bluuebunny/crossref_metadata_2025 huggingface dataset:
Ernährungsdogmen durch den Fleischwolf: Wie viel bleibt am Knochen?
Authors: Fäh David
Published: March 2017

Zusammenfassung. Ernährungsempfehlungen stehen auf wackligen Füssen [1, 2]. Dies im Widerspruch zur Wahrnehmung vieler Menschen, dass Gebote und Verbote rund ums Essen und Trinken Dogma-Charakter haben. Da diese von den Medien gebetsmühlenartig wiederholt werden, ohne dass Wert auf Alter, Zahl, Art, Unabhängigkeit und Qualität der ursprünglichen Studien gelegt wird, halten sich vermeintliche Ernährungsweisheiten hartnäckig. Empfehlungen beruhen auf Expertenkonsens, die sich wiederum meistens auf Beobachtungsstudien stützen. Diese Studien haben zahlreiche Schwächen und lassen damit viel Raum für fehlerhafte Resultate und Interpretationen [1,2]. Somit können wir mit einer gewissen Entspanntheit an den Esstisch sitzen und uns auch mal zwischendurch etwas (angeblich) «Ungesundes» gönnen. Dies umso mehr, als dass es wahrscheinlich auch nicht schadet sich an eine Empfehlung zu halten, auch wenn sie nicht fundiert ist. Die Empfehlung täglich 1.5 bis zwei Liter Wasser kann kaum schaden, selbst wenn ihr Nutzen unklar ist [3 – 5]. Wichtig ist aber Augen und Ohren offen halten und Studienresultate kritisch zu werten und zu hinterfragen. Vom Knochen allein wird schliesslich niemand satt. Zugegeben: Manchmal fällt es einem schwer sich von fixen Vorstellungen zu lösen und neue Erkenntnisse anzunehmen: Wer hätte schon vor kurzem noch seinem allergiegefährdeten Kleinkind Erdnüsse zur Prophylaxe vorgesetzt [6]?
Possible Deep Cuts to NOAA Funding Worry Agency Supporters
Authors: Showstack Randy
Published: March 2017

The agency's acting administrator characterized the budget figures as preliminary and said NOAA is not being targeted.
miR-377 induces senescence in human skin fibroblasts by targeting DNA methyltransferase 1
Authors: Xie Hong-fu , Liu Ying-zi , Du Rui , Wang Ben , Chen Meng-ting , Zhang Yi-ya , Deng Zhi-li , Li Ji
Published: March 2017

Skin aging is a complicated physiological process and epigenetic feature, including microRNA-mediated regulation and DNA methylation, have been shown to contribute to this process. DNA methylation is regulated by DNA methyltransferase, of which DNA methyltransferase 1 (DNMT1) is the most abundantly known. But evidence supporting its role in skin aging remains scarce, and no report regards its specifical upstream-regulating molecules in the process of skin aging so far. Here, we found that DNMT1 expression was markedly higher in young human skin fibroblasts (HSFs) than that in passage-aged HSFs, and DNMT1 knockdown significantly induced the senescence phenotype in young HSFs. We predicted the upstream miRNAs which could regulate DNMT1 with miRNA databases and foundmiR-377had high homology with a sequence in the 3′-UTR of human DNMT1 mRNA. We confirmed thatmiR-377was a potential regulator of DNMT1 by luciferase reporter assays.miR-377expression in passage-aged HSFs was markedly higher than that in the young HSFs.miR-377overexpression promoted senescence in young HSFs, and inhibition ofmiR-377reduced senescence in passage-aged HSFs. Moreover, these functions were mediated by targeting DNMT1. Microfluidic PCR and next-generation bisulfite sequencing of 24 senescent-associated genes’ promoters revealed alterations of the promoter methylation levels ofFoxD3,p53,andUTF1in HSFs treated withmiR-377mimics or inhibitors. We also verified that themiR-377-mediated changes in p53 expression could be reversed by regulation of DNMT1 in HSFs. Similarly, there was a negative correlation betweenmiR-377and DNMT1 expression in young and photoaged HSFs, HSFs, or skin tissues from UV-unexposed areas of different aged donors. Our results highlight a novel role formiR-377-DNMT1-p53 axis in HSF senescence. These findings shed new light on the mechanisms of skin aging and identify future opportunities for its therapeutic prevention.
BBC3 in macrophages promoted pulmonary fibrosis development through inducing autophagy during silicosis
Authors: Liu Haijun , Cheng Yusi , Yang Jian , Wang Wei , Fang Shencun , Zhang Wei , Han Bing , Zhou Zewei , Yao Honghong , Chao Jie , Liao Hong
Published: March 2017

Following inhalation into the lungs, silica particles are engulfed by alveolar macrophages, which triggers endogenous or exogenous apoptosis signaling pathways. As an inducer of apoptosis, the role of BBC3/PUMA (BCL2-binding component 3) in macrophages during silicosis remains unknown. Here, we exposed U937 cell-derived macrophages (UDMs) to SiO2in vitro to explore the function of BBC3 in SiO2-induced disease. We found that SiO2 induced increased BBC3 expression, as well as macrophage activation and apoptosis. Knockdown of Bbc3 with specific siRNA significantly mitigated the SiO2-induced effects. In addition, our results clearly showed increased levels of autophagy in macrophages exposed to SiO2. However, inhibition of BBC3 decreased the occurrence of autophagy. Furthermore, we observed that the blockade of autophagy with 3-MA, an autophagy inhibitor, inhibited SiO2-induced macrophage activation and apoptosis. In contrast, rapamycin, an autophagy inducer, further enhanced the effects induced by SiO2. The conditioned medium from macrophages exposed to SiO2 promoted the proliferation and migration of fibroblasts, and the inhibition of BBC3/autophagy reduced the effects of the conditioned medium on fibroblasts. In the mouse model of silicosis, Bbc3 knockout mice clearly exhibited decreased levels of autophagy and fibrosis progression. These results suggest that downregulation of BBC3 expression may become a novel therapeutic strategy for the treatment of silicosis.
Long noncoding RNA BLACAT1 indicates a poor prognosis of colorectal cancer and affects cell proliferation by epigenetically silencing of p15
Authors: Su Jun , Zhang Erbao , Han Liang , Yin Dandan , Liu Zhili , He Xuezhi , Zhang Yuhong , Lin Feng , Lin Qingfeng , Mao Peiyao , Mao Weidong , Shen Dong
Published: March 2017

