bluuebunny/crossref_metadata_2025 huggingface dataset:
Is it possible to register the ideas, concerns and expectations behind the reason for encounter as a means of classifying patient preferences with ICPC-2?
Authors: Schrans Diego , Boeckxstaens Pauline , De Sutter An , Willems Sara , Avonts Dirk , Christiaens Thierry , Matthys Jan , Kühlein Thomas
Published: September 2017

Background

Family practice aims to recognize the health problems and needs expressed by the person rather than only focusing on the disease. Documenting person-related information will facilitate both the understanding and delivery of person-focused care.

Aim

To explore if the patients’ ideas, concerns and expectations (ICE) behind the reason for encounter (RFE) can be coded with the International Classification of Primary Care, version 2 (ICPC-2) and what kinds of codes are missing to be able to do so.

Methods

In total, 613 consultations were observed, and patients’ expressions of ICE were narratively recorded. These descriptions were consequently translated to ICPC codes by two researchers. Descriptions that could not be translated were qualitatively analysed in order to identify gaps in ICPC-2.

Results

In all, 613 consultations yielded 672 ICE expressions. Within the 123 that could not be coded with ICPC-2, eight categories could be defined: concern about the duration/time frame; concern about the evolution/severity; concern of being contagious or a danger to others; patient has no concern, but others do; expects a confirmation of something; expects a solution for the symptoms without specification of what it should be; expects a specific procedure; and expects that something is not done.

Discussion

Although many ICE can be registered with ICPC-2, adding eight new categories would capture almost all ICE.
Psychological morbidity and parenting stress in mothers of primary school children by timing of acquisition of HIV infection: a longitudinal cohort study in rural South Africa
Authors: Rochat T. J. , Houle B. , Stein A. , Pearson R. M. , Newell M. L. , Bland R. M.
Published: September 2017

Longitudinal maternal mental health data are needed from high HIV prevalence settings. The Siyakhula Cohort (SC) is a population-based cohort of HIV-positive and negative mothers (n=1506) with HIV-negative children (n=1536) from rural South Africa. SC includes 767 HIV-negative mothers; 465 HIV-positive in pregnancy; 272 HIV-positive since pregnancy (n=2 missing HIV status). A subgroup (n=890) participated in a non-randomized breastfeeding intervention [Vertical Transmission Study (VTS)]; the remaining (n=616) were resident in the same area and received antenatal care at the time of the VTS, but were not part of the VTS, instead receiving the standard of care Prevention of Mother-to-Child Transmission (PMTCT) Programme. In secondary analysis we investigated the prevalence of, and factors associated with, psychological morbidity amongst mothers who were still the primary caregiver of the child (1265 out of 1506) at follow-up (7–11 years post-birth). We measured maternal depression (Patient Health Questionnaire-9), anxiety (General Anxiety Disorder Scale-7) and parenting stress (Parenting Stress Index-36), using standardized cut-offs and algorithms. In total, 75 (5.9%) mothers met criteria for depression, 37 (2.9%) anxiety and 134 (10.6%) parenting stress. Using complete case logistic regression (n=1206 out of 1265 mothers) as compared to being HIV-negative, testing HIV-positive in pregnancy doubled odds of depression [adjusted odd ratios (aOR)=1.96 [1.0–3.7] P=0.039]. Parenting stress was positively associated with acquisition of HIV after pregnancy (aOR=3.11 [1.9–5.2] P<0.001) and exposure to household crime (aOR=2.02 [1.3–3.2] P=0.003); negatively associated with higher maternal education (aOR=0.29 [0.1–0.8] P=0.014), maternal employment (aOR=0.55 [0.3–0.9] P=0.024). Compared with the standard of care PMTCT, VTS mothers had reduced odds of parenting stress (aOR=0.61 [0.4–0.9] P=0.016). Integrating parental support into mostly bio-medical treatment programmes, during and beyond pregnancy, is important.
Nonreciprocal reconfigurable microwave optomechanical circuit
Authors: Bernier N. R. , Tóth L. D. , Koottandavida A. , Ioannou M. A. , Malz D. , Nunnenkamp A. , Feofanov A. K. , Kippenberg T. J.
Published: September 2017

Nonreciprocal microwave devices are ubiquitous in radar and radio communication and indispensable in the readout chains of superconducting quantum circuits. Since they commonly rely on ferrite materials requiring large magnetic fields that make them bulky and lossy, there has been significant interest in magnetic-field-free on-chip alternatives, such as those recently implemented using the Josephson nonlinearity. Here, we realize reconfigurable nonreciprocal transmission between two microwave modes using purely optomechanical interactions in a superconducting electromechanical circuit. The scheme relies on the interference in two mechanical modes that mediate coupling between the microwave cavities and requires no magnetic field. We analyse the isolation, transmission and the noise properties of this nonreciprocal circuit. Finally, we show how quantum-limited circulators can be realized with the same principle. All-optomechanically mediated nonreciprocity demonstrated here can also be extended to directional amplifiers, and it forms the basis towards realizing topological states of light and sound.
Tumor-associated B-cells induce tumor heterogeneity and therapy resistance
Authors: Somasundaram Rajasekharan , Zhang Gao , Fukunaga-Kalabis Mizuho , Perego Michela , Krepler Clemens , Xu Xiaowei , Wagner Christine , Hristova Denitsa , Zhang Jie , Tian Tian , Wei Zhi , Liu Qin , Garg Kanika , Griss Johannes , Hards Rufus , Maurer Margarita , Hafner Christine , Mayerhöfer Marius , Karanikas Georgios , Jalili Ahmad , Bauer-Pohl Verena , Weihsengruber Felix , Rappersberger Klemens , Koller Josef , Lang Roland , Hudgens Courtney , Chen Guo , Tetzlaff Michael , Wu Lawrence , Frederick Dennie Tompers , Scolyer Richard A. , Long Georgina V. , Damle Manashree , Ellingsworth Courtney , Grinman Leon , Choi Harry , Gavin Brian J. , Dunagin Margaret , Raj Arjun , Scholler Nathalie , Gross Laura , Beqiri Marilda , Bennett Keiryn , Watson Ian , Schaider Helmut , Davies Michael A. , Wargo Jennifer , Czerniecki Brian J. , Schuchter Lynn , Herlyn Dorothee , Flaherty Keith , Herlyn Meenhard , Wagner Stephan N.
Published: September 2017

