bluuebunny/crossref_metadata_2025 huggingface dataset:
PINDAR AS LAVDATOR EQVORVM IN HORACE, CARMINA 4.2.17–20 AND ARS POETICA 83–5
Authors: Kovacs David
Published: October 2017

At Carm. (Odes) 4.2.17–20 Horace's catalogue of Pindar's poetry reaches his victory odes:siue quos Elea domum reducitpalma caelestis pugilemue equumuedicit et centum potiore signismunere donat;                                            20The text, transmitted without variants in our manuscripts, means ‘(Pindar deserves the laurel wreath whether he writes bold dithyrambs or sings of gods and heroes) or tells of those escorted home as gods by the Elean palm-branch, whether boxer or horse, and bestows on them a gift more valuable than a hundred statues’. The two italicized expressions are more difficult than the commentators seem willing to admit. I discuss them separately.
Bioenergetics and stellar luminosities
Authors: Sivaram C , Arun K , Kiren O V
Published: October 2017

We draw attention to a curious coincidence wherein the most (steadily emitting) luminous objects in the Universe from stellar X-ray sources to ultra-luminous quasars and Ultra Luminous Infrared Galaxies, steadily emit a power per unit mass, which is just the same value as the maximal metabolic rate in (warm-blooded) bio-organisms.
EPA Proposes Repealing Its Own Obama Era Clean Power Plan
Authors: Showstack Randy
Published: October 2017

The action of the agency, now realigned by the Trump administration, “just begins the battle,” according to environmentalists and others who plan to challenge EPA’s proposed repeal of the rule.
Caregiver Perspectives on Family Psychosocial Risks and Resiliencies in Pediatric Sickle Cell Disease: Informing the Adaptation of the Psychosocial Assessment Tool
Authors: Reader Steven K. , Ruppe Nicole M. , Deatrick Janet A. , Rash-Ellis Diana L. , Wadman Jean R. , Miller Robin E. , Kazak Anne E.
Published: October 2017

There were 2 related objectives of this qualitative study focused on caregivers of children with sickle cell disease (SCD): (1) to assess caregiver perspectives on the acceptability and utility of the Psychosocial Assessment Tool (PAT) as a screener of family psychosocial risk in pediatric SCD and (2) to examine caregiver perspectives on psychosocial risk factors, as well as their resiliencies and coping strategies, to help inform possible modifications to the PAT. Caregivers ( n = 43) of youth with SCD completed the PAT to assess feasibility of administration and a subset ( n = 22) completed a qualitative interview organized around principles of cognitive interviewing for instrument validation. Constant comparative analyses involved coding interviews, organizing coding categories into themes, and systematically reintegrating themes regarding caregiver perspectives. Caregivers had positive reactions to the PAT, including its ability to broadly assess risk factors, potential utility in helping connect families to resources, and the brevity and ease of completion. Caregivers described salient family stressors as well as adaptive coping strategies that generally aligned well with areas assessed by the PAT, and also provided feedback that can help inform modification of the PAT to better fit the SCD population. Families of youth with SCD face significant psychosocial stressors but demonstrate resiliency in using adaptive coping strategies. Study results support the continuing development of the PAT as a family psychosocial risk screener in pediatric SCD that can enhance the delivery of evidence-based care and reduce health disparities.
Adiponectin controls the apoptosis and the expression of tight junction proteins in brain endothelial cells through AdipoR1 under beta amyloid toxicity
Authors: Song Juhyun , Choi Seong-Min , Whitcomb Daniel J , Kim Byeong C
Published: October 2017

Alzheimer’s disease (AD) is the most common neurodegenerative disease, characterized by excessive beta amyloid (Aβ) deposition in brain, leading to blood–brain barrier (BBB) disruption. The mechanisms of BBB disruption in AD are still unclear, despite considerable research. The adipokine adiponectin is known to regulate various metabolic functions and reduce inflammation. Though adiponectin receptors have been reported in the brain, its role in the central nervous system has not been fully characterized. In the present study, we investigate whether adiponectin contributes to the tight junction integrity and cell death of brain endothelial cells under Aβ-induced toxicity conditions. We measured the expression of adiponectin receptors (AdipoR1 and AdipoR2) and the alteration of tight junction proteins in in vivo 5xFAD mouse brain. Moreover, we examined the production of reactive oxygen species (ROS) and the loss of tight junction proteins such as Claudin 5, ZO-1, and inflammatory signaling in in vitro brain endothelial cells (bEnd.3 cells) under Aβ toxicity. Our results showed that Acrp30 (a globular form of adiponectin) reduces the expression of proinflammatory cytokines and the expression of RAGE as Aβ transporters into brain. Moreover, we found that Acrp 30 attenuated the apoptosis and the tight junction disruption through AdipoR1-mediated NF-κB pathway in Aβ-exposed bEnd.3 cells. Thus, we suggest that adiponectin is an attractive therapeutic target for treating BBB breakdown in AD brain.
Alternative mechanisms of miR-34a regulation in cancer
Authors: Slabáková Eva , Culig Zoran , Remšík Ján , Souček Karel
Published: October 2017