Recently, a novel class of transcripts, long noncoding RNAs (lncRNAs), is being identified at a rapid pace. These RNAs have critical roles in diverse biological processes, including tumorigenesis. One of them, BLACAT1, a cancer-associated long noncoding RNA, exerts regulatory functions in various biological processes in cancer cells, however, the role of BLACAT1 in colon cancer remains unclear. Our experiments showed that increased BLACAT1 was an independent unfavorable prognostic indicator for colorectal cancer, and revealed that BLACAT1 knockdown significantly repressed proliferation, both in vitro and in vivo. Mechanistic investigations demonstrated that BLACAT1 had a key role in G1/G0 arrest, and showed that BLACAT1 can repress p15 expression by binding to EZH2, thus contributing to the regulation of CRC cell cycle and proliferation. Our results suggest that BLACAT1, as a cell cycle regulator, may serve as a potential target for colon cancer prevention and treatment in human CRC.
The Shc1 adaptor simultaneously balances Stat1 and Stat3 activity to promote breast cancer immune suppression
Authors: Ahn Ryuhjin , Sabourin Valérie , Bolt Alicia M. , Hébert Steven , Totten Stephanie , De Jay Nicolas , Festa Maria Carolina , Young Yoon Kow , Im Young Kyuen , Pawson Tony , Koromilas Antonis E. , Muller William J. , Mann Koren K. , Kleinman Claudia L. , Ursini-Siegel Josie
Published: March 2017

Tyrosine kinase signalling within cancer cells is central to the establishment of an immunosuppressive microenvironment. Although tyrosine kinase inhibitors act, in part, to augment adaptive immunity, the increased heterogeneity and functional redundancy of the tyrosine kinome is a hurdle to achieving durable responses to immunotherapies. We previously identified the Shc1 (ShcA) scaffold, a central regulator of tyrosine kinase signalling, as essential for promoting breast cancer immune suppression. Herein we show that the ShcA pathway simultaneously activates STAT3 immunosuppressive signals and impairs STAT1-driven immune surveillance in breast cancer cells. Impaired Y239/Y240-ShcA phosphorylation selectively reduces STAT3 activation in breast tumours, profoundly sensitizing them to immune checkpoint inhibitors and tumour vaccines. Finally, the ability of diminished tyrosine kinase signalling to initiate STAT1-driven immune surveillance can be overcome by compensatory STAT3 hyperactivation in breast tumours. Our data indicate that inhibition of pY239/240-ShcA-dependent STAT3 signalling may represent an attractive therapeutic strategy to sensitize breast tumours to multiple immunotherapies.
Intervalley scattering by acoustic phonons in two-dimensional MoS2 revealed by double-resonance Raman spectroscopy
Authors: Carvalho Bruno R. , Wang Yuanxi , Mignuzzi Sandro , Roy Debdulal , Terrones Mauricio , Fantini Cristiano , Crespi Vincent H. , Malard Leandro M. , Pimenta Marcos A.
Published: March 2017

Double-resonance Raman scattering is a sensitive probe to study the electron-phonon scattering pathways in crystals. For semiconducting two-dimensional transition-metal dichalcogenides, the double-resonance Raman process involves different valleys and phonons in the Brillouin zone, and it has not yet been fully understood. Here we present a multiple energy excitation Raman study in conjunction with density functional theory calculations that unveil the double-resonance Raman scattering process in monolayer and bulk MoS2. Results show that the frequency of some Raman features shifts when changing the excitation energy, and first-principle simulations confirm that such bands arise from distinct acoustic phonons, connecting different valley states. The double-resonance Raman process is affected by the indirect-to-direct bandgap transition, and a comparison of results in monolayer and bulk allows the assignment of each Raman feature near the M or K points of the Brillouin zone. Our work highlights the underlying physics of intervalley scattering of electrons by acoustic phonons, which is essential for valley depolarization in MoS2.
Niobium pentoxide: a promising surface-enhanced Raman scattering active semiconductor substrate
Authors: Shan Yufeng , Zheng Zhihui , Liu Jianjun , Yang Yong , Li Zhiyuan , Huang Zhengren , Jiang Dongliang
Published: March 2017