In melanoma, therapies with inhibitors to oncogenic BRAFV600E are highly effective but responses are often short-lived due to the emergence of drug-resistant tumor subpopulations. We describe here a mechanism of acquired drug resistance through the tumor microenvironment, which is mediated by human tumor-associated B cells. Human melanoma cells constitutively produce the growth factor FGF-2, which activates tumor-infiltrating B cells to produce the growth factor IGF-1. B-cell-derived IGF-1 is critical for resistance of melanomas to BRAF and MEK inhibitors due to emergence of heterogeneous subpopulations and activation of FGFR-3. Consistently, resistance of melanomas to BRAF and/or MEK inhibitors is associated with increased CD20 and IGF-1 transcript levels in tumors and IGF-1 expression in tumor-associated B cells. Furthermore, first clinical data from a pilot trial in therapy-resistant metastatic melanoma patients show anti-tumor activity through B-cell depletion by anti-CD20 antibody. Our findings establish a mechanism of acquired therapy resistance through tumor-associated B cells with important clinical implications.
miR-9a modulates maintenance and ageing of Drosophila germline stem cells by limiting N-cadherin expression
Authors: Epstein Yehonatan , Perry Noam , Volin Marina , Zohar-Fux Maayan , Braun Rachel , Porat-Kuperstein Lilach , Toledano Hila
Published: September 2017

Ageing is characterized by a decline in stem cell functionality leading to dampened tissue regeneration. While the expression of microRNAs across multiple species is markedly altered with age, the mechanism by which they govern stem cell-sustained tissue regeneration is unknown. We report that in the Drosophila testis, the conserved miR-9a is expressed in germline stem cells and its levels are significantly elevated during ageing. Transcriptome and functional analyses show that miR-9a directly regulates the expression of the adhesion molecule N-cadherin (N-cad). miR-9a null mutants maintain a higher number of stem cells even in the aged tissue. Remarkably, this rise fails to improve tissue regeneration and results in reduced male fertility. Similarly, overexpression of N-cad also results in elevated stem cell number and decreased regeneration. We propose that miR-9a downregulates N-cad to enable adequate detachment of stem cells toward differentiation, thus providing the necessary directionality toward terminal differentiation and spermatogenesis.
Dimerization regulates both deaminase-dependent and deaminase-independent HIV-1 restriction by APOBEC3G
Authors: Morse Michael , Huo Ran , Feng Yuqing , Rouzina Ioulia , Chelico Linda , Williams Mark C.
Published: September 2017

APOBEC3G (A3G) is a human enzyme that inhibits human immunodeficiency virus type 1 (HIV-1) infectivity, in the absence of the viral infectivity factor Vif, through deoxycytidine deamination and a deamination-independent mechanism. A3G converts from a fast to a slow binding state through oligomerization, which suggests that large A3G oligomers could block HIV-1 reverse transcriptase-mediated DNA synthesis, thereby inhibiting HIV-1 replication. However, it is unclear how the small number of A3G molecules found in the virus could form large oligomers. Here we measure the single-stranded DNA binding and oligomerization kinetics of wild-type and oligomerization-deficient A3G, and find that A3G first transiently binds DNA as a monomer. Subsequently, A3G forms N-terminal domain-mediated dimers, whose dissociation from DNA is reduced and their deaminase activity inhibited. Overall, our results suggest that the A3G molecules packaged in the virion first deaminate viral DNA as monomers before dimerizing to form multiple enzymatically deficient roadblocks that may inhibit reverse transcription.
Hydrodeoxygenation of water-insoluble bio-oil to alkanes using a highly dispersed Pd–Mo catalyst
Authors: Duan Haohong , Dong Juncai , Gu Xianrui , Peng Yung-Kang , Chen Wenxing , Issariyakul Titipong , Myers William K. , Li Meng-Jung , Yi Ni , Kilpatrick Alexander F. R. , Wang Yu , Zheng Xusheng , Ji Shufang , Wang Qian , Feng Junting , Chen Dongliang , Li Yadong , Buffet Jean-Charles , Liu Haichao , Tsang Shik Chi Edman , O’Hare Dermot
Published: September 2017

