bluuebunny/crossref_metadata_2025 huggingface dataset:
A new caenagnathid dinosaur from the Upper Cretaceous Wangshi Group of Shandong, China, with comments on size variation among oviraptorosaurs
Authors: Yu Yilun , Wang Kebai , Chen Shuqing , Sullivan Corwin , Wang Shuo , Wang Peiye , Xu Xing
Published: March 2018

The bone-beds of the Upper Cretaceous Wangshi Group in Zhucheng, Shandong, China are rich in fossil remains of the gigantic hadrosaurid Shantungosaurus. Here we report a new oviraptorosaur, Anomalipes zhaoi gen. et sp. nov., based on a recently collected specimen comprising a partial left hindlimb from the Kugou Locality in Zhucheng. This specimen’s systematic position was assessed by three numerical cladistic analyses based on recently published theropod phylogenetic datasets, with the inclusion of several new characters. Anomalipes zhaoi differs from other known caenagnathids in having a unique combination of features: femoral head anteroposteriorly narrow and with significant posterior orientation; accessory trochanter low and confluent with lesser trochanter; lateral ridge present on femoral lateral surface; weak fourth trochanter present; metatarsal III with triangular proximal articular surface, prominent anterior flange near proximal end, highly asymmetrical hemicondyles, and longitudinal groove on distal articular surface; and ungual of pedal digit II with lateral collateral groove deeper and more dorsally located than medial groove. The holotype of Anomalipes zhaoi is smaller than is typical for Caenagnathidae but larger than is typical for the other major oviraptorosaurian subclade, Oviraptoridae. Size comparisons among oviraptorisaurians show that the Caenagnathidae vary much more widely in size than the Oviraptoridae.
Dual role of YM1+ M2 macrophages in allergic lung inflammation
Authors: Draijer Christina , Robbe Patricia , Boorsma Carian E. , Hylkema Machteld N. , Melgert Barbro N.
Published: March 2018

Alternatively activated (M2 or YM1+) macrophages have been associated with the development of asthma but their contribution to disease initiation and progression remains unclear. To assess the therapeutic potential of modulating these M2 macrophages, we have studied inhibition of M2 polarisation during and after development of allergic lung inflammation by treating with cynaropicrin, a galectin-3 pathway inhibitor. Mice that were treated with this inhibitor of M2 polarisation during induction of allergic inflammation developed less severe eosinophilic lung inflammation and less collagen deposition around airways, while the airway α-smooth muscle actin layer was unaffected. When we treated with cynaropicrin after induction of inflammation, eosinophilic lung inflammation and collagen deposition were also inhibited though to a lesser extent. Unexpectedly, both during and after induction of allergic inflammation, inhibition of M2 polarisation resulted in a shift towards neutrophilic inflammation. Moreover, airway hyperresponsiveness was worse in mice treated with cynaropicrin as compared to allergic mice without inhibitor. These results show that M2 macrophages are associated with remodeling and development of eosinophilic lung inflammation, but prevent development of neutrophilic lung inflammation and worsening of airway hyperresponsiveness. This study suggests that macrophages contribute to determining development of eosinophilic or neutrophilic lung inflammation in asthma.
Three-dimensional Epigenome Statistical Model: Genome-wide Chromatin Looping Prediction
Authors: Al Bkhetan Ziad , Plewczynski Dariusz
Published: March 2018

This study aims to understand through statistical learning the basic biophysical mechanisms behind three-dimensional folding of epigenomes. The 3DEpiLoop algorithm predicts three-dimensional chromatin looping interactions within topologically associating domains (TADs) from one-dimensional epigenomics and transcription factor profiles using the statistical learning. The predictions obtained by 3DEpiLoop are highly consistent with the reported experimental interactions. The complex signatures of epigenomic and transcription factors within the physically interacting chromatin regions (anchors) are similar across all genomic scales: genomic domains, chromosomal territories, cell types, and different individuals. We report the most important epigenetic and transcription factor features used for interaction identification either shared, or unique for each of sixteen (16) cell lines. The analysis shows that CTCF interaction anchors are enriched by transcription factors yet deficient in histone modifications, while the opposite is true in the case of RNAP II mediated interactions. The code is available at the repository https://bitbucket.org/4dnucleome/3depiloop.
Rac1 in podocytes promotes glomerular repair and limits the formation of sclerosis
Authors: Asao Rin , Seki Takuto , Takagi Miyuki , Yamada Hiroyuki , Kodama Fumiko , Hosoe-Nagai Yoshiko , Tanaka Eriko , Trejo Juan Alejandro Oliva , Yamamoto-Nonaka Kanae , Sasaki Yu , Hidaka Teruo , Ueno Takashi , Yanagita Motoko , Suzuki Yusuke , Tomino Yasuhiko , Asanuma Katsuhiko
Published: March 2018

Rac1, a Rho family member, is ubiquitously expressed and participates in various biological processes. Rac1 expression is induced early in podocyte injury, but its role in repair is unclear. To investigate the role of Rac1 expression in podocytes under pathological conditions, we used podocyte-specific Rac1 conditional knock-out (cKO) mice administered adriamycin (ADR), which causes nephrosis and glomerulosclerosis. Larger areas of detached podocytes, more adhesion of the GBM to Bowman’s capsule, and a higher ratio of sclerotic glomeruli were observed in Rac1 cKO mice than in control mice, whereas no differences were observed in glomerular podocyte numbers in both groups after ADR treatment. The mammalian target of rapamycin (mTOR) pathway, which regulates the cell size, was more strongly suppressed in the podocytes of Rac1 cKO mice than in those of control mice under pathological conditions. In accordance with this result, the volumes of podocytes in Rac1 cKO mice were significantly reduced compared with those of control mice. Experiments using in vitro ADR-administered Rac1 knockdown podocytes also supported that a reduction in Rac1 suppressed mTOR activity in injured podocytes. Taken together, these data indicate that Rac1-associated mTOR activation in podocytes plays an important role in preventing the kidneys from developing glomerulosclerosis.
Insulin Regulates Adrenal Steroidogenesis by Stabilizing SF-1 Activity
Authors: Kinyua Ann W. , Doan Khanh V. , Yang Dong Joo , Huynh My Khanh Q. , Choi Yun-Hee , Shin Dong Min , Kim Ki Woo
Published: March 2018

