bluuebunny/crossref_metadata_2025 huggingface dataset:
4-(E)-{(p-tolylimino)-methylbenzene-1,2-diol} (TIMBD) suppresses HIV1-gp120 mediated production of IL6 and IL8 but not CCL5
Authors: Abdalla Fatma , Nookala Anantha , Padhye Subhash B. , Kumar Anil , Bhat Hari K.
Published: August 2017

Human immunodeficiency virus (HIV) has been associated with inflammatory effects that may potentially result in neurodegenerative changes and a number of newer chemotherapeutic agents are being tested to ameliorate these effects. In this study, we investigated the anti-neuroinflammatory activity of a novel resveratrol analog 4-(E)-{(p-tolylimino)-methylbenzene-1,2-diol} (TIMBD) against HIV1-gp120 induced neuroinflammation in SVG astrocytes. SVG astrocytic cells were pretreated with TIMBD or resveratrol (RES) and then transfected with a plasmid encoding HIV1-gp120. The mRNA and protein expression levels of proinflammatory cytokines IL6, IL8 and CCL5 were determined. Protein expression levels of NF-κB, AP1, p-STAT3, p-AKT, p-IKKs and p-p38 MAPK were also determined. TIMBD inhibited gp120-induced RNA and protein expression levels of IL6 and IL8, but not that of CCL5 in SVG astrocytes. Moreover, TIMBD attenuated gp120-induced phosphorylation of cJUN, cFOS, STAT3, p38-MAPK, AKT and IKKs, and the nuclear translocation of NF-κB p-65 subunit whereas RES mostly affected NF-κB protein expression levels. Our results suggest that TIMBD exerts anti-inflammatory effects better than that of RES in SVG astrocytes in vitro. These effects seem to be regulated by AP1, STAT-3 and NF-κB signaling pathways. TIMBD may thus have a potential of being a novel agent for treating HIV1-gp120-mediated neuroinflammatory diseases.
The study of electronic nematicity in an overdoped (Bi, Pb)2Sr2CuO6+δ superconductor using scanning tunneling spectroscopy
Authors: Zheng Yuan , Fei Ying , Bu Kunliang , Zhang Wenhao , Ding Ying , Zhou Xingjiang , Hoffman Jennifer E. , Yin Yi
Published: August 2017

The pseudogap (PG) state and its related intra-unit-cell symmetry breaking remain the focus in the research of cuprate superconductors. Although the nematicity has been studied in Bi2Sr2CaCu2O8+δ, especially underdoped samples, its behavior in other cuprates and different doping regions is still unclear. Here we apply a scanning tunneling microscope to explore an overdoped (Bi, Pb)2Sr2CuO6+δ with a large Fermi surface (FS). The establishment of a nematic order and its real-space distribution is visualized as the energy scale approaches the PG.
Combination of chemical fingerprint and bioactivity evaluation to explore the antibacterial components of Salvia miltiorrhizae
Authors: Kong Wei-Jun , Zhang Shan-Shan , Zhao Yan-Ling , Wu Ming-Quan , Chen Ping , Wu Xiao-Ru , Ma Xin-Ping , Guo Wei-Ying , Yang Mei-Hua
Published: August 2017

The aim of this study was to explore the possible antibacterial components of Salvia miltiorrhizae on Pseudomonas aeruginosa using a combination of chemical fingerprint and bioactivity evaluation. The chemical fingerprints of 32 batches of S. miltiorrhizae samples from different sources were developed using high-performance liquid chromatography with diode array detection, and then were evaluated by similarity analysis and hierarchical clustering analysis. Anti-P. aeruginosa activity was determined by microcalorimetry. Some crucial thermokinetic parameters obtained from the heat-flow power-time curves of P. aeruginosa growth in the absence or presence of these S. miltiorrhizae samples were evaluated using principal component analysis. Thereafter, multiple linear regression analysis was used to analyze the fingerprint-activity relationship between the chemical fingerprints and anti-P. aeruginosa activity. This established the related equation between the inhibition ratio (I, %) of S. miltiorrhizae samples on P. aeruginosa and the peak areas of the common peaks. The results showed that the 32S. miltiorrhizae samples could be grouped into three clusters according to their chemical fingerprints and anti-P. aeruginosa activities. Protocatechualdehyde, salvianolic acid B, together with three unidentified compounds might be the major components that contributed largely to the antibacterial properties of S. miltiorrhizae and should be the focus of S. miltiorrhizae quality control. Thus, this study provided a preferred way for exploring the bioactive components of medicinal plants.
Species distribution models of two critically endangered deep-sea octocorals reveal fishing impacts on vulnerable marine ecosystems in central Mediterranean Sea
Authors: Lauria V. , Garofalo G. , Fiorentino F. , Massi D. , Milisenda G. , Piraino S. , Russo T. , Gristina M.
Published: August 2017

Deep-sea coral assemblages are key components of marine ecosystems that generate habitats for fish and invertebrate communities and act as marine biodiversity hot spots. Because of their life history traits, deep-sea corals are highly vulnerable to human impacts such as fishing. They are an indicator of vulnerable marine ecosystems (VMEs), therefore their conservation is essential to preserve marine biodiversity. In the Mediterranean Sea deep-sea coral habitats are associated with commercially important crustaceans, consequently their abundance has dramatically declined due to the effects of trawling. Marine spatial planning is required to ensure that the conservation of these habitats is achieved. Species distribution models were used to investigate the distribution of two critically endangered octocorals (Funiculina quadrangularis and Isidella elongata) in the central Mediterranean as a function of environmental and fisheries variables. Results show that both species exhibit species-specific habitat preferences and spatial patterns in response to environmental variables, but the impact of trawling on their distribution differed. In particular F. quadrangularis can overlap with fishing activities, whereas I. elongata occurs exclusively where fishing is low or absent. This study represents the first attempt to identify key areas for the protection of soft and compact mud VMEs in the central Mediterranean Sea.
The proteasome deubiquitinase inhibitor b-AP15 enhances DR5 activation-induced apoptosis through stabilizing DR5
Authors: Oh You-Take , Deng Liang , Deng Jiusheng , Sun Shi-Yong
Published: August 2017