MicroRNA miR-34a is recognized as a master regulator of tumor suppression. The strategy of miR-34a replacement has been investigated in clinical trials as the first attempt of miRNA application in cancer treatment. However, emerging outcomes promote the re-evaluation of existing knowledge and urge the need for better understanding the complex biological role of miR-34a. The targets of miR-34a encompass numerous regulators of cancer cell proliferation, survival and resistance to therapy. MiR-34a expression is transcriptionally controlled by p53, a crucial tumor suppressor pathway, often disrupted in cancer. Moreover, miR-34a abundance is fine-tuned by context-dependent feedback loops. The function and effects of exogenously delivered or re-expressed miR-34a on the background of defective p53 therefore remain prominent issues in miR-34a based therapy. In this work, we review p53-independent mechanisms regulating the expression of miR-34a. Aside from molecules directly interacting with MIR34A promoter, processes affecting epigenetic regulation and miRNA maturation are discussed. Multiple mechanisms operate in the context of cancer-associated phenomena, such as aberrant oncogene signaling, EMT or inflammation. Since p53-dependent tumor-suppressive mechanisms are disturbed in a substantial proportion of malignancies, we summarize the effects of miR-34a modulation in cell and animal models in the clinically relevant context of disrupted or insufficient p53 function.
Ligand-dependent EphA7 signaling inhibits prostate tumor growth and progression
Authors: Li Shibao , Wu Zhiyuan , Ma Ping , Xu Yinhai , Chen Yuming , Wang Hua , He Ping , Kang Zhihua , Yin Lingyu , Zhao Yao , Zhang Xinju , Xu Xiao , Ma Xiaochao , Guan Ming
Published: October 2017

The downregulation of receptor tyrosine kinase EphA7 is frequent in epithelial cancers and linked to tumor progression. However, the detailed mechanism of EphA7-mediated prostate tumor progression remains elusive. To test the role of EphA7 receptor in prostate cancer (PCa) progression directly, we generated EphA7 receptor variants that were either lacking the cytoplasmic domain or carrying a point mutation that inhibits its phosphorylation by site-directed mutagenesis. Overexpression of wild-type (WT) EphA7 in PCa cells resulted in decreased tumor volume and increased tumor apoptosis in primary tumors. In addition, ectopic expression of WT EphA7 both can delay PCa cell proliferation and could inhibit PCa cell migration and invasion. This protein can also induce PCa cell apoptosis that correlated with increasing the protein expression levels of Bax, elevating the caspase-3 activities, reducing the protein expression levels of Bcl-2 and facilitating the dephosphorylation of Akt, which is further increased by the stimulation of ephrinA5-Fc. However, expression of these EphA7 mutants in PCa cells has no effect in vivo and in vitro. The expression of EphA7 and ephrinA5 was significantly decreased in PCa specimens compared with BPH tissues or paired normal tissues. Moreover, the phosphorylation of EphA7 was positively related with ephrinA5 expression in human prostate tissues. In sum, receptor phosphorylation of EphA7, at least in part, suppress PCa tumor malignancy through targeting PI3K/Akt signaling pathways.
Robust Bain distortion in the premartensite phase of a platinum-substituted Ni2MnGa magnetic shape memory alloy
Authors: Singh Sanjay , Dutta B. , D’Souza S. W. , Zavareh M. G. , Devi P. , Gibbs A. S. , Hickel T. , Chadov S. , Felser C. , Pandey D.
Published: October 2017

The premartensite phase of shape memory and magnetic shape memory alloys (MSMAs) is believed to be a precursor state of the martensite phase with preserved austenite phase symmetry. The thermodynamic stability of the premartensite phase and its relation to the martensitic phase is still an unresolved issue, even though it is critical to the understanding of the functional properties of MSMAs. We present here unambiguous evidence for macroscopic symmetry breaking leading to robust Bain distortion in the premartensite phase of 10% Pt-substituted Ni2MnGa. We show that the robust Bain-distorted premartensite (T2) phase results from another premartensite (T1) phase with preserved cubic-like symmetry through an isostructural phase transition. The T2 phase finally transforms to the martensite phase with additional Bain distortion on further cooling. Our results demonstrate that the premartensite phase should not be considered as a precursor state with the preserved symmetry of the cubic austenite phase.
DNA-binding of the Tet-transactivator curtails antigen-induced lymphocyte activation in mice
Authors: Ottina Eleonora , Peperzak Victor , Schoeler Katia , Carrington Emma , Sgonc Roswitha , Pellegrini Marc , Preston Simon , Herold Marco J. , Strasser Andreas , Villunger Andreas
Published: October 2017

The Tet-On/Off system for conditional transgene expression constitutes state-of-the-art technology to study gene function by facilitating inducible expression in a timed and reversible manner. Several studies documented the suitability and versatility of this system to trace lymphocyte fate and to conditionally express oncogenes or silence tumour suppressor genes in vivo. Here, we show that expression of the tetracycline/doxycycline-controlled Tet-transactivator, while tolerated well during development and in immunologically unchallenged animals, impairs the expansion of antigen-stimulated T and B cells and thereby curtails adaptive immune responses in vivo. Transactivator-mediated cytotoxicity depends on DNA binding, but can be overcome by BCL2 overexpression, suggesting that apoptosis induction upon lymphocyte activation limits cellular and humoral immune responses. Our findings suggest a possible system-intrinsic biological bias of the Tet-On/Off system in vivo that will favour the outgrowth of apoptosis resistant clones, thus possibly confounding data published using such systems.
Large second harmonic generation enhancement in Si3N4 waveguides by all-optically induced quasi-phase-matching
Authors: Billat Adrien , Grassani Davide , Pfeiffer Martin H. P. , Kharitonov Svyatoslav , Kippenberg Tobias J. , Brès Camille-Sophie
Published: October 2017