Development of metabolic syndrome is associated with hyperactivity of the HPA axis characterized by elevated levels of circulating adrenal hormones including cortisol and aldosterone. However, the molecular mechanism leading to the dysregulation of the HPA axis is not well elucidated. In this study, we found that insulin regulates adrenal steroidogenesis by increasing the expression and activity of steroidogenic factor 1 (SF-1) both in vitro and in vivo and this insulin effect was partly through inhibition of FoxO1. Specifically, insulin increased the protein and RNA levels of SF-1 and steroidogenic target genes. Further, adrenal SF-1 expression was significantly increased by hyperactivation of insulin signaling in mice. Together with the elevated SF-1 expression in adrenal glands, hyperactivation of insulin signaling led to increased aldosterone and corticosterone levels. On the other hand, suppressing the insulin signaling using streptozotocin markedly reduced the expression of adrenal SF-1 in mice. In addition, overexpression of FoxO1 significantly suppressed SF-1 and its steroidogenic target genes implying that the positive effect of insulin on SF-1 activity might be through suppression of FoxO1 in the adrenal gland. Taken together, these results indicate that insulin regulates adrenal steroidogenesis through coordinated control of SF-1 and FoxO1.
Scale-up and large-scale production of Tetraselmis sp. CTP4 (Chlorophyta) for CO2 mitigation: from an agar plate to 100-m3 industrial photobioreactors
Authors: Pereira Hugo , Páramo Jaime , Silva Joana , Marques Ana , Barros Ana , Maurício Dinis , Santos Tamára , Schulze Peter , Barros Raúl , Gouveia Luísa , Barreira Luísa , Varela João
Published: March 2018

Industrial production of novel microalgal isolates is key to improving the current portfolio of available strains that are able to grow in large-scale production systems for different biotechnological applications, including carbon mitigation. In this context, Tetraselmis sp. CTP4 was successfully scaled up from an agar plate to 35- and 100-m3 industrial scale tubular photobioreactors (PBR). Growth was performed semi-continuously for 60 days in the autumn-winter season (17th October – 14th December). Optimisation of tubular PBR operations showed that improved productivities were obtained at a culture velocity of 0.65–1.35 m s−1 and a pH set-point for CO2 injection of 8.0. Highest volumetric (0.08 ± 0.01 g L−1 d−1) and areal (20.3 ± 3.2 g m−2 d−1) biomass productivities were attained in the 100-m3 PBR compared to those of the 35-m3 PBR (0.05 ± 0.02 g L−1 d−1 and 13.5 ± 4.3 g m−2 d−1, respectively). Lipid contents were similar in both PBRs (9–10% of ash free dry weight). CO2 sequestration was followed in the 100-m3 PBR, revealing a mean CO2 mitigation efficiency of 65% and a biomass to carbon ratio of 1.80. Tetraselmis sp. CTP4 is thus a robust candidate for industrial-scale production with promising biomass productivities and photosynthetic efficiencies up to 3.5% of total solar irradiance.
Inhibitory effect of surface pre-reacted glass-ionomer (S-PRG) eluate against adhesion and colonization by Streptococcus mutans
Authors: Nomura Ryota , Morita Yumiko , Matayoshi Saaya , Nakano Kazuhiko
Published: March 2018

Surface Pre-reacted Glass-ionomer (S-PRG) filler is a bioactive filler produced by PRG technology, which has been applied to various dental materials. A S-PRG filler can release multiple ions from a glass-ionomer phase formed in the filler. In the present study, detailed inhibitory effects induced by S-PRG eluate (prepared with S-PRG filler) against Streptococcus mutans, a major pathogen of dental caries, were investigated. S-PRG eluate effectively inhibited S. mutans growth especially in the bacterium before the logarithmic growth phase. Microarray analysis was performed to identify changes in S. mutans gene expression in the presence of the S-PRG eluate. The S-PRG eluate prominently downregulated operons related to S. mutans sugar metabolism, such as the pdh operon encoding the pyruvate dehydrogenase complex and the glg operon encoding a putative glycogen synthase. The S-PRG eluate inhibited several in vitro properties of S. mutans relative to the development of dental caries especially prior to active growth. These results suggest that the S-PRG eluate may effectively inhibit the bacterial growth of S. mutans following downregulation of operons involved in sugar metabolism resulting in attenuation of the cariogenicity of S. mutans, especially before the active growth phase.
S-Nitrosoglutathione Reductase Underlies the Dysfunctional Relaxation to Nitric Oxide in Preterm Labor
Authors: Barnett Scott D. , Smith Christina R. , Ulrich Craig C. , Baker Josh E. , Buxton Iain L. O.
Published: March 2018