b-AP15 and its derivatives block proteasome deubiquitinase (DUB) activity and have been developed and tested in the clinic as potential cancer therapeutic agents. b-AP15 induces apoptosis in cancer cells, but the underlying mechanisms are largely undefined. The current study focuses on studying the modulatory effects of b-AP15 on death receptor 5 (DR5) levels and DR5 activation-induced apoptosis as well as on understanding the underlying mechanisms. Treatment with b-AP15 potently increased DR5 levels including cell surface DR5 in different cancer cell lines with limited or no effects on the levels of other related proteins including DR4, c-FLIP, FADD, and caspase-8. b-AP15 substantially slowed the degradation of DR5, suggesting that it stabilizes DR5. Moreover, b-AP15 effectively augmented apoptosis when combined with TRAIL or the DR5 agonistic antibody AMG655; these effects are DR5-dependent because DR5 deficiency abolished the ability of b-AP15 to enhance TRAIL- or AMG655-induced apoptosis. Therefore, it is clear that b-AP15, and possibly its derivatives, can stabilize DR5 and increase functional cell surface DR5 levels, resulting in enhancement of DR5 activation-induced apoptosis. Our findings suggest that b-AP15 and its derivatives may have potential in sensitizing cancer cells to DR5 activation-based cancer therapy.
Dysregulation of photosynthetic genes in oceanic Prochlorococcus populations exposed to organic pollutants
Authors: Fernández-Pinos Maria-Carmen , Vila-Costa Maria , Arrieta Jesús M. , Morales Laura , González-Gaya Belén , Piña Benjamin , Dachs Jordi
Published: August 2017

The impact of organic pollutants on oceanic ecosystem functioning is largely unknown. Prochlorococcus, the most abundant known photosynthetic organism on Earth, has been suggested to be especially sensible to exposure to organic pollutants, but the sub-lethal effects of organic pollutants on its photosynthetic function at environmentally relevant concentrations and mixtures remain unexplored. Here we show the modulation of the expression of two photosynthetic genes, rbcL (RuBisCO large subunit) and psbA (PSII D1 protein), of oceanic populations of Prochlorococcus from the Atlantic, Indian and Pacific Oceans when exposed to mixtures of organic pollutants consisting of the non-polar fraction of a seawater extract. This mixture included most persistent organic pollutants, semivolatile aromatic-like compounds, and the unresolved complex mixture of hydrocarbons. Prochlorococcus populations in the controls showed the expected diel cycle variations in expression of photosynthetic genes. However, exposure to a complex mixture at concentrations only 2-fold above the environmental levels resulted in a decrease of expression of both genes, suggesting an effect on the photosynthetic function. While organic pollutant effects on marine phytoplankton have been already demonstrated at the cellular level, this is the first field study showing alterations at the molecular level of the photosynthetic function due to organic pollutants.
Effects of latitude and depth on the beta diversity of New Zealand fish communities
Authors: Zintzen Vincent , Anderson Marti J. , Roberts Clive D. , Harvey Euan S. , Stewart Andrew L.
Published: August 2017

Marine ecosystems are difficult to sample quantitatively at increasing depth. Hence, few studies attempt to measure patterns of beta diversity for ecological communities in the deep sea. Here we (i) present and quantify large-scale gradients in fish community structure along depth and latitude gradients of the New Zealand EEZ, (ii) obtain rigorous quantitative estimates of these depth (50–1200 m) and latitudinal effects (29.15–50.91°S) and their interaction, and (iii) explicitly model how latitudinal beta diversity of fishes varies with depth. The sampling design was highly structured, replicated and stratified for latitude and depth, using data obtained from 345 standardised baited remote underwater stereo-video deployments. Results showed that gradients in fish community structure along depth and latitude were strong and interactive in New Zealand waters; latitudinal variation in fish communities progressively decreased with depth following an exponential decay (r2 = 0.96), revealing increasingly similar fish communities with increasing depth. In contrast, variation in fish community structure along the depth gradient was of a similar magnitude across all of the latitudes investigated here. We conclude that an exponential decay in beta diversityvsdepth exists for fish communities present in areas shallower than the New Zealand upper continental slope.
Gene editing in clinical isolates of Candida parapsilosis using CRISPR/Cas9
Authors: Lombardi Lisa , Turner Siobhán A. , Zhao Fang , Butler Geraldine
Published: August 2017

Candida parapsilosis is one of the most common causes of candidiasis, particularly in the very young and the very old. Studies of gene function are limited by the lack of a sexual cycle, the diploid genome, and a paucity of molecular tools. We describe here the development of a plasmid-based CRISPR-Cas9 system for gene editing in C. parapsilosis. A major advantage of the system is that it can be used in any genetic background, which we showed by editing genes in 20 different isolates. Gene editing is carried out in a single transformation step. The CAS9 gene is expressed only when the plasmid is present, and it can be removed easily from transformed strains. There is theoretically no limit to the number of genes that can be edited in any strain. Gene editing is increased by homology-directed repair in the presence of a repair template. Editing by non-homologous end joining (NHEJ) also occurs in some genetic backgrounds. Finally, we used the system to introduce unique tags at edited sites.
Light Guided In-vivo Activation of Innate Immune Cells with Photocaged TLR 2/6 Agonist
Authors: Ryu Keun Ah , McGonnigal Bethany , Moore Troy , Kargupta Tawnya , Mancini Rock J. , Esser-Kahn Aaron P.
Published: August 2017