Bio-oil, produced by the destructive distillation of cheap and renewable lignocellulosic biomass, contains high energy density oligomers in the water-insoluble fraction that can be utilized for diesel and valuable fine chemicals productions. Here, we show an efficient hydrodeoxygenation catalyst that combines highly dispersed palladium and ultrafine molybdenum phosphate nanoparticles on silica. Using phenol as a model substrate this catalyst is 100% effective and 97.5% selective for hydrodeoxygenation to cyclohexane under mild conditions in a batch reaction; this catalyst also demonstrates regeneration ability in long-term continuous flow tests. Detailed investigations into the nature of the catalyst show that it combines hydrogenation activity of Pd and high density of both Brønsted and Lewis acid sites; we believe these are key features for efficient catalytic hydrodeoxygenation behavior. Using a wood and bark-derived feedstock, this catalyst performs hydrodeoxygenation of lignin, cellulose, and hemicellulose-derived oligomers into liquid alkanes with high efficiency and yield.
Andreev molecules in semiconductor nanowire double quantum dots
Authors: Su Zhaoen , Tacla Alexandre B. , Hocevar Moïra , Car Diana , Plissard Sébastien R. , Bakkers Erik P. A. M. , Daley Andrew J. , Pekker David , Frolov Sergey M.
Published: September 2017

Chains of quantum dots coupled to superconductors are promising for the realization of the Kitaev model of a topological superconductor. While individual superconducting quantum dots have been explored, control of longer chains requires understanding of interdot coupling. Here, double quantum dots are defined by gate voltages in indium antimonide nanowires. High transparency superconducting niobium titanium nitride contacts are made to each of the dots in order to induce superconductivity, as well as probe electron transport. Andreev bound states induced on each of dots hybridize to define Andreev molecular states. The evolution of these states is studied as a function of charge parity on the dots, and in magnetic field. The experiments are found in agreement with a numerical model.
Soft material for soft actuators
Authors: Miriyev Aslan , Stack Kenneth , Lipson Hod
Published: September 2017

Inspired by natural muscle, a key challenge in soft robotics is to develop self-contained electrically driven soft actuators with high strain density. Various characteristics of existing technologies, such as the high voltages required to trigger electroactive polymers ( > 1KV), low strain ( < 10%) of shape memory alloys and the need for external compressors and pressure-regulating components for hydraulic or pneumatic fluidicelastomer actuators, limit their practicality for untethered applications. Here we show a single self-contained soft robust composite material that combines the elastic properties of a polymeric matrix and the extreme volume change accompanying liquid–vapor transition. The material combines a high strain (up to 900%) and correspondingly high stress (up to 1.3 MPa) with low density (0.84 g cm−3). Along with its extremely low cost (about 3 cent per gram), simplicity of fabrication and environment-friendliness, these properties could enable new kinds of electrically driven entirely soft robots.
Agonist immunotherapy restores T cell function following MEK inhibition improving efficacy in breast cancer
Authors: Dushyanthen Sathana , Teo Zhi Ling , Caramia Franco , Savas Peter , Mintoff Christopher P. , Virassamy Balaji , Henderson Melissa A. , Luen Stephen J. , Mansour Mariam , Kershaw Michael H. , Trapani Joseph A. , Neeson Paul J. , Salgado Roberto , McArthur Grant A. , Balko Justin M. , Beavis Paul A. , Darcy Phillip K. , Loi Sherene
Published: September 2017

The presence of tumor-infiltrating lymphocytes in triple-negative breast cancers is correlated with improved outcomes. Ras/MAPK pathway activation is associated with significantly lower levels of tumor-infiltrating lymphocytes in triple-negative breast cancers and while MEK inhibition can promote recruitment of tumor-infiltrating lymphocytes to the tumor, here we show that MEK inhibition adversely affects early onset T-cell effector function. We show that α-4-1BB and α-OX-40 T-cell agonist antibodies can rescue the adverse effects of MEK inhibition on T cells in both mouse and human T cells, which results in augmented anti-tumor effects in vivo. This effect is dependent upon increased downstream p38/JNK pathway activation. Taken together, our data suggest that although Ras/MAPK pathway inhibition can increase tumor immunogenicity, the negative impact on T-cell activity is functionally important. This undesirable impact is effectively prevented by combination with T-cell immune agonist immunotherapies resulting in superior therapeutic efficacy.
Mild hypothermia provides Treg stability
Authors: Marek-Trzonkowska Natalia , Piekarska Karolina , Filipowicz Natalia , Piotrowski Arkadiusz , Gucwa Magdalena , Vogt Katrin , Sawitzki Birgit , Siebert Janusz , Trzonkowski Piotr
Published: September 2017

Regulatory T cells (Tregs) play crucial role in maintenance of peripheral tolerance. Recent clinical trials confirmed safety and efficacy of Treg treatment of deleterious immune responses. However, Tregs lose their characteristic phenotype and suppressive potential during expansionex vivo. Therefore, multiple research teams have been studding Treg biology in aim to improve their stabilityin vitro. In the current paper, we demonstrate that mild hypothermia of 33 °C induces robust proliferation of Tregs, preserves expression of FoxP3, CD25 and Helios, and prevents TSDR methylation during culturein vitro. Tregs expanded at 33 °C have stronger immunosuppressive potential and remarkably anti-inflammatory phenotype demonstrated by the whole transcriptome sequencing. These observations shed new light on impact of temperature on regulation of immune response. We show that just a simple change in temperature can preserve Treg stability, function and accelerate their proliferation, responding to unanswered question- how to preserve Treg stabilityin vitro.
Granule cells control recovery from classical conditioned fear responses in the zebrafish cerebellum
Authors: Matsuda Koji , Yoshida Masayuki , Kawakami Koichi , Hibi Masahiko , Shimizu Takashi
Published: September 2017