Tocolytics show limited efficacy to prevent preterm delivery. In uterine smooth muscle cGMP accumulation following addition of nitric oxide (NO) has little effect on relaxation suggesting a role for protein S-nitrosation. In human myometrial tissues from women in labor at term (TL), or spontaneously in labor preterm (sPTL), direct stimulation of soluble guanylyl cyclase (sGC) fails to relax myometrium, while the same treatment relaxes vascular smooth muscle completely. Unlike term myometrium, effects of NO are not only blunted in sPTL, but global protein S-nitrosation is also diminished, suggesting a dysfunctional response to NO-mediated protein S-nitrosation. Examination of the enzymatic regulator of endogenous S-nitrosoglutathione availability, S-nitrosoglutathione reductase, reveals increased expression of the reductase in preterm myometrium associated with decreased total protein S-nitrosation. Blockade of S-nitrosoglutathione reductase relaxes sPTL tissue. Addition of NO donor to the actin motility assay attenuates force. Failure of sGC activation to mediate relaxation in sPTL tissues, together with the ability of NO to relax TL, but not sPTL myometrium, suggests a unique pathway for NO-mediated relaxation in myometrium. Our results suggest that examining the action of S-nitrosation on critical contraction associated proteins central to the regulation of uterine smooth muscle contraction can reveal new tocolytic targets.
Author Correction: The responses of cancer cells to PLK1 inhibitors reveal a novel protective role for p53 in maintaining centrosome separation
Authors: Smith Linda , Farzan Raed , Ali Simak , Buluwela Laki , T. Saurin Adrian , Meek David W.
Published: March 2018

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has been fixed in the paper.
MicroRNA-1 suppresses proliferation, migration and invasion by targeting Notch2 in esophageal squamous cell carcinoma
Authors: Liu Wenzhi , Li Mengkao , Chen Xiangming , Zhu Shan , Shi Hailong , Zhang Dawei , Cheng Cheng , Li Baosheng
Published: March 2018

MicroRNAs play an important role in the migration and invasion of tumors, and lower expression of microRNA-1 (miR-1) has been proven in a variety of malignant tumors, including esophageal squamous cell carcinoma (ESCC). In this study, we found that miR-1 expression levels in tumor tissues and preoperative serum from esophageal carcinoma patients were lower than those in non-tumorous tissues and healthy volunteers. miR-1 expression in tissues and plasma was closely related to invasion, lymph node metastasis and TNM staging. Additionally, miR-1 expression levels in tissues and plasma were positively correlated. miR-1 inhibited cell proliferation, migration and invasion. Overexpression of miR-1 in ESCC cells reduced Notch2 protein but not mRNA levels, whereas suppression of miR-1 led to an increase in Notch2 protein but not mRNA levels. A dual-luciferase experiment validated that Notch2 was a direct target of miR-1. Introducing Notch2 mRNA into cells over-expressing miR-1 partially abrogated the effects of miR-1 on migration and invasion. Further studies verified that miR-1 regulates EMT signalling pathways directly through Notch2. Therefore, these results confirm that, as a tumor suppressor gene, miR-1 may be a potential tumor marker for the early diagnosis of ESCC and a new drug target.
Structural Implications of Mutations Conferring Rifampin Resistance in Mycobacterium leprae
Authors: Vedithi Sundeep Chaitanya , Malhotra Sony , Das Madhusmita , Daniel Sheela , Kishore Nanda , George Anuja , Arumugam Shantha , Rajan Lakshmi , Ebenezer Mannam , Ascher David B. , Arnold Eddy , Blundell Tom L.
Published: March 2018

TherpoBgene encodes the β subunit of RNA polymerase holoenzyme inMycobacterium leprae (M.leprae). Missense mutations in therpoBgene were identified as etiological factors for rifampin resistance in leprosy. In the present study, we identified mutations corresponding to rifampin resistance in relapsed leprosy cases from three hospitals in southern India which treat leprosy patients. DNA was extracted from skin biopsies of 35 relapse/multidrug therapy non-respondent leprosy cases, and PCR was performed to amplify the 276 bp rifampin resistance-determining region of therpoBgene. PCR products were sequenced, and mutations were identified in four out of the 35 cases at codon positions D441Y, D441V, S437L and H476R. The structural and functional effects of these mutations were assessed in the context of three-dimensional comparative models of wild-type and mutantM.lepraeRNA polymerase holoenzyme (RNAP), based on the recently solved crystal structures of RNAP ofMycobacterium tuberculosis,containing a synthetic nucleic acid scaffold and rifampin. The resistance mutations were observed to alter the hydrogen-bonding and hydrophobic interactions of rifampin and the 5′ ribonucleotide of the growing RNA transcript. This study demonstrates that rifampin-resistant strains ofM.lepraeamong leprosy patients in southern India are likely to arise from mutations that affect the drug-binding site and stability of RNAP.
Giant thermal hysteresis in Verwey transition of single domain Fe3O4 nanoparticles
Authors: Kim Taehun , Lim Sumin , Hong Jaeyoung , Kwon Soon Gu , Okamoto Jun , Chen Zhi Ying , Jeong Jaehong , Kang Soonmin , Leiner Jonathan C. , Lim Jung Tae , Kim Chul Sung , Huang Di Jing , Hyeon Taeghwan , Lee Soonchil , Park Je-Geun
Published: March 2018

Most interesting phenomena of condensed matter physics originate from interactions among different degrees of freedom, making it a very intriguing yet challenging question how certain ground states emerge from only a limited number of atoms in assembly. This is especially the case for strongly correlated electron systems with overwhelming complexity. The Verwey transition of Fe3O4 is a classic example of this category, of which the origin is still elusive 80 years after the first report. Here we report, for the first time, that the Verwey transition of Fe3O4 nanoparticles exhibits size-dependent thermal hysteresis in magnetization, 57Fe NMR, and XRD measurements. The hysteresis width passes a maximum of 11 K when the size is 120 nm while dropping to only 1 K for the bulk sample. This behavior is very similar to that of magnetic coercivity and the critical sizes of the hysteresis and the magnetic single domain are identical. We interpret it as a manifestation of charge ordering and spin ordering correlation in a single domain. This work paves a new way of undertaking researches in the vibrant field of strongly correlated electron physics combined with nanoscience.
Integrating Free-Form Nanostructured GRIN Microlenses with Single-Mode Fibers for Optofluidic Systems
Authors: Kasztelanic Rafal , Filipkowski Adam , Anuszkiewicz Alicja , Stafiej Paulina , Stepniewski Grzegorz , Pysz Dariusz , Krzyzak Konrad , Stepien Ryszard , Klimczak Mariusz , Buczynski Ryszard
Published: March 2018

