bluuebunny/crossref_metadata_2025 huggingface dataset:
Intergenerational and early life influences on the well-being of Australian Aboriginal and Torres Strait Islander children: overview and selected findings fromFootprints in Time, the Longitudinal Study of Indigenous Children
Authors: Salmon M. , Skelton F. , Thurber K. A. , Bennetts Kneebone L. , Gosling J. , Lovett R. , Walter M.
Published: May 2018

Footprints in Time: The Longitudinal Study of Indigenous Children (LSIC) is a national study of 1759 Australian Aboriginal and Torres Strait Islander children living across urban, regional and remote areas of Australia. The study is in its 11th wave of annual data collection, having collected extensive data on topics including birth and early life influences, parental health and well-being, identity, cultural engagement, language use, housing, racism, school engagement and academic achievement, and social and emotional well-being. The current paper reviews a selection of major findings fromFootprints in Timerelating to the developmental origins of health and disease for Australian Aboriginal and Torres Strait Islander peoples. Opportunities for new researchers to conduct further research utilizing the LSIC data set are also presented.
Physiological Basis for Tall Fescue (Festuca arundinacea) Tolerance to Florasulam
Authors: Yu Jialin , McCullough Patrick E. , Czarnota Mark A.
Published: May 2018

Tall fescue is susceptible to injury from many acetolactate synthase (ALS) inhibitors used for broadleaf weed control in turfgrass. Florasulam is an ALS inhibitor that selectively controls broadleaf weeds in tall fescue, but the mechanisms for selectivity are not well understood. The objective of this research was to evaluate the physiological basis of tall fescue tolerance to florasulam. In greenhouse experiments, florasulam rates required to injure tall fescue 20% (I20) and white clover 80% (I80) measured 320 and 65 g ai ha–1, respectively. The I20and I80values of another ALS inhibitor, flucarbazone, on these species measured 33 and 275 g ai ha–1, respectively. In laboratory experiments, the time required to reach 50% foliar uptake for14C-florasulam and14C-flucarbazone measured 23 and 62 h for white clover, respectively, and >72 h for both herbicides in tall fescue. The half-lives of florasulam and flucarbazone in tall fescue were 15 and 40 h, respectively, whereas the half-life in white clover was >72 h for both herbicides. The concentrations of florasulam and flucarbazone required to inhibit ALS enzymes 50% in excised leaves of tall fescue measured >1,000 and 32 μM, respectively. The selectivity of florasulam for white clover control in tall fescue is associated with differential levels of absorption and metabolism between species. Tall fescue has faster metabolism and less ALS enzyme inhibition from florasulam as compared to a more injurious ALS inhibitor, flucarbazone, which contributes to the differential tolerance levels between these herbicides.
Effect of Reimpacting Debris on the Solidification of the Lunar Magma Ocean
Authors: Perera Viranga , Jackson Alan P. , Elkins‐Tanton Linda T. , Asphaug Erik
Published: May 2018

Anorthosites that comprise the bulk of the lunar crust are believed to have formed during solidification of a lunar magma ocean (LMO) in which these rocks would have floated to the surface. This early flotation crust would have formed a thermal blanket over the remaining LMO, prolonging solidification. Geochronology of lunar anorthosites indicates a long timescale of LMO cooling, or remelting and recrystallization in one or more late events. To better interpret this geochronology, we model LMO solidification in a scenario where the Moon is being continuously bombarded by returning projectiles released from the Moon‐forming giant impact. More than one lunar mass of material escaped the Earth‐Moon system onto heliocentric orbits following the giant impact, much of it to come back on returning orbits for a period of 100 Myr. If large enough, these projectiles would have punctured holes in the nascent floatation crust of the Moon, exposing the LMO to space and causing more rapid cooling. We model these scenarios using a thermal evolution model of the Moon that allows for production (by cratering) and evolution (solidification and infill) of holes in the flotation crust that insulates the LMO. For effective hole production, solidification of the magma ocean can be significantly expedited, decreasing the cooling time by more than a factor of 5. If hole production is inefficient, but shock conversion of projectile kinetic energy to thermal energy is efficient, then LMO solidification can be somewhat prolonged, lengthening the cooling time by 50% or more.
Mimicking the surface and prebiotic chemistry of early Earth using flow chemistry
Authors: Ritson Dougal J. , Battilocchio Claudio , Ley Steven V. , Sutherland John D.
Published: May 2018

When considering life’s aetiology, the first questions that must be addressed are “how?” and “where?” were ostensibly complex molecules, considered necessary for life’s beginning, constructed from simpler, more abundant feedstock molecules on primitive Earth. Previously, we have used multiple clues from the prebiotic synthetic requirements of (proto)biomolecules to pinpoint a set of closely related geochemical scenarios that are suggestive of flow and semi-batch chemistries. We now wish to report a multistep, uninterrupted synthesis of a key heterocycle (2-aminooxazole) en route to activated nucleotides starting from highly plausible, prebiotic feedstock molecules under conditions which mimic this scenario. Further consideration of the scenario has uncovered additional pertinent and novel aspects of prebiotic chemistry, which greatly enhance the efficiency and plausibility of the synthesis.
Supersonic propagation of lattice energy by phasons in fresnoite
Authors: Manley M. E. , Stonaha P. J. , Abernathy D. L. , Chi S. , Sahul R. , Hermann R. P. , Budai J. D.
Published: May 2018