Although previous studies show that the cerebellum is involved in classical fear conditioning, it is not clear which components in the cerebellum control it or how. We addressed this issue using a delayed fear-conditioning paradigm with late-stage zebrafish larvae, with the light extinguishment as the conditioned stimulus (CS) and an electric shock as the unconditioned stimulus (US). The US induced bradycardia in the restrained larvae. After paired-associate conditioning with the CS and US, a substantial population of the larvae displayed CS-evoked bradycardia responses. To investigate the roles of the zebrafish cerebellum in classical fear conditioning, we expressed botulinum toxin or the Ca2+ indicator GCaMP7a in cerebellar neurons. The botulinum-toxin-dependent inhibition of granule-cell transmissions in the corpus cerebelli (CCe, the medial lobe) did not suppress the CS-evoked bradycardia response, but rather prolonged the response. We identified cerebellar neurons with elevated CS-evoked activity after the conditioning. The CS-evoked activity of these neurons was progressively upregulated during the conditioning and was downregulated with repetition of the unpaired CS. Some of these neurons were activated immediately upon the CS presentation, whereas others were activated after a delay. Our findings indicate that granule cells control the recovery from conditioned fear responses in zebrafish.
Atorvastatin but Not Pravastatin Impairs Mitochondrial Function in Human Pancreatic Islets and Rat β-Cells. Direct Effect of Oxidative Stress
Authors: Urbano Francesca , Bugliani Marco , Filippello Agnese , Scamporrino Alessandra , Di Mauro Stefania , Di Pino Antonino , Scicali Roberto , Noto Davide , Rabuazzo Agata Maria , Averna Maurizio , Marchetti Piero , Purrello Francesco , Piro Salvatore
Published: September 2017

Statins are a class of drugs widely prescribed as frontline therapy for lowering plasma LDL-cholesterol in cardiovascular risk prevention. Several clinical reports have recently suggested an increased risk of type 2 diabetes associated with chronic use of these drugs. The pathophysiology of this effect remains to be fully elucidated but impaired β-cell function constitutes a potential mechanism. The aim of this study was to explore the effect of a chronic treatment with lipophilic and hydrophilic statins on β-cell function, using human pancreatic islets and rat insulin-secreting INS-1 cells; we particularly focused on the role of mitochondria and oxidative stress. The present study demonstrates, for the first time, that atorvastatin (lipophilic) but not pravastatin (hydrophilic) affected insulin release and mitochondrial metabolism due to the suppression of antioxidant defense system and induction of ROS production in pancreatic β-cell models. Mevalonate addition and treatment with a specific antioxidant (N-AcetylCysteine) effectively reversed the observed defects. These data demonstrate that mitochondrial oxidative stress is a key element in the pathogenesis of statin-related diabetes and may have clinical relevance to design strategies for prevention or reduction of statin induced β-cell dysfunction and diabetes in patients treated with lipophilic statins.
Methanogens predominate in natural corrosion protective layers on metal sheet piles
Authors: Kip Nardy , Jansen Stefan , Leite Marcio F. A. , de Hollander Mattias , Afanasyev Michael , Kuramae Eiko E. , Veen Johannes A. Van
Published: September 2017

Microorganisms are able to cause, but also to inhibit or protect against corrosion. Corrosion inhibition by microbial processes may be due to the formation of mineral deposition layers on metal objects. Such deposition layers have been found in archaeological studies on ancient metal objects, buried in soil, which were hardly corroded. Recent field investigations showed that natural mineral deposition layers can be found on sheet piles in soil. We investigated the microbial communities of these deposition layers and the adjacent soil. Our data, from five different sampling sites, all show striking differences between microbial communities of the deposition layer versus the adjacent soil over the depth profile. Bacterial species dominated in top soil while archaeal sequences increased in abundance with depth. All mineral deposition layers from the steel surface were dominated by Euryarchaeota, of which almost all sequences were phylogenetically related with the Methanobacteria genus. The mineral layer consisted of carbonate precipitates. Based on 16S rDNA gene sequencing data we hypothesize that the methanogens directly extract electrons from the metal surface, thereby, initially inducing mild corrosion, but simultaneously, inducing carbonate precipitation. This, will cause encrustation of the archaea, which drastically slow down their activity and create a natural protective layer against further corrosion.
Multiple Genome Constellations of Similar and Distinct Influenza A Viruses Co-Circulate in Pigs During Epidemic Events
Authors: Diaz Andres , Marthaler Douglas , Corzo Cesar , Muñoz-Zanzi Claudia , Sreevatsan Srinand , Culhane Marie , Torremorell Montserrat
Published: September 2017

Swine play a key role in the ecology and transmission of influenza A viruses (IAVs) between species. However, the epidemiology and diversity of swine IAVs is not completely understood. In this cohort study, we sampled on a weekly basis 132 3-week old pigs for 15 weeks. We found two overlapping epidemic events of infection in which most pigs (98.4%) tested PCR positive for IAVs. The prevalence rate of infection ranged between 0 and 86% per week and the incidence density ranged between 0 and 71 cases per 100 pigs-week. Three distinct influenza viral groups (VGs) replicating as a “swarm” of viruses were identified (swine H1-gamma, H1-beta, and H3-cluster-IV IAVs) and co-circulated at different proportions over time suggesting differential allele fitness. Furthermore, using deep genome sequencing 13 distinct viral genome constellations were differentiated. Moreover, 78% of the pigs had recurrent infections with IAVs closely related to each other or IAVs clearly distinct. Our results demonstrated the molecular complexity of swine IAVs during natural infection of pigs in which novel strains of IAVs with zoonotic and pandemic potential can emerge. These are key findings to design better health interventions to reduce the transmission of swine IAVs and minimize the public health risk.
Bacterial communities 16S rDNA fingerprinting as a potential tracing tool for cultured seabass Dicentrarchus labrax
Authors: Pimentel Tânia , Marcelino Joana , Ricardo Fernando , Soares Amadeu M. V. M. , Calado Ricardo
Published: September 2017