The complexity of the immune system creates challenges in exploring its importance and robustness. To date, there have been few techniques developed to manipulate individual components of the immune system in an in vivo environment. Here we show a light-based dendritic cell (DC) activation allowing spatial and temporal control of immune activation in vivo. Additionally, we show time dependent changes in RNA profiles of the draining lymph node, suggesting a change in cell profile following DC migration and indicating that the cells migrating have been activated towards antigen presentation.
Structure formation during translocon-unassisted co-translational membrane protein folding
Authors: Harris Nicola J. , Reading Eamonn , Ataka Kenichi , Grzegorzewski Lucjan , Charalambous Kalypso , Liu Xia , Schlesinger Ramona , Heberle Joachim , Booth Paula J.
Published: August 2017

Correctly folded membrane proteins underlie a plethora of cellular processes, but little is known about how they fold. Knowledge of folding mechanisms centres on reversible folding of chemically denatured membrane proteins. However, this cannot replicate the unidirectional elongation of the protein chain during co-translational folding in the cell, where insertion is assisted by translocase apparatus. We show that a lipid membrane (devoid of translocase components) is sufficient for successful co-translational folding of two bacterial α-helical membrane proteins, DsbB and GlpG. Folding is spontaneous, thermodynamically driven, and the yield depends on lipid composition. Time-resolving structure formation during co-translational folding revealed different secondary and tertiary structure folding pathways for GlpG and DsbB that correlated with membrane interfacial and biological transmembrane amino acid hydrophobicity scales. Attempts to refold DsbB and GlpG from chemically denatured states into lipid membranes resulted in extensive aggregation. Co-translational insertion and folding is thus spontaneous and minimises aggregation whilst maximising correct folding.
Cesium ion detection by terahertz light
Authors: Ohkoshi Shin-ichi , Yoshikiyo Marie , Namai Asuka , Nakagawa Kosuke , Chiba Kouji , Fujiwara Rei , Tokoro Hiroko
Published: August 2017

Recent developments in terahertz technologies provide new tools for analysis, inspection, and nondestructive sensing. If a heavy atom is encapsulated in a cage of a porous material, the atom should vibrate slowly and resonate with a low-frequency terahertz light. From this perspective, a cyanide-bridged metal framework is a suitable system because it contains many cages that can adsorb Cs ions. Herein we show the vibration mode of a Cs ion in a cage of a cyanide-bridged metal framework. First-principles phonon mode calculations and terahertz time-domain spectroscopy (THz-TDS) measurements indicate that the vibration mode of a Cs ion in a cyanide-bridged manganese-iron framework is at 1.5 THz, which is significantly apart from other lattice vibrations. Taking advantage of this feature, we develop a THz-light detection method for Cs ions, which is useful for non-contact sensing of Cs ions in dangerous environments or harmful circumstances.
The effect of androgen excess on maternal metabolism, placental function and fetal growth in obese dams
Authors: Fornes Romina , Maliqueo Manuel , Hu Min , Hadi Laila , Jimenez-Andrade Juan M. , Ebefors Kerstin , Nyström Jenny , Labrie Fernand , Jansson Thomas , Benrick Anna , Stener-Victorin Elisabet
Published: August 2017

Pregnant women with polycystic ovary syndrome (PCOS) are often overweight or obese. To study the effects of maternal androgen excess in obese dams on metabolism, placental function and fetal growth, female C57Bl6J mice were fed a control (CD) or a high fat/high sucrose (HF/HS) diet for 4–10 weeks, and then mated. On gestational day (GD) 15.5–17.5, dams were injected with dihydrotestosterone (CD-DHT, HF/HS-DHT) or a vehicle (CD-Veh, HF/HS-Veh). HF/HS dams had higher fat content, both before mating and on GD18.5, with no difference in glucose homeostasis, whereas the insulin sensitivity was higher in DHT-exposed dams. Compared to the CD groups, the livers from HF/HS dams weighed more on GD18.5, the triglyceride content was higher, and there was a dysregulation of liver enzymes related to lipogenesis and higher mRNA expression of Fitm1. Fetuses from HF/HS-Veh dams had lower liver triglyceride content and mRNA expression of Srebf1c. Maternal DHT exposure, regardless of diet, decreased fetal liver Pparg mRNA expression and increased placental androgen receptor protein expression. Maternal diet-induced obesity, together with androgen excess, affects maternal and fetal liver function as demonstrated by increased triglyceride content and dysfunctional expression of enzymes and transcription factors involved in de novo lipogenesis and fat storage.
Effect of Nitric Oxide on Human Corneal Epithelial Cell Viability and Corneal Wound Healing
Authors: Park Joo-Hee , Kim Ja-Yeon , Kim Dong Ju , Kim Martha , Chang Minwook , Chuck Roy S. , Park Choul Yong
Published: August 2017

Although the wound healing effects of nitric oxide (NO) are known, the mechanism by which NO modulates corneal wound healing remains unclear. In this study, we investigated the effect of exogenous NO donor (NaNO2) on corneal wound healing. We found that NaNO2(0.1 μM to 100 μM) increased human corneal epithelial cell (HCEC) viability and migration. It also modulated the phosphorylation of mitogen-activated protein kinases (MAPKs) in a time- dependent manner in those HCECs. Further, p38 MAPK phosphorylation increased at 6 h and normalized at 24 h, while the phosphorylation of extracellular signal regulated kinase (ERK) was increased both at 6 h and 24 h. Topical treatment with NaNO2(10 μM) enhanced corneal epithelial healing and decreased corneal opacity in murine corneal alkali burn model by modulating inflammatory cytokines. Our findings suggest that NO increased HCEC proliferation and migration via time-dependent MAPK activation and eventually enhanced corneal recovery from the alkali burn.
Transcriptional profiling identifies differential expression of long non-coding RNAs in Jo-1 associated and inclusion body myositis
Authors: Hamann Philip D. , Roux Benoit T. , Heward James A. , Love Seth , McHugh Neil J. , Jones Simon W. , Lindsay Mark A.
Published: August 2017