Surface-enhanced Raman scattering technique, as a powerful tool to identify the molecular species, has been severely restricted to the noble metals. The surface-enhanced Raman scattering substrates based on semiconductors would overcome the shortcomings of metal substrates and promote development of surface-enhanced Raman scattering technique in surface science, spectroscopy, and biomedicine studies. However, the detection sensitivity and enhancement effects of semiconductor substrates are suffering from their weak activities. In this work, a semiconductor based on Nb2O5 is reported as a new candidate for highly sensitive surface-enhanced Raman scattering detection of dye molecules. The largest enhancement factor value greater than 107 was observed with the laser excitation at 633 and 780 nm for methylene blue detection. As far as literature review shows, this is in the rank of the highest sensitivity among semiconductor materials; even comparable to the metal nanostructure substrates with “hot spots”. The impressive surface-enhanced Raman scattering activities can be attributed to the chemical enhancement dominated by the photo-induced charge transfer, as well as the electromagnetic enhancement, which have been supported by the density-functional-theory and finite element method calculation results. The chemisorption of dye on Nb2O5 creates a new highest occupied molecular orbital and lowest unoccupied molecular orbital contributed by both fragments in the molecule-Nb2O5 system, which makes the charge transfer more feasible with longer excitation wavelength. In addition, the electromagnetic enhancement mechanism also accounts for two orders of magnitude enhancement in the overall enhancement factor value. This work has revealed Nb2O5 nanoparticles as a new semiconductor surface-enhanced Raman scattering substrate that is able to replace noble metals and shows great potentials applied in the fields of biology related.
Distribution and impact on quality of life of the pain modalities assessed by the King’s Parkinson’s disease pain scale
Authors: Martinez-Martin Pablo , Manuel Rojo-Abuin Jose , Rizos Alexandra , Rodriguez-Blazquez Carmen , Trenkwalder Claudia , Perkins Lauren , Sauerbier Anna , Odin Per , Antonini Angelo , Chaudhuri Kallol Ray ,   on behalf of KPPS, EUROPAR and the IPMDS Non Motor PD Study Group
Published: March 2017

In Parkinson’s disease, pain is a prevalent and complex symptom of diverse origin. King’s Parkinson’s disease pain scale, assesses different pain syndromes, thus allowing exploration of its differential prevalence and influence on the health-related quality of life of patients. Post hoc study 178 patients and 83 matched controls participating in the King’s Parkinson’s disease pain scale validation study were used. For determining the respective distribution, King’s Parkinson’s disease pain scale items and domains scores = 0 meant absence and ≥1 presence of the symptom. The regular scores were used for the other analyses. Health-related quality of lifewas evaluated with EQ-5D-3L and PDQ-8 questionnaires. Parkinson’s disease patients experienced more pain modalities than controls. In patients, Pain around joints (King’s Parkinson’s disease pain scale item 1) and Pain while turning in bed (item 8) were the most prevalent types of pain, whereas Burning mouth syndrome (item 11) and Pain due to grinding teeth (item 10) showed the lowest frequency. The total number of experienced pain modalities closely correlated with the PDQ-8 index, but not with other variables. For all pain types except Pain around joints (item 1) and pain related to Periodic leg movements/RLS (item 7), patients with pain had significantly worse health-related quality of life. The influence of pain, as a whole, on the health-related quality of life was not remarkable after adjustment by other variables. When the particular types of pain were considered, adjusted by sex, age, and Parkinson’s disease duration, pain determinants were different for EQ-5D-3L and PDQ-8. King’s Parkinson’s disease pain scale allows exploring the distribution of the diverse syndromic pain occurring in Parkinson’s disease and its association with health-related quality of life.
The combination of three-dimensional and rotary cell culture system promotes the proliferation and maintains the differentiation potential of rat BMSCs
Authors: Tang Yilong , Xu Yan , Xiao Zhifeng , Zhao Yannan , Li Jing , Han Sufang , Chen Lei , Dai Bin , Wang Ling , Chen Bing , Wang Hong
Published: March 2017

Bone marrow mesenchymal stem cells (BMSCs) are a good candidate for tissue engineering and clinical application. One of the challenges in its cell therapy is how to quickly obtain an adequate number of seed cells and meanwhile maintain suitable differentiation potential. In this study we combined three-dimensional (3D) collagen porous scaffolds with rotary cell culture system (RCCS) (RCCS-3D) to create a stereoscopic dynamic environment for the amplification of rat BMSCs in vitro. The results revealed that this RCCS-3D system could enhance BMSCs’ proliferation and colony formation, as well as maintain the differentiation potential compared with conventional static two-dimensional (2D) and 3D cell culture conditions. In addition, high-throughput microarray analysis showed that gene expressions of RCCS-3D system displayed significant differences in cell proliferation and differentiation compared with static-2D conditions. Thus, RCCS-3D system could provide an effective means for BMSCs cell proliferation in vitro and meanwhile maintain differentiation potential in tissue engineering.
Proteomic analysis of proteome and histone post-translational modifications in heat shock protein 90 inhibition-mediated bladder cancer therapeutics
Authors: Li Qingdi Quentin , Hao Jian-Jiang , Zhang Zheng , Krane L. Spencer , Hammerich Kai H. , Sanford Thomas , Trepel Jane B. , Neckers Len , Agarwal Piyush K.
Published: March 2017

Heat shock protein 90 (HSP90) inhibition is an attractive strategy for cancer treatment. Several HSP90 inhibitors have shown promising effects in clinical oncology trials. However, little is known about HSP90 inhibition-mediated bladder cancer therapy. Here, we report a quantitative proteomic study that evaluates alterations in protein expression and histone post-translational modifications (PTMs) in bladder carcinoma in response to HSP90 inhibition. We show that 5 HSP90 inhibitors (AUY922, ganetespib, SNX2112, AT13387, and CUDC305) potently inhibited the proliferation of bladder cancer 5637 cells in a dose- and time-dependent manner. Our proteomic study quantified 518 twofold up-regulated and 811 twofold down-regulated proteins common to both AUY922 and ganetespib treatment. Bioinformatic analyses revealed that those differentially expressed proteins were involved in multiple cellular processes and enzyme-regulated signaling pathways, including chromatin modifications and cell death-associated pathways. Furthermore, quantitative proteome studies identified 14 types of PTMs with 93 marks on the core histones, including 34 novel histone marks of butyrylation, citrullination, 2-hydroxyisobutyrylation, methylation, O-GlcNAcylation, propionylation, and succinylation in AUY922- and ganetespib-treated 5637 cells. Together, this study outlines the association between proteomic changes and histone PTMs in response to HSP90 inhibitor treatment in bladder carcinoma cells, and thus intensifies the understanding of HSP90 inhibition-mediated bladder cancer therapeutics.
Role for the ATPase inhibitory factor 1 in the environmental carcinogen-induced Warburg phenotype
Authors: Hardonnière Kévin , Fernier Morgane , Gallais Isabelle , Mograbi Baharia , Podechard Normand , Le Ferrec Eric , Grova Nathalie , Appenzeller Brice , Burel Agnès , Chevanne Martine , Sergent Odile , Huc Laurence , Bortoli Sylvie , Lagadic-Gossmann Dominique
Published: March 2017