We present both a theoretical and an experimental study of a novel compact lensed fiber system utilizing a nanostructured GRIN lens. The lens can be integrated with an optical fiber, which ensures a unique and efficient focusing in any high index medium, such as a liquid. We use the effective medium approach to design lenses with arbitrary refractive index. To fabricate lenses, we utilize a discrete array of nano-sized rods made of two types of glasses, and apply a standard stack-and-draw fiber drawing technology. The fabricated nanostructured GRIN lenses have a parabolic refractive index profile with a diameter of a standard fiber, very short working distances (55 µm in the air) and a high numerical aperture (NA = 0.16). As a proof-of-concept of the new micro-lensed fiber system, we demonstrate an experiment on optical trapping of micrometer-sized glass beads. We also show that our method is compatible with optical fiber technology and allows for any shape of the refractive index distribution in 2D. Thanks to that a new functionality could be achieved by replacing the GRIN lens with an axicon lens, vortex type elements, micro-lenses arrays or diffraction elements.
In vivo depletion of serum IgG by an affibody molecule binding the neonatal Fc receptor
Authors: Seijsing Johan , Yu Shengze , Frejd Fredrik Y , Höiden-Guthenberg Ingmarie , Gräslund Torbjörn
Published: March 2018

Lowering the total level of Immunoglobulin G (IgG) in circulation is a promising general treatment option for many autoimmune diseases driven by pathogenic autoantibodies. The half-life of IgG in circulation is unusually long as a consequence of its interaction with the neonatal Fc receptor (FcRn), which protects it from lysosomal degradation by cells in contact with blood. Blocking the IgG/FcRn interaction prevents FcRn-mediated rescue, which may lead to increased catabolism and a lowering of the total IgG level. Here, we find that an engineered alternative scaffold protein, an affibody molecule, interacting specifically with FcRn, is able to block the IgG/FcRn interaction in vitro. The affibody molecule (ZFcRn) was expressed alone or as a fusion to an albumin binding domain (ABD), to extend its half-life in circulation, in both cases with retained affinity and blocking potential. Repeated i.v. injections in mice of ZFcRn and ZFcRn-ABD were found to result in an up to 40% reduction of the IgG serum-level after 5 days. Potential applications of ZFcRn as a general treatment modality for autoimmune diseases are discussed.
Soluble epoxide hydrolase inhibition decreases reperfusion injury after focal cerebral ischemia
Authors: Tu Ranran , Armstrong Jillian , Lee Kin Sing Stephen , Hammock Bruce D. , Sapirstein Adam , Koehler Raymond C.
Published: March 2018

Epoxyeicosatrienoic acids (EETs) are produced by cytochrome P450 epoxygenases from arachidonic acid, and their rapid metabolism is mainly through soluble epoxide hydrolase (sEH). EETs exert vasodilatory, anti-inflammatory, anti-apoptotic, and pro-angiogenic effects. Administration of sEH inhibitors before or at the onset of stroke is protective, but the effects of post-treatment at reperfusion, when inflammation is augmented, has not been as well studied. We tested the hypothesis that 1-Trifluoromethoxyphenyl-3-(1-propionylpiperidin-4-yl)urea (TPPU), a potent and highly selective sEH inhibitor, suppresses inflammation and protects the brain when administered at reperfusion. Vehicle or 1 mg/kg TPPU was administered at reperfusion after 90 minutes of focal ischemia and again 24 hours later. Protein expression and activity of sEH increased after reperfusion and activity was decreased by TPPU administration. TPPU decreased infarct volume by 50%, reduced neurologic deficits and improved performance on sensorimotor tasks. Furthermore, TPPU significantly lowered the mRNA expression of interleukin-1beta by 3.5-fold and tumor necrosis factor-alpha by 2.2-fold, increased transforming growth factor-beta mRNA by 1.8-fold, and augmented immunostaining of vascular endothelial growth factor in peri-infarct cortex. Thus, inhibition of sEH at reperfusion significantly reduces infarction and improves sensorimotor function, possibly by suppressing early proinflammatory cytokines and promoting reparative cytokines and growth factors.
Concurrent action of purifying selection and gene conversion results in extreme conservation of the major stress-inducible Hsp70 genes in mammals
Authors: Hess Kyle , Oliverio Ryan , Nguyen Peter , Le Dat , Ellis Jacqueline , Kdeiss Brianna , Ord Sara , Chalkia Dimitra , Nikolaidis Nikolas
Published: March 2018