Myositis is characterised by muscle inflammation and weakness. Although generally thought to be driven by a systemic autoimmune response, increasing evidence suggests that intrinsic changes in the muscle might also contribute to the pathogenesis. Long non-coding RNAs (lncRNAs) are a family of novel genes that regulate gene transcription and translation. To determine the potential role of lncRNAs, we employed next generation sequencing to examine the transcriptome in muscle biopsies obtained from two histologically distinct patient populations, inclusion body myositis (IBM) and anti-Jo-1-associated myositis (Jo-1). 1287 mRNAs and 1068 mRNAs were differentially expressed in the muscle from Jo-1 and IBM patients, respectively. Pathway analysis showed the top canonical pathway in both Jo-1 and IBM was oxidative phosphorylation and mitochondrial dysfunction. We identified 731 known and 325 novel lncRNAs in the muscles biopsies. Comparison with controls showed 55 and 46 lncRNAs were differentially expressed in IBM and Jo-1 myositis, respectively. Of these, 16 lncRNAs were differentially expressed in both IBM and Jo-1 myositis and included upregulated H19, lncMyoD and MALAT1. Given that these are known to regulate muscle proliferation and differentiation, we speculate that changes in lncRNAs might contribute to the phenotypic changes in Jo-1 and IBM myositis.
Generation and characterization of a mouse line for monitoring translation in dopaminergic neurons
Authors: Dougherty Joseph D.
Published: August 2017

We developed a mouse line targeting midbrain dopamine neurons for Translating Ribosome Affinity Purification(TRAP). Here, we briefly report on the basic characterization of this mouse line including confirmation of expression of the transgene in midbrain dopamine neurons and validation of its effectiveness in capturing mRNA from these cells. We also report a translational profile of these neurons which may be of use to investigators studying the gene expression of these cells. Finally, we have provided the line to Jackson Laboratories for distribution and use in future studies.
Age- and sex-dependency of the association between systemic antioxidant potential and glaucomatous damage
Authors: Asano Yoshimi , Himori Noriko , Kunikata Hiroshi , Yamazaki Mai , Shiga Yukihiro , Omodaka Kazuko , Takahashi Hidetoshi , Nakazawa Toru
Published: August 2017

Systemic oxidative stress is thought to be an important factor in the pathogenesis of glaucoma. In particular, low systemic antioxidative capacity, which normally counters oxidative stress, may contribute to glaucoma. Thus, we investigated the association between biological antioxidant potential (BAP), a biomarker of systemic antioxidative capacity, and glaucoma severity in patients with open-angle glaucoma (OAG). This study included 480 eyes of 240 patients with OAG and 66 healthy control eyes. We measured the BAP serum level with a free radical analyzer and compared it with a weighted estimate of the number of retinal ganglion cells (wrgc), derived from circumpapillary retinal nerve fiber layer thickness and visual field mean deviation. We found that wrgc was uncorrelated with BAP in the overall, male, and female OAG patients, but was correlated in young (aged ≤ 65 years) male OAG patients (better eye: r = 0.33, P = 0.02; worse eye: r = 0.27, P = 0.047). Furthermore, a mixed-effects regression analysis revealed that BAP was an independent contributing factor to wrgc in young male OAG patients (P = 0.02). Thus, systemic antioxidant capacity was associated with glaucomatous damage in relatively young male patients, suggesting that anti-oxidant therapy might be more effective in these patients.
Temperature-dependent birefringence of lithium triborate, LBO in the THz regime
Authors: Song Kechao , Tian Zhen , Zhang Weili , Wang Mingwei
Published: August 2017

Optical properties of lithium triborate (LBO) in the terahertz regime (0.2–2 THz) were characterized using broadband terahertz time-domain spectroscopy. The frequency dependence of refractive index and absorption coefficient of the LBO crystal was experimentally investigated over the temperature range of 77–297 K, which the experimental results indicated that LBO has very low optical absorption coefficient at terahertz frequencies especially for the beam polarization along the crystal’s principal dielectric axis X. Moreover, a giant birefringence was observed, and the refractive index difference between the axis X and Z gradually decreased with decreasing temperature, which is attributed to the behavior of the TO phonon modes of B1 and B2 symmetries at low frequencies at different temperatures. As potential applications, LBO can be exemplarily used as terahertz wave shapers, beam splitters, terahertz wave plates, circular polarizers and other polarization devices.
Differentiating peripheral cholangiocarcinoma in stages T1N0M0 and T2N0M0 from hepatic hypovascular nodules using dynamic contrast-enhanced MRI
Authors: Li Shihong , Qian Haizhen , Peng Yu , Jia Huihui , Lin Guangwu
Published: August 2017

Because cholangiocarcinoma shows no specific clinical signs or symptoms and presents with non-specific biological and tumor markers in the early stages, MRI findings often lack typical features before this lesion becomes symptomatic and might be mistaken for other liver lesions. An evaluation of relevant radiological findings in nodular cholangiocarcinoma (≤3 cm) in stages T1N0M0 and T2N0M0 is urgently needed. In our study, we compared two groups of liver hypovascular nodules and found that a distinct margin and enhanced area/nodule size >2/3 in the delayed phase were more frequently observed in cholangiocarcinoma cases than in metastatic nodule cases in which markedly high signal intensity on T2WI was common (p < 0.05). The results also revealed that in the both the portal and delayed phases, an enhanced area/nodule size >2/3 favored cholangiocarcinoma, whereas the presence of regional markedly higher SI on T2WI favored benign nodules. Furthermore, signs of peripheral washout in the delayed phase only appeared in cholangiocarcinoma cases.
Resonance optimization of polychromatic light in disordered structures
Authors: Yin Hongwei , Gbadebo Adenowo , Turitsyna Elena G. , Turitsyn Sergei K.
Published: August 2017

