bluuebunny/crossref_metadata_2025 huggingface dataset:
Reactive Oxygen Species‐Regulating Polymersome as an Antiviral Agent against Influenza Virus
Authors: Kim Hyun‐Ouk , Yeom Minjoo , Kim Jihye , Kukreja Aastha , Na Woonsung , Choi Jihye , Kang Aram , Yun Dayeon , Lim Jong‐Woo , Song Daesub , Haam Seungjoo
Published: July 2017

Reactive oxygen species (ROS) produced during mitochondrial oxidative phosphorylation play an important role as signal messengers in the immune system and also regulate signal transduction. ROS production, initiated as a consequence of microbial invasion, if generated at high levels, induces activation of the MEK (mitogen‐activated protein kinase kinase)/ERK (extracellular signal‐regulated kinase) pathway to promote cell survival and proliferation. However, viruses hijack the host cells' pathways, causing biphasic activation of the MEK/ERK cascade. Thus, regulation of ROS leads to concomitant inhibition of virus replication. In the present study, poly(aniline‐co‐pyrrole) polymerized nanoregulators (PASomes) to regulate intracellular ROS levels are synthesized, exploiting their oxidizing‐reducing characteristics. Poly(aniline‐co‐pyrrole) embedded within an amphiphilic methoxy polyethylene glycol‐block‐polyphenylalanine copolymer (mPEG‐b‐pPhe) are used. It is demonstrated that the PASomes are water soluble, biocompatible, and could control ROS levels successfully in vitro, inhibiting viral replication and cell death. Furthermore, the effects of homopolymerized nanoregulators (polypyrrole assembled with mPEG‐b‐pPhe or polyaniline assembled with mPEG‐b‐pPhe) are compared with those of the PASomes. Consequently, it is confirmed that the PASomes can regulate intracellular ROS levels successfully and suppress viral infection, thereby increasing the cell survival rate.
Duration effect of spectrally matched ground motion records on collapse resistance capacity evaluation of RC frame structures
Authors: Han Jianping , Sun Xiaoyun , Zhou Ying
Published: July 2017

As one of the most important characteristics of strong ground motion, duration is intuitively expected to influence the seismic responses of structures. Up to now, the prescriptive provisions on ground motion duration are not clear in current seismic design codes around the world. For collapse resistance capacity evaluation of the structures under severe earthquake, it is more urgent to investigate the influence of ground motion duration and appropriate consideration for evaluation. Because the factors to be considered in the modeling and dynamic analysis are not very comprehensive, previous studies on the effect of ground motion duration on structural response have not got a consistent conclusion. In this study, a spectral matching approach is used to decouple the influence of the frequency content of ground motion on structural seismic response. And the effect of the infill wall, the strength and stiffness degradation of the structural components, and the axial‐shear‐flexure interaction are also considered. First, the 60 ground motion records with different duration and peak ground acceleration were selected from PEER strong ground motion database and matched spectrally. Then, the three‐dimensional numerical model for an infilled RC frame structure was built via OpenSees, and the incremental dynamic analysis was carried out under the matched ground motion records. The geometric mean incremental dynamic analysis curves of the structure for 30 long‐duration ground motion records and 30 short‐duration ground motion records were obtained. And the correlation between maximum residual roof displacement and maximum residual inter‐story drift ratio with the significant duration was further investigated. Finally, the correlation between collapse resistance capacity in terms of the spectral acceleration at the fundamental period of the structure Sa(T1) and significant duration of all ground motion records was discussed, and collapse probability under different Sa(T1) were obtained. The analytical results show that with the same intensity measure, ground motion records with longer duration may induce larger inter‐story drift ratio, larger residual displacement, and higher collapse probability for the structure. It is also shown that the collapse resistance capacity of the structure tends to decrease with the increase of the significant duration of ground motion.
Does Black Socioeconomic Mobility Explain Recent Progress Toward Black-White Residential Integration?
Authors: Wagmiller Robert L. , Gage-Bouchard Elizabeth , Karraker Amelia
Published: July 2017

Studies of racial residential segregation have found that black-white segregation in U.S. metropolitan areas has declined slowly but steadily since the early 1970s. As of this writing, black-white residential segregation in the United States is approximately 25 % lower than it was in 1970. To identify the sources of this decline, we used individual-level, geocoded data from the Panel Study of Income Dynamics (PSID) to compare the residential attainment of different cohorts of blacks. We analyzed these data using Blinder-Oaxaca regression decomposition techniques that partition the decline in residential segregation among cohorts into the decline resulting from (1) changes in the social and economic characteristics of blacks and (2) changes in the association between blacks’ social and economic characteristics and the level of residential segregation they experience. Our findings show that black cohorts entering adulthood prior to the civil rights movement of the 1960s experienced consistently high levels of residential segregation at middle age, but that cohorts transitioning to adulthood during and after this period of racial progress experienced significantly lower levels of residential segregation. We find that the decline in black-white residential segregation for these later cohorts reflects both their greater social and economic attainment and a strengthening of the association between socioeconomic characteristics and residential segregation. Educational gains for the post–civil rights era cohorts and improved access to integrated neighborhoods for high school graduates and college attendees in these later cohorts were the principal source of improved residential integration over this period.
Efficient aerodynamic derivative calculation in three-dimensional transonic flow
Authors: Thormann R. , Timme S.
Published: July 2017

