25S and V124F substitutions exist in low-abundance quasispecies in treatment-naïve patients, suggesting potential clinical relevance.
Adaptability of small brown planthopper to four rice cultivars using life table and population projection method
Authors: Zheng Xiao-Min , Tao Yun-Li , Chi Hsin , Wan Fang-Hao , Chu Dong
Published: February 2017

In this study, we evaluated the adaptability of the small brown planthopper (SBPH), Laodelphax striatellus (Hemiptera: Delphacidae) to four rice cultivars including Shengdao13 (SD13), Shengdao14 (SD14), Shengdao15 (SD15), and Zixiangnuo (ZXN) using the age-stage, two-sex life table with a simplified method for recording egg production (i.e., every five days vs. daily). The intrinsic rate of increase (r) of the SBPH was the highest (0.1067 d−1) on cultivar SD15, which was similar to the rate on SD14 (0.1029 d−1), but was significantly higher than that occurring on ZXN (0.0897 d−1) and SD13 (0.0802 d−1). The differences of the finite rate of increase (λ) on the four rice cultivars were consistent with the r values. Population projection predicted an explosive population growth of the SBPH occurring in a relatively short time when reared on SD14 and SD15. These findings demonstrated that the SBPH can successfully survive on the four rice cultivars, although there were varying host adaptabilities.
Connexin30.3 is expressed in mouse embryonic stem cells and is responsive to leukemia inhibitory factor
Authors: Saito Mikako , Asai Yuma , Imai Keiichi , Hiratoko Shoya , Tanaka Kento
Published: February 2017

The expression of 19 connexin (Cx) isoforms was observed in the mouse embryonic stem (ES) cell line, EB3. Their expression patterns could be classified into either pluripotent state-specific, differentiating stage-specific, or non-specificCxs. We focused onCx30.3as typical of the first category.Cx30.3was pluripotent state-specific and upregulated by leukemia inhibitory factor (LIF), a specific cytokine that maintains the pluripotent state of ES cell, via a Jak signaling pathway. Cx30.3 protein was localized to both the cell membrane and cytosol. The dynamic movement of Cx30.3 in the cell membrane was suggested by the imaging analysis by means of overexpressed Cx30.3-EGFP fusion protein. The cytosolic portion was postulated to be a ready-to-use Cx pool. TheCx30.3expression level in ES cell colonies dramatically decreased immediately after their separation into single cells. It was suggested that mRNA forCx30.3and Cx30.3 protein might be decomposed more rapidly than mRNA for Cx43 and Cx43 protein, respectively. These indicate possible involvement of Cx30.3 in the rapid formation and/or decomposition of gap junctions; implying a functional relay between Cx30.3 and other systems such as adhesion proteins.
A high sensitive fiber-optic strain sensor with tunable temperature sensitivity for temperature-compensation measurement
Authors: Hu Jie , Huang Hui , Bai Min , Zhan TingTing , Yang ZhiBo , Yu Yan , Qu Bo
Published: February 2017

A high sensitive fiber-optic strain sensor, which consists of a cantilever, a tandem rod and a fiber collimator, was proposed. The tandem rod, which transfer the applied strain to the cantilever, was used for tuning the temperature sensitivity from −0.15 to 0.19 dB/°C via changing the length ratio of the rods. Moreover, due to the small beam divergence of the collimator, high strain sensitivity can be realized via incident-angle sensitive detection-mechanism. A strain detection-range of 1.1 × 103 με (with a sensing length of 21.5 mm), a detection limit of 5.7 × 10−3 με, and a maximum operating frequency of 1.18 KHz were demonstrated. This sensor is promising for compensating the thermal-expansion of various target objects.
Network growth models: A behavioural basis for attachment proportional to fitness
Authors: Bell Michael , Perera Supun , Piraveenan Mahendrarajah , Bliemer Michiel , Latty Tanya , Reid Chris
Published: February 2017

Several growth models have been proposed in the literature for scale-free complex networks, with a range of fitness-based attachment models gaining prominence recently. However, the processes by which such fitness-based attachment behaviour can arise are less well understood, making it difficult to compare the relative merits of such models. This paper analyses an evolutionary mechanism that would give rise to a fitness-based attachment process. In particular, it is proven by analytical and numerical methods that in homogeneous networks, the minimisation of maximum exposure to node unfitness leads to attachment probabilities that are proportional to node fitness. This result is then extended to heterogeneous networks, with supply chain networks being used as an example.
Subthalamic Neurons Encode Both Single- and Multi-Limb Movements in Parkinson’s Disease Patients
Authors: Tankus Ariel , Strauss Ido , Gurevich Tanya , Mirelman Anat , Giladi Nir , Fried Itzhak , Hausdorff Jeffrey M.
Published: February 2017