Disorder offers rich possibilities for manipulating the phase and intensity of light and designing photonic devices for various applications including random lasers, light storage, and speckle-free imaging. Disorder-based optical systems can be implemented in one-dimensional structures based on random or pseudo-random alternating layers with different refractive indices. Such structures can be treated as sequences of scatterers, in which spatial light localization is characterized by random sets of spectral transmission resonances, each accompanied by a relatively high-intensity concentration. The control and manipulation of resonances is the key element in designing disorder-based photonic systems. In this work, we introduce a method of controlling disorder-induced resonances by using the established non-trivial interconnection between the symmetry of bi-directional light propagation properties and the features of the resonant transmissions. Considering a fiber with resonant Bragg gratings as an example, the mechanism of enhancing or suppressing the resonant transmission of polychromatic light and the effectiveness of the method have been demonstrated both theoretically and experimentally. The proposed algorithm of controlling disorder-induced resonances is general and applicable to classical waves and quantum particles, for disordered systems both with and without gain.
Histone deacetylase 6 (HDAC6) is an essential factor for oocyte maturation and asymmetric division in mice
Authors: Zhou Dongjie , Choi Yun-Jung , Kim Jin-Hoi
Published: August 2017

Tubastatin A (Tub-A), a highly selective histone deacetylase 6 (HDAC6) inhibitor, has been widely used as a cytotoxic anticancer agent, or for the treatment of patients with asthma. However, the potential toxicity of Tub-A on oocyte maturation and asymmetric division is still unclear. Therefore, the present study was designed to examine the effect and potential regulatory role of Tub-A on the meiotic maturation of oocytes. We observed that Tub-A treatment induced an increased level of the acetylation of α-tubulin, and a failure of spindle migration and actin cap formation. Based on the spindle structure, most Tub-A treated oocytes were arrested in an MI-like or a GVBD-like stage and exhibited decondensed chromosomes in a dose dependent manner. Moreover, Tub-A treatment decreased the protein expression of mTOR, a factor responsible for spindle formation, and the expression of mDia1, an inhibitor of actin assembly, in an HDAC6 expression-dependent manner. Importantly, following Tub-A supplementation, most oocytes failed to extrude the first polar body, which indicates that these defects are closely linked to abnormal oocyte maturation. Taken together, our data demonstrates that HDAC6 is one of the essential factors for oocyte maturation and asymmetric division via the HDAC6/mTOR or mDia1 pathway in mice.
Antitumor properties of Coenzyme Q0 against human ovarian carcinoma cells via induction of ROS-mediated apoptosis and cytoprotective autophagy
Authors: Hseu You-Cheng , Tsai Tai-Jung , Korivi Mallikarjuna , Liu Jer-Yuh , Chen Hui-Jye , Lin Chung-Ming , Shen Yi-Chun , Yang Hsin-Ling
Published: August 2017

Coenzyme Q0 (CoQ0, 2,3-dimethoxy-5-methyl-1,4-benzoquinone) has been reported to exert anticancer properties against human breast/lung cancer cells. This study investigated the in vitro and in vivo anticancer properties of CoQ0 on human ovarian carcinoma (SKOV-3) cells and xenografted nude mice, and revealed the underlying molecular mechanism. CoQ0 induced G2/M arrest through downregulation of cyclin B1/A and CDK1/K2 expressions. CoQ0-induced autophagy as a survival mechanism was evidenced by increased accumulation of LC3-II, GFP-LC3 puncta, AVOs formation and Beclin-1/Bcl-2 dysregulation. Increased TUNEL-positive cells and Annexin-V/PI stained cells indicated CoQ0-induced late apoptosis. Both mitochondrial (caspase-3, PARP and Bax/Bcl-2 dysregulation) and ER stress (caspase-12 and Hsp70) signals are involved in execution of apoptosis. Interestingly, CoQ0-induced apoptosis/autophagy is associated with suppression of HER-2/neu and PI3K/AKT signalling cascades. CoQ0 triggered intracellular ROS production, whereas antioxidant N-acetylcysteine prevented CoQ0-induced apoptosis, but not autophagy. Inhibition of apoptosis by Z-VAD-FMK suppressed CoQ0-induced autophagy (diminished LC3-II/AVOs), indicates CoQ0-induced apoptosis led to evoke autophagy. Contrary, inhibition of autophagy by 3-MA/CQ potentiated CoQ0-induced apoptosis (increased DNA fragmentation/PARP cleavage). Furthermore, CoQ0 treatment to SKOV-3 xenografted nude mice reduced tumor incidence and burden. Histopathological analyses confirmed that CoQ0 modulated xenografted tumor progression by apoptosis induction. Our findings emphasize that CoQ0 triggered ROS-mediated apoptosis and cytoprotective autophagy.
Krüppel-like factor 6 is a transcriptional activator of autophagy in acute liver injury
Authors: Sydor Svenja , Manka Paul , Best Jan , Jafoui Sami , Sowa Jan-Peter , Zoubek Miguel Eugenio , Hernandez-Gea Virginia , Cubero Francisco Javier , Kälsch Julia , Vetter Diana , Fiel Maria Isabel , Hoshida Yujin , Bian C. Billie , Nelson Leonard J. , Moshage Han , Faber Klaas Nico , Paul Andreas , Baba Hideo A. , Gerken Guido , Friedman Scott L. , Canbay Ali , Bechmann Lars P.
Published: August 2017