Controlling the thermal energy of lattice vibrations separately from electrons is vital to many applications including electronic devices and thermoelectric energy conversion. To remove heat without shorting electrical connections, heat must be carried in the lattice of electrical insulators. Phonons are limited to the speed of sound, which, compared to the speed of electronic processes, puts a fundamental constraint on thermal management. Here we report a supersonic channel for the propagation of lattice energy in the technologically promising piezoelectric mineral fresnoite (Ba2TiSi2O8) using neutron scattering. Lattice energy propagates 2.8−4.3 times the speed of sound in the form of phasons, which are caused by an incommensurate modulation in the flexible framework structure of fresnoite. The phasons enhance the thermal conductivity by 20% at room temperature and carry lattice-energy signals at speeds beyond the limits of phonons.
Quantum cascade lasers grown on silicon
Authors: Nguyen-Van Hoang , Baranov Alexei N. , Loghmari Zeineb , Cerutti Laurent , Rodriguez Jean-Baptiste , Tournet Julie , Narcy Gregoire , Boissier Guilhem , Patriarche Gilles , Bahriz Michael , Tournié Eric , Teissier Roland
Published: May 2018

Technological platforms offering efficient integration of III-V semiconductor lasers with silicon electronics are eagerly awaited by industry. The availability of optoelectronic circuits combining III-V light sources with Si-based photonic and electronic components in a single chip will enable, in particular, the development of ultra-compact spectroscopic systems for mass scale applications. The first circuits of such type were fabricated using heterogeneous integration of semiconductor lasers by bonding the III-V chips onto silicon substrates. Direct epitaxial growth of interband III-V laser diodes on silicon substrates has also been reported, whereas intersubband emitters grown on Si have not yet been demonstrated. We report the first quantum cascade lasers (QCLs) directly grown on a silicon substrate. These InAs/AlSb QCLs grown on Si exhibit high performances, comparable with those of the devices fabricated on their native InAs substrate. The lasers emit near 11 µm, the longest emission wavelength of any laser integrated on Si. Given the wavelength range reachable with InAs/AlSb QCLs, these results open the way to the development of a wide variety of integrated sensors.
Diversity time-period and diversity-time-area relationships exemplified by the human microbiome
Authors: Ma Zhanshan
Published: May 2018

We extend the ecological laws of species-time relationship (STR) and species-time-area relationship (STAR) to general diversity time-period relationship (DTR) and diversity-time-area relationship (DTAR), and test the extensions with the human vaginal microbiome datasets by building 1460 DTR/DTAR models. Our extensions were inspired by the observation that Hill numbers, well regarded as the most appropriate measure of alpha-diversity and also particularly suitable for multiplicative beta-diversity partitioning, are actually in the units of effective species, and therefore, should be able to substitute for species in the STR and STAR. We found that the traditional power law (PL) model is only applicable for DTR at diversity order zero (i.e., species richness); at higher diversity orders (q = 1–4), the power law with exponent cutoff (PLEC) and power law with inverse exponent cutoff (PLIEC) are more appropriate. In particular, PLEC has an advantage over PLIEC in predicting maximal accumulation diversity (MAD) over time. In fact, with the DTR extensions, we can construct DTR and MAD profiles. To the best of our knowledge, this is the first comprehensive investigation of the DTR/DTAR in human microbiome. Methodologically, our DTR/DTAR profiles can characterize general diversity scaling beyond species richness, covering both alpha- and beta-diversity regimes across different diversity orders.
AutoCellSeg: robust automatic colony forming unit (CFU)/cell analysis using adaptive image segmentation and easy-to-use post-editing techniques
Authors: Khan Arif ul Maula , Torelli Angelo , Wolf Ivo , Gretz Norbert
Published: May 2018

In biological assays, automated cell/colony segmentation and counting is imperative owing to huge image sets. Problems occurring due to drifting image acquisition conditions, background noise and high variation in colony features in experiments demand a user-friendly, adaptive and robust image processing/analysis method. We present AutoCellSeg (based on MATLAB) that implements a supervised automatic and robust image segmentation method. AutoCellSeg utilizes multi-thresholding aided by a feedback-based watershed algorithm taking segmentation plausibility criteria into account. It is usable in different operation modes and intuitively enables the user to select object features interactively for supervised image segmentation method. It allows the user to correct results with a graphical interface. This publicly available tool outperforms tools like OpenCFU and CellProfiler in terms of accuracy and provides many additional useful features for end-users.
The influence of different pH on the electrophoretic behaviour of Saccharomyces cerevisiae modified by calcium ions
Authors: Rogowska Agnieszka , Pomastowski Paweł , Złoch Michał , Railean-Plugaru Viorica , Król Anna , Rafińska Katarzyna , Szultka-Młyńska Małgorzata , Buszewski Bogusław
Published: May 2018