Traceability of seafood has become crucial with market globalization and consumer’s awareness. The present study used PCR-DGGE and 454 pyrosequencing to assess if bacterial communities fingerprint associated to seabass (Dicentrarchus labrax) skin mucus can be used to discriminate the geographic origin of fishes cultured in three semi-intensive fish farms. PCR-DGGE and pyrosequencing results were congruent and suggested that this molecular approach has the potential to trace fish farms with a spatial resolution <500 m. Pyrosequencing results provided a detailed insight into the bacterial community composition of seabass skin mucus and revealed the existence of a core of bacterial communities within family Pseudomonadaceae and Rhodobacteraceae. This approach also allowed to recognized key OTUs that are potentially relevant to discriminate the geographic origin of the fish being surveyed. Overall, the present study increased our knowledge on farmed seabass microbiome and demonstrated that specific and unique bacterial taxa can act as natural signatures that allow us to trace fish to its respective geographic origin. Our study provides valuable clues that should be more investigated in future studies as a way to fulfill current traceability needs in the global trade of seafood.
Disruption to schizophrenia-associated gene Fez1 in the hippocampus of HDAC11 knockout mice
Authors: Bryant Dale T. , Landles Christian , Papadopoulou Aikaterini S. , Benjamin Agnesska C. , Duckworth Joshua K. , Rosahl Thomas , Benn Caroline L. , Bates Gillian P.
Published: September 2017

Histone Deacetylase 11 (HDAC11) is highly expressed in the central nervous system where it has been reported to have roles in neural differentiation. In contrast with previous studies showing nuclear and cytoplasmic localisation, we observed synaptic enrichment of HDAC11. Knockout mouse models for HDACs 1–9 have been important for guiding the development of isoform specific HDAC inhibitors as effective therapeutics. Given the close relationship between HDAC11 and neural cells in vitro, we examined neural tissue in a previously uncharacterised Hdac11 knockout mouse (Hdac11KO/KO). Loss of HDAC11 had no obvious impact on brain morphology and neural stem/precursor cells isolated from Hdac11KO/KO mice had comparable proliferation and differentiation characteristics. However, in differentiating neural cells we observed decreased expression of schizophrenia-associated gene Fez1 (fasciculation and elongation protein zeta 1), a gene previously reported to be regulated by HDAC11 activity. FEZ1 has been associated with the dendritic growth of neurons and risk of schizophrenia via its interaction with DISC1 (disrupted in schizophrenia 1). Examination of cortical, cerebellar and hippocampal tissue reveal decreased Fez1 expression specifically in the hippocampus of adult mice. The results of this study demonstrate that loss of HDAC11 has age dependent and brain-region specific consequences.
Simultaneous measurements of top surface and its underlying film surfaces in multilayer film structure
Authors: Ghim Young-Sik , Rhee Hyug-Gyo , Davies Angela
Published: September 2017

With the growth of 3D packaging technology and the development of flexible, transparent electrodes, the use of multilayer thin-films is steadily increasing throughout high-tech industries including semiconductor, flat panel display, and solar photovoltaic industries. Also, this in turn leads to an increase in industrial demands for inspection of internal analysis. However, there still remain many technical limitations to overcome for measurement of the internal structure of the specimen without damage. In this paper, we propose an innovative optical inspection technique for simultaneous measurements of the surface and film thickness corresponding to each layer of multilayer film structures by computing the phase and reflectance over a wide range of wavelengths. For verification of our proposed method, the sample specimen of multilayer films was fabricated via photolithography process, and the surface profile and film thickness of each layer were measured by two different techniques of a stylus profilometer and an ellipsometer, respectively. Comparison results shows that our proposed technique enables simultaneous measurements of the top surface and its underlying film surfaces with high precision, which could not be measured by conventional non-destructive methods.
Male-male lethal combat in the quasi-gregarious parasitoid Anastatus disparis (Hymenoptera: Eupelmidae)
Authors: Liu Peng-Cheng , Wei Jian-Rong , Tian Shuo , Hao De-Jun
Published: September 2017

Most animals employ aggressive behaviours to acquire resources such as food, territory and mates. Although mating is important for males, which typically exhibit competitive behaviours to gain mating opportunities, they generally tend to avoid conflict escalation; while extreme combat also occurs in some species and results in death. In this study, male-male lethal combat behaviour in Anastatus disparis was examined (Hymenoptera: Eupelmidae) by investigating the characteristics of fighting and the factors that influence fighting intensity in this species. Male fight intensity in A. disparis increased with both competitor density and female presence, while it was not influenced by the relatedness among male competitors. By comparing the frequency of received attacks between injured and non-injured males, we found that the former were more vulnerable to attack. In contrast to death due to lethal attack, death that occurs as a result of A. disparis combat may be the cumulative effect of injuries sustained over repeated competitive encounters. Combined with the biological characters of A. disparis, we discuss potential factors contributing to the evolution of fatal conflict in this species.
Flow of Tunable Elastic Microcapsules through Constrictions
Authors: do Nascimento Débora F. , Avendaño Jorge A. , Mehl Ana , Moura Maria J. B. , Carvalho Marcio S. , Duncanson Wynter J.
Published: September 2017