One key task in computational aeroelasticity is to calculate frequency response functions of aerodynamic coefficients due to structural excitation or external disturbance. Computational fluid dynamics methods are applied for this task at edge-of-envelope flow conditions. Assuming a dynamically linear response around a non-linear steady state, two computationally efficient approaches in time and frequency domain are discussed. A non-periodic, time-domain function can be used, on the one hand, to excite a broad frequency range simultaneously giving the frequency response function in a single non-linear, time-marching simulation. The frequency-domain approach, on the other hand, solves a large but sparse linear system of equations, resulting from the linearisation about the non-linear steady state for each frequency of interest successively. Results are presented for a NACA 0010 aerofoil and a generic civil aircraft configuration in very challenging transonic flow conditions with strong shock-wave/boundary-layer interaction in the pre-buffet regime. Computational cost savings of up to 1 order of magnitude are observed in the time domain for the all-frequencies-at-once approach compared with single-frequency simulations, while an additional order of magnitude is obtained for the frequency-domain method. The paper demonstrates the readiness of computational aeroelasticity tools at edge-of-envelope flow conditions.
Helminth community structure of 13 species of anurans from Atlantic rainforest remnants, Brazil
Authors: Toledo G.M. , Schwartz H.O. , Nomura H.A.Q. , Aguiar A. , Velota R.A.M.V. , da Silva R.J. , Anjos L.A.
Published: July 2017

This study aimed to evaluate the community composition and structure of the helminths found in 13 anuran species, and to evaluate whether this parasite community is determined by anuran characteristics. We found that the helminth fauna of the amphibians from five anuran families consisted of 13 taxa and that Cosmocercidae gen. sp. was the most prevalent taxon, followed byOswaldocruzia subauricularis. Host body size was a determining factor of the composition and structure of the parasitic fauna. Helminth abundance and richness were positively correlated with host body size. The hostLeptodactylus latranshad the highest helminth richness (n= 8). The frogHypsiboas faberhad the greatest helminth diversity (H′ = 0.711). The mean helminth species richness and diversity differed significantly between host species (P< 0.05). Taken together, our data indicate that, in sympatric species of amphibians, the morphological and behavioural characteristics of the hosts are important for structuring the helminth parasite communities.
Feeding habits and trophic level of the shovelnose guitarfish (Pseudobatos productus) in the upper Gulf of California
Authors: Valenzuela-Quiñonez Fausto , Galván-Magaña Felipe , Ebert David A. , Aragón-Noriega E. Alberto
Published: July 2017

The shovelnose guitarfish (Pseudobatos productus) is the most abundant and economically important batoid in Gulf of California fisheries. Despite the importance of the guitarfish in the demersal ecosystem, its trophic relationships are poorly understood. Results from stomach content and stable isotope analysis indicateP. productusis a specialist predator that feeds on coastal benthic organisms, mainly crustaceans, followed by fishes and cephalopods in the Upper Gulf of California. Males and females did not differ in dietary composition and isotopic values.Pseudobatos productusdisplayed ontogenetic changes in the diet, with smaller, immature individuals having a more specialized diet and mature individuals becoming generalist predators. Size classes I (<570 mm) and II (>570 mm) fed almost exclusively on crustaceans (99.78% and 82.37 %IRI, respectively). Size class III (>832 mm) increased consumption of fishes (22.11 %IRI) and squid (6.54 %IRI). Ontogenetic diet shifts were strongly supported by the SIAR mixing model. Stomach content and stable isotope analyses classifyP. productusas a second-order predator.
Introduction to Snapshot: Brazil
Authors: TATINGE NASCIMENTO CLÁUDIA
Published: July 2017

This short dossier on contemporary Brazilian theatre offers the reader a snapshot of how artists have responded to the ongoing political crisis. The massive protests that erupted across the nation in June 2013 paved the way for the impeachment of President Dilma Rousseff in 2016, and left the economy in a shambles. Though flawed, the leftist political projects of former president Luiz Inácio Lula da Silva (2003–10) and of Rousseff, his successor in the presidency (2011–16), privileged social inclusion. A great part of the Brazilian middle and upper classes resented the resulting socio-economic ascension of historically underserved populations. Much like the reactions sparked by the spike in popularity of conservative leaders in Europe and the United States, the Brazilian opposition's political manoeuvre to oust Rousseff in 2016 has divided the nation. A solid majority of the artistic class has sided with compatriots who call the impeachment a coup, albeit not a military one.
Roberto Alvim Rereads the Slave-Owning, Oligarchic Heritage of Brazil in Leite Derramado
Authors: ROMAGNOLLI LUCIANA
Published: July 2017

Using Chico Buarque's novel Leite Derramado (Spilt Milk), the director Roberto Alvim perfects his formal system as grand theatre. Nothing is gained by trying to define the place that the protagonist Lalinho occupies in his family, or the years covered in his story over the course of 195 pages in Chico Buarque's novel. In the stage version written and directed by Alvim, generations and eras are embodied by the voice of the actor Juliana Galdino, transfigured in the centenarian Eulálio D'Assumpção. Grandparents, parents and children, who are indistinguishable from the delirium of his hospital bed, populate the schizophrenic dialogue.
SETIin vivo: testing the we-are-them hypothesis
Authors: Makukov Maxim A. , shCherbak Vladimir I.
Published: July 2017