The effect of a different pH on Saccharomyces cerevisiae cells modified with calcium ions was investigated by the capillary zone electrophoresis technique. For the identification of the wild strain of S. cerevisiae, the ribosomal nucleic acid sequencing and internal transcribed spacer sequencing as well as spectrometric approach were applied. The potentiometric titration and Fourier transform infrared spectroscopy have shown the occurrence of active functional groups such as carboxyl, amine/hydroxyl, phosphate/hydrogen phosphate groups on the surface of native yeast cells. Moreover, the spectroscopy study in a medium infrared range was carried out to identify the functional groups of yeast cells that participate in calcium ions binding interaction. Furthermore, the microscopic and spectrometric analysis shows that the pH value of the calcium ions solution has a significant effect on the intensity yeast cells clumping. Additionally, the impact of yeast cell clumping on the electrophoretic behaviours was examined. The modification of surface functional groups by calcium ions significantly affected the efficiency of electrophoretic separation. However, these changes did not affect the accuracy of S. cerevisiae identification by MALDI equipment with BioTyper platform. These results form the analytical solution for coupling of electrophoresis and MALDI-TOF MS technique.
Author Correction: Efficient communication dynamics on macro-connectome, and the propagation speed
Authors: Shimono Masanori , Hatano Naomichi
Published: May 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.
Author Correction: Influence of chromium hyperdoping on the electronic structure of CH3NH3PbI3 perovskite: a first-principles insight
Authors: García Gregorio , Palacios Pablo , Menéndez-Proupin Eduardo , Montero-Alejo Ana L. , Conesa José C. , Wahnón Perla
Published: May 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.
TASI: A software tool for spatial-temporal quantification of tumor spheroid dynamics
Authors: Hou Yue , Konen Jessica , Brat Daniel J. , Marcus Adam I. , Cooper Lee A. D.
Published: May 2018

Spheroid cultures derived from explanted cancer specimens are an increasingly utilized resource for studying complex biological processes like tumor cell invasion and metastasis, representing an important bridge between the simplicity and practicality of 2-dimensional monolayer cultures and the complexity and realism of in vivo animal models. Temporal imaging of spheroids can capture the dynamics of cell behaviors and microenvironments, and when combined with quantitative image analysis methods, enables deep interrogation of biological mechanisms. This paper presents a comprehensive open-source software framework for Temporal Analysis of Spheroid Imaging (TASI) that allows investigators to objectively characterize spheroid growth and invasion dynamics. TASI performs spatiotemporal segmentation of spheroid cultures, extraction of features describing spheroid morpho-phenotypes, mathematical modeling of spheroid dynamics, and statistical comparisons of experimental conditions. We demonstrate the utility of this tool in an analysis of non-small cell lung cancer spheroids that exhibit variability in metastatic and proliferative behaviors.
Impact of 18F-FET PET on Target Volume Definition and Tumor Progression of Recurrent High Grade Glioma Treated with Carbon-Ion Radiotherapy
Authors: Debus Charlotte , Waltenberger Maria , Floca Ralf , Afshar-Oromieh Ali , Bougatf Nina , Adeberg Sebastian , Heiland Sabine , Bendszus Martin , Wick Wolfgang , Rieken Stefan , Haberkorn Uwe , Debus Jürgen , Knoll Maximilian , Abdollahi Amir
Published: May 2018

High-precision radiotherapy (HPR) of recurrent high grade glioma (HGG) requires accurate spatial allocation of these infiltrative tumors. We investigated the impact of 18F-FET PET on tumor delineation and progression of recurrent HGG after HPR with carbon ions. T1 contrast enhanced MRI and 18F-FET-PET scans of 26 HGG patients were fused with radiotherapy planning volumes. PET-positive (PET+) tumor volumes using different isocontours (I%) were systematically investigated and compared with MRI-derived gross tumor volumes (GTV). Standardized uptake ratios (SUR) were further correlated with GTV and tumor progression patterns. In grade IV glioma, SUR > 2.92 significantly correlated with poor median overall survival (6.5 vs 13.1 months, p = 0.00016). We found no reliable SUR cut-off criteria for definition of PET+ volumes. Overall conformity between PET and MRI-based contours was low, with maximum conformities between 0.42–0.51 at I40%. The maximum sensitivity and specificity for PET+ volumes outside of GTV predicting tumor progression were 0.16 (I40%) and 0.52 (I50%), respectively. In 75% of cases, FLAIR hyperintense area covered over 80% of PET+ volumes. 18F-FET-PET derived SUR has a prognostic impact in grade IV glioma. The value of substantial mismatches between MRI-based GTV and PET+ volumes to improve tumor delineation in radiotherapy awaits further validation in randomized prospective trials.
Invasive lobular and ductal breast carcinoma differ in immune response, protein translation efficiency and metabolism
Authors: Du Tian , Zhu Li , Levine Kevin M. , Tasdemir Nilgun , Lee Adrian V. , Vignali Dario A. A. , Houten Bennett Van , Tseng George C. , Oesterreich Steffi
Published: May 2018

Invasive lobular carcinoma (ILC) is the second most common histological subtype of breast cancer following invasive ductal carcinoma (IDC). ILC differs from IDC in a number of histological and clinical features, such as single strand growth, difficulty in detection, and frequent late recurrences. To understand the molecular pathways involved in the clinical characteristics of ILC, we compared the gene expression profiles of luminal A ILC and luminal A IDC using data from TCGA and utilized samples from METABRIC as a validation data set. Top pathways that were significantly enriched in ILC were related to immune response. ILC exhibited a higher activity of almost all types of immune cells based on cell type-specific signatures compared to IDC. Conversely, pathways that were less enriched in ILC were related to protein translation and metabolism, which we functionally validated in cell lines. The higher immune activity uncovered in our study highlights the currently unexplored potential of a response to immunotherapy in a subset of patients with ILC. Furthermore, the lower rates of protein translation and metabolism - known features of tumor dormancy - may play a role in the late recurrences of ILC and lower detection rate in mammography and PET scanning.
Antimicrobial photodynamic therapy mediated by methylene blue and potassium iodide to treat urinary tract infection in a female rat model
Authors: Huang Ying-Ying , Wintner Anton , Seed Patrick C. , Brauns Timothy , Gelfand Jeffrey A. , Hamblin Michael R.
Published: May 2018