We design and fabricate elastically tunable monodisperse microcapsules using microfluidics and cross-linkable polydimethylsiloxane (PDMS). The overall stiffness of the microcapsules is governed by both the thickness and cross-link ratio of the polymer shell. Flowing suspensions of microcapsules through constricted spaces leads to transient blockage of fluid flow, thus altering the flow behavior. The ability to tune microcapsule mechanical properties enables the design of elastic microcapsules that can be tailored for desired flow behavior in a broad range of applications such as oil recovery, reactor feeding, red blood cell flow and chemical targeted delivery.
Nanoscale compositional mapping of cells, tissues, and polymers with ringing mode of atomic force microscopy
Authors: Dokukin M. E. , Sokolov I.
Published: September 2017

Recently developed sub-resonance tapping modes (such as Digital Pulse, Peak Force Tapping, HybriD, etc.) of atomic force microscopy (AFM) allow imaging of compositional contrast of (bio)materials and biological cells down to the nanoscale. Here we report on a powerful extension of those modes, “ringing” mode, which more than doubles the number of non-trivial physical channels that can be collected with a regular sub-resonance tapping. It can simultaneously record five new additional compositional parameters related to adhesive and viscoelastic properties of the sample surface: the restored (averaged) adhesion, adhesion height, pull-off neck height, detachment distance, and detachment energy losses. Ringing mode can be up to 20 times faster and showing fewer artifacts compared to the existing sub-resonance tapping modes. Ringing mode is based on an analysis of ringing signal of the AFM cantilever after detaching the AFM probe from the sample surface (this signal is currently treated as noise, and typically filtered out in the existing modes). We demonstrate that this new mode allows recording robust and unique information on fixed human epithelial cells, corneocyte skin flakes, and polymers used for bioimplants.
Probing nanoscale damage gradients in ion-irradiated metals using spherical nanoindentation
Authors: Pathak Siddhartha , Kalidindi Surya R. , Weaver Jordan S. , Wang Yongqiang , Doerner Russell P. , Mara Nathan A.
Published: September 2017

We discuss and demonstrate the application of recently developed spherical nanoindentation stress-strain protocols in characterizing the mechanical behavior of tungsten polycrystalline samples with ion-irradiated surfaces. It is demonstrated that a simple variation of the indenter size (radius) can provide valuable insights into heterogeneous characteristics of the radiation-induced-damage zone. We have also studied the effect of irradiation for the different grain orientations in the same sample.
Ang-(1-7) is an endogenous β-arrestin-biased agonist of the AT1 receptor with protective action in cardiac hypertrophy
Authors: Teixeira Larissa B. , Parreiras-e-Silva Lucas T. , Bruder-Nascimento Thiago , Duarte Diego A. , Simões Sarah C. , Costa Rafael M. , Rodríguez Deisy Y. , Ferreira Pedro A. B. , Silva Carlos A. A. , Abrao Emiliana P. , Oliveira Eduardo B. , Bouvier Michel , Tostes Rita C. , Costa-Neto Claudio M.
Published: September 2017

The renin-angiotensin system (RAS) plays a key role in the control of vasoconstriction as well as sodium and fluid retention mediated mainly by angiotensin (Ang) II acting at the AT1 receptor (AT1R). Ang-(1-7) is another RAS peptide, identified as the endogenous ligand of the Mas receptor and known to counterbalance many of the deleterious effects of AngII. AT1R signaling triggered by β-arrestin-biased agonists has been associated to cardioprotection. Because position 8 in AngII is important for G protein activation, we hypothesized that Ang-(1-7) could be an endogenous β-arrestin-biased agonist of the AT1R. Here we show that Ang-(1-7) binds to the AT1R without activating Gq, but triggering β-arrestins 1 and 2 recruitment and activation. Using an in vivo model of cardiac hypertrophy, we show that Ang-(1-7) significantly attenuates heart hypertrophy by reducing both heart weight and ventricular wall thickness and the increased end-diastolic pressure. Whereas neither the single blockade of AT1 or Mas receptors with their respective antagonists prevented the cardioprotective action of Ang1-7, combination of the two antagonists partially impaired the effect of Ang-(1-7). Taken together, these data indicate that Ang-(1-7) mediates at least part of its cardioprotective effects by acting as an endogenous β-arrestin-biased agonist at the AT1R.
Rethinking the Origin of Primates by Reconstructing Their Diel Activity Patterns Using Genetics and Morphology
Authors: Wu Yonghua , Wang Haifeng , Wang Haitao , Hadly Elizabeth A.
Published: September 2017

Phylogenetic inference typically invokes nocturnality as ancestral in primates; however, some recent studies posit that diurnality is. Here, through adaptive evolutionary analyses of phototransduction genes by using a variety of approaches (restricted branch/branch-site models and unrestricted branch-site-based models (BS-REL, BUSTED and RELAX)), our results consistently showed that ancestral primates were subjected to enhanced positive selection for bright-light vision and relatively weak selection for dim-light vision. These results suggest that ancestral primates were mainly diurnal with some crepuscularity and support diurnality as plesiomorphic from Euarchontoglires. Our analyses show relaxed selection on motion detection in ancestral primates, suggesting that ancestral primates decreased their emphasis on mobile prey (e.g., insects). However, within primates, the results show that ancestral Haplorrhini were likely nocturnal, suggesting that evolution of the retinal fovea occurred within ancestral primates rather than within haplorrhines as was previously hypothesized. Our findings offer a reassessment of the visual adaptation of ancestral primates. The evolution of the retinal fovea, trichromatic vision and orbital convergence in ancestral primates may have helped them to efficiently discriminate, target, and obtain edible fruits and/or leaves from a green foliage background instead of relying on mobile insect prey.
Oligo-Fucoidan prevents IL-6 and CCL2 production and cooperates with p53 to suppress ATM signaling and tumor progression
Authors: Chen Li-Mei , Liu Po-Yen , Chen Yen-An , Tseng Hong-Yu , Shen Pei-Chun , Hwang Pai-An , Hsu Hsin-Ling
Published: September 2017