Several evolutionary mechanisms alter the fate of mutations and genes within populations based on their exhibited functional effects. To understand the underlying mechanisms involved in the evolution of the cellular stress response, a very conserved mechanism in the course of organismal evolution, we studied the patterns of natural genetic variation and functional consequences of polymorphisms of two stress-inducible Hsp70 genes. These genes, HSPA1A and HSPA1B, are major orchestrators of the cellular stress response and are associated with several human diseases. Our phylogenetic analyses revealed that the duplication of HSPA1A and HSPA1B originated in a lineage proceeding to placental mammals, and henceforth they remained in conserved synteny. Additionally, analyses of synonymous and non-synonymous changes suggest that purifying selection shaped the HSPA1 gene diversification, while gene conversion resulted in high sequence conservation within species. In the human HSPA1-cluster, the vast majority of mutations are synonymous and specific genic regions are devoid of mutations. Furthermore, functional characterization of several human polymorphisms revealed subtle differences in HSPA1A stability and intracellular localization. Collectively, the observable patterns of HSPA1A-1B variation describe an evolutionary pattern, in which purifying selection and gene conversion act simultaneously and conserve a major orchestrator of the cellular stress response.
The effects of hydroxyethyl starch and gelatine on pulmonary cytokine production and oedema formation
Authors: Krabbe Julia , Ruske Nadine , Braunschweig Till , Kintsler Svetlana , Spillner Jan W. , Schröder Thomas , Kalverkamp Sebastian , Kanzler Stephanie , Rieg Annette D. , Uhlig Stefan , Martin Christian
Published: March 2018

Recently, side effects of plasma expanders like hydroxyethyl starch and gelatine gained considerable attention. Most studies have focused on the kidneys; lungs remain unconsidered. Isolated mouse lungs were perfused for 4 hours with buffer solutions based on hydroxyethyl starch (HES) 130/0.4, HES 200/0.5 or gelatine and ventilated with low or high pressure under physiological pH and alkalosis. Outcome parameters were cytokine levels and the wet-to-dry ratio. For cytokine release, murine and human PCLS were incubated in three different buffers and time points.In lungs perfused with the gelatine based buffer IL-6, MIP-2 and KC increased when ventilated with high pressure. Wet-to-dry ratios increased stronger in lungs perfused with gelatine - compared to HES 130/0.4. Alkalotic perfusion resulted in higher cytokine levels but normal wet-to-dry ratio. Murine PCLS supernatants showed increased IL-6 and KC when incubated in gelatine based buffer, whereas in human PCLS IL-8 was elevated. In murine IPL HES 130/0.4 has lung protective effects in comparison to gelatine based infusion solutions, especially in the presence of high-pressure ventilation. Gelatine perfusion resulted in increased cytokine production. Our findings suggest that gelatine based solutions may have side effects in patients with lung injury or lung oedema.
Loss of Stemness, EMT, and Supernumerary Tooth Formation in Cebpb−/−Runx2+/− Murine Incisors
Authors: Saito Kazuyuki , Takahashi Katsu , Huang Boyen , Asahara Masakazu , Kiso Honoka , Togo Yumiko , Tsukamoto Hiroko , Mishima Sayaka , Nagata Masaki , Iida Machiko , Tokita Yoshihito , Asai Masato , Shimizu Akira , Komori Toshihisa , Harada Hidemitsu , MacDougall Mary , Sugai Manabu , Bessho Kazuhisa
Published: March 2018

Adult Cebpb KO mice incisors present amelogenin-positive epithelium pearls, enamel and dentin allopathic hyperplasia, fewer Sox2-positive cells in labial cervical loop epitheliums, and reduced Sox2 expression in enamel epithelial stem cells. Thus, Cebpb acts upstream of Sox2 to regulate stemness. In this study, Cebpb KO mice demonstrated cementum-like hard tissue in dental pulp, loss of polarity by ameloblasts, enamel matrix in ameloblastic layer, and increased expression of epithelial-mesenchymal transition (EMT) markers in a Cebpb knockdown mouse enamel epithelial stem cell line. Runx2 knockdown in the cell line presented a similar expression pattern. Therefore, the EMT enabled disengaged odontogenic epithelial stem cells to develop supernumerary teeth. Cebpb and Runx2 knockdown in the cell line revealed higher Biglycan and Decorin expression, and Decorin-positive staining in the periapical region, indicating their involvement in supernumerary tooth formation. Cebpb and Runx2 acted synergistically and played an important role in the formation of supernumerary teeth in adult incisors.
A unified framework for modelling sediment fate from source to sink and its interactions with reef systems over geological times
Authors: Salles Tristan , Ding Xuesong , Webster Jody M. , Vila-Concejo Ana , Brocard Gilles , Pall Jodie
Published: March 2018

Understanding the effects of climatic variability on sediment dynamics is hindered by limited ability of current models to simulate long-term evolution of sediment transfer from source to sink and associated morphological changes. We present a new approach based on a reduced-complexity model which computes over geological time: sediment transport from landmasses to coasts, reworking of marine sediments by longshore currents, and development of coral reef systems. Our framework links together the main sedimentary processes driving mixed siliciclastic-carbonate system dynamics. It offers a methodology for objective and quantitative sediment fate estimations over regional and millennial time-scales. A simulation of the Holocene evolution of the Great Barrier Reef shows: (1) how high sediment loads from catchments erosion prevented coral growth during the early transgression phase and favoured sediment gravity-flows in the deepest parts of the northern region basin floor (prior to 8 ka before present (BP)); (2) how the fine balance between climate, sea-level, and margin physiography enabled coral reefs to thrive under limited shelf sedimentation rates after ~6 ka BP; and, (3) how since 3 ka BP, with the decrease of accommodation space, reduced of vertical growth led to the lateral extension of reefs consistent with available observational data.
Chitosan and cloxacillin combination improve antibiotic efficacy against different lifestyle of coagulase-negative Staphylococcus isolates from chronic bovine mastitis
Authors: Breser María L. , Felipe Verónica , Bohl Luciana P. , Orellano María S. , Isaac Paula , Conesa Agustín , Rivero Virginia E. , Correa Silvia G. , Bianco Ismael D. , Porporatto Carina
Published: March 2018