Drug-resistant urinary tract infections (UTIs) are difficult and sometimes impossible to treat. Many UTIs are caused by uropathogenic Escherichia coli (UPEC). We developed an intact rat model of UTI, by catheterizing female rats and introducing a bioluminescent UPEC strain into the female rat bladder which lasted for up to six days. We recently showed that antimicrobial photodynamic inactivation (aPDI) of a bacterial infection mediated by the well-known phenothiazinium salt, methylene blue (MB) could be strongly potentiated by addition of the non-toxic salt potassium iodide (KI). In the intact rat model we introduced MB into the bladder by catheter, followed by KI solution and delivered intravesicular illumination with a diffusing fiber connected to a 1 W 660 nm laser. Bioluminescent imaging of the bacterial burden was carried out during the procedure and for 6 days afterwards. Light-dose dependent loss of bioluminescence was observed with the combination of MB followed by KI, but recurrence of infection was seen the next day in some cases. aPDT with MB + KI gave a significantly shorter duration of infection compared to untreated controls. aPDT with MB alone was the least effective. No signs of aPDT damage to the bladder lining were detected. This procedure to treat urinary tract infections without antibiotics by using already approved pharmaceutical substances (MB and KI) may have clinical applicability, either initially as a stand-alone therapy, or as an adjunct to antibiotic therapy by a rapid and substantial reduction of the bacterial burden.
Matrix metalloproteinases (MMPs) mediate leukocyte recruitment during the inflammatory phase of zebrafish heart regeneration
Authors: Xu Shisan , Webb Sarah E. , Lau Terrence Chi Kong , Cheng Shuk Han
Published: May 2018

In zebrafish, the role of matrix metalloproteinases (MMPs) in the inflammatory phase of heart regeneration following cryoinjury remains poorly understood. Here, we demonstrated an increase in MMP enzymatic activity and elevated expression of mmp9 and mmp13 in the injured area (IA) of hearts from as early as 1 day post-cryoinjury (dpc). Treatment with the broad-spectrum MMP inhibitor, GM6001, during the first week after cryoinjury resulted in impaired heart regeneration, as indicated by the larger scar and reduced numbers of proliferating cardiomyocytes. GM6001 also significantly reduced the number of leukocytes to the IA at 0.5 dpc to 4 dpc. Specific inhibition of both MMP-9 and MMP-13 also resulted in impaired regeneration and leukocyte recruitment. However, chemokine rescue with recombinant CXCL8 and CCL2 restored the recruitment of macrophages and the cardiac regenerative capability in GM6001-treated fish. MMP-9 and MMP-13 cleaved zebrafish CXCL8 at the same site, and the truncated form was more chemotactic than the intact form. In contrast, CCL2 did not have an MMP-9 or MMP-13 cleavage site. Together, these data suggest that MMPs might play a key role in the inflammatory phase of heart regeneration in zebrafish, by mediating leukocyte recruitment via the activation of chemokines.
The Role of Electrostatic Repulsion on Increasing Surface Activity of Anionic Surfactants in the Presence of Hydrophilic Silica Nanoparticles
Authors: Vatanparast Hamid , Shahabi Farshid , Bahramian Alireza , Javadi Aliyar , Miller Reinhard
Published: May 2018

Hydrophilic silica nanoparticles alone are not surface active. They, however, develop a strong electrostatic interaction with ionic surfactants and consequently affect their surface behavior. We report the interfacial behavior of n-heptane/anionic-surfactant-solutions in the presence of hydrophilic silica nanoparticles. The surfactants are sodium dodecyl sulfate (SDS) and dodecyl benzene sulfonic acid (DBSA), and the diameters of the used particles are 9 and 30 nm. Using experimental tensiometry, we show that nanoparticles retain their non-surface-active nature in the presence of surfactants and the surface activity of surfactant directly increases with the concentration of nanoparticles. This fact was attributed to the electrostatic repulsive interaction between the negatively charged nanoparticles and the anionic surfactant molecules. The role of electrostatic repulsion on increasing surface activity of the surfactant has been discussed. Further investigations have been performed for screening the double layer charge of the nanoparticles in the presence of salt. Moreover, the hydrolysis of SDS molecules in the presence of silica nanoparticles and the interaction of nanoparticles with SDS inherent impurities have been studied. According to our experimental observations, silica nanoparticles alleviate the effects of dodecanol, formed by SDS hydrolysis, on the interfacial properties of SDS solution.
Exosome markers associated with immune activation and oxidative stress in HIV patients on antiretroviral therapy
Authors: Chettimada Sukrutha , Lorenz David R. , Misra Vikas , Dillon Simon T. , Reeves R. Keith , Manickam Cordelia , Morgello Susan , Kirk Gregory D. , Mehta Shruti H. , Gabuzda Dana
Published: May 2018