Krüppel-like factor 6 (KLF6) is a transcription factor and tumor suppressor. We previously identified KLF6 as mediator of hepatocyte glucose and lipid homeostasis. The loss or reduction of KLF6 is linked to the progression of hepatocellular carcinoma, but its contribution to liver regeneration and repair in acute liver injury are lacking so far. Here we explore the role of KLF6 in acute liver injury models in mice, and in patients with acute liver failure (ALF). KLF6 was induced in hepatocytes in ALF, and in both acetaminophen (APAP)- and carbon tetrachloride (CCl4)-treated mice. In mice with hepatocyte-specific Klf6 knockout (DeltaKlf6), cell proliferation following partial hepatectomy (PHx) was increased compared to controls. Interestingly, key autophagic markers and mediators LC3-II, Atg7 and Beclin1 were reduced in DeltaKlf6 mice livers. Using luciferase assay and ChIP, KLF6 was established as a direct transcriptional activator of ATG7 and BECLIN1, but was dependent on the presence of p53. Here we show, that KLF6 expression is induced in ALF and in the regenerating liver, where it activates autophagy by transcriptional induction of ATG7 and BECLIN1 in a p53-dependent manner. These findings couple the activity of an important growth inhibitor in liver to the induction of autophagy in hepatocytes.
Novel twin-roll-cast Ti/Al clad sheets with excellent tensile properties
Authors: Kim Dae Woong , Lee Dong Ho , Kim Jung-Su , Sohn Seok Su , Kim Hyoung Seop , Lee Sunghak
Published: August 2017

Pure Ti or Ti alloys are recently spot-lighted in construction industries because they have excellent resistance to corrosions, chemicals, and climates as well as various coloring characteristics, but their wide applications are postponed by their expensiveness and poor formability. We present a new fabrication process of Ti/Al clad sheets by bonding a thin Ti sheet on to a 5052 Al alloy melt during vertical-twin-roll casting. This process has merits of reduced production costs as well as improved tensile properties. In the as-twin-roll-cast clad sheet, the homogeneously cast microstructure existed in the Al alloy substrate side, while the Ti/Al interface did not contain any reaction products, pores, cracks, or lateral delamination, which indicated the successful twin-roll casting. When this sheet was annealed at 350 °C~600 °C, the metallurgical bonding was expanded by interfacial diffusion, thereby leading to improvement in tensile properties over those calculated by a rule of mixtures. The ductility was also improved over that of 5052-O Al alloy (25%) or pure Ti (25%) by synergic effect of homogeneous deformation due to excellent Ti/Al bonding. This work provides new applications of Ti/Al clad sheets to lightweight-alloy clad sheets requiring excellent formability and corrosion resistance as well as alloy cost saving.
Stress hormone rapidly tunes synaptic NMDA receptor through membrane dynamics and mineralocorticoid signalling
Authors: Mikasova Lenka , Xiong Hui , Kerkhofs Amber , Bouchet Delphine , Krugers Harm J. , Groc Laurent
Published: August 2017

Stress hormones, such as corticosteroids, modulate the transmission of hippocampal glutamatergic synapses and NMDA receptor (NMDAR)-dependent synaptic plasticity, favouring salient behavioural responses to the environment. The corticosterone-induced synaptic adaptations partly rely on changes in NMDAR signalling, although the cellular pathway underlying this effect remains elusive. Here, we demonstrate, using single molecule imaging and electrophysiological approaches in hippocampal neurons, that corticosterone specifically controls GluN2B-NMDAR surface dynamics and synaptic content through mineralocorticoid signalling. Strikingly, extracellular corticosterone was sufficient to increase the trapping of GluN2B-NMDAR within synapses. Functionally, corticosterone-induced potentiation of AMPA receptor content in synapses required the changes in NMDAR surface dynamics. These high-resolution imaging data unveiled that, in hippocampal networks, corticosterone is a natural, potent, fast and specific regulator of GluN2B-NMDAR membrane trafficking, tuning NMDAR-dependent synaptic adaptations.
Drug-induced Extrapyramidal Symptoms Scale (DIEPSS) Serbian Language version: Inter-rater and Test-retest Reliability
Authors: Peljto Ami , Zamurovic Ljubica , Milovancevic Milica Pejovic , Aleksic Branko , Tosevski Dusica Lecic , Inada Toshiya
Published: August 2017

Drug-induced Extrapyramidal Symptoms Scale (DIEPSS) is developed in the era of second-generation antipsychotics and is suitable for evaluation of the low incidence of extrapyramidal symptoms occurring in the treatment of atypical antipsychotics, as well as the relationship between personal and social functioning. The study was carried out at the Institute of Mental Health in Serbia in 2015 Study used the 127 DIEPSS video clips material, recorded from 1987 till 2015. Four raters performed the assessment simultaneously, individually rating one assigned item immediately after seeing the video clip. For the purpose of evaluating test-retest reliability the second assessment of the same material was performed nine months after the first assessment. Inter-rater reliability was high for each individual item, with ICCs ranging from 0.769 to 0.949. The inter-rater reliability was highest for akathisia item and lowest for dyskinesia. The test-retest reliability was high for each individual item, with ICC ranging from 0.713 to 0.935. The test-retest reliability was highest for bradykinesia item and lowest for dystonia. The Serbian version of DIEPSS has high level of inter-rater and test-retest reliability. High values of concordance rates (ICC > 0.7) for each evaluated individual item suggest that items of DIEPSS are well defined.
Milk microbiome and bacterial load following dry cow therapy without antibiotics in dairy cows with healthy mammary gland
Authors: Bonsaglia Erika C. R. , Gomes Marilia S. , Canisso Igor F. , Zhou Ziyao , Lima Svetlana F. , Rall Vera L. M. , Oikonomou Georgios , Bicalho Rodrigo C. , Lima Fabio S.
Published: August 2017