Bovine mastitis affects the health of dairy cows and the profitability of herds worldwide. Coagulase-negative staphylococci (CNS) are the most frequently isolated pathogens in bovine intramammary infection. Based on the wide range of antimicrobial, mucoadhesive and immunostimulant properties demonstrated by chitosan, we have evaluated therapy efficiency of chitosan incorporation to cloxacillin antibiotic as well as its effect against different bacterial lifestyles of seven CNS isolates from chronic intramammary infections. The therapeutic effects of combinations were evaluated on planktonic cultures, bacterial biofilms and intracellular growth in mammary epithelial cells. We found that biofilms and intracellular growth forms offered a strong protection against antibiotic therapy. On the other hand, we found that chitosan addition to cloxacillin efficiently reduced the antibiotic concentration necessary for bacterial killing in different lifestyle. Remarkably, the combined treatment was not only able to inhibit bacterial biofilm establishment and increase preformed biofilm eradication, but it also reduced intracellular bacterial viability while it increased IL-6 secretion by infected epithelial cells. These findings provide a new approach to prophylactic drying therapy that could help to improve conventional antimicrobial treatment against different forms of bacterial growth in an efficient, safer and greener manner reducing multiresistant bacteria generation and spread.
Computer simulation study of early bacterial biofilm development
Authors: Acemel Rafael D. , Govantes Fernando , Cuetos Alejandro
Published: March 2018

Most bacteria form organized sessile communities, known as biofilms. Their ubiquity and relevance have stimulated the development of efficient mathematical models able to predict biofilm evolution and characteristics at different conditions. Here we present a study of the early stages of bacterial biofilm formation modeled by means of individual cell-based computer simulation. Simulation showed that clusters with different degrees of internal and orientational order were formed as a function of the aspect ratio of the individual particles and the relation between the diffusion and growth rates. Analysis of microscope images of early biofilm formation by the Gram-negative bacterium Pseudomonas putida at varying diffusion rates revealed a good qualitative agreement with the simulation results. Our model is a good predictor of microcolony morphology during early biofilm development, showing that the competition between diffusion and growth rates is a key aspect in the formation of stable biofilm microcolonies.
Slab narrowing in the Central Mediterranean: the Calabro-Ionian subduction zone as imaged by high resolution seismic tomography
Authors: Scarfì L. , Barberi G. , Barreca G. , Cannavò F. , Koulakov I. , Patanè D.
Published: March 2018

A detailed 3D image of the Calabro-Ionian subduction system in the central Mediterranean was obtained by means of a seismic tomography, exploiting a large dataset of local earthquakes and computing algorithms able to build a dense grid of measure nodes. Results show that the slab is continuous below the southern sector of the Calabro-Peloritan Arc, but the deformation processes developing at its edges are leading to its progressive narrowing, influencing tectonics and magmatism at the surface, and with possible stress concentration in the tip zones. In the southwest, the deformation occurring at a free slab edge lead to propagation of a vertical lithospheric tear in the overriding plate, which extends along a NW-SE fault system (Aeolian-Tindari-Letojanni) up to about 30 km into the Ionian Sea; further southeast, the lithosphere appears only flexed and not broken yet. In the northeast, the slab seems to break progressively, parallel to the trench. Finally, northwest of Mt. Etna, the tomography highlights low VP that can be related to an upwelling of deep mantle material likely flowing laterally through a window opened by the complete slab detachment.
ARE-mediated decay controls gene expression and cellular metabolism upon oxygen variations
Authors: de Toeuf Bérengère , Soin Romuald , Nazih Abdelkarim , Dragojevic Marija , Jurėnas Dukas , Delacourt Nadège , Vo Ngoc Long , Garcia-Pino Abel , Kruys Véronique , Gueydan Cyril
Published: March 2018

Hypoxia triggers profound modifications of cellular transcriptional programs. Upon reoxygenation, cells return to a normoxic gene expression pattern and mRNA produced during the hypoxic phase are degraded. TIS11 proteins control deadenylation and decay of transcripts containing AU-rich elements (AREs). We observed that the level of dTIS11 is decreased in hypoxic S2 Drosophila cells and returns to normal level upon reoxygenation. Bioinformatic analyses using the ARE-assessing algorithm AREScore show that the hypoxic S2 transcriptome is enriched in ARE-containing transcripts and that this trend is conserved in human myeloid cells. Moreover, an efficient down-regulation of Drosophila ARE-containing transcripts during hypoxia/normoxia transition requires dtis11 expression. Several of these genes encode proteins with metabolic functions. Here, we show that ImpL3 coding for Lactate Dehydrogenase in Drosophila, is regulated by ARE-mediated decay (AMD) with dTIS11 contributing to ImpL3 rapid down-regulation upon return to normal oxygen levels after hypoxia. More generally, we observed that dtis11 expression contributes to cell metabolic and proliferative recovery upon reoxygenation. Altogether, our data demonstrate that AMD plays an important role in the control of gene expression upon variation in oxygen concentration and contributes to optimal metabolic adaptation to oxygen variations.
Investigation of the Oxidation Behaviour of Ti and Al in Inconel 718 Superalloy During Electroslag Remelting
Authors: Duan Shengchao , Shi Xiao , Mao Mingtao , Yang Wensheng , Han Shaowei , Guo Hanjie , Guo Jing
Published: March 2018