Exosomes are nanovesicles released from most cell types including immune cells. Prior studies suggest exosomes play a role in HIV pathogenesis, but little is known about exosome cargo in relation to immune responses and oxidative stress. Here, we characterize plasma exosomes in HIV patients and their relationship to immunological and oxidative stress markers. Plasma exosome fractions were isolated from HIV-positive subjects on ART with suppressed viral load and HIV-negative controls. Exosomes were characterized by electron microscopy, nanoparticle tracking, immunoblotting, and LC-MS/MS proteomics. Plasma exosomes were increased in HIV-positive subjects compared to controls, and correlated with increased oxidative stress markers (cystine, oxidized cys-gly) and decreased PUFA (DHA, EPA, DPA). Untargeted proteomics detected markers of exosomes (CD9, CD63, CD81), immune activation (CD14, CRP, HLA-A, HLA-B), oxidative stress (CAT, PRDX1, PRDX2, TXN), and Notch4 in plasma exosomes. Exosomal Notch4 was increased in HIV-positive subjects versus controls and correlated with immune activation markers. Treatment of THP-1 monocytic cells with patient-derived exosomes induced expression of genes related to interferon responses and immune activation. These results suggest that exosomes in ART-treated HIV patients carry proteins related to immune activation and oxidative stress, have immunomodulatory effects on myeloid cells, and may have pro-inflammatory and redox effects during pathogenesis.
Osmotic modulation of chromatin impacts on efficiency and kinetics of cell fate modulation
Authors: Lima A. F. , May G. , Díaz-Colunga J. , Pedreiro S. , Paiva A. , Ferreira L. , Enver T. , Iborra F. J. , Pires das Neves R.
Published: May 2018

Chromatin structure is a major regulator of transcription and gene expression. Herein we explore the use of osmotic modulation to modify the chromatin structure and reprogram gene expression. In this study we use the extracellular osmotic pressure as a chromatin structure and transcriptional modulator. Hyposmotic modulation promotes chromatin loosening and induces changes in RNA polymerase II (Pol II) activity. The chromatin decondensation opens space for higher amounts of DNA engaged RNA Pol II. Hyposmotic modulation constitutes an alternative route to manipulate cell fate decisions. This technology was tested in model protocols of induced pluripotency and transdifferentiation in cells growing in suspension and adherent to substrates, CD34+umbilical-cord-blood (UCB), fibroblasts and B-cells. The efficiency and kinetics of these cell fate modulation processes were improved by transient hyposmotic modulation of the cell environment.
Assessment of ECG and respiration recordings from simulated emergency landings of ultra light aircraft
Authors: Bruna Ondřej , Levora Tomáš , Holub Jan
Published: May 2018

Pilots of ultra light aircraft have limited training resources, but with the use of low cost simulators it might be possible to train and test some parts of their training on the ground. The purpose of this paper is to examine possibility of stress inducement on a low cost flight simulator. Stress is assessed from electrocardiogram and respiration. Engine failure during flight served as a stress inducement stimuli. For one flight, pilots had access to an emergency navigation system. There were recorded some statistically significant changes in parameters regarding breathing frequency. Although no significant change was observed in ECG parameters, there appears to be an effect on respiration parameters. Physiological signals processed with analysis of variance suggest, that the moment of engine failure and approach for landing affected average breathing frequency. Presence of navigation interface does not appear to have a significant effect on pilots.
Inhibition of poly-LacNAc biosynthesis with release of CMP-Neu5Ac feedback inhibition increases the sialylation of recombinant EPO produced in CHO cells
Authors: Lee Chung-Geun , Oh Myung Jin , Park Seung-Yeol , An Hyun Joo , Kim Jung Hoe
Published: May 2018

Sialylation of recombinant therapeutic glycoproteins modulates their pharmacokinetic properties by affecting their in vivo half-life. N-glycan branching on glycoproteins increases the number of potential attachment sites for sialic acid. Here, we introduce a new approach for increasing the sialylation of recombinant human erythropoietin (rhEPO) produced in CHO cells by modulating poly-N-acetyllactosamine (poly-LacNAc) biosynthesis. We did not observe an increase in rhEPO sialylation, however, until the feedback inhibition by intracellular cytidine monophosphate-N-acetylneuraminic acid (CMP-Neu5Ac), which is a limiting factor for sialylation, was released. Thus, we found that a combined approach inhibiting poly-LacNAc biosynthesis and releasing CMP-Neu5Ac feedback inhibition produces the most significant increase in rhEPO sialylation in metabolically engineered CHO cells. Furthermore, a detailed analysis of the resulting N-glycan structures using LC/MS revealed increased tri- and tetra- sialylated N-glycan structures accompanied by a reduction of di-sialylated N-glycan structures. These results validate our new approach for glycosylation engineering, and we expect this approach will be useful in future efforts to enhance the efficacy of other therapeutic glycoproteins.
Mechanical adaptation of trabecular bone morphology in the mammalian mandible
Authors: Watson Peter J. , Fitton Laura C. , Meloro Carlo , Fagan Michael J. , Gröning Flora
Published: May 2018