Most tumors undergo metabolic reprogramming towards glycolysis, the so-called Warburg effect, to support growth and survival. Overexpression of IF1, the physiological inhibitor of the F0F1ATPase, has been related to this phenomenon and appears to be a relevant marker in cancer. Environmental contributions to cancer development are now widely accepted but little is known about the underlying intracellular mechanisms. Among the environmental pollutants humans are commonly exposed to, benzo[a]pyrene (B[a]P), the prototype molecule of polycyclic aromatic hydrocarbons (PAHs), is a well-known human carcinogen. Besides apoptotic signals, B[a]P can also induce survival signals in liver cells, both likely involved in cancer promotion. Our previous works showed that B[a]P elicited a Warburg-like effect, thus favoring cell survival. The present study aimed at further elucidating the molecular mechanisms involved in the B[a]P-induced metabolic reprogramming, by testing the possible involvement of IF1. We presently demonstrate, both in vitro and in vivo, that PAHs, especially B[a]P, strongly increase IF1 expression. Such an increase, which might rely on β2-adrenergic receptor activation, notably participates to the B[a]P-induced glycolytic shift and cell survival in liver cells. By identifying IF1 as a target of PAHs, this study provides new insights about how environmental factors may contribute to related carcinogenesis.
The Size of Spontaneous Pneumothorax is a Predictor of Unsuccessful Catheter Drainage
Authors: Tsai Tung-Ming , Lin Mong-Wei , Li Yao-Jen , Chang Chin-Hao , Liao Hsien-Chi , Liu Chao-Yu , Hsu Hsao-Hsun , Chen Jin-Shing
Published: March 2017

Small-bore thoracic catheter drainage is recommended for a first large or symptomatic episode of primary spontaneous pneumothorax (PSP). However, one-third of these patients require a second procedure because of treatment failure. We investigated the factors associated with unsuccessful pigtail catheter drainage in the management of PSP. In this retrospective study, using a prospectively collected database, we enrolled 253 consecutive patients with PSP who underwent pigtail catheter drainage as initial treatment, from December 2006 to June 2011. The chest radiograph was reviewed in each case and pneumothorax size was estimated according to Light’s index. Other demographic factors and laboratory data were collected via chart review. Pigtail catheter drainage was successful in 71.9% (182/253) of cases. Treatment failure rates were 42.9%, 25.9%, and 15.5% in patients with pneumothorax sizes of >62.6%, 38–62.6%, and <38%, respectively (tertiles). An alternative cut-off point of 92.5% lung collapse was defined using a classification and regression tree method. According to the multivariate analysis, a large-size pneumothorax (p = 0.009) was the only significant predictor of initial pigtail catheter drainage treatment failure in patients with PSP. Early surgical treatment could be considered for those patients with a large-sized pneumothorax.
MKL1 defines the H3K4Me3 landscape for NF-κB dependent inflammatory response
Authors: Yu Liming , Fang Fei , Dai Xin , Xu Huihui , Qi Xiaohong , Fang Mingming , Xu Yong
Published: March 2017

Macrophage-dependent inflammatory response is considered a pivotal biological process that contributes to a host of diseases when aberrantly activated. The underlying epigenetic mechanism is not completely understood. We report here that MKL1 was both sufficient and necessary for p65-dependent pro-inflammatory transcriptional program in immortalized macrophages, in primary human and mouse macrophages, and in an animal model of systemic inflammation (endotoxic shock). Extensive chromatin immunoprecipitation (ChIP) profiling and ChIP-seq analyses revealed that MKL1 deficiency erased key histone modifications synonymous with transactivation on p65 target promoters. Specifically, MKL1 defined histone H3K4 trimethylation landscape for NF-κB dependent transcription. MKL1 recruited an H3K4 trimethyltransferase SET1 to the promoter regions of p65 target genes. There, our work has identified a novel modifier of p65-dependent pro-inflammatory transcription, which may serve as potential therapeutic targets in treating inflammation related diseases.
Fast and precise detection of DNA methylation with tetramethylammonium-filled nanopore
Authors: Wang Ying , Zhang Yani , Guo Yanli , Kang Xiao-feng
Published: March 2017

The tremendous demand for detecting methylated DNA has stimulated intensive studies on developing fast single-molecule techniques with excellent sensitivity, reliability, and selectivity. However, most of these methods cannot directly detect DNA methylation at single-molecule level, which need either special recognizing elements or chemical modification of DNA. Here, we report a tetramethylammonium-based nanopore (termed TMA-NP) sensor that can quickly and accurately detect locus-specific DNA methylation, without bisulfite conversion, chemical modification or enzyme amplification. In the TMA-NP sensor, TMA-Cl is utilized as a nanopore-filling electrolyte to record the ion current change in a single nanopore triggered by methylated DNA translocation through the pore. Because of its methyl-philic nature, TMA can insert into the methylcytosine-guanine (mC-G) bond and then effectively unfasten and reduce the mC-G strength by 2.24 times. Simultaneously, TMA can increase the stability of A-T to the same level as C-G. The abilities of TMA (removing the base pair composition dependence of DNA strands, yet highly sensing for methylated base sites) endow the TMA-NP sensor with high selectivity and high precision. Using nanopore to detect dsDNA stability, the methylated and unmethylated bases are easily distinguished. This simple single-molecule technique should be applicable to the rapid analysis in epigenetic research.
Ascl1 promotes tangential migration and confines migratory routes by induction of Ephb2 in the telencephalon
Authors: Liu Yuan-Hsuan , Tsai Jin-Wu , Chen Jia-Long , Yang Wan-Shan , Chang Pei-Ching , Cheng Pei-Lin , Turner David L. , Yanagawa Yuchio , Wang Tsu-Wei , Yu Jenn-Yah
Published: March 2017