After it was proposed that life on Earth might descend from seeding by an earlier extraterrestrial civilization motivated to secure and spread life, some authors noted that this alternative offers a testable implication: microbial seeds could be intentionally supplied with a durable signature that might be found in extant organisms. In particular, it was suggested that the optimal location for such an artefact is the genetic code, as the least evolving part of cells. However, as the mainstream view goes, this scenario is too speculative and cannot be meaningfully tested because encoding/decoding a signature within the genetic code is something ill-defined, so any retrieval attempt is doomed to guesswork. Here we refresh the seeded-Earth hypothesis in light of recent observations, and discuss the motivation for inserting a signature. We then show that ‘biological SETI’ involves even weaker assumptions than traditional SETI and admits a well-defined methodological framework. After assessing the possibility in terms of molecular and evolutionary biology, we formalize the approach and, adopting the standard guideline of SETI that encoding/decoding should follow from first principles and be convention-free, develop a universal retrieval strategy. Applied to the canonical genetic code, it reveals a non-trivial precision structure of interlocked logical and numerical attributes of systematic character (previously we found these heuristically). To assess this result in view of the initial assumption, we perform statistical, comparison, interdependence and semiotic analyses. Statistical analysis reveals no causal connection of the result to evolutionary models of the genetic code, interdependence analysis precludes overinterpretation, and comparison analysis shows that known variations of the code lack any precision-logic structures, in agreement with these variations being post-LUCA (i.e. post-seeding) evolutionary deviations from the canonical code. Finally, semiotic analysis shows that not only the found attributes are consistent with the initial assumption, but that they make perfect sense from SETI perspective, as they ultimately maintain some of the most universal codes of culture.
Evaluating feasibility and acceptability of a group WHO trans-diagnostic intervention for women with common mental disorders in rural Pakistan: a cluster randomised controlled feasibility trial
Authors: Khan M. N. , Hamdani S. U. , Chiumento A. , Dawson K. , Bryant R. A. , Sijbrandij M. , Nazir H. , Akhtar P. , Masood A. , Wang D. , Wang E. , Uddin I. , van Ommeren M. , Rahman A.
Published: July 2017

Aims:

The aim of this feasibility trial was to evaluate the feasibility and acceptability of the locally adapted Group Problem Management Plus (PM+) intervention for women in the conflict affected settings in Swat, Pakistan.

Methods:

This mixed-methods study incorporated a quantitative component consisting of a two arm cluster randomised controlled feasibility trial, and qualitative evaluation of the acceptability of the Group PM+ to a range of stakeholder groups. For the quantitative component, on average from each of the 20 Lady Health Workers (LHWs) catchment area (20 clusters), six women were screened and recruited for the trial with score of >2 on the General Health Questionnaire and score of >16 on the WHO Disability Assessment Schedule. These LHW clusters were randomised on a 1 : 1 allocation ratio using a computer-based software through a simple randomisation method to the Group PM+ intervention or Enhanced Usual Care. The Group PM+ intervention consisted of five weekly sessions of 2 h duration delivered by local non-specialist females under supervision. The primary outcome was individual psychological distress, measured by levels of anxiety and depression on the Hospital Anxiety and Depression Scale at 7thweek after baseline. Secondary outcomes include symptoms of depression, post-traumatic stress disorder (PTSD), general psychological profile, levels of functioning and generalised psychological distress. Intervention acceptability was explored through in-depth interviews.

Results:

The results show that lay-helpers with no prior mental health experience can be trained to achieve the desired competency to successfully deliver the intervention in community settings under supervision. There was a good intervention uptake, with Group PM+ considered useful by participants, their families and lay-helpers. The outcome evaluation, which was not based on a large enough study to identify statistically significant results, indicated statistically significant improvements in depression, anxiety, general psychological profile and functioning. The PTSD symptoms and depressive disorder scores showed a trend in favour of the intervention.

Conclusion:

This trial showed robust acceptance in the local settings with delivery by non-specialists under supervision by local trained females. The trial paves the way for further adaptation and exploration of the outcomes through larger-scale implementation and definitive randomised controlled trials in the local settings.
The More Negative the More Impact
Authors: Engel Julia , Bless Herbert
Published: July 2017

Abstract. The present research investigates the relation between different domain satisfactions (e.g., health, income, etc.) and overall life satisfaction. Based on theorizing on the differences between positive and negative information, we assumed that specific domain satisfactions particularly are correlated with overall life satisfaction when the specific domain satisfactions (a) are low rather than high and (b) have declined rather than increased. Relying on a nationally representative sample of the German population (Socio-Economic Panel), we tested these considerations with both a cross-sectional and a longitudinal design. The findings strongly support that the more negative the domain satisfaction the more pronounced was the relation between domain and overall life satisfaction – both when negativity was assessed relative to other domains as well as when negativity was assessed relative to prior satisfaction with the same domain.
Crosstalk and the evolvability of intracellular communication
Authors: Rowland Michael A. , Greenbaum Joseph M. , Deeds Eric J.
Published: July 2017