Alveolar bone, together with the underlying trabecular bone, fulfils an important role in providing structural support against masticatory forces. Diseases such as osteoporosis or periodontitis cause alveolar bone resorption which weakens this structural support and is a major cause of tooth loss. However, the functional relationship between alveolar bone remodelling within the molar region and masticatory forces is not well understood. This study investigated this relationship by comparing mammalian species with different diets and functional loading (Felis catus, Cercocebus atys, Homo sapiens, Sus scrofa, Oryctolagus cuniculus, Ovis aries). We performed histomorphometric analyses of trabecular bone morphology (bone volume fraction, trabecular thickness and trabecular spacing) and quantified the variation of bone and tooth root volumes along the tooth row. A principal component analysis and non-parametric MANOVA showed statistically significant differences in trabecular bone morphology between species with contrasting functional loading, but these differences were not seen in sub-adult specimens. Our results support a strong, but complex link between masticatory function and trabecular bone morphology. Further understanding of a potential functional relationship could aid the diagnosis and treatment of mandibular diseases causing alveolar bone resorption, and guide the design and evaluation of dental implants.
Discovery and functional characterisation of a luqin-type neuropeptide signalling system in a deuterostome
Authors: Yañez-Guerra Luis Alfonso , Delroisse Jérôme , Barreiro-Iglesias Antón , Slade Susan E. , Scrivens James H. , Elphick Maurice R.
Published: May 2018

Neuropeptides are diverse and evolutionarily ancient regulators of physiological/behavioural processes in animals. Here we have investigated the evolution and comparative physiology of luqin-type neuropeptide signalling, which has been characterised previously in protostomian invertebrates. Phylogenetic analysis indicates that luqin-type receptors and tachykinin-type receptors are paralogous and probably originated in a common ancestor of the Bilateria. In the deuterostomian lineage, luqin-type signalling has been lost in chordates but interestingly it has been retained in ambulacrarians. Therefore, here we characterised luqin-type signalling for the first time in an ambulacrarian – the starfish Asterias rubens (phylum Echinodermata). A luqin-like neuropeptide with a C-terminal RWamide motif (ArLQ; EEKTRFPKFMRW-NH2) was identified as the ligand for two luqin-type receptors in A. rubens, ArLQR1 and ArLQR2. Furthermore, analysis of the expression of the ArLQ precursor using mRNA in situ hybridisation revealed expression in the nervous system, digestive system and locomotory organs (tube feet) and in vitro pharmacology revealed that ArLQ causes dose-dependent relaxation of tube feet. Accordingly, previous studies have revealed that luqin-type signalling regulates feeding and locomotor activity in protostomes. In conclusion, our phylogenetic analysis combined with characterisation of luqin-type signalling in a deuterostome has provided new insights into neuropeptide evolution and function in the animal kingdom.
Tumor heterogeneity of pancreas head cancer assessed by CT texture analysis: association with survival outcomes after curative resection
Authors: Yun Gabin , Kim Young Hoon , Lee Yoon Jin , Kim Bohyoung , Hwang Jin-Hyeok , Choi Dong Joon
Published: May 2018

The value of image based texture features as a powerful method to predict prognosis and assist clinical management in cancer patients has been established recently. However, texture analysis using histograms and grey-level co-occurrence matrix in pancreas cancer patients has rarely been reported. We aimed to analyze the association of survival outcomes with texture features in pancreas head cancer patients. Eighty-eight pancreas head cancer patients who underwent preoperative CT images followed by curative resection were included. Texture features using different filter values were obtained. The texture features of average, contrast, correlation, and standard deviation with no filter, and fine to medium filter values as well as the presence of nodal metastasis were significantly different between the recurred (n = 70, 79.5%) and non-recurred group (n = 18, 20.5%). In the multivariate Cox regression analysis, lower standard deviation and contrast and higher correlation with lower average value representing homogenous texture were significantly associated with poorer DFS (disease free survival), along with the presence of lymph node metastasis. Texture parameters from routinely performed pre-operative CT images could be used as an independent imaging tool for predicting the prognosis in pancreas head cancer patients who underwent curative resection.
Tortuous Pore Path Through the Glaucomatous Lamina Cribrosa
Authors: Wang Bo , Lucy Katie A. , Schuman Joel S. , Sigal Ian A. , Bilonick Richard A. , Lu Chen , Liu Jonathan , Grulkowski Ireneusz , Nadler Zachary , Ishikawa Hiroshi , Kagemann Larry , Fujimoto James G. , Wollstein Gadi
Published: May 2018

The lamina cribrosa is a primary site of damage in glaucoma. While mechanical distortion is hypothesized to cause reduction of axoplasmic flow, little is known about how the pores, which contains the retinal ganglion cell axons, traverse the lamina cribrosa. We investigated lamina cribrosa pore paths in vivo to quantify differences in tortuosity of pore paths between healthy and glaucomatous eyes. We imaged 16 healthy, 23 glaucoma suspect and 48 glaucomatous eyes from 70 subjects using a swept source optical coherence tomography system. The lamina cribrosa pores were automatically segmented using a previously described segmentation algorithm. Individual pore paths were automatically tracked through the depth of the lamina cribrosa using custom software. Pore path convergence to the optic nerve center and tortuosity was quantified for each eye. We found that lamina cribrosa pore pathways traverse the lamina cribrosa closer to the optic nerve center along the depth of the lamina cribrosa regardless of disease severity or diagnostic category. In addition, pores of glaucoma eyes take a more tortuous path through the lamina cribrosa compared to those of healthy eyes, suggesting a potential mechanism for reduction of axoplasmic flow in glaucoma.
Periodical reactivation under the effect of caffeine attenuates fear memory expression in rats
Authors: Pedraza Lizeth K. , Sierra Rodrigo O. , Lotz Fernanda N. , de Oliveira Alvares Lucas
Published: May 2018