Efficient second harmonic generation in integrated platforms is usually achieved by resonant structures, intermodal phase-matching or quasi-phase matching by periodically poling ferroelectric waveguides. However, in all these structures, it is impossible to reconfigure the phase-matching condition in an all-optical way. Here, we demonstrate that a Watt-level laser causes a periodic modification of the second-order susceptibility in a silicon nitride waveguide, allowing for quasi-phase-matching between the pump and second harmonic modes for arbitrary wavelengths inside the erbium band. The grating is long-term inscribed, and leads to a second harmonic generation enhancement of more than 30 dB. We estimate a χ
(2)
on the order of 0.3 pm/V, with a maximum conversion efficiency of 0.05% W−1. We explain the observed phenomenon with the coherent photogalvanic effect model, which correctly agrees with the retrieved experimental parameters.
Coherent coupling between a quantum dot and a donor in silicon
Authors: Harvey-Collard Patrick , Jacobson N. Tobias , Rudolph Martin , Dominguez Jason , Ten Eyck Gregory A. , Wendt Joel R. , Pluym Tammy , Gamble John King , Lilly Michael P. , Pioro-Ladrière Michel , Carroll Malcolm S.
Published: October 2017

Individual donors in silicon chips are used as quantum bits with extremely low error rates. However, physical realizations have been limited to one donor because their atomic size causes fabrication challenges. Quantum dot qubits, in contrast, are highly adjustable using electrical gate voltages. This adjustability could be leveraged to deterministically couple donors to quantum dots in arrays of qubits. In this work, we demonstrate the coherent interaction of a 31P donor electron with the electron of a metal-oxide-semiconductor quantum dot. We form a logical qubit encoded in the spin singlet and triplet states of the two-electron system. We show that the donor nuclear spin drives coherent rotations between the electronic qubit states through the contact hyperfine interaction. This provides every key element for compact two-electron spin qubits requiring only a single dot and no additional magnetic field gradients, as well as a means to interact with the nuclear spin qubit.
Successful amplification of DNA aboard the International Space Station
Authors: Boguraev Anna-Sophia , Christensen Holly C. , Bonneau Ashley R. , Pezza John A. , Nichols Nicole M. , Giraldez Antonio J. , Gray Michelle M. , Wagner Brandon M. , Aken Jordan T. , Foley Kevin D. , Copeland D. Scott , Kraves Sebastian , Alvarez Saavedra Ezequiel
Published: October 2017

As the range and duration of human ventures into space increase, it becomes imperative that we understand the effects of the cosmic environment on astronaut health. Molecular technologies now widely used in research and medicine will need to become available in space to ensure appropriate care of astronauts. The polymerase chain reaction (PCR) is the gold standard for DNA analysis, yet its potential for use on-orbit remains under-explored. We describe DNA amplification aboard the International Space Station (ISS) through the use of a miniaturized miniPCR system. Target sequences in plasmid, zebrafish genomic DNA, and bisulfite-treated DNA were successfully amplified under a variety of conditions. Methylation-specific primers differentially amplified bisulfite-treated samples as would be expected under standard laboratory conditions. Our findings establish proof of concept for targeted detection of DNA sequences during spaceflight and lay a foundation for future uses ranging from environmental monitoring to on-orbit diagnostics.
SalmoNet, an integrated network of ten Salmonella enterica strains reveals common and distinct pathways to host adaptation
Authors: Métris Aline , Sudhakar Padhmanand , Fazekas David , Demeter Amanda , Ari Eszter , Olbei Marton , Branchu Priscilla , Kingsley Rob A. , Baranyi Jozsef , Korcsmáros Tamas
Published: October 2017

Salmonella entericais a prominent bacterial pathogen with implications on human and animal health.Salmonellaserovars could be classified as gastro-intestinal or extra-intestinal. Genome-wide comparisons revealed that extra-intestinal strains are closer relatives of gastro-intestinal strains than to each other indicating a parallel evolution of this trait. Given the complexity of the differences, a systems-level comparison could reveal key mechanisms enabling extra-intestinal serovars to cause systemic infections. Accordingly, in this work, we introduce a unique resource, SalmoNet, which combines manual curation, high-throughput data and computational predictions to provide an integrated network forSalmonellaat the metabolic, transcriptional regulatory and protein-protein interaction levels. SalmoNet provides the networks separately for five gastro-intestinal and five extra-intestinal strains. As a multi-layered, multi-strain database containing experimental data, SalmoNet is the first dedicated network resource forSalmonella. It comprehensively contains interactions between proteins encoded inSalmonellapathogenicity islands, as well as regulatory mechanisms of metabolic processes with the option to zoom-in and analyze the interactions at specific loci in more detail. Application of SalmoNet is not limited to strain comparisons as it also provides aSalmonellaresource for biochemical network modeling, host-pathogen interaction studies, drug discovery, experimental validation of novel interactions, uncovering new pathological mechanisms from emergent properties and epidemiological studies. SalmoNet is available athttp://salmonet.org.
Effects of vessel traffic and underwater noise on the movement, behaviour and vocalisations of bottlenose dolphins in an urbanised estuary
Authors: Marley Sarah A. , Salgado Kent Chandra P. , Erbe Christine , Parnum Iain M.
Published: October 2017