Low-molecular-weight Fucoidan (Oligo-Fucoidan) is a sulfated polysaccharide that has a variety of biological effects and has also been shown to have beneficial health effects. However, the molecular mechanisms underlying the therapeutic effects of Oligo-Fucoidan in patients with cancer remain unclear. Using human colorectal cancer HCT116 cells with (p53+/+) or without (p53−/−) normal p53 expression, we found that Oligo-Fucoidan treatment reduces the occurrence of spontaneous DNA lesions. Etoposide induces double strand DNA breaks. Subsequent administration of Oligo-Fucoidan to etoposide-treated cells promotes p53 accumulation, p21 expression and significant decreases in ataxia-telangiectasia-mutated (ATM), checkpoint kinase 1 (Chk1) and γ-H2AX phosphorylation in p53+/+ cells compared with p53−/− cells. Similarly, co-administration of Oligo-Fucoidan with etoposide inhibits ATM, Chk1 and γ-H2AX phosphorylation, particularly in the presence of p53. Furthermore, Oligo-Fucoidan supplementation increases cancer cell death and attenuates the adverse effects induced by etoposide that decreases production of the pro-inflammatory cytokine IL-6 and chemokine CCL2/MCP-1. Importantly, Oligo-Fucoidan decreases the tumor-promoting M2 macrophages in microenvironment as well as collaborates with p53 and works in combination with etoposide to prevent HCT116 tumorigenicity. Our results first demonstrate that p53 enables Oligo-Fucoidan to effectively inhibit tumor progression, and Oligo-Fucoidan minimizes the side effects of chemotherapy and alters tumor microenvironment.
Bi-directional effects of vitamin B12 and methotrexate on Daphnia magna fitness and genomic methylation
Authors: Kusari Fitore , O’Doherty Alan M. , Hodges Nikolas J. , Wojewodzic Marcin W.
Published: September 2017

Here we interrogated, using three separate but complementary experimental approaches, the impact of vitamin B12 availability and methotrexate exposure on Daphnia magna, which we hypothesised should have an opposite effect on One carbon metabolism (OCM). OCM is a vital biological process supporting a variety of physiological processes, including DNA methylation. Contrary to mammalian models, this process remains largely unexplored in invertebrates. The purpose of this study was to elucidate the impact of OCM short-term alteration on the fitness and epigenome of the keystone species, Daphnia. We used maternal age at reproduction, brood size and survival rates in combination with DNA methylation sensitive comet assay to determine the effects of vitamin B12 or MTX on fitness and the epigenome. Vitamin B12 had a positive influence on Daphnia fitness and we provide evidence demonstrating that this may be associated with an increased level of genome-wide DNA methylation. Conversely, exposing D. magna to MTX negatively influenced the fitness of the animals and was associated with loss of global DNA methylation, translating in decreased fitness. These results highlight the potential importance of OCM in invertebrates, providing novel evidence supporting a potential role for epigenetic modifications to the genome in D. magna environmental adaptability.
Interaction between karst terrain and bauxites: evidence from Quaternary orebody distribution in Guangxi, SW China
Authors: Yang Lin , Wang Qingfei , Zhang Qizuan , Carranza Emmanuel John M. , Liu Huan , Liu Xuefei , Deng Jun
Published: September 2017

Most bauxite in China is located upon the karst surface, yet the relation between karstification process and bauxite formation is barely known. Here we discuss how the relation affects the karst and bauxite evolution through analyzing distributions of orebody parameters from 9,007 exploration wells (434 orebodies) in western Guangxi, South China block. In high-elevation karst terrain dominated by peaks, orebodies have greater average thickness, lower Al2O3 and higher Fe2O3T than those in low-elevation region dominated by depressions. Principal component and multifractal analyses show that the Al2O3, Fe2O3T and LOI and the orebody thickness, determined by depression geometry, have more even distributions in high-elevation terrain. This explains that the interaction between the oxidized, alkaline water in karst surface and the ferrous clay minerals that released H+ during bauxite secondary weathering was more intensive in high-elevation terrain than in low-elevation one. The interaction with self-organized nature is considered responsible for the even development of karstic depressions and bauxite orebody thicknesses in high-elevation terrain. In comparison, SiO2 distribution is more even in low-elevation terrain, where connected depressions near the phreatic zone facilitated SiO2 mobilization and even distribution.
Bisphenol A Affects on the Functional Properties and Proteome of Testicular Germ Cells and Spermatogonial Stem Cells in vitro Culture Model
Authors: Karmakar Polash Chandra , Kang Hyun-Gu , Kim Yong-Hee , Jung Sang-Eun , Rahman Md. Saidur , Lee Hee-Seok , Kim Young-Hyun , Pang Myung-Geol , Ryu Buom-Yong
Published: September 2017