In the current study, the thermodynamics of the slag-metal equilibrium reaction between Inconel 718 Ni-based alloy and CaF2-CaO-Al2O3-MgO-TiO2 electroslag remelting (ESR)-type slags were systematically investigated in the temperature range from 1773 to 1973 K (1500 to 1700 °C). The equilibrium Al content increased with increasing temperature, whereas the equilibrium Ti content decreased with increasing temperature at a fixed slag composition. The important factors for controlling the oxidation of Al and Ti in the Inconel 718 superalloy were TiO2 > Al2O3 > CaO > CaF2 > MgO in ESR-type slag and Al > Ti in a consumable electrode. The conventional method of sampling by means of a quartz tube could result in contamination of the molten metal and changes in the size of the “special reaction interface”. Therefore, a novel method was used in the present study to investigate the slag-metal reaction kinetics to accurately obtain the kinetic parameters. The mass transfer coefficient was determined by coupling with the kinetic model derived from the assumption that the reaction rate ([Al] + (TiO2) = [Ti] + (Al2O3)) was controlled by the mass transfer of [Ti], [Al], (TiO2) and (Al2O3) in the boundary layer, respectively.
Caffeine Augments Anesthesia Neurotoxicity in the Fetal Macaque Brain
Authors: Noguchi Kevin K. , Johnson Stephen A. , Manzella Francesca M. , Masuoka Kobe L. , Williams Sasha L. , Martin Lauren D. , Dissen Gregory A. , Ikonomidou Chrysanthy , Schenning Katie J. , Olney John W. , Brambrink Ansgar M.
Published: March 2018

Caffeine is the most frequently used medication in premature infants. It is the respiratory stimulant of choice for apnea associated with prematurity and has been called the silver bullet in neonatology because of many proven benefits and few known risks. Research has revealed that sedative/anesthetic drugs trigger apoptotic death of neurons and oligodendrocytes in developing mammalian brains. Here we evaluated the influence of caffeine on the neurotoxicity of anesthesia in developing nonhuman primate brains. Fetal macaques (n = 7–8/group), at a neurodevelopmental age comparable to premature human infants, were exposed in utero for 5 hours to no drug (control), isoflurane, or isoflurane + caffeine and examined for evidence of apoptosis. Isoflurane exposure increased apoptosis 3.3 fold for neurons and 3.4 fold for oligodendrocytes compared to control brains. Isoflurane + caffeine caused neuronal apoptosis to increase 8.0 fold compared to control levels but did not augment oligoapoptosis. Neuronal death was particularly pronounced in the basal ganglia and cerebellum. Higher blood levels of caffeine within the range considered therapeutic and safe for human infants correlated with increased neuroapoptosis. Caffeine markedly augments neurotoxicity of isoflurane in the fetal macaque brain and challenges the assumption that caffeine is safe for premature infants.
Extensive molecular tinkering in the evolution of the membrane attachment mode of the Rheb GTPase
Authors: Záhonová Kristína , Petrželková Romana , Valach Matus , Yazaki Euki , Tikhonenkov Denis V. , Butenko Anzhelika , Janouškovec Jan , Hrdá Štěpánka , Klimeš Vladimír , Burger Gertraud , Inagaki Yuji , Keeling Patrick J. , Hampl Vladimír , Flegontov Pavel , Yurchenko Vyacheslav , Eliáš Marek
Published: March 2018

Rheb is a conserved and widespread Ras-like GTPase involved in cell growth regulation mediated by the (m)TORC1 kinase complex and implicated in tumourigenesis in humans. Rheb function depends on its association with membranes via prenylated C-terminus, a mechanism shared with many other eukaryotic GTPases. Strikingly, our analysis of a phylogenetically rich sample of Rheb sequences revealed that in multiple lineages this canonical and ancestral membrane attachment mode has been variously altered. The modifications include: (1) accretion to the N-terminus of two different phosphatidylinositol 3-phosphate-binding domains, PX in Cryptista (the fusion being the first proposed synapomorphy of this clade), and FYVE in Euglenozoa and the related undescribed flagellate SRT308; (2) acquisition of lipidic modifications of the N-terminal region, namely myristoylation and/or S-palmitoylation in seven different protist lineages; (3) acquisition of S-palmitoylation in the hypervariable C-terminal region of Rheb in apusomonads, convergently to some other Ras family proteins; (4) replacement of the C-terminal prenylation motif with four transmembrane segments in a novel Rheb paralog in the SAR clade; (5) loss of an evident C-terminal membrane attachment mechanism in Tremellomycetes and some Rheb paralogs of Euglenozoa. Rheb evolution is thus surprisingly dynamic and presents a spectacular example of molecular tinkering.
Non-invasive detection of severe neutropenia in chemotherapy patients by optical imaging of nailfold microcirculation
Authors: Bourquard Aurélien , Pablo-Trinidad Alberto , Butterworth Ian , Sánchez-Ferro Álvaro , Cerrato Carolina , Humala Karem , Fabra Urdiola Marta , Del Rio Candice , Valles Betsy , Tucker-Schwartz Jason M. , Lee Elizabeth S. , Vakoc Benjamin J. , Padera Timothy P. , Ledesma-Carbayo María J. , Chen Yi-Bin , Hochberg Ephraim P. , Gray Martha L. , Castro-González Carlos
Published: March 2018

White-blood-cell (WBC) assessment is employed for innumerable clinical procedures as one indicator of immune status. Currently, WBC determinations are obtained by clinical laboratory analysis of whole blood samples. Both the extraction of blood and its analysis limit the accessibility and frequency of the measurement. In this study, we demonstrate the feasibility of a non-invasive device to perform point-of-care WBC analysis without the need for blood draws, focusing on a chemotherapy setting where patients’ neutrophils—the most common type of WBC—become very low. In particular, we built a portable optical prototype, and used it to collect 22 microcirculatory-video datasets from 11 chemotherapy patients. Based on these videos, we identified moving optical absorption gaps in the flow of red cells, using them as proxies to WBC movement through nailfold capillaries. We then showed that counting these gaps allows discriminating cases of severe neutropenia (<500 neutrophils per µL), associated with increased risks of life-threatening infections, from non-neutropenic cases (>1,500 neutrophils per µL). This result suggests that the integration of optical imaging, consumer electronics, and data analysis can make non-invasive screening for severe neutropenia accessible to patients. More generally, this work provides a first step towards a long-term objective of non-invasive WBC counting.
Constitutive modeling of high temperature flow behavior in a Ti-45Al-8Nb-2Cr-2Mn-0.2Y alloy
Authors: Ge Gengwu , Zhang Laiqi , Xin Jingjing , Lin Junpin , Aindow Mark , Zhang Lichun
Published: March 2018