Metazoan signalling networks are complex, with extensive crosstalk between pathways. It is unclear what pressures drove the evolution of this architecture. We explore the hypothesis that crosstalk allows different cell types, each expressing a specific subset of signalling proteins, to activate different outputs when faced with the same inputs, responding differently to the same environment. We find that the pressure to generate diversity leads to the evolution of networks with extensive crosstalk. Using available data, we find that human tissues exhibit higher levels of diversity between cell types than networks with random expression patterns or networks with no crosstalk. We also find that crosstalk and differential expression can influence drug activity: no protein has the same impact on two tissues when inhibited. In addition to providing a possible explanation for the evolution of crosstalk, our work indicates that consideration of cellular context will likely be crucial for targeting signalling networks.
Unique adjustable UC luminescence pattern and directional radiation of peculiar-shaped NaYF4: Yb3+/Er3+ microcrystal particle
Authors: Han Qingyan , Zhang Chengyun , Wang Chi , Wang Zhaojin , Li Caixia , Gao Wei , Dong Jun , He Enjie , Zhang Zhenglong , Zheng Hairong
Published: July 2017

A new design of peculiar-shaped β-NaYF4: 20% Yb3+/2% Er3+ hexagonal microcrystal (PSβHM) is proposed and its upconversion (UC) luminescence with adjustable color pattern is studied with near infrared excitation. Flower-like green UC luminescence emission pattern from blooming to withering process and intensive directional red emission are achieved by simply adjusting the focal point position of the excitation light. The mechanism that determines the unique UC luminescence phenomena are investigated systematically. The function of the internal light reflection and waveguide effect with annular microcavity is explored based on the structure characteristic of the hexagonal microplate. The current work may have great significant and potential applications in the development of optoelectronic device, color display, directional light and laser emission of microsystem.
Seed coat thinning during horsegram (Macrotyloma uniflorum) domestication documented through synchrotron tomography of archaeological seeds
Authors: Murphy Charlene , Fuller Dorian Q.
Published: July 2017

Reduction of seed dormancy mechanisms, allowing for rapid germination after planting, is a recurrent trait in domesticated plants, and can often be linked to changes in seed coat structure, in particular thinning. We report evidence for seed coat thinning between 2,000 BC and 1,200 BC, in southern Indian archaeological horsegram (Macrotyloma uniflorum), which it has been possible to document with high precision and non-destructively, through high resolution x-ray computed tomography using a synchrotron. We find that this trait underwent stepped change, from thick to semi-thin to thin seed coats, and that the rate of change was gradual. This is the first time that the rate of evolution of seed coat thinning in a legume crop has been directly documented from archaeological remains, and it contradicts previous predictions that legume domestication occurred through selection of pre-adapted low dormancy phenotypes from the wild.
CalQuo 2 : Automated Fourier-space, population-level quantification of global intracellular calcium responses
Authors: Lee Angela M. , Colin-York Huw , Fritzsche Marco
Published: July 2017

Intracellular calcium acts as a secondary messenger in a wide variety of crucial biological signaling processes. Advances in fluorescence microscopy and calcium sensitive dyes has led to the routine quantification of calcium responses in non-excitable cells. However, the automatization of global intracellular calcium analysis at the single-cell level within a large population simultaneously remains challenging. One software,CalQuo(Calcium Quantification), offers some automatic features in calcium analysis. Here, we present an advanced version of the software package:CalQuo2.CalQuo2analyzes the calcium response in the Fourier-domain, allowing the number of user-defined filtering parameters to be reduced to one and a greater diversity of calcium responses to be recognized, compared toCalQuothat directly interprets the calcium intensity signal.CalQuo2differentiates cells that release a single calcium response and those that release oscillatory calcium fluxes. We have demonstrated the use ofCalQuo2by measuring the calcium response in genetically modified Jurkat T-cells under varying ligand conditions, in which we show that peptide:MHCs and anti-CD3 antibodies trigger a fraction of T cells to release oscillatory calcium fluxes that increase with increasing koffrates. These results show thatCalQuo2is a robust and user-friendly tool for characterizing global, single cell calcium responses.
Bromodomain factors of BET family are new essential actors of pericentric heterochromatin transcriptional activation in response to heat shock
Authors: Col Edwige , Hoghoughi Neda , Dufour Solenne , Penin Jessica , Koskas Sivan , Faure Virginie , Ouzounova Maria , Hernandez-Vargash Hector , Reynoird Nicolas , Daujat Sylvain , Folco Eric , Vigneron Marc , Schneider Robert , Verdel André , Khochbin Saadi , Herceg Zdenko , Caron Cécile , Vourc’h Claire
Published: July 2017

The heat shock response is characterized by the transcriptional activation of both hsp genes and noncoding and repeated satellite III DNA sequences located at pericentric heterochromatin. Both events are under the control of Heat Shock Factor I (HSF1). Here we show that under heat shock, HSF1 recruits major cellular acetyltransferases, GCN5, TIP60 and p300 to pericentric heterochromatin leading to a targeted hyperacetylation of pericentric chromatin. Redistribution of histone acetylation toward pericentric region in turn directs the recruitment of Bromodomain and Extra-Terminal (BET) proteins BRD2, BRD3, BRD4, which are required for satellite III transcription by RNAP II. Altogether we uncover here a critical role for HSF1 in stressed cells relying on the restricted use of histone acetylation signaling over pericentric heterochromatin (HC).
Combination therapy for tuberculosis treatment: pulmonary administration of ethionamide and booster co-loaded nanoparticles
Authors: Costa-Gouveia Joana , Pancani Elisabetta , Jouny Samuel , Machelart Arnaud , Delorme Vincent , Salzano Giuseppina , Iantomasi Raffaella , Piveteau Catherine , Queval Christophe J. , Song Ok-Ryul , Flipo Marion , Deprez Benoit , Saint-André Jean-Paul , Hureaux José , Majlessi Laleh , Willand Nicolas , Baulard Alain , Brodin Priscille , Gref Ruxandra
Published: July 2017