The subthalamic nucleus (STN) is the main target for neurosurgical treatment of motor signs of Parkinson’s disease (PD). Despite the therapeutic effect on both upper and lower extremities, its role in motor control and coordination and its changes in Parkinson’s disease are not fully clear. We intraoperatively recorded single unit activity in ten patients with PD who performed repetitive feet or hand movements while undergoing implantation of a deep brain stimulator. We found both distinct and overlapping representations of upper and lower extremity movement kinematics in subthalamic units and observed evidence for re-routing to a multi-limb representation that participates in limb coordination. The well-known subthalamic somatotopy showed a large overlap of feet and hand representations in the PD patients. This overlap and excessive amounts of kinematics or coordination units may reflect pathophysiology or compensatory mechanisms. Our findings thus explain, at the single neuron level, the important subthalamic role in motor control and coordination and indicate the effect of PD on the neuronal representation of movement.
Metronomic capecitabine versus best supportive care as second-line treatment in hepatocellular carcinoma: a retrospective study
Authors: Casadei Gardini Andrea , Foca Flavia , Scartozzi Mario , Silvestris Nicola , Tamburini Emiliano , Faloppi Luca , Brunetti Oronzo , Rudnas Britt , Pisconti Salvatore , Valgiusti Martina , Marisi Giorgia , Foschi Francesco Giuseppe , Ercolani Giorgio , Tassinari Davide , Cascinu Stefano , Frassineti Giovanni Luca
Published: February 2017

Preliminary studies suggest that capecitabine may be safe and effective in HCC patients. The aim of this study was to retrospectively evaluate the safety and efficacy of metronomic capecitabine as second-line treatment. This multicentric study retrospectively analyzed data of HCC patients unresponsive or intolerant to sorafenib treatment with metronomic capecitabine or best supportive care (BSC).Median progression free survival was 3.1 months in patients treated with capecitabine (95%CI: 2.7–3.5). Median overall survival was 12.0 months (95% CI: 10.7–15.8) in patients receiving capecitabine, while 9.0 months (95% CI: 6.5–13.9) in patients receiving BSC. The result of univariate unweighted Cox regression model shows a 46% reduction in death risk for patients on capecitabine (95%CI: 0.357–0.829; p =0.005) compared to patients receiving BSC alone. After weighting for potential confounders, death risk remained essentially unaltered (45%; 95%CI: 0.354–0.883; p = 0.013). Metronomic capecitabine seems a safe second-line treatment for HCC patients in terms of management of adverse events, showing a potential anti-tumour activity which needs further evaluation in phase III studies.
Link between plasminogen activator inhibitor-1 and cardiovascular risk in chronic hepatitis C after viral clearance
Authors: Chang Ming-Ling , Lin Yu-sheng , Pao Li-Heng , Huang Hsin-Chih , Chiu Cheng-Tang
Published: February 2017

The pathophysiological implications of plasminogen activator inhibitor-1 (PAI-1) in HCV infection remain obscure. This prospective study evaluated 669 HCV patients, of whom 536 had completed a course of anti-HCV therapy and had pre-, peri- and post-therapy measurements of various profiles, including PAI-1 levels. Multivariate analysis demonstrated, before anti-HCV-therapy, platelet count and PAI-1-rs1799889 genotype were associated with PAI-1 levels. Among patients with a sustained virological response (SVR, n = 445), platelet count was associated with PAI-1 level at 24 weeks post-therapy. GEE analysis showed that PAI-1-rs-1799889 and interferon-λ3-rs12979860 genotypes affected PAI-1 levels early and late in therapy, respectively. At 24 weeks post-therapy, higher lipid, brain natriuretic peptide, homocysteine and PAI-1 levels and PAI-1 activity were noted only in SVR patients compared with pre-therapy levels. Within 24 weeks post-therapy, 2.2% of the SVR (mean age: 57.8 yr; 8 smoking males; the 2 females had pre-therapy hypercholesteremia or cardiovascular family history of disease) and 0% of the non-SVR patients experienced a new cardiovascular event. Platelet counts consistently correlated with PAI-1 levels regardless of HCV infection. PAI-1-rs-1799889 and interferon-λ3-rs12979860 genotypes mainly affected PAI-1 levels longitudinally. Within 24 weeks post-anti-HCV therapy, the SVR patients showed increasing PAI-1 levels with accelerating cardiovascular risk, especially the vulnerable cases.