Preventive infusion of antibiotics in the mammary gland of cows consumes 11 tons/year of medically relevant antimicrobials, yet, this practice might not be critical to prevent new infections in the healthy mammary gland of cows. Here, we used next-generation sequencing and quantitative real-time PCR to determine the impact of dry cow therapy without antibiotics on milk microbiome and bacterial load, respectively. Cows diagnosed as negative for mastitis at dry off were randomly allocated to receive antibiotic (intramammary ceftiofur hydrochloride) and teat sealant or just teat sealant. Firmicutes was the most abundant phylum, and Corynebacterium, Acinetobacter, and Staphylococcus, often involved in mastitis cases, were the most abundant genera across treatments and time. However, there were no effects of antimicrobial on milk microbiome and bacterial load. Bacterial load was greater at seven days postpartum than at dry off. Dry cow therapy based on teat sealant without antibiotics can be used with no detrimental impacts on milk microbiome and bacterial load in cows with a healthy mammary gland.
Hypothalamic effects of progesterone on regulation of the pulsatile and surge release of luteinising hormone in female rats
Authors: He Wen , Li Xiaofeng , Adekunbi Daniel , Liu Yali , Long Hui , Wang Li , Lyu Qifeng , Kuang Yanping , O’Byrne Kevin T.
Published: August 2017

Progesterone can block the oestradiol-induced GnRH/LH surge and inhibit LH pulse frequency. Recent studies reported that progesterone prevented premature LH surges during ovarian hyperstimulation in women. As the most potent stimulator of GnRH/LH release, kisspeptin is believed to mediate the positive and negative feedback effects of oestradiol in the hypothalamic anteroventral periventricular (AVPV) and arcuate (ARC) nuclei, while the region-specific role of progesterone receptors in these nuclei remains unknown. This study examined the hypothesis that progesterone inhibits LH surge and pulsatile secretion via its receptor in the ARC and/or AVPV nuclei. Adult female rats received a single injection of pregnant mare serum gonadotropin followed by progesterone or vehicle. Progesterone administration resulted in a significant prolongation of the oestrous cycle and blockade of LH surge. However, microinjection of the progesterone receptor antagonist, RU486, into the AVPV reversed the prolonged cycle length and rescued the progesterone blockade LH surge, while RU486 into the ARC shortened LH pulse interval in the progesterone treated rats. These results demonstrated that progesterone’s inhibitory effect on the GnRH/LH surge and pulsatile secretion is mediated by its receptor in the kisspeptin enriched hypothalamic AVPV and ARC respectively, which are essential for progesterone regulation of oestrous cyclicity in rats.
Molecular MR imaging of fibrosis in a mouse model of pancreatic cancer
Authors: Polasek Miloslav , Yang Yan , Schühle Daniel T. , Yaseen Mohammad A. , Kim Young R. , Sung Yu Sub , Guimaraes Alexander R. , Caravan Peter
Published: August 2017

Fibrosis with excessive amounts of type I collagen is a hallmark of many solid tumours, and fibrosis is a promising target in cancer therapy, but tools for its non-invasive quantification are missing. Here we used magnetic resonance imaging with a gadolinium-based probe targeted to type I collagen (EP-3533) to image and quantify fibrosis in pancreatic ductal adenocarcinoma. An orthotopic syngeneic mouse model resulted in tumours with 2.3-fold higher collagen level compared to healthy pancreas. Animals were scanned at 4.7 T before, during and up to 60 min after i.v. injection of EP-3533, or of its non-binding isomer EP-3612. Ex-vivo quantification of gadolinium showed significantly higher uptake of EP-3533 compared to EP-3612 in tumours, but not in surrounding tissue (blood, muscle). Uptake of EP-3533 visualized in T1-weighted MRI correlated well with spatial distribution of collagen determined by second harmonic generation imaging. Differences in the tumour pharmacokinetic profiles of EP-3533 and EP-3612 were utilized to distinguish specific binding to tumour collagen from non-specific uptake. A model-free pharmacokinetic measurement based on area under the curve was identified as a robust imaging biomarker of fibrosis. Collagen-targeted molecular MRI with EP-3533 represents a new tool for non-invasive visualization and quantification of fibrosis in tumour tissue.
Long-term chloride concentrations in North American and European freshwater lakes
Authors: Dugan Hilary A. , Summers Jamie C. , Skaff Nicholas K. , Krivak-Tetley Flora E. , Doubek Jonathan P. , Burke Samantha M. , Bartlett Sarah L. , Arvola Lauri , Jarjanazi Hamdi , Korponai János , Kleeberg Andreas , Monet Ghislaine , Monteith Don , Moore Karen , Rogora Michela , Hanson Paul C. , Weathers Kathleen C.
Published: August 2017

Anthropogenic sources of chloride in a lake catchment, including road salt, fertilizer, and wastewater, can elevate the chloride concentration in freshwater lakes above background levels. Rising chloride concentrations can impact lake ecology and ecosystem services such as fisheries and the use of lakes as drinking water sources. To analyze the spatial extent and magnitude of increasing chloride concentrations in freshwater lakes, we amassed a database of 529 lakes in Europe and North America that had greater than or equal to ten years of chloride data. For each lake, we calculated climate statistics of mean annual total precipitation and mean monthly air temperatures from gridded global datasets. We also quantified land cover metrics, including road density and impervious surface, in buffer zones of 100 to 1,500 m surrounding the perimeter of each lake. This database represents the largest global collection of lake chloride data. We hope that long-term water quality measurements in areas outside Europe and North America can be added to the database as they become available in the future.
The steroid metabolome in women with premenstrual dysphoric disorder during GnRH agonist-induced ovarian suppression: effects of estradiol and progesterone addback
Authors: Nguyen T V , Reuter J M , Gaikwad N W , Rotroff D M , Kucera H R , Motsinger-Reif A , Smith C P , Nieman L K , Rubinow D R , Kaddurah-Daouk R , Schmidt P J
Published: August 2017