During development, cortical interneurons generated from the ventral telencephalon migrate tangentially into the dorsal telencephalon. Although Achaete-scute family bHLH transcription factor 1 (Ascl1) plays important roles in the developing telencephalon, whether Ascl1 regulates tangential migration remains unclear. Here, we found that Ascl1 promoted tangential migration along the ventricular zone/subventricular zone (VZ/SVZ) and intermediate zone (IZ) of the dorsal telencephalon. Distal-less homeobox 2 (Dlx2) acted downstream of Ascl1 in promoting tangential migration along the VZ/SVZ but not IZ. We further identified Eph receptor B2 (Ephb2) as a direct target of Ascl1. Knockdown of EphB2 disrupted the separation of the VZ/SVZ and IZ migratory routes. Ephrin-A5, a ligand of EphB2, was sufficient to repel both Ascl1-expressing cells in vitro and tangentially migrating cortical interneurons in vivo. Together, our results demonstrate that Ascl1 induces expression of Dlx2 and Ephb2 to maintain distinct tangential migratory routes in the dorsal telencephalon.
Correction: Corrigendum: The green peach aphid Myzus persicae perform better on pre-infested Chinese cabbage Brassica pekinensis by enhancing host plant nutritional quality
Authors: Cao He-He , Liu Hui-Ru , Zhang Zhan-Feng , Liu Tong-Xian
Published: March 2017

Scientific Reports 6: Article number: 21954; published online: 24 February 2016; updated: 09 March 2017 In the original version of this Article, Affiliations 1 and 2 were incomplete. The correct affiliations are listed below. State Key Laboratory for Crop Stress Biology in Arid Areas, Northwest A&F University, Yangling, Shaanxi, 712100, China.
Correction: Corrigendum: Trade-offs between driving nodes and time-to-control in complex networks
Authors: Pequito Sérgio , Preciado Victor M. , Barabási Albert-László , Pappas George J.
Published: March 2017

Scientific Reports 7: Article number: 39978; published online: 05 January 2017; updated: 09 March 2017 This Article contains an error in the order of the Figures. Figures 1, 2, 3 and 4 were published as Figures 2, 4, 1 and 3 respectively. The correct Figures appear below. The Figure legends are correct.
Beta-trace Protein as a new non-invasive immunological Marker for Quinolinic Acid-induced impaired Blood-Brain Barrier Integrity
Authors: Baranyi Andreas , Amouzadeh-Ghadikolai Omid , Lewinski Dirk von , Breitenecker Robert J. , Stojakovic Tatjana , März Winfried , Robier Christoph , Rothenhäusler Hans-Bernd , Mangge Harald , Meinitzer Andreas
Published: March 2017

Quinolinic acid, a macrophage/microglia-derived excitotoxin fulfills a plethora of functions such as neurotoxin, gliotoxin, and proinflammatory mediator, and it alters the integrity and cohesion of the blood-brain barrier in several pathophysiological states. Beta-trace protein (BTP), a monomeric glycoprotein, is known to indicate cerebrospinal fluid leakage. Thus, the prior aim of this study was to investigate whether BTP might non-invasively indicate quinolinic acid-induced impaired blood-brain barrier integrity. The research hypotheses were tested in three subsamples with different states of immune activation (patients with HCV-infection and interferon-α, patients with major depression, and healthy controls). BTP has also been described as a sensitive marker in detecting impaired renal function. Thus, the renal function has been considered. Our study results revealed highest quinolinic acid and highest BTP- levels in the subsample of patients with HCV in comparison with the other subsamples with lower or no immune activation (quinolinic acid: F = 21.027, p < 0.001 [ANOVA]; BTP: F = 6.792, p < 0.01 [ANOVA]). In addition, a two-step hierarchical linear regression model showed that significant predictors of BTP levels are quinolinic acid, glomerular filtration rate and age. The neurotoxin quinolinic acid may impair blood-brain barrier integrity. BTP might be a new non-invasive biomarker to indicate quinolinic acid-induced impaired blood-brain barrier integrity.
High-frequency Coastal Overwash Deposits from Phra Thong Island, Thailand
Authors: Gouramanis Chris , Switzer Adam D. , Jankaew Kruawun , Bristow Charles S. , Pham Dat T. , Ildefonso Sorvigenaleon R.
Published: March 2017

The 26th December 2004 Indian Ocean Tsunami (IOT) emanated from an Mw 9.2 earthquake that generated a 1600 km-long rupture along the Sumatran Megathrust and generated tsunami waves up to 30 m high. The IOT directly impacted the Bay of Bengal and east Africa, with over 283,000 people perishing. At the time, this catastrophic event was considered unprecedented and sparked intense investigations to test this claim. It is now believed that four pre-2004 IOT events have occurred in the last 2500 years, recurring every 550 to 700 years. Much of this information comes from Phra Thong Island, Thailand, where a sequence of four stacked sandsheets separated by organic units has been recognised and compared to the 2004 IOT event. Recently, ground-penetrating radar on Phra Thong Island identified a region that could not be explained by the known stratigraphy. The stratigraphy of the area was investigated from auger cores and pits, and several previously-unrecognised sandsheets were identified and compared to the known tsunami sandsheets. The proximity of the newly-recognised sandsheets to the palaeo-coastline of Phra Thong Island does not preclude the impacts of localised storms in sandsheet emplacement or that tsunamigenic earthquake recurrence may have been more frequent in the past.
Blood DNA methylation pattern is altered in mesial temporal lobe epilepsy
Authors: Long Hong-Yu , Feng Li , Kang Jin , Luo Zhao-Hui , Xiao Wen-Biao , Long Li-Li , Yan Xiao-Xin , Zhou Luo , Xiao Bo
Published: March 2017