Abstarct

The potential disturbance of dolphins from tourism boats has been widely discussed in the literature, in terms of both physical vessel presence and associated underwater noise. However, less attention has been paid to the potential impact of non-tourism vessels, despite these being much more widespread and occurring in greater numbers throughout coastal dolphin habitats. The Indo-Pacific bottlenose dolphin (T. aduncus) community using the Fremantle Inner Harbour, Western Australia, is exposed to high levels of vessel traffic. To investigate whether behavioural responses could be occurring, a non-invasive combination of visual and acoustic monitoring was conducted using a theodolite and an autonomous acoustic logger. Dolphins significantly increased their average movement speeds in high vessel densities, but only for some activity states. Behavioural budgets also changed in the presence of vessels, with animals spending greater time travelling and less time resting or socialising. Finally, multiple whistle characteristics varied with rising levels of broadband noise, and other contextual variables. Despite being acoustically specialised for higher frequencies, dolphins had the strongest acoustic variation during low-frequency noise. This study highlights the complexity of disturbance responses in this species, confirming the need for consideration of both surface and acoustic behaviour alongside appropriate contextual data.
Priming with FGF2 stimulates human dental pulp cells to promote axonal regeneration and locomotor function recovery after spinal cord injury
Authors: Nagashima Kosuke , Miwa Takahiro , Soumiya Hitomi , Ushiro Daisuke , Takeda-Kawaguchi Tomoko , Tamaoki Naritaka , Ishiguro Saho , Sato Yumi , Miyamoto Kei , Ohno Takatoshi , Osawa Masatake , Kunisada Takahiro , Shibata Toshiyuki , Tezuka Ken-ichi , Furukawa Shoei , Fukumitsu Hidefumi
Published: October 2017

Human dental pulp cells (DPCs), adherent cells derived from dental pulp tissues, are potential tools for cell transplantation therapy. However, little work has been done to optimize such transplantation. In this study, DPCs were treated with fibroblast growth factor-2 (FGF2) for 5–6 consecutive serial passages and were transplanted into the injury site immediately after complete transection of the rat spinal cord. FGF2 priming facilitated the DPCs to promote axonal regeneration and to improve locomotor function in the rat with spinal cord injury (SCI). Additional analyses revealed that FGF2 priming protected cultured DPCs from hydrogen-peroxide–induced cell death and increased the number of DPCs in the SCI rat spinal cord even 7 weeks after transplantation. The production of major neurotrophic factors was equivalent in FGF2-treated and untreated DPCs. These observations suggest that FGF2 priming might protect DPCs from the post-trauma microenvironment in which DPCs infiltrate and resident immune cells generate cytotoxic reactive oxygen species. Surviving DPCs could increase the availability of neurotrophic factors in the lesion site, thereby promoting axonal regeneration and locomotor function recovery.
Diabetes in Iran: Prospective Analysis from First Nationwide Diabetes Report of National Program for Prevention and Control of Diabetes (NPPCD-2016)
Authors: Esteghamati Alireza , Larijani Bagher , Aghajani Mohammad Haji , Ghaemi Fatemeh , Kermanchi Jamshid , Shahrami Ali , Saadat Mohammad , Esfahani Ensieh Nasli , Ganji Morsaleh , Noshad Sina , Khajeh Elias , Ghajar Alireza , Heidari Behnam , Afarideh Mohsen , Mechanick Jeffrey I. , Ismail-Beigi Faramarz
Published: October 2017

We estimated proportions of different types of diabetes, comorbidities, treatment (the use of oral glucose-lowering agents and insulin), control (hyperglycemia, dyslipidemia and hypertension) and chronic microvascular and macrovascular complications among people with diabetes presenting to the tertiary-care academic diabetes outpatient clinics in Iran. This study is the prospective analysis of data (n = 30,202) from the registry of university-affiliated adult outpatient diabetes clinics in the country during 2015–2016. The proportions of type 1 diabetes, types 2 diabetes, and other types of diabetes were 11.4%, 85.5%, and 1.3%, respectively. The frequencies of drug-naivety, use of oral agents, insulin monotherapy and insulin combination therapy were 2.9%, 60.5%, 11.5%, and 25.1%, respectively. Around 13.2%, 11.9% and 43.3% of patients with diabetes had controlled hyperglycemia, hyperlipidemia and hypertension, respectively. The proportions of retinopathy, nephropathy, peripheral neuropathy, diabetic foot, and ischemic heart disease were 21.9%, 17.6%, 28.0%, 6.2%, and 23.9%, respectively. Despite the wide availability of medications and insulin coverage in Iran, the estimated national control of hyperglycemia, hyperlipidemia and hypertension (especially for young men and old women) remains subpar. The present study further suggests that the frequencies of chronic vascular complications among patients with diabetes are relatively high in Iran.
A high-speed single sideband generator using a magnetic tunnel junction spin torque nano-oscillator
Authors: Sharma Raghav , Sisodia Naveen , Iacocca Ezio , Awad Ahmad A. , Åkerman Johan , Muduli P. K.
Published: October 2017

An important property of spin-torque nano-oscillators (STNOs) is their ability to produce a frequency modulated (FM) signal, which is very critical for communication applications. We here demonstrate a novel single sideband (SSB) modulation phenomenon using a magnetic tunnel junction (MTJ)-based STNO, which saves transmission bandwidth and in principle should minimize attenuation for wireless communication. Experimentally, lower single sidebands (LSSBs) have been successfully demonstrated over a wide range of modulation frequency, f
m
 = 150 MHz-1 GHz. The observed LSSBs are determined by the intrinsic properties of the device, which can be modeled well by a nonlinear frequency and amplitude modulation formulation and reproduced in macrospin simulations. Moreover, our macrospin simulation results show that the range of modulation current and modulation frequency for generating SSBs can be controlled by the field-like torque and biasing conditions.
Characterization of a New Protein Family Associated With the Silica Deposition Vesicle Membrane Enables Genetic Manipulation of Diatom Silica
Authors: Tesson Benoit , Lerch Sarah J. L. , Hildebrand Mark
Published: October 2017