In the last decade, several studies have shown that fear memories can be attenuated by interfering with reconsolidation. However, most of the pharmacological agents used in preclinical studies cannot be administered to humans. Caffeine is one of the world’s most popular psychoactive drugs and its effects on cognitive and mood states are well documented. Nevertheless, the influence of caffeine administration on fear memory processing is not as clear. We employed contextual fear conditioning in rats and acute caffeine administration under a standard memory reconsolidation protocol or periodical memory reactivation. Additionally, potential rewarding/aversion and anxiety effects induced by caffeine were evaluated by conditioning place preference or open field, respectively. Caffeine administration was able to attenuate weak fear memories in a standard memory reconsolidation protocol; however, periodical memory reactivation under caffeine effect was necessary to attenuate strong and remote memories. Moreover, caffeine promoted conditioned place preference and anxiolytic-like behavior, suggesting that caffeine weakens the initial learning during reactivation through counterconditioning mechanisms. Thus, our study shows that rewarding and anxiolytic effects of caffeine during fear reactivation can change the emotional valence of fear memory. It brings a new promising pharmacological approach based on drugs widely used such as caffeine to treat fear-related disorders.
Tissue distribution and cell tropism of Brucella canis in naturally infected canine foetuses and neonates
Authors: de Souza Tayse Domingues , de Carvalho Tatiane Furtado , Mol Juliana Pinto da Silva , Lopes João Vítor Menezes , Silva Monique Ferreira , da Paixão Tatiane Alves , Santos Renato Lima
Published: May 2018

Brucella canis infection is an underdiagnosed zoonotic disease. Knowledge about perinatal brucellosis in dogs is extremely limited, although foetuses and neonates are under risk of infection due to vertical transmission. In this study, immunohistochemistry was used to determine tissue distribution and cell tropism of B. canis in canine foetuses and neonates. Diagnosis of B. canis in tissues of naturally infected pups was based on PCR and sequencing of amplicons, bacterial isolation, and immunohistochemistry, whose specificity was confirmed by laser capture microdissection. PCR positivity among 200 puppies was 21%, and nine isolates of B. canis were obtained. Tissues from 13 PCR-positive puppies (4 stillborn and 9 neonates) presented widespread immunolabeling. Stomach, intestines, kidney, nervous system, and umbilicus were positive in all animals tested. Other frequently infected organs included the liver (92%), lungs (85%), lymph nodes (69%), and spleen (62%). Immunolabeled coccobacilli occurred mostly in macrophages, but they were also observed in erythrocytes, epithelial cells of gastrointestinal mucosa, renal tubules, epidermis, adipocytes, choroid plexus, ependyma, neuroblasts, blood vessels endothelium, muscle cells, and in the intestinal lumen. These results largely expand our knowledge about perinatal brucellosis in the dog, clearly demonstrating a pantropic distribution of B. canis in naturally infected foetuses and neonates.
Tuning the electrical properties of the p-type transparent conducting oxide Cu1−xCr1+xO2 by controlled annealing
Authors: Lunca-Popa P. , Afonso J. , Grysan P. , Crêpellière J. , Leturcq R. , Lenoble D.
Published: May 2018

Off-stoichiometric copper chromium oxide delafossite received lately a great interest due to its high p-type electrical conductivity and adequate optical transmittance in the visible range. However, for a suitable integration in active devices such as p-n junctions, transistors or optoelectronic devices, the electronic properties must be efficiently tailored. Here, post-deposition thermal treatment is proven as an adequate approach for finely controlling the electrical properties of this former degenerate semiconducting material. The energetics of the annealing process are investigated using two different approaches, as a function of the annealing temperature and as a function of the annealing time, allowing the accurate determination of the activation energy of the annealing of defects. By using this method, the electrical carrier concentration was varied in the 1021 – 1017 cm−3 range while the recorded changes in the drift mobility covered three orders of magnitude. Moreover, we demonstrate the ability to accurately manipulate the Fermi level of such materials, which is of great importance in controlling the carrier injection and extraction in optoelectronic active layers.
Magnetic resonance imaging provides evidence of glymphatic drainage from human brain to cervical lymph nodes
Authors: Eide Per Kristian , Vatnehol Svein Are Sirirud , Emblem Kyrre Eeg , Ringstad Geir
Published: May 2018

Pre-clinical research in rodents provides evidence that the central nervous system (CNS) has functional lymphatic vessels. In-vivo observations in humans, however, are not demonstrated. We here show data on CNS lymphatic drainage to cervical lymph nodes in-vivo by magnetic resonance imaging (MRI) enhanced with an intrathecal contrast agent as a cerebrospinal fluid (CSF) tracer. Standardized MRI of the intracranial compartment and the neck were acquired before and up to 24–48 hours following intrathecal contrast agent administration in 19 individuals. Contrast enhancement was radiologically confirmed by signal changes in CSF nearby inferior frontal gyrus, brain parenchyma of inferior frontal gyrus, parahippocampal gyrus, thalamus and pons, and parenchyma of cervical lymph node, and with sagittal sinus and neck muscle serving as reference tissue for cranial and neck MRI acquisitions, respectively. Time series of changes in signal intensity shows that contrast enhancement within CSF precedes glymphatic enhancement and peaks at 4–6 hours following intrathecal injection. Cervical lymph node enhancement coincides in time with peak glymphatic enhancement, with peak after 24 hours. Our findings provide in-vivo evidence of CSF tracer drainage to cervical lymph nodes in humans. The time course of lymph node enhancement coincided with brain glymphatic enhancement rather than with CSF enhancement.
Clathrin-mediated endocytosis is a candidate entry sorting mechanism for Bombyx mori cypovirus
Authors: Chen Fei , Zhu Liyuan , Zhang Yiling , Kumar Dhiraj , Cao Guangli , Hu Xiaolong , Liang Zi , Kuang Sulan , Xue Renyu , Gong Chengliang
Published: May 2018