Mesial temporal lobe epilepsy (MTLE) is a common epileptic disorder; little is known whether it is associated with peripheral epigenetic changes. Here we compared blood whole genomic DNA methylation pattern in MTLE patients (n = 30) relative to controls (n = 30) with the Human Methylation 450 K BeadChip assay, and explored genes and pathways that were differentially methylated using bioinformatics profiling. The MTLE and control groups showed significantly different (P < 1.03e-07) DNA methylation at 216 sites, with 164 sites involved hyper- and 52 sites hypo- methylation. Two hyper- and 32 hypo-methylated sites were associated with promoters, while 87 hyper- and 43 hypo-methylated sites corresponded to coding regions. The differentially methylated genes were largely related to pathways predicted to participate in anion binding, oxidoreductant activity, growth regulation, skeletal development and drug metabolism, with the most distinct ones included SLC34A2, CLCN6, CLCA4, CYP3A43, CYP3A4 and CYP2C9. Among the MTLE patients, panels of genes also appeared to be differentially methylated relative to disease duration, resistance to anti-epileptics and MRI alterations of hippocampal sclerosis. The peripheral epigenetic changes observed in MTLE could be involved in certain disease-related modulations and warrant further translational investigations.
Coral reef grazer-benthos dynamics complicated by invasive algae in a small marine reserve
Authors: Stamoulis Kostantinos A. , Friedlander Alan M. , Meyer Carl G. , Fernandez-Silva Iria , Toonen Robert J.
Published: March 2017

Blooms of alien invasive marine algae have become common, greatly altering the health and stability of nearshore marine ecosystems. Concurrently, herbivorous fishes have been severely overfished in many locations worldwide, contributing to increases in macroalgal cover. We used a multi-pronged, interdisciplinary approach to test if higher biomass of herbivorous fishes inside a no-take marine reserve makes this area more resistant to invasive algal overgrowth. Over a two year time period, we (1) compared fish biomass and algal cover between two fished and one unfished patch reef in Hawai’i, (2) used acoustic telemetry to determine fidelity of herbivorous fishes to the unfished reef, and (3) used metabarcoding and next-generation sequencing to determine diet composition of herbivorous fishes. Herbivore fish biomass was significantly higher in the marine reserve compared to adjacent fished reefs, whereas invasive algal cover differed by species. Herbivorous fish movements were largely confined to the unfished patch reef where they were captured. Diet analysis indicated that the consumption of invasive algae varied among fish species, with a high prevalence of comparatively rare native algal species. Together these findings demonstrate that the contribution of herbivores to coral reef resilience, via resistance to invasive algae invasion, is complex and species-specific.
Subliminal stimuli modulate somatosensory perception rhythmically and provide evidence for discrete perception
Authors: Baumgarten Thomas J. , Königs Sara , Schnitzler Alfons , Lange Joachim
Published: March 2017

Despite being experienced as continuous, there is an ongoing debate if perception is an intrinsically discrete process, with incoming sensory information treated as a succession of single perceptual cycles. Here, we provide causal evidence that somatosensory perception is composed of discrete perceptual cycles. We used in humans an electrotactile temporal discrimination task preceded by a subliminal (i.e., below perceptual threshold) stimulus. Although not consciously perceived, subliminal stimuli are known to elicit neuronal activity in early sensory areas and modulate the phase of ongoing neuronal oscillations. We hypothesized that the subliminal stimulus indirectly, but systematically modulates the ongoing oscillatory phase in S1, thereby rhythmically shaping perception. The present results confirm that, without being consciously perceived, the subliminal stimulus critically influenced perception in the discrimination task. Importantly, perception was modulated rhythmically, in cycles corresponding to the beta-band (13–18 Hz). This can be compellingly explained by a model of discrete perceptual cycles.
The human mitochondrial transcription factor A is a versatile G-quadruplex binding protein
Authors: Lyonnais Sébastien , Tarrés-Solé Aleix , Rubio-Cosials Anna , Cuppari Anna , Brito Reicy , Jaumot Joaquim , Gargallo Raimundo , Vilaseca Marta , Silva Cristina , Granzhan Anton , Teulade-Fichou Marie-Paule , Eritja Ramon , Solà Maria
Published: March 2017

The ability of the guanine-rich strand of the human mitochondrial DNA (mtDNA) to form G-quadruplex structures (G4s) has been recently highlighted, suggesting potential functions in mtDNA replication initiation and mtDNA stability. G4 structures in mtDNA raise the question of their recognition by factors associated with the mitochondrial nucleoid. The mitochondrial transcription factor A (TFAM), a high-mobility group (HMG)-box protein, is the major binding protein of human mtDNA and plays a critical role in its expression and maintenance. HMG-box proteins are pleiotropic sensors of DNA structural alterations. Thus, we investigated and uncovered a surprising ability of TFAM to bind to DNA or RNA G4 with great versatility, showing an affinity similar than to double-stranded DNA. The recognition of G4s by endogenous TFAM was detected in mitochondrial extracts by pull-down experiments using a G4-DNA from the mtDNA conserved sequence block II (CSBII). Biochemical characterization shows that TFAM binding to G4 depends on both the G-quartets core and flanking single-stranded overhangs. Additionally, it shows a structure-specific binding mode that differs from B-DNA, including G4-dependent TFAM multimerization. These TFAM-G4 interactions suggest functional recognition of G4s in the mitochondria.
Experimental assessment of the safety and potential efficacy of high irradiance photostimulation of brain tissues
Authors: Senova Suhan , Scisniak Ilona , Chiang Chih-Chieh , Doignon Isabelle , Palfi Stéphane , Chaillet Antoine , Martin Claire , Pain Frédéric
Published: March 2017