Clinical evidence suggests that symptoms in premenstrual dysphoric disorder (PMDD) reflect abnormal responsivity to ovarian steroids. This differential steroid sensitivity could be underpinned by abnormal processing of the steroid signal. We used a pharmacometabolomics approach in women with prospectively confirmed PMDD (n=15) and controls without menstrual cycle-related affective symptoms (n=15). All were medication-free with normal menstrual cycle lengths. Notably, women with PMDD were required to show hormone sensitivity in an ovarian suppression protocol. Ovarian suppression was induced for 6 months with gonadotropin-releasing hormone (GnRH)-agonist (Lupron); after 3 months all were randomized to 4 weeks of estradiol (E2) or progesterone (P4). After a 2-week washout, a crossover was performed. Liquid chromatography/tandem mass spectrometry measured 49 steroid metabolites in serum. Values were excluded if >40% were below the limit of detectability (n=21). Analyses were performed with Wilcoxon rank-sum tests using false-discovery rate (q<0.2) for multiple comparisons. PMDD and controls had similar basal levels of metabolites during Lupron and P4-derived neurosteroids during Lupron or E2/P4 conditions. Both groups had significant increases in several steroid metabolites compared with the Lupron alone condition after treatment with E2 (that is, estrone-SO4 (q=0.039 and q=0.002, respectively) and estradiol-3-SO4 (q=0.166 and q=0.001, respectively)) and after treatment with P4 (that is, allopregnanolone (q=0.001 for both PMDD and controls), pregnanediol (q=0.077 and q=0.030, respectively) and cortexone (q=0.118 and q=0.157, respectively). Only sulfated steroid metabolites showed significant diagnosis-related differences. During Lupron plus E2 treatment, women with PMDD had a significantly attenuated increase in E2-3-sulfate (q=0.035) compared with control women, and during Lupron plus P4 treatment a decrease in DHEA-sulfate (q=0.07) compared with an increase in controls. Significant effects of E2 addback compared with Lupron were observed in women with PMDD who had significant decreases in DHEA-sulfate (q=0.065) and pregnenolone sulfate (q=0.076), whereas controls had nonsignificant increases (however, these differences did not meet statistical significance for a between diagnosis effect). Alterations of sulfotransferase activity could contribute to the differential steroid sensitivity in PMDD. Importantly, no differences in the formation of P4-derived neurosteroids were observed in this otherwise highly selected sample of women studied under controlled hormone exposures.
Identification of types of membrane injuries and cell death using whole cell-based proton-sensitive field-effect transistor systems
Authors: Imaizumi Yuki , Goda Tatsuro , Matsumoto Akira , Miyahara Yuji
Published: August 2017

Membrane injury and apoptosis of mammalian cells by chemical stimuli were distinguished using ammonia-perfused continuous pH-sensing systems.
Strategies for large-scale analysis of non-histone protein methylation by LC-MS/MS
Authors: Wang Qi , Wang Keyun , Ye Mingliang
Published: August 2017

Protein methylation is an important post-translational modification (PTM) that plays crucial roles in the regulation of diverse biological processes.
Unveiling universal trends for the energy level alignment in organic/oxide interfaces
Authors: Martínez José I. , Flores Fernando , Ortega José , Rangan Sylvie , Ruggieri Charles M. , Bartynski Robert A.
Published: August 2017

Organic/oxide interfaces exhibit an energy-level-alignment universal behaviour when a bias is applied. Coulomb-blockade regime is ruled by the organic electronegativity.
Critical adsorption of periodic and random polyampholytes onto charged surfaces
Authors: Caetano Daniel L. Z. , de Carvalho Sidney J. , Metzler Ralf , Cherstvy Andrey G.
Published: August 2017

What are the properties of critical adsorption of polyampholytes and polyelectrolytes onto charged surfaces?
Surface pKa of octanoic, nonanoic, and decanoic fatty acids at the air–water interface: applications to atmospheric aerosol chemistry
Authors: Wellen Bethany A. , Lach Evan A. , Allen Heather C.
Published: August 2017

Surface-pKa of medium-chain fatty acids, determined by surface tension titration, is different from the bulk value.
Monitoring thermally induced structural deformation and framework decomposition of ZIF-8 through in situ temperature dependent measurements
Authors: Xu Ben , Mei Yingjie , Xiao Zhenyu , Kang Zixi , Wang Rongming , Sun Daofeng
Published: August 2017

ZIF-8 undergoes three transition stages, which are lattice expansion stage, “reversible” structural deformation stage, and decomposition/collapse stage.
Photo-induced re-modulation of Pt particles loaded on V-TiO2 for enhanced CO photocatalytic oxidation
Authors: Xu Liming , Wang Shuting , Zhang Tingting , Chen Feng
Published: August 2017

On defective TiO2, photo-irradiation induces the re-modulation of Pt nanoparticles, which leads to an enhanced activity for CO photocatalytic oxidation.
Structure and catalytic activity of a newly proposed titanium species in a Ti-YNU-1 zeolite: a density functional theory study
Authors: Li Mengzhao , Wang Yichen , Wu Yue , Wang Meiqi , Zhou Danhong
Published: August 2017

Density functional theory was applied to investigate the structure of the framework titanium (Ti) species in the Ti-YNU-1 zeolite, and to evaluate its catalytic activity for 1-hexene epoxidation with H2O2 as the oxidant.
Antioxidant and anti-inflammatory activities of Geranium robertianum L. decoctions
Authors: Catarino Marcelo D. , Silva Artur M. S. , Cruz Maria Teresa , Cardoso Susana M.
Published: August 2017

The phenolic profile ofGeranium robertianumL. decoctions as well as their antioxidant and anti-inflammatory activities were investigated.