Diatoms are known for their intricate, silicified cell walls (frustules). Silica polymerization occurs in a compartment called the silica deposition vesicle (SDV) and it was proposed that the cytoskeleton influences silica patterning through the SDV membrane (silicalemma) via interactions with transmembrane proteins. In this work we identify a family of proteins associated with the silicalemma, named SAPs for Silicalemma Associated Proteins. The T. pseudonana SAPs (TpSAPs) are characterized by their motif organization; each contains a transmembrane domain, serine rich region and a conserved cytoplasmic domain. Fluorescent tagging demonstrated that two of the TpSAPs were localized to the silicalemma and that the intralumenal region of TpSAP3 remained embedded in the silica while the cytoplasmic region was cleaved. Knockdown lines of TpSAP1 and 3 displayed malformed valves; which confirmed their roles in frustule morphogenesis. This study provides the first demonstration of altering silica structure through manipulation of a single gene.
Modeling and Preventing Progressive Hearing Loss in Usher Syndrome III
Authors: Geng Ruishuang , Omar Akil , Gopal Suhasini R. , Chen Daniel H.-C. , Stepanyan Ruben , Basch Martin L. , Dinculescu Astra , Furness David N. , Saperstein David , Hauswirth William , Lustig Lawrence R. , Alagramam Kumar N.
Published: October 2017

Usher syndrome type III (USH3) characterized by progressive loss of vision and hearing is caused by mutations in the clarin-1 gene (CLRN1). Clrn1 knockout (KO) mice develop hair cell defects by postnatal day 2 (P2) and are deaf by P21-P25. Early onset profound hearing loss in KO mice and lack of information about the cochlear cell type that requires Clrn1 expression pose challenges to therapeutic investigation. We generated KO mice harboring a transgene, TgAC1, consisting of Clrn1-UTR (Clrn1 cDNA including its 5′ and 3′ UTR) under the control of regulatory elements (Atoh1 3′ enhancer/β-globin basal promoter) to direct expression of Clrn1 in hair cells during development and down regulate it postnatally. The KO-TgAC1 mice displayed delayed onset progressive hearing loss associated with deterioration of the hair bundle structure, leading to the hypothesis that hair cell expression of Clrn1 is essential for postnatal preservation of hair cell structure and hearing. Consistent with that hypothesis, perinatal transfection of hair cells in KO-TgAC1 mice with a single injection of AAV-Clrn1-UTR vector showed correlative preservation of the hair bundle structure and hearing through adult life. Further, the efficacy of AAV-Clrn1 vector was significantly attenuated, revealing the potential importance of UTR in gene therapy.
Global Identification, Classification, and Expression Analysis of MAPKKK genes: Functional Characterization of MdRaf5 Reveals Evolution and Drought-Responsive Profile in Apple
Authors: Sun Meihong , Xu Yang , Huang Jinguang , Jiang Zesheng , Shu Huairui , Wang Huasen , Zhang Shizhong
Published: October 2017

Mitogen-activated protein kinase kinase kinases (MAPKKKs) are pivotal components of Mitogen-activated protein kinase (MAPK) cascades, which play a significant role in many biological processes. Although genome-wide analysis of MAPKKKs has been conducted in many species, extant results in apple are scarce. In this study, a total of 72 putative MdMAPKKKs in Raf-like group, 11 in ZIK-like group and 37 in MEEK were identified in apple firstly. Predicted MdMAPKKKs were located in 17 chromosomes with diverse densities, and there was a high-level of conservation in and among the evolutionary groups. Encouragingly, transcripts of 12 selected MdMAPKKKs were expressed in at least one of the tested tissues, indicating that MdMAPKKKs might participate in various physiological and developmental processes in apple. Moreover, they were found to respond to drought stress in roots and leaves, which suggested a possible conserved response to drought stress in different species. Overexpression of MdRaf5 resulted in a hyposensitivity to drought stress, which was at least partially due to the regulation of stomatal closure and transpiration rates. To the best of our knowledge, this is the first genome-wide functional analysis of the MdMAPKKK genes in apple, and it provides valuable information for understanding MdMAPKKKs signals and their putative functions.
Structural and Mechanistic Analysis of Drosophila melanogaster Agmatine N-Acetyltransferase, an Enzyme that Catalyzes the Formation of N-Acetylagmatine
Authors: Dempsey Daniel R. , Nichols Derek A. , Battistini Matthew R. , Pemberton Orville , Ospina Santiago Rodriguez , Zhang Xiujun , Carpenter Anne-Marie , O’Flynn Brian G. , Leahy James W. , Kanwar Ankush , Lewandowski Eric M. , Chen Yu , Merkler David J.
Published: October 2017

Agmatine N-acetyltransferase (AgmNAT) catalyzes the formation of N-acetylagmatine from acetyl-CoA and agmatine. Herein, we provide evidence that Drosophila melanogaster AgmNAT (CG15766) catalyzes the formation of N-acetylagmatine using an ordered sequential mechanism; acetyl-CoA binds prior to agmatine to generate an AgmNAT•acetyl-CoA•agmatine ternary complex prior to catalysis. Additionally, we solved a crystal structure for the apo form of AgmNAT with an atomic resolution of 2.3 Å, which points towards specific amino acids that may function in catalysis or active site formation. Using the crystal structure, primary sequence alignment, pH-activity profiles, and site-directed mutagenesis, we evaluated a series of active site amino acids in order to assign their functional roles in AgmNAT. More specifically, pH-activity profiles identified at least one catalytically important, ionizable group with an apparent pKa of ~7.5, which corresponds to the general base in catalysis, Glu-34. Moreover, these data led to a proposed chemical mechanism, which is consistent with the structure and our biochemical analysis of AgmNAT.
Enterococci Mediate the Oviposition Preference of Drosophila melanogaster through Sucrose Catabolism
Authors: Liu Wei , Zhang Ke , Li Yujuan , Su Wanzhen , Hu Kunkun , Jin Shan
Published: October 2017