Optogenetics is widely used in fundamental neuroscience. Its potential clinical translation for brain neuromodulation requires a careful assessment of the safety and efficacy of repeated, sustained optical stimulation of large volumes of brain tissues. This study was performed in rats and not in non-human primates for ethical reasons. We studied the spatial distribution of light, potential damage, and non-physiological effects in vivo, in anesthetized rat brains, on large brain volumes, following repeated high irradiance photo-stimulation. We generated 2D irradiance and temperature increase surface maps based on recordings taken during optical stimulation using irradiance and temporal parameters representative of common optogenetics experiments. Irradiances of 100 to 600 mW/mm2 with 5 ms pulses at 20, 40, and 60 Hz were applied during 90 s. In vivo electrophysiological recordings and post-mortem histological analyses showed that high power light stimulation had no obvious phototoxic effects and did not trigger non-physiological functional activation. This study demonstrates the ability to illuminate cortical layers to a depth of several millimeters using pulsed red light without detrimental thermal damages.
NV Proteins of Fish Novirhabdovirus Recruit Cellular PPM1Bb Protein Phosphatase and Antagonize RIG-I-Mediated IFN Induction
Authors: Biacchesi Stéphane , Mérour Emilie , Chevret Didier , Lamoureux Annie , Bernard Julie , Brémont Michel
Published: March 2017

Non virion (NV) protein expression is critical for fish Novirhabdovirus, viral hemorrhagic septicemia virus (VHSV) and infectious hematopoietic necrosis virus (IHNV), in vivo pathogenesis. However, the mechanism by which NV promotes the viral replication is still unclear. We developed an approach based on reverse genetics and interactomic and identified several NV-associated cellular partners underlying cellular pathways as potential viral targets. Among these cell partners, we showed that NV proteins specifically interact with a protein phosphatase, Mg2+/Mn2+-dependent, 1Bb (PPM1Bb) and recruit it in the close vicinity of mitochondria, a subcellular compartment important for retinoic acid-inducible gene-I- (RIG-I)-mediated interferon induction pathway. PPM1B proteins belong to the PP2C family of serine/threonine (Ser/Thr) protein phosphatase and have recently been shown to negatively regulate the host antiviral response via dephosphorylating Traf family member-associated NF-κB activator (TANK)-binding kinase 1 (TBK1). We demonstrated that NV proteins and PPM1Bb counteract RIG-I- and TBK1-dependent interferon (IFN) and IFN-stimulated gene promoter induction in fish cells and, hence, the establishment of an antiviral state. Furthermore, the expression of VHSV NV strongly reduced TBK1 phosphorylation and thus its activation. Our findings provide evidence for a previously undescribed mechanism by which a viral protein recruits PPM1Bb protein phosphatase to subvert innate immune recognition.
Identification of berberine as a direct thrombin inhibitor from traditional Chinese medicine through structural, functional and binding studies
Authors: Wang Xing , Zhang Yuxin , Yang Ying , Wu Xia , Fan Hantian , Qiao Yanjiang
Published: March 2017

Thrombin acts as a key enzyme in the blood coagulation cascade and represents a potential drug target for the treatment of several cardiovascular diseases. The aim of this study was to identify small-molecule direct thrombin inhibitors from herbs used in traditional Chinese medicine (TCM). A pharmacophore model and molecular docking were utilized to virtually screen a library of chemicals contained in compositions of traditional Chinese herbs, and these analyses were followed by in vitro bioassay validation and binding studies. Berberine (BBR) was first confirmed as a thrombin inhibitor using an enzymatic assay. The BBR IC50 value for thrombin inhibition was 2.92 μM. Direct binding studies using surface plasmon resonance demonstrated that BBR directly interacted with thrombin with a KD value of 16.39 μM. Competitive binding assay indicated that BBR could bind to the same argartroban/thrombin interaction site. A platelet aggregation assay demonstrated that BBR had the ability to inhibit thrombin-induced platelet aggregation in washed platelets samples. This study proved that BBR is a direct thrombin inhibitor that has activity in inhibiting thrombin-induced platelet aggregation. BBR may be a potential candidate for the development of safe and effective thrombin-inhibiting drugs.
Engineering a vascularised 3D in vitro model of cancer progression
Authors: Magdeldin Tarig , López-Dávila Víctor , Pape Judith , Cameron Grant W. W. , Emberton Mark , Loizidou Marilena , Cheema Umber
Published: March 2017