Tuberculosis (TB) is a leading infectious cause of death worldwide. The use of ethionamide (ETH), a main second line anti-TB drug, is hampered by its severe side effects. Recently discovered “booster” molecules strongly increase the ETH efficacy, opening new perspectives to improve the current clinical outcome of drug-resistant TB. To investigate the simultaneous delivery of ETH and its booster BDM41906 in the lungs, we co-encapsulated these compounds in biodegradable polymeric nanoparticles (NPs), overcoming the bottlenecks inherent to the strong tendency of ETH to crystallize and the limited water solubility of this Booster. The efficacy of the designed formulations was evaluated in TB infected macrophages using an automated confocal high-content screening platform, showing that the drugs maintained their activity after incorporation in NPs. Among tested formulations, “green” β-cyclodextrin (pCD) based NPs displayed the best physico-chemical characteristics and were selected for in vivo studies. The NPs suspension, administered directly into mouse lungs using a Microsprayer®, was proved to be well-tolerated and led to a 3-log decrease of the pulmonary mycobacterial load after 6 administrations as compared to untreated mice. This study paves the way for a future use of pCD NPs for the pulmonary delivery of the [ETH:Booster] pair in TB chemotherapy.
Doping-induced carrier profiles in organic semiconductors determined from capacitive extraction-current transients
Authors: Nyman Mathias , Sandberg Oskar J. , Dahlström Staffan , Spoltore Donato , Körner Christian , Zhang Yadong , Barlow Stephen , Marder Seth R. , Leo Karl , Vandewal Koen , Österbacka Ronald
Published: July 2017

A method to determine the doping induced charge carrier profiles in lightly and moderately doped organic semiconductor thin films is presented. The theory of the method of Charge Extraction by a Linearly Increasing Voltage technique in the doping-induced capacitive regime (doping-CELIV) is extended to the case with non-uniform doping profiles and the analytical description is verified with drift-diffusion simulations. The method is demonstrated experimentally on evaporated organic small-molecule thin films with a controlled doping profile, and solution-processed thin films where the non-uniform doping profile is unintentional, probably induced during the deposition process, and a priori unknown. Furthermore, the method offers a possibility of directly probing charge-density distributions at interfaces between highly doped and lightly doped or undoped layers.
Non-ketogenic combination of nutritional strategies provides robust protection against seizures
Authors: Dallérac Glenn , Moulard Julien , Benoist Jean-François , Rouach Stefan , Auvin Stéphane , Guilbot Angèle , Lenoir Loïc , Rouach Nathalie
Published: July 2017

Epilepsy is a neurological condition that affects 1% of the world population. Conventional treatments of epilepsy use drugs targeting neuronal excitability, inhibitory or excitatory transmission. Yet, one third of patients presents an intractable form of epilepsy and fails to respond to pharmacological anti-epileptic strategies. The ketogenic diet is a well-established non-pharmacological treatment that has been proven to be effective in reducing seizure frequency in the pharmaco-resistant patients. This dietary solution is however extremely restrictive and can be associated with complications caused by the high [fat]:[carbohydrate + protein] ratio. Recent advances suggest that the traditional 4:1 ratio of the ketogenic diet is not a requisite for its therapeutic effect. We show here that combining nutritional strategies targeting specific amino-acids, carbohydrates and fatty acids with a low [fat]:[proteins + carbohydrates] ratio also reduces excitatory drive and protects against seizures to the same extent as the ketogenic diet. Similarly, the morphological and molecular correlates of temporal lobe seizures were reduced in animals fed with the combined diet. These results provide evidence that low-fat dietary strategies more palatable than the ketogenic diet could be useful in epilepsy.
miRNAs in the alga Chlamydomonas reinhardtii are not phylogenetically conserved and play a limited role in responses to nutrient deprivation
Authors: Voshall Adam , Kim Eun-Jeong , Ma Xinrong , Yamasaki Tomohito , Moriyama Etsuko N. , Cerutti Heriberto
Published: July 2017

The unicellular alga Chlamydomonas reinhardtii contains many types of small RNAs (sRNAs) but the biological role(s) of bona fide microRNAs (miRNAs) remains unclear. To address their possible function(s) in responses to nutrient availability, we examined miRNA expression in cells cultured under different trophic conditions (mixotrophic in the presence of acetate or photoautotrophic in the presence or absence of nitrogen). We also reanalyzed miRNA expression data in Chlamydomonas subject to sulfur or phosphate deprivation. Several miRNAs were differentially expressed under the various trophic conditions. However, in transcriptome analyses, the majority of their predicted targets did not show expected changes in transcript abundance, suggesting that they are not subject to miRNA-mediated RNA degradation. Mutant strains, defective in sRNAs or in ARGONAUTE3 (a key component of sRNA-mediated gene silencing), did not display major phenotypic defects when grown under multiple nutritional regimes. Additionally, Chlamydomonas miRNAs were not conserved, even in algae of the closely related Volvocaceae family, and many showed features resembling those of recently evolved, species-specific miRNAs in the genus Arabidopsis. Our results suggest that, in C. reinhardtii, miRNAs might be subject to relatively fast evolution and have only a minor, largely modulatory role in gene regulation under diverse trophic states.
Takotsubo Syndrome – Predictable from brain imaging data
Authors: Klein Carina , Hiestand Thierry , Ghadri Jelena-Rima , Templin Christian , Jäncke Lutz , Hänggi Jürgen
Published: July 2017