Sucrose, one of the main products of photosynthesis in plants, functions as a universal biomarker for nutritional content and maturity of different fruits across diverse ecological niches. Drosophila melanogaster congregates to lay eggs in rotting fruits, yet the factors that influence these decisions remains uncovered. Here, we report that lactic acid bacteria Enterococci are critical modulators to attract Drosophila to lay eggs on decaying food. Drosophila-associated Enterococci predominantly catabolize sucrose for growing their population in fly food, and thus generate a unique ecological niche with depleted sucrose, but enriched bacteria. Female flies navigate these favorable oviposition sites by probing the sucrose cue with their gustatory sensory neurons. Acquirement of indigenous microbiota facilitated the development and systemic growth of Drosophila, thereby benefiting the survival and fitness of their offspring. Thus, our finding highlights the pivotal roles of commensal bacteria in influencing host behavior, opening the door to a better understanding of the ecological relationships between the microbial and metazoan worlds.
Modulating hemispheric lateralization by brain stimulation yields gain in mental and physical activity
Authors: Zich Catharina , Harty Siobhán , Kranczioch Cornelia , Mansfield Karen L. , Sella Francesco , Debener Stefan , Cohen Kadosh Roi
Published: October 2017

Imagery plays an important role in our life. Motor imagery is the mental simulation of a motor act without overt motor output. Previous studies have documented the effect of motor imagery practice. However, its translational potential for patients as well as for athletes, musicians and other groups, depends largely on the transfer from mental practice to overt physical performance. We used bilateral transcranial direct current stimulation (tDCS) over sensorimotor areas to modulate neural lateralization patterns induced by unilateral mental motor imagery and the performance of a physical motor task. Twenty-six healthy older adults participated (mean age = 67.1 years) in a double-blind cross-over sham-controlled study. We found stimulation-related changes at the neural and behavioural level, which were polarity-dependent. Specifically, for the hand contralateral to the anode, electroencephalographic activity induced by motor imagery was more lateralized and motor performance improved. In contrast, for the hand contralateral to the cathode, hemispheric lateralization was reduced. The stimulation-related increase and decrease in neural lateralization were negatively related. Further, the degree of stimulation-related change in neural lateralization correlated with the stimulation-related change on behavioural level. These convergent neurophysiological and behavioural effects underline the potential of tDCS to improve mental and physical motor performance.
Materials analysis and focused ion beam nanofabrication of topological insulator Bi2Se3
Authors: Friedensen Sarah , Mlack Jerome T. , Drndić Marija
Published: October 2017

Focused ion beam milling allows manipulation of the shape and size of nanostructures to create geometries potentially useful for opto-electronics, thermoelectrics, and quantum computing. We focus on using the ion beam to control the thickness of Bi2Se3 and to create nanowires from larger structures. Changes in the material structure of Bi2Se3 nanomaterials that have been milled using a focused ion beam are presented. In order to characterize the effects of ion beam processing on the samples, we use a variety of techniques including analytical transmission electron microscopy and atomic force microscopy. The results show that while part of the material remains intact after shaping, amorphous regions form where the beam has been used to thin the sample. For wires created by thinning the material down to the substrate, the sidewalls of the wires appear intact based on diffraction images from samples cut at an angle, but thin crystalline regions remain at the wire edges. Even with the resulting defects and limitations when thinning, focused ion beam milling can be used to fabricate custom geometries of Bi2Se3 nanostructures.
The histone variant H3.3 G34W substitution in giant cell tumor of the bone link chromatin and RNA processing
Authors: Lim Jinyeong , Park Joo Hyun , Baude Annika , Yoo Yeongran , Lee Yeon Kyu , Schmidt Christopher R. , Park Jong Bae , Fellenberg Jörg , Zustin Josef , Haller Florian , Krücken Irene , Kang Hyun Guy , Park Yoon Jung , Plass Christoph , Lindroth Anders M.
Published: October 2017

While transcription as regulated by histones and their post-translational modifications has been well described, the function of histone variants in this process remains poorly characterized. Potentially important insight into this process pertain to the frequently occurring mutations of H3.3, leading to G34 substitutions in childhood glioblastoma and giant cell tumor of the bone (GCTB). In this study, we have established primary cell lines from GCTB patients and used them to uncover the influence of H3.3 G34W substitutions on cellular growth behavior, gene expression, and chromatin compaction. Primary cell lines with H3.3 G34W showed increased colony formation, infiltration and proliferation, known hallmarks of tumor development. Isogenic cell lines with H3.3 G34W recapitulated the increased proliferation observed in primary cells. Transcriptomic analysis of primary cells and tumor biopsies revealed slightly more downregulated gene expression, perhaps by increased chromatin compaction. We identified components related to splicing, most prominently hnRNPs, by immunoprecipitation and mass spectrometry that specifically interact with H3.3 G34W in the isogenic cell lines. RNA-sequencing analysis and hybridization-based validations further enforced splicing aberrations. Our data uncover a role for H3.3 in RNA processing and chromatin modulation that is blocked by the G34W substitution, potentially driving the tumorigenic process in GCTB.
Palmitate-induced lipotoxicity alters acetylation of multiple proteins in clonal β cells and human pancreatic islets
Authors: Ciregia Federica , Bugliani Marco , Ronci Maurizio , Giusti Laura , Boldrini Claudia , Mazzoni Maria R , Mossuto Sandra , Grano Francesca , Cnop Miriam , Marselli Lorella , Giannaccini Gino , Urbani Andrea , Lucacchini Antonio , Marchetti Piero
Published: October 2017