The hallmark of tumours is the ability of cancerous cells to promote vascular growth, to disseminate and invade to distant organs. The metastatic process is heavily influenced by the extracellular matrix (ECM) density and composition of the surrounding tumour microenvironment. These microenvironmental cues, which include hypoxia, also regulate the angiogenic processes within a tumour, facilitating the spread of cancer cells. We engineered compartmentalized biomimetic colorectal tumouroids with stromal surrounds that comprised a range of ECM densities, composition and stromal cell populations. Recapitulating tissue ECM composition and stromal cell composition enhanced cancer cell invasion. Manipulation of ECM density was associated with an altered migration pattern from glandular buds (cellular aggregates) to epithelial cell sheets. Laminin appeared to be a critical component in regulating endothelial cell morphology and vascular network formation. Interestingly, the disruption of vascular networks by cancer cells was driven by changes in expression of several anti-angiogenic genes. Cancer cells cultured in our biomimetic tumouroids exhibited intratumoural heterogeneity that was associated with increased tumour invasion into the stroma. These findings demonstrate that our 3D in vitro tumour model exhibits biomimetic attributes that may permit their use in studying microenvironment clues of tumour progression and angiogenesis.
Meprin Metalloproteases Generate Biologically Active Soluble Interleukin-6 Receptor to Induce Trans-Signaling
Authors: Arnold Philipp , Boll Inga , Rothaug Michelle , Schumacher Neele , Schmidt Frederike , Wichert Rielana , Schneppenheim Janna , Lokau Juliane , Pickhinke Ute , Koudelka Tomas , Tholey Andreas , Rabe Björn , Scheller Jürgen , Lucius Ralph , Garbers Christoph , Rose-John Stefan , Becker-Pauly Christoph
Published: March 2017

Soluble Interleukin-6 receptor (sIL-6R) mediated trans-signaling is an important pro-inflammatory stimulus associated with pathological conditions, such as arthritis, neurodegeneration and inflammatory bowel disease. The sIL-6R is generated proteolytically from its membrane bound form and A Disintegrin And Metalloprotease (ADAM) 10 and 17 were shown to perform ectodomain shedding of the receptorin vitroandin vivo. However, under certain conditions not all sIL-6R could be assigned to ADAM10/17 activity. Here, we demonstrate that the IL-6R is a shedding substrate of soluble meprin α and membrane bound meprin β, resulting in bioactive sIL-6R that is capable of inducing IL-6 trans-signaling. We determined cleavage within the N-terminal part of the IL-6R stalk region, distinct from the cleavage site reported for ADAM10/17. Interestingly, meprin β can be shed from the cell surface by ADAM10/17 and the observation that soluble meprin β is not capable of shedding the IL-6R suggests a regulatory mechanism towards trans-signaling. Additionally, we observed a significant negative correlation of meprin β expression and IL-6R levels on human granulocytes, providing evidence forin vivofunction of this proteolytic interaction.
Processing of fair and unfair offers in the ultimatum game under social observation
Authors: Peterburs Jutta , Voegler Rolf , Liepelt Roman , Schulze Anna , Wilhelm Saskia , Ocklenburg Sebastian , Straube Thomas
Published: March 2017

Social context influences social decisions and outcome processing, partially depending on inter-individual differences. The present study investigated social context-dependent modulation of behavior and feedback processing in the ultimatum game (UG) in relation to inter-individual differences in social anxiety. Thirty-two healthy adults completed the UG both under social observation and without observation. Offers were allegedly either randomly generated by the computer or drawn from a pool of offers from previous human players. Overall, fewer unfair than fair offers were accepted. Observation decreased acceptance rates for unfair offers. The feedback-locked feedback-related negativity (FRN) but not the P3 was modulated by observation and fairness, with stronger differential coding of unfair/fair under observation. This effect was strongly correlated with individual levels of social anxiety, with higher levels associated with stronger differential fairness coding in the FRN under observation. Behavioral findings support negative reciprocity in the UG, suggesting that (implicit) social norms overwrite explicit task instructions even in the absence of (alleged) social interaction. Observation enhances this effect. Fairness coding in the FRN was modulated by observation as a function of social anxiety, supporting the notion that altered sensitivity to equality in a social context may contribute to social avoidance in socially anxious individuals.
Significant improvement in Mn2O3 transition metal oxide electrical conductivity via high pressure
Authors: Hong Fang , Yue Binbin , Hirao Naohisa , Liu Zhenxian , Chen Bin
Published: March 2017

Highly efficient energy storage is in high demand for next-generation clean energy applications. As a promising energy storage material, the application of Mn2O3 is limited due to its poor electrical conductivity. Here, high-pressure techniques enhanced the electrical conductivity of Mn2O3 significantly. In situ synchrotron micro X-Ray diffraction, Raman spectroscopy and resistivity measurement revealed that resistivity decreased with pressure and dramatically dropped near the phase transition. At the highest pressure, resistivity reduced by five orders of magnitude and the sample showed metal-like behavior. More importantly, resistivity remained much lower than its original value, even when the pressure was fully released. This work provides a new method to enhance the electronic properties of Mn2O3 using high-pressure treatment, benefiting its applications in energy-related fields.
Modulation of p-eIF2α cellular levels and stress granule assembly/disassembly by trehalose
Authors: Dimasi Pasquale , Quintiero Annamaria , Shelkovnikova Tatyana A. , Buchman Vladimir L.
Published: March 2017

Stress granules (SGs) are an important component of cellular stress response. Compromised assembly of SGs as well as their premature or delayed disassembly affect physiology and survival of cells under stress or during recovery from stress. Consequently, abnormal turnover of SGs has been implicated in the development of various pathologies, including neurodegeneration. We found that pretreatment of cells with a natural disaccharide trehalose, a known autophagy enhancer, delays SG assembly and facilitates their premature post-stress disassembly. Mechanistically, the effect of trehalose on SGs is mediated via the p-eIF2α rather than autophagosome pathway. Trehalose increases pre-stress levels of p-eIF2α and its phosphatase subunits and promotes post-stress translational recovery. Upon prolonged treatment, trehalose impairs basal translation affecting production of transiently expressed proteins. Early translational recovery and SG disassembly induced by trehalose pretreatment can sensitise cells to stress and impair survival. Our study has important implications for the use of trehalose in studies of autophagic clearance of misfolded proteins and for targeting SGs as a possible therapeutic approach in neurodegenerative and other diseases.