A constitutive equation based on the hyperbolic sinusoidal Arrhenius-type model has been developed to describe the hot deformation behavior of a β-γ Ti-Al alloy containing 8 at.% of Nb. Experimental true stress-true strain data were acquired from isothermal hot compression tests conducted across a wide range of temperatures (1273 K~1473 K) and strain rates (0.001 s−1~1 s−1), and the changes in the experimental conditions were reflected in the values of the Zener-Hollomon parameter. The impact of true strain was expressed through material constants (A, α, n and Q), and it was found that a 7th order polynomial is appropriate to express the relations between the true strain and these material constants. The average absolute relative error (AARE) and correlation coefficient (R) were used to evaluate the accuracy of the constitutive equation, and the values obtained were 6.009% and 0.9961, respectively. These results indicate that the type of constitutive equation developed here can predict the flow stress for this alloy with good accuracy over a wide range of experimental conditions. Thus, equations of this form could be applied more widely to analyses of hot deformation mechanism and microstructure evolution.
Synthesis of NiMn-LDH Nanosheet@Ni3S2 Nanorod Hybrid Structures for Supercapacitor Electrode Materials with Ultrahigh Specific Capacitance
Authors: Yu Shuai , Zhang Yingxi , Lou Gaobo , Wu Yatao , Zhu Xinqiang , Chen Hao , Shen Zhehong , Fu Shenyuan , Bao Binfu , Wu Limin
Published: March 2018

One of the key challenges for pseudocapacitive electrode materials with highly effective capacitance output and future practical applications is how to rationally construct hierarchical and ordered hybrid nanoarchitecture through the simple process. Herein, we design and synthesize a novel NiMn-layered double hydroxide nanosheet@Ni3S2 nanorod hybrid array supported on porous nickel foam via a one-pot hydrothermal method. Benefited from the ultrathin and rough nature, the well-defined porous structure of the hybrid array, as well as the synergetic effect between NiMn-layered double hydroxide nanosheets and Ni3S2 nanorods, the as-fabricated hybrid array-based electrode exhibits an ultrahigh specific capacitance of 2703 F g−1 at 3 A g−1. Moreover, the asymmetric supercapacitor with this hybrid array as a positive electrode and wood-derived activated carbon as a negative electrode demonstrates high energy density (57 Wh Kg−1 at 738 W Kg−1) and very good electrochemical cycling stability.
Dominating role of crystal structure over defect chemistry in black and white zirconia on visible light photocatalytic activity
Authors: Teeparthi Sri Ramya , Awin Eranezhuth Wasan , Kumar Ravi
Published: March 2018

Nanometric powder particles of white zirconia were synthesized through precursor route by the pyrolysis of zirconium (IV) butoxide at varied temperatures in air ranging from 900–1400 °C and were predominantly monoclinic in nature. To control the defect chemistry, the precursor was also pyrolyzed in a reduced atmosphere at 900 °C, eventually resulting in black zirconia. The stabilization of tetragonal phase and observed color change from white to black in samples pyrolyzed under reduced atmosphere was attributed to the creation of oxygen vacancies and disorder. The black and white zirconia produced delineated the influence of crystal structure and oxygen vacancies on the photocatalytic performance. Furthermore, zirconia synthesized at lower temperatures (600 and 800 °C) in air confirmed the detrimental role of tetragonal phase on the degradation behavior of methylene blue dye. High photocatalytic degradation rate for white zirconia was attributed to the presence of increased density of nano-sized pores and low recombination rate of electron-hole pairs as confirmed by PL measurements. Interestingly, black zirconia exemplified relatively limited activity albeit presence of oxygen vacancies. This negative effect was attributed to the presence of tetragonal phase and possibly, the insufficient creation of new energy states near valence and conduction band towards Fermi energy level.
High fat diet alters Drosophila melanogaster sexual behavior and traits: decreased attractiveness and changes in pheromone profiles
Authors: Schultzhaus Janna N. , Bennett Chloe J. , Iftikhar Hina , Yew Joanne Y. , Mallett Jason , Carney Ginger E.
Published: March 2018

Sexual traits convey information about individual quality to potential mates. Environmental and genetic factors affect sexual trait expression and perception via effects on animal condition and health. High fat diet (HFD) is one environmental factor that adversely affects Drosophila melanogaster health, and its effects on animal health are mediated through conserved metabolic signaling pathways. HFD decreases female attractiveness, resulting in reduced male mating behaviors toward HFD females. HFD also affects the ability of males to judge mate attractiveness and likely alters fly condition and sexual traits to impact mating behavior. Here we show that HFD affects both visual (body size) and non-visual (pheromone profiles) sexual traits, which likely contribute to decreased fly attractiveness. We also demonstrate that adult-specific HFD effects on male mate preference can be rescued by changing metabolic signaling. These results demonstrate that HFD alters Drosophila sexual cues to reflect concurrent effects on condition and that less severe behavioral defects can be reversed by genetic manipulations that rescue fly health. This work expands on current knowledge of the role that metabolic signaling pathways play in linking animal health, sexual traits, and mating behavior, and provides a robust assay in a genetically tractable system to continue examining these processes.