Type 2 diabetes is characterized by progressive β cell dysfunction, with lipotoxicity playing a possible pathogenetic role. Palmitate is often used to examine the direct effects of lipotoxicity and it may cause mitochondrial alterations by activating protein acetylation. However, it is unknown whether palmitate influences protein acetylation in β cells. We investigated lysine acetylation in mitochondrial proteins from INS-1E β cells (INS-1E) and in proteins from human pancreatic islets (HPI) after 24 h palmitate exposure. First, we confirmed that palmitate damages β cells and demonstrated that chemical inhibition of deacetylation also impairs INS-1E function and survival. Then, by 2-D gel electrophoresis, Western Blot and Liquid Chromatography-Mass Spectrometry we evaluated the effects of palmitate on protein acetylation. In mitochondrial preparations from palmitate-treated INS-1E, 32 acetylated spots were detected, with 13 proteins resulting over-acetylated. In HPI, 136 acetylated proteins were found, of which 11 were over-acetylated upon culture with palmitate. Interestingly, three proteins, glutamate dehydrogenase, mitochondrial superoxide dismutase, and SREBP-1, were over-acetylated in both INS-1E and HPI. Therefore, prolonged exposure to palmitate induces changes in β cell protein lysine acetylation and this modification could play a role in causing β cell damage. Dysregulated acetylation may be a target to counteract palmitate-induced β cell lipotoxicity.
Proteomic Analysis Reveals Dab2 Mediated Receptor Endocytosis Promotes Liver Sinusoidal Endothelial Cell Dedifferentiation
Authors: Lao Yuanxiang , Li Yanyan , Hou Yufang , Chen Huahai , Qiu Bintao , Lin Weiran , Sun Aihua , Wei Handong , Jiang Ying , He Fuchu
Published: October 2017

Sinusoidal dedifferentiation is a complicated process induced by several factors, and exists in early stage of diverse liver diseases. The mechanism of sinusoidal dedifferentiation is poorly unknown. In this study, we established a NaAsO2-induced sinusoidal dedifferentiation mice model. Liver sinusoidal endothelial cells were isolated and isobaric tag for relative and absolute quantitation (iTRAQ) based proteomic approach was adopted to globally examine the effects of arsenic on liver sinusoidal endothelial cells (LSECs) during the progression of sinusoidal dedifferentiation. In all, 4205 proteins were identified and quantified by iTRAQ combined with LC-MS/MS analysis, of which 310 proteins were significantly changed in NaAsO2 group, compared with the normal control. Validation by western blot showed increased level of clathrin-associated sorting protein Disabled 2 (Dab2) in NaAsO2 group, indicating that it may regulate receptor endocytosis, which served as a mechanism to augment intracellular VEGF signaling. Moreover, we found that knockdown of Dab2 reduced the uptake of VEGF in LSECs, furthermore blocking VEGF-mediated LSEC dedifferentiation and angiogenesis.
Tuneable dielectric and optical characteristics of tailor-made inorganic electro-chromic materials
Authors: Bulja S. , Kopf R. , Nolan K. , Lundy R. , Tate A. , Hu T. C. , Norooziarab M. , Cahill R. , Templ W.
Published: October 2017

Electro-chromic materials (EC) are a new class of electronically reconfigurable thin films that have the ability to reversibly change optical properties by electric charge insertion/extraction. Since their discovery by Deb, they have been employed in applications related to display technology, such as smart windows and mirrors and active optical filters. In this sense, a variety of studies related to the tuneable optical characteristics of EC materials have recently been reported, however, their microwave tuneable dielectric characteristics have been left somewhat unexplored. In 2016 Bulja showed that dc bias voltage induced modulation of the optical characteristics of an inorganic Conductor/WO3/LiNbO3/NiO/Conductor EC cell isaccompanied by the modulation of its high frequency (1–20 GHz) dielectric characteristics. In general, according to the state of the art, cells of different material compositions are needed to produce devices of tailor made characteristics. Here, we report the discovery that the microwave dielectric and the optical characteristics of an EC cell can be engineered to suit a variety of applications without changing their material composition. The obtained results indicate the potential for producing novel, tuneable and tailor-engineered materials that can be used to create next generation agile microwave-optical devices.
Effect of laser surface remelting on the microstructure and properties of Al-Al2Cu-Si ternary eutectic alloy
Authors: Ramakrishnan Bhupendera Prashanth , Lei Qian , Misra Amit , Mazumder Jyoti
Published: October 2017