Takotsubo syndrome (TTS) is characterized by acute left ventricular dysfunction, with a hospital-mortality rate similar to acute coronary syndrome (ACS). However, the aetiology of TTS is still unknown. In the present study, a multivariate pattern analysis using machine learning with multimodal magnetic resonance imaging (MRI) data of the human brain of TTS patients and age- and gender-matched healthy control subjects was performed. We found consistent structural and functional alterations in TTS patients compared to the control group. In particular, anatomical and neurophysiological measures from brain regions constituting the emotional-autonomic control system contributed to a prediction accuracy of more than 82%. Thus, our findings demonstrate homogeneous neuronal alterations in TTS patients and substantiate the importance of the concept of a brain-heart interaction in TTS.
Dietary geranylgeraniol can limit the activity of pitavastatin as a potential treatment for drug-resistant ovarian cancer
Authors: de Wolf Elizabeth , Abdullah Marwan Ibrahim , Jones Stefanie M. , Menezes Karen , Moss Darren M. , Drijfhout Falko P. , Hart Sarah R. , Hoskins Clare , Stronach Euan A. , Richardson Alan
Published: July 2017

Pre-clinical and retrospective studies of patients using statins to reduce plasma cholesterol have suggested that statins may be useful to treat cancer. However, prospective clinical trials have yet to demonstrate significant efficacy. We have previously shown that this is in part because a hydrophobic statin with a long half-life is necessary. Pitavastatin, the only statin with this profile, has not undergone clinical evaluation in oncology. The target of pitavastatin, hydroxymethylglutarate coenzyme-A reductase (HMGCR), was found to be over-expressed in all ovarian cancer cell lines examined and upregulated by mutated TP53, a gene commonly altered in ovarian cancer. Pitavastatin-induced apoptosis was blocked by geranylgeraniol and mevalonate, products of the HMGCR pathway, confirming that pitavastatin causes cell death through inhibition of HMGCR. Solvent extracts of human and mouse food were also able to block pitavastatin-induced apoptosis, suggesting diet might influence the outcome of clinical trials. When nude mice were maintained on a diet lacking geranylgeraniol, oral pitavastatin caused regression of Ovcar-4 tumour xenografts. However, when the animal diet was supplemented with geranylgeraniol, pitavastatin failed to prevent tumour growth. This suggests that a diet containing geranylgeraniol can limit the anti-tumour activity of pitavastatin and diet should be controlled in clinical trials of statins.
Electric field control of magnetization direction across the antiferromagnetic to ferromagnetic transition
Authors: Zheng Guohui , Ke San-Huang , Miao Maosheng , Kim Jinwoong , Ramesh R. , Kioussis Nicholas
Published: July 2017

Electric-field-induced magnetic switching can lead to a new paradigm of ultra-low power nonvolatile magnetoelectric random access memory (MeRAM). To date the realization of MeRAM relies primarily on ferromagnetic (FM) based heterostructures which exhibit low voltage-controlled magnetic anisotropy (VCMA) efficiency. On the other hand, manipulation of magnetism in antiferromagnetic (AFM) based nanojunctions by purely electric field means (rather than E-field induced strain) remains unexplored thus far. Ab initio electronic structure calculations reveal that the VCMA of ultrathin FeRh/MgO bilayers exhibits distinct linear or nonlinear behavior across the AFM to FM metamagnetic transition depending on the Fe- or Rh-interface termination. We predict that the AFM Fe-terminated phase undergoes an E-field magnetization switching with large VCMA efficiency and a spin reorientation across the metamagnetic transition. In sharp contrast, while the Rh-terminated interface exhibits large out-of-plane (in-plane) MA in the FM (AFM) phase, its magnetization is more rigid to external E-field. These findings demonstrate that manipulation of the AFM Néel-order magnetization direction via purely E-field means can pave the way toward ultra-low energy AFM-based MeRAM devices.
Gene Network Dysregulation in Dorsolateral Prefrontal Cortex Neurons of Humans with Cocaine Use Disorder
Authors: Ribeiro Efrain A. , Scarpa Joseph R. , Garamszegi Susanna P. , Kasarskis Andrew , Mash Deborah C. , Nestler Eric J.
Published: July 2017