Bombyx mori cypovirus (BmCPV), a member of the Reoviridae, specifically infects silkworms and causes extensive economic losses to the sericulture industry. To date, the entry mechanism of BmCPV into cells is unclear. Here we used electron microscopy to study the route of entry of BmCPV into cells, and the results demonstrated that the entry of BmCPV into BmN cells was mediated by endocytosis. Blocking the entry pathway with four endocytosis inhibitors, including dansylcadaverine, chlorpromazine, genistein, and PP2, significantly decreased the infectivity of BmCPV. This indicates that BmCPV enters BmN cells via endocytosis, and that clathrin-mediated sorting is the predominant entry method. After the relative expression levels of clathrin heavy chain (clathrin, GenBank accession No. NM_001142971.1) and the adaptor protein complex-1 gamma subunit AP-1 (AP-1, GenBank accession No. JQ824201.1), which are involved in clathrin-mediated endocytosis, were inhibited by RNA interference or abolishing the functions of clathrin and AP-1 with their corresponding antibodies, the infectivity of BmCPV was reduced significantly, which suggests that clathrin-mediated endocytosis contributed to the entry of BmCPV into cells. Our findings suggest that the clathrin-mediated endocytosis pathway is a candidate for the development of therapeutics for silkworm cytoplasmic polyhedrosis.
Systematic realization of double-zero-index phononic crystals with hard inclusions
Authors: Hyun Jaeyub , Choi Wonjae , Wang Semyung , Park Choon-su , Kim Miso
Published: May 2018

A systematic process is described to realize double-zero-index phononic crystals with Dirac-like points experimentally. This type of crystal normally has softer inclusion material than its surroundings medium, allowing mapping into a zero-index medium under certain conditions but also making experimental implementation difficult. On the other hand, realizing phononic crystals with hard inclusions can be experimentally more feasible, but the mapping conditions cannot be directly applied to hard-inclusion crystals such that mapping is not systematically guaranteed in these cases. Moreover, even if such crystals become realizable, there is a lack of a systematic design process which can be used to optimize or to redesign the crystals, which largely limits their potential applications. In this paper, we discover the essential conditions for realizing phononic crystals with hard inclusions and propose a methodology for the systematic design of these crystals using homogenization based on the effective medium theory. Using the proposed method, a double-zero-index phononic crystal with hard inclusions is optimized and experimentally realized for an underwater ultrasonic wave collimator.
Genetic and Environmental Influences on Fetal Growth Vary during Sensitive Periods in Pregnancy
Authors: Workalemahu Tsegaselassie , Grantz Katherine L. , Grewal Jagteshwar , Zhang Cuilin , Louis Germaine M. Buck , Tekola-Ayele Fasil
Published: May 2018

Aberrant fetal growth is associated with morbidities and mortality during childhood and adult life. Although genetic and environmental factors are known to influence in utero growth, their relative contributions over pregnancy is unknown. We estimated, across gestation, the genetic heritability, contribution of shared environment, and genetic correlations of fetal growth measures (abdominal circumference (AC), humerus length (HL), femur length (FL), and estimated fetal weight (EFW)) in a prospective cohort of dichorionic twin gestations recruited through the NICHD Fetal Growth Studies. Structural equation models were fit at the end of first trimester, during mid-gestation, late second trimester, and third trimester of pregnancy. The contribution of fetal genetics on fetal size increased with gestational age, peaking in late second trimester (AC = 53%, HL = 57%, FL = 72%, EFW = 71%; p < 0.05). In contrast, shared environment explained most of phenotypic variations in fetal growth in the first trimester (AC = 50%, HL = 54%, FL = 47%, EFW = 54%; p < 0.05), suggesting that the first trimester presents an intervention opportunity for a more optimal early fetal growth. Genetic correlations between growth traits (range 0.34–1.00; p < 0.05) were strongest at the end of first trimester and declined with gestation, suggesting that different fetal growth measures are more likely to be influenced by the same genes in early pregnancy.
Naked Gold Nanoparticles and hot Electrons in Water
Authors: Ghandi Khashayar , Wang Furong , Landry Cody , Mostafavi Mehran
Published: May 2018

The ionizing radiation in aqueous solutions of gold nanoparticles, stabilized by electrostatic non-covalent intermolecular forces and steric interactions, with antimicrobial compounds, are investigated with picosecond pulse radiolysis techniques. Upon pulse radiolysis of an aqueous solution containing very low concentrations of gold nanoparticles with naked surfaces available in water (not obstructed by chemical bonds), a change to Cerenkov spectrum over a large range of wavelengths are observed and pre-solvated electrons are captured by gold nanoparticles exclusively (not by ionic liquid surfactants used to stabilize the nanoparticles). The solvated electrons are also found to decay rapidly compared with the decay kinetics in water. These very fast reactions with electrons in water could provide an enhanced oxidizing zone around gold nanoparticles and this could be the reason for radio sensitizing behavior of gold nanoparticles in radiation therapy.