Bimodal ultrafine eutectic composites (BUECs) exhibit a good combination of strength and plasticity owing to a dual-hierarchy in eutectic length-scales in the microstructure. The present study investigates the variation of phase, morphology, feature length-scales and modality of microstructures obtained in a Al81Cu13Si6 (at. %) ternary alloy after laser surface remelting. A novel approach of varying component bimodal eutectic volume fractions by controlling the cooling rate of the laser solidification process has been presented. The volume fraction of the fine eutectic matrix has a profound effect on the flow strength. Laser remelted microstructures with volume fractions of the fine eutectic varying from 25 to 40% exhibiting compressive flow strengths ranging from 500 to 900 MPa have been obtained. The volume fraction of the fine eutectic decreased with cooling rate and completely ceased to exist at cooling rates greater than $$4\times {10}^{4}\,^\circ {\rm{C}}/{\rm{s}}$$
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Skin transcriptome reveals the intrinsic molecular mechanisms underlying hair follicle cycling in Cashmere goats under natural and shortened photoperiod conditions
Authors: Yang Min , Song Shen , Dong Kunzhe , Chen XiaoFei , Liu Xuexue , Rouzi Marhaba , Zhao Qianjun , He Xiaohong , Pu Yabin , Guan Weijun , Ma Yuehui , Jiang Lin
Published: October 2017

The growth of cashmere exhibits a seasonal pattern arising from photoperiod change. However, the underlying molecular mechanism remains unclear. We profiled the skin transcriptome of six goats at seven time points during hair follicle cycling via RNA-seq. The six goats comprised three goats exposed to a natural photoperiod and three exposed to a shortened photoperiod. During hair cycle transition, 1713 genes showed differential expression, and 332 genes showed a pattern of periodic expression. Moreover, a short photoperiod induced the hair follicle to enter anagen early, and 246 genes overlapped with the periodic genes. Among these key genes, cold-shock domain containing C2 (CSDC2) was highly expressed in the epidermis and dermis of Cashmere goat skin, although its function in hair-follicle development remains unknown. CSDC2 silencing in mouse fibroblasts resulted in the decreased mRNA expression of two key hair-follicle factors, leading to reduced cell numbers and a lower cell density. Cashmere growth or molting might be controlled by a set of periodic regulatory genes. The appropriate management of short light exposure can induce hair follicles to enter full anagen early through the activation of these regulators. The CSDC2 gene is a potentially important transcription factor in the hair growth cycle.
microRNA-181b is increased in cystic fibrosis cells and impairs lipoxin A4 receptor-dependent mechanisms of inflammation resolution and antimicrobial defense
Authors: Pierdomenico Anna Maria , Patruno Sara , Codagnone Marilina , Simiele Felice , Mari Veronica Cecilia , Plebani Roberto , Recchiuti Antonio , Romano Mario
Published: October 2017

The involvement of microRNA (miR) in cystic fibrosis (CF) pathobiology is rapidly emerging. We previously documented that miR-181b controls the expression of the ALX/FPR2 receptor, which is recognized by the endogenous proresolution ligand, lipoxin (LX)A4. Here, we examined whether the miR-181b-ALX/FPR2 circuit was altered in CF. We examined human airways epithelial cells, normal (16HBE14o-), carrying the ΔF508 mutation (CFBE41o-) or corrected for this mutation (CFBE41o-/CEP-CFTR wt 6.2 kb), as well as monocyte-derived macrophages (MΦs) from CF patients. CFBE41o- cells exhibited higher miR-181b and reduced ALX/FPR2 levels compared to 16HBE14o- and CFBE41o-/CEP-CFTR wt 6.2 kb cells. An anti-mir-181b significantly enhanced ALX/FPR2 expression (+ 60%) as well as LXA4-induced increase in transepithelial electric resistance (+ 25%) in CFBE41o- cells. MΦs from CF patients also displayed increased miR-181b (+ 100%) and lower ALX/FPR2 levels (− 20%) compared to healthy cells. An anti-mir-181b enhanced ALX/FPR2 expression (+ 40%) and normalized receptor-dependent LXA4-induced phagocytosis of fluorescent-labeled zymosan particles as well as ofPseudomonas aeruginosaby CF-MΦs. These results provide the first evidence that miR-181b is overexpressed in CF cells, impairing some mechanisms of the ALX/FPR2-dependent pathway of inflammation resolution. Thus, targeting miR-181b may represent a strategy to enhance anti-inflammatory and anti-microbial defense mechanisms in CF.
A Skeletal Muscle Model of Infantile-onset Pompe Disease with Patient-specific iPS Cells
Authors: Yoshida Takeshi , Awaya Tomonari , Jonouchi Tatsuya , Kimura Ryo , Kimura Shigemi , Era Takumi , Heike Toshio , Sakurai Hidetoshi
Published: October 2017

Pompe disease is caused by an inborn defect of lysosomal acid α-glucosidase (GAA) and is characterized by lysosomal glycogen accumulation primarily in the skeletal muscle and heart. Patients with the severe type of the disease, infantile-onset Pompe disease (IOPD), show generalized muscle weakness and heart failure in early infancy. They cannot survive over two years. Enzyme replacement therapy with recombinant human GAA (rhGAA) improves the survival rate, but its effect on skeletal muscle is insufficient compared to other organs. Moreover, the patho-mechanism of skeletal muscle damage in IOPD is still unclear. Here we generated induced pluripotent stem cells (iPSCs) from patients with IOPD and differentiated them into myocytes. Differentiated myocytes showed lysosomal glycogen accumulation, which was dose-dependently rescued by rhGAA. We further demonstrated that mammalian/mechanistic target of rapamycin complex 1 (mTORC1) activity was impaired in IOPD iPSC-derived myocytes. Comprehensive metabolomic and transcriptomic analyses suggested the disturbance of mTORC1-related signaling, including deteriorated energy status and suppressed mitochondrial oxidative function. In summary, we successfully established an in vitro skeletal muscle model of IOPD using patient-specific iPSCs. Disturbed mTORC1 signaling may contribute to the pathogenesis of skeletal muscle damage in IOPD, and may be a potential therapeutic target for Pompe disease.