Metabolic and functional alterations of neurons in the dorsolateral prefrontal cortex (dlPFC) are thought to contribute to impulsivity, which is a hallmark of addictive behaviors that underlie compulsive drug seeking and taking in humans. To determine if there is a transcriptional signature in dlPFC neurons of humans with cocaine use disorder, we performed total RNA-sequencing on neuronal nuclei isolated from post-mortem dlPFC of cocaine addicts and healthy controls. Our results point toward a transcriptional mechanism whereby cocaine alters specific gene networks in dlPFC neurons. In particular, we identified an AP-1 regulated transcriptional network in dlPFC neurons associated with cocaine use disorder that contains several differentially expressed hub genes. Several of these hub genes are GWAS hits for traits that might involve dysfunction of brain reward circuitry (Body-Mass Index, Obesity) or dlPFC (Bipolar disorder, Schizophrenia). Further study is warranted to determine their potential pathophysiological role in cocaine addiction.
Influence of biochar and nitrogen on fine root morphology, physiology, and chemistry of Acer mono
Authors: Razaq Muhammad , Salahuddin  , Shen Hai-long , Sher Hassan , Zhang Peng
Published: July 2017

Fine roots play an important role in the overall functions of individual plants. Previous studies showed that fertilization and available soil resources have a notably profound effect on fine root, but there is lack of study centered on how fine root morphology, physiology, and chemistry respond to biochar with N additions. Different levels of biochar (0, 10, 15, and 20 g) and N (0, 2, 4 and 6 g) were applied to Acer mono seedling plants in a field nursery. The root system morphology and root chemistry and physiology were evaluated in line with root length, root diameter, SRL, N and N: C and root respiration. Biochar and N significantly affected root morphology, chemistry and root respiration. Morphological, chemical and physiological parameters were found to be at their maximum with 20 g biochar and 6 g N; however, no significant effect was noted on fourth- and fifth-order roots. Furthermore, a significant increase in root respiration was recognized with the increase in root tissue N concentration and the negative relationship of root respiration with higher branch order. Thus, overall, study parameters indicate that biochar and nitrogen positively influence the Acer mono fine root, and therefore should be used to improve fine root health.
Comprehensive transcriptomics and proteomics analyses of pollinated and parthenocarpic litchi (Litchi chinensis Sonn.) fruits during early development
Authors: Liu Wei , Chen Maoshan , Bai Lijun , Zhuang Zhenhua , Fan Chao , Jiang Nonghui , Zhao Junsheng , Ma Shuaipeng , Xiang Xu
Published: July 2017

Litchi (Litchi chinensis Sonn.) is an important fruit that is widely cultivated in tropical and subtropical areas. In this study, we used RNA-Seq and iTRAQ technologies to compare the transcriptomes and proteomes of pollinated (polLFs) and parthenocarpic (parLFs) litchi fruits during early development (1 day, 2 days, 4 days and 6 days). We identified 4,864 DEGs in polLFs and 3,672 in parLFs, of which 2,835 were shared and 1,051 were specifically identified in parLFs. Compared to po1LFs, 768 DEGs were identified in parLFs. iTRAQ analysis identified 551 DEPs in polLFs and 1,021 in parLFs, of which 305 were shared and 526 were exclusively identified in parLFs. We found 1,127 DEPs in parLFs compared to polLFs at different stages. Further analysis revealed some DEGs/DEPs associated with abscisic acid, auxin, ethylene, gibberellin, heat shock protein (HSP), histone, ribosomal protein, transcription factor and zinc finger protein (ZFP). WGCNA identified a large set of co-expressed genes/proteins in polLFs and parLFs. In addition, a cross-comparison of transcriptomic and proteomic data identified 357 consistent DEGs/DEPs in polLFs and parLFs. This is the first time that protein/gene changes have been studied in polLFs and parLFs, and the findings improve our understanding of litchi parthenocarpy.
Self-diffusivity, M–S and Fick diffusivity of CO2 in Na-clay: The influences of concentration and temperature
Authors: Hu Haixiang , Xing Yanfei , Li Xiaochun
Published: July 2017

Storing CO2 in underground saline aquifers is an important way to reduce CO2 emission in atmosphere, where gas/fluid diffusion in clay plays a key role in CO2 leakage and migration. Various diffusivities, self-diffusivity, Maxwell–Stefan (M–S) diffusivity and Fick diffusivity, in clay interlayer are investigated by molecular dynamics (MD). Self-diffusivity varies with CO2 concentration, and reaches the maximum value at 2 molecules/unit-cell. High fluid concentration leads to clay swelling, thereby increasing self-diffusivity. However, the fractional free volume of clay explains the trend of CO2 self-diffusivity, which does not decrease with CO2 concentration monotonously but reaches the maximum when CO2 concentration reaches 2. Displacement distribution of CO2 molecules is analysed to explore the microscopic diffusion mechanism, which is characterised by logarithmic normal distribution. The mean value of such distribution further explains the self-diffusivity dependence on CO2 concentration. M–S and Fick diffusivities of CO2 are calculated by MD for the first time, both of which increase with increasing CO2 and H2O concentration and temperature. Based on self-diffusivity and M–S diffusivity, a quantity representing the coupling strength between CO2 molecules is presented; it increases firstly with CO2 concentration but begins to decrease when CO2 concentration is beyond 2.
Electron-transfer chain in respiratory complex I
Authors: Martin Daniel R. , Matyushov Dmitry V.
Published: July 2017