The endocrine disruptor bisphenol A (BPA) is well known for its adverse effect on male fertility. Growing evidence suggests that BPA may interact with testicular germ cells and cause infertility as a result of its estrogenic activity. Objective of current in vitro study was to investigate the proliferation, survivability and stemness properties of mouse testicular germ cells exposed to BPA, and to evaluate possible expression of cellular proteome. Our results showed that germ cell viability and proliferation were not affected by low concentrations (0.01, 0.1, 1, and 10 µM) although significant reduction observed at 100 µM BPA. Germ cell self-renewal and differentiation related marker proteins expression found unchanged at those concentrations. When BPA-exposed germ cells were transplanted into recipient testes, we observed fewer colonies at higher concentrations (10 and 100 µM). Additionally, a significant frequency of recombination failure during meiosis was observed in 10 µM BPA-exposed germ cell transplanted recipient. Moreover, experiment on continuous BPA-exposed and 100 µM BPA-recovered germ cells suggested that spermatogonial stem cells are more potential to survive in adverse environment. Finally, scrutinizing differentially expressed cellular proteins resulted from our proteomic analysis, we conclude that BPA exposure might be associated with several health risks and infertility.
CRISPR/Cas9-induced Targeted Mutagenesis and Gene Replacement to Generate Long-shelf Life Tomato Lines
Authors: Yu Qing-hui , Wang Baike , Li Ning , Tang Yaping , Yang Shengbao , Yang Tao , Xu Juan , Guo Chunmiao , Yan Peng , Wang Qiang , Asmutola Patiguli
Published: September 2017

Quickly and precisely gain genetically enhanced breeding elites with value-adding performance traits is desired by the crop breeders all the time. The present of gene editing technologies, especially the CRISPR/Cas9 system with the capacities of efficiency, versatility and multiplexing provides a reasonable expectation towards breeding goals. For exploiting possible application to accelerate the speed of process at breeding by CRISPR/Cas9 technology, in this study, the Agrobacterium tumefaciens-mediated CRISPR/Cas9 system transformation method was used for obtaining tomato ALC gene mutagenesis and replacement, in absence and presence of the homologous repair template. The average mutation frequency (72.73%) and low replacement efficiency (7.69%) were achieved in T0 transgenic plants respectively. None of homozygous mutation was detected in T0 transgenic plants, but one plant carry the heterozygous genes (Cas9/*-ALC/alc) was stably transmitted to T1 generations for segregation and genotyping. Finally, the desired alc homozygous mutants without T-DNA insertion (*/*-alc/alc) in T1 generations were acquired and further confirmed by genotype and phenotype characterization, with highlight of excellent storage performance, thus the recessive homozygous breeding elites with the character of long-shelf life were generated. Our results support that CRISPR/Cas9-induced gene replacement via HDR provides a valuable method for breeding elite innovation in tomato.
Double deficiency of Trex2 and DNase1L2 nucleases leads to accumulation of DNA in lingual cornifying keratinocytes without activating inflammatory responses
Authors: Manils Joan , Fischer Heinz , Climent Joan , Casas Eduard , García-Martínez Celia , Bas Jordi , Sukseree Supawadee , Vavouri Tanya , Ciruela Francisco , de Anta Josep Maria , Tschachler Erwin , Eckhart Leopold , Soler Concepció
Published: September 2017

The cornification of keratinocytes on the surface of skin and oral epithelia is associated with the degradation of nuclear DNA. The endonuclease DNase1L2 and the exonuclease Trex2 are expressed specifically in cornifying keratinocytes. Deletion of DNase1L2 causes retention of nuclear DNA in the tongue epithelium but not in the skin. Here we report that lack of Trex2 results in the accumulation of DNA fragments in the cytoplasm of cornifying lingual keratinocytes and co-deletion of DNase1L2 and Trex2 causes massive accumulation of DNA fragments throughout the cornified layers of the tongue epithelium. By contrast, cornification-associated DNA breakdown was not compromised in the epidermis. Aberrant retention of DNA in the tongue epithelium was associated neither with enhanced expression of DNA-driven response genes, such as Ifnb, Irf7 and Cxcl10, nor with inflammation. Of note, the expression of Tlr9, Aim2 and Tmem173, key DNA sensor genes, was markedly lower in keratinocytes and keratinocyte-built tissues than in macrophages and immune tissues, and DNA-driven response genes were not induced by introduction of DNA in keratinocytes. Altogether, our results indicate that DNase1L2 and Trex2 cooperate in the breakdown and degradation of DNA during cornification of lingual keratinocytes and aberrant DNA retention is tolerated in the oral epithelium.
Increased TREM-2 expression on the subsets of CD11c+ cells in the lungs and lymph nodes during allergic airway inflammation
Authors: Hall Sannette C. , Agrawal Devendra K.
Published: September 2017

Dendritic cells (DCs) are professional APCs that traffic to the draining lymph nodes where they present processed antigens to naïve T-cells. The recently discovered triggering receptor expressed on myeloid cells (TREM)-2 has been shown to be expressed on DCs in several disease models, however, its role in asthma is yet to be elucidated. In the present study, we examined the effect of allergen exposure on TREM-2 expression in the airways and on DC subsets in the lung and lymph nodes in murine model of allergic airway inflammation. Sensitization and challenge with ovalbumin reproduced hallmark features of asthma. TREM-2 mRNA expression in the whole lung was significantly higher in the OVA-sensitized and -challenged mice which was associated with increased protein expression in the lungs. Analysis of CD11c+MHC-IIhi DCs in the lung and draining lymph nodes revealed that allergen exposure increased TREM-2 expression on all DC subsets with significantly higher expression in the lymph nodes. This was associated with increased mRNA expression of Th2 and Th17 cytokines. Further analyses showed that these TREM-2+ cells expressed high levels of CCR-7 and CD86 suggesting a potential role of TREM-2 in mediating maturation and migration of DC subsets in allergic airway inflammation.