Complex I is a part of the respiration energy chain converting the redox energy into the cross-membrane proton gradient. The electron-transfer chain of iron-sulfur cofactors within the water-soluble peripheral part of the complex is responsible for the delivery of electrons to the proton pumping subunit. The protein is porous to water penetration and the hydration level of the cofactors changes when the electron is transferred along the chain. High reaction barriers and trapping of the electrons at the iron-sulfur cofactors are prevented by the combination of intense electrostatic noise produced by the protein-water interface with the high density of quantum states in the iron-sulfur clusters caused by spin interactions between paramagnetic iron atoms. The combination of these factors substantially lowers the activation barrier for electron transfer compared to the prediction of the Marcus theory, bringing the rate to the experimentally established range. The unique role of iron-sulfur clusters as electron-transfer cofactors is in merging protein-water fluctuations with quantum-state multiplicity to allow low activation barriers and robust operation. Water plays a vital role in electron transport energetics by electrowetting the cofactors in the chain upon arrival of the electron. A general property of a protein is to violate the fluctuation-dissipation relation through nonergodic sampling of its landscape. High functional efficiency of redox enzymes is a direct consequence of nonergodicity.
Endothelial cells by inactivation of VHL gene direct angiogenesis, not vasculogenesis via Twist1 accumulation associated with hemangioblastoma neovascularization
Authors: Wang Ying , Chen Dan-Qi , Chen Ming-Yu , Ji Kai-Yuan , Ma De-Xuan , Zhou Liang-Fu
Published: July 2017

Inactivation of the VHL tumour suppressor gene is a highly frequent genetic event in the carcinogenesis of central nervous system-(CNS) hemangioblastomas (HBs). The patterning of the similar embryonic vasculogenesis is an increasing concern in HB-neovascularization, and the classic vascular endothelial growth factor (VEGF)-mediated angiogenesis driven by VHL loss-of-function from human endothelium have been questioned. With this regard, we identify a distinct, VHL silencing-driven mechanism in which human vascular endothelial cells by means of increasing cell proliferation and decreasing cell apoptosis, is concomitant with facilitating accumulation of Twist1 protein in vascular endothelial cells in vitro. Importantly, this molecular mechanism is also pinpointed in CNS-HBs, and associated with the process of HB-neovascularization. In contrast with recent studies of HB-neovascularization, these modified cells did not endow with the typical features of vasculogenesis, indicating that this is a common angiogenesis implementing the formation of the vascular network. Taken together, these findings suggest that vasculogenesis and angiogenesis may constitute complementary mechanisms for HB-neovascularization, and could provide a rational recognition of single anti-angiogenic intervention including targeting to the Twist1 signalling for HBs.
Methyl-CpG binding domain proteins inhibit interspecies courtship and promote aggression in Drosophila
Authors: Gupta Tarun , Morgan Hannah R. , Andrews Jonathan C. , Brewer Edmond R. , Certel Sarah J.
Published: July 2017

Reproductive isolation and speciation are driven by the convergence of environmental and genetic variation. The integration of these variation sources is thought to occur through epigenetic marks including DNA methylation. Proteins containing a methyl-CpG-binding domain (MBD) bind methylated DNA and interpret epigenetic marks, providing a dynamic yet evolutionarily adapted cellular output. Here, we report the Drosophila MBD-containing proteins, dMBD-R2 and dMBD2/3, contribute to reproductive isolation and survival behavioral strategies. Drosophila melanogaster males with a reduction in dMBD-R2 specifically in octopamine (OA) neurons exhibit courtship toward divergent interspecies D. virilis and D. yakuba females and a decrease in conspecific mating success. Conspecific male-male courtship is increased between dMBD-R2-deficient males while aggression is reduced. These changes in adaptive behavior are separable as males with a hypermethylated OA neuronal genome exhibited a decrease in aggression without altering male-male courtship. These results suggest Drosophila MBD-containing proteins are required within the OA neural circuitry to inhibit interspecies and conspecific male-male courtship and indicate that the genetically hard-wired neural mechanisms enforcing behavioral reproductive isolation include the interpretation of the epigenome.
Pathological effect of arterial ischaemia and venous congestion on rat testes
Authors: Hirai Shuichi , Hatayama Naoyuki , Naito Munekazu , Nagahori Kenta , Kawata Shinichi , Hayashi Shogo , Qu Ning , Terayama Hayato , Shoji Sunao , Itoh Masahiro
Published: July 2017

Many studies on various organs have concluded that venous congestion (VC) causes severe organ dysfunction with elevation of oxidative stress relative to that of arterial ischaemia (AI). However, a comparison of the pathological effects of AI and VC on the testes has not been conducted. In this study, models of AI and VC and their reperfusion in rat testes, respectively, were developed and analysed. Testicular arteries or veins were interrupted for 6 h, re-perfused and kept for 4 weeks; the effects on the testes were then evaluated. Severe spermatogenic disturbances were observed at 4 weeks after reperfusion in AI but not in VC. At 6 h after blood flow interruption, oxidative stress was significantly increased and germ cells were severely damaged in AI compared with those in VC. RT-PCR analyses revealed that haem oxygenase-1, which exhibits anti-oxidative effects, and vascular endothelial growth factor-A, which exhibits vasculogenic effects, were significantly increased in VC but not in AI. Surprisingly, the results of our experiment in rat testes differed from those of experiments in previous studies performed in other organs. Oxidative stress in testes was more easily elevated by AI than it was by VC, explainable by the different experimental conditions.