bluuebunny/crossref_metadata_2025 huggingface dataset:
Clinical outcomes and causes of arthroscopic hip revision surgery
Authors: Gao Guanying , Zhang Xin , Xu Yan , Wang Jianquan
Published: February 2019

Hip arthroscopic surgery has become a common technique during the past decade, leading to an increased number of arthroscopic hip revision surgeries. This study aimed to evaluate the clinical outcomes in a series of revision hip arthroscopies to analyse the causes of reoperation in the short to medium-term follow-up. We retrospectively analysed 22 patients who underwent arthroscopic hip revision surgery in our institute. All patients accepted a detailed physical examination and obtained radiographs to measure the centre edge angle, the alpha angle and the offset. Three-dimensional computed tomography was used to evaluate the deformities. The modified Harris Hip Score, visual analogue scale and patient self-reported satisfaction were collected and analysed preoperatively and postoperatively. Our results demonstrated that the modified Harris Hip Score improved from 52.8 to 81.6, and the visual analogue scale decreased from 5.0 to 1.1. Patient self-reported satisfaction was 8.5. In conclusion, patients who underwent arthroscopic hip revision surgery exhibited significant improvement in patient-centred outcomes in the short- to medium-term follow-up, and the outcomes indicated the effectiveness of revision surgery. Residual femoroacetabular impingement and extra-articular impingement are common reasons for arthroscopic hip revision surgery. Misdiagnosis of osteoid osteoma and relapse of synovial chondromatosis are also important reasons for revision.
Mucin staining is of limited value in addition to basic immunohistochemical analyses in the diagnostics of non-small cell lung cancer
Authors: Micke Patrick , Botling Johan , Mattsson Johanna Sofia Margareta , Planck Maria , Tran Lena , Vidarsdottir Halla , Nodin Björn , Jirström Karin , Brunnström Hans
Published: February 2019

Accurate diagnosis of histological type is important for therapy selection in lung cancer. Immunohistochemical (IHC) and histochemical stains are often used to complement morphology for definite diagnosis and are incorporated in the WHO classification. Our main aim was to compare different mucin stains and assess their value in relation to common IHC analyses in lung cancer diagnostics. Using tissue microarrays from 657 surgically treated primary lung cancers, we evaluated the mucin stains periodic acid-Schiff with diastase (PASD), alcian blue–periodic acid-Schiff (ABPAS) and mucicarmine, and compared with the IHC markers p40, p63, cytokeratin 5, thyroid transcription factor 1 (TTF-1), napsin A and cytokeratin 7. Ten or more cytoplasmic mucin inclusions in a tissue microarray core were seen in 51%, 48% and 31% of the 416 adenocarcinomas and 3%, 4% and 0.5% of the 194 squamous cell carcinomas with PASD, ABPAS and mucicarmine, respectively. Diagnostic pitfalls, such as entrapped benign epithelium, apoptotic/necrotic cells and glycogen, partly differed for the mucin stains. TTF-1 and napsin A IHC stainings had similar specificity but better sensitivity for adenocarcinoma than the mucin stains, but addition of PASD or ABPAS identified more tumors as adenocarcinomas (n = 8 and n = 10, respectively) than napsin A (n = 1) in cases with solid growth that were negative for TTF-1 and p40. We conclude that PASD and ABPAS have similar diagnostic performance and that these markers are of value in poorly differentiated cases. However, morphology and TTF-1 and p40 IHC staining is sufficient for correct diagnosis in most non-small cell lung cancers.
Merging Orthovoltage X-Ray Minibeams spare the proximal tissues while producing a solid beam at the target
Authors: Dilmanian F. Avraham , Krishnan Sunil , McLaughlin William E. , Lukaniec Brendan , Baker Jameson T. , Ailawadi Sandeep , Hirsch Kara N. , Cattell Renee F. , Roy Rahul , Helfer Joel , Kruger Kurt , Spuhler Karl , He Yulun , Tailor Ramesh , Vassantachart April , Heaney Dakota C. , Zanzonico Pat , Gobbert Matthias K. , Graf Jonathan S. , Nassimi Jessica R. , Fatemi Nasrin N. , Schweitzer Mark E. , Bangiyev Lev , Eley John G.
Published: February 2019

Conventional radiation therapy of brain tumors often produces cognitive deficits, particularly in children. We investigated the potential efficacy of merging Orthovoltage X-ray Minibeams (OXM). It segments the beam into an array of parallel, thin (~0.3 mm), planar beams, called minibeams, which are known from synchrotron x-ray experiments to spare tissues. Furthermore, the slight divergence of the OXM array make the individual minibeams gradually broaden, thus merging with their neighbors at a given tissue depth to produce a solid beam. In this way the proximal tissues, including the cerebral cortex, can be spared. Here we present experimental results with radiochromic films to characterize the method’s dosimetry. Furthermore, we present our Monte Carlo simulation results for physical absorbed dose, and a first-order biologic model to predict tissue tolerance. In particular, a 220-kVp orthovoltage beam provides a 5-fold sharper lateral penumbra than a 6-MV x-ray beam. The method can be implemented in arc-scan, which may include volumetric-modulated arc therapy (VMAT). Finally, OXM’s low beam energy makes it ideal for tumor-dose enhancement with contrast agents such as iodine or gold nanoparticles, and its low cost, portability, and small room-shielding requirements make it ideal for use in the low-and-middle-income countries.
Spatially Controlled Surface Modification of Porous Silicon for Sustained Drug Delivery Applications
Authors: Zhang De-Xiang , Yoshikawa Chiaki , Welch Nicholas G. , Pasic Paul , Thissen Helmut , Voelcker Nicolas H.
Published: February 2019

A new and facile approach to selectively functionalize the internal and external surfaces of porous silicon (pSi) for drug delivery applications is reported. To provide a surface that is suitable for sustained drug release of the hydrophobic cancer chemotherapy drug camptothecin (CPT), the internal surfaces of pSi films were first modified with 1-dodecene. To further modify the external surface of the pSi samples, an interlayer was applied by silanization with (3-aminopropyl)triethoxysilane (APTES) following air plasma treatment. In addition, copolymers of N-(2-hydroxypropyl) acrylamide (HPAm) and N-benzophenone acrylamide (BPAm) were grafted onto the external pSi surfaces by spin-coating and UV crosslinking. Each modification step was verified using attenuated total reflection-Fourier transform infrared (ATR-FTIR) spectroscopy, water contact angle (WCA) measurements, X-ray photoelectron spectroscopy (XPS) and scanning electron microscopy (SEM). In order to confirm that the air plasma treatment and silanization step only occurred on the top surface of pSi samples, confocal microscopy was employed after fluorescein isothiocyanate (FITC) conjugation. Drug release studies carried out over 17 h in PBS demonstrated that the modified pSi reservoirs released CPT continuously, while showing excellent stability. Furthermore, protein adsorption and cell attachment studies demonstrated the ability of the graft polymer layer to reduce both significantly. In combination with the biocompatible pSi substrate material, the facile modification strategy described in this study provides access to new multifunctional drug delivery systems (DDS) for applications in cancer therapy.
Magnocellular Based Visual Motion Training Improves Reading in Persian
Authors: Ebrahimi Leila , Pouretemad Hamidreza , Khatibi Ali , Stein John
Published: February 2019

The visual magnocellular system is thought to play a crucial role in learning to read. Here therefore, we examined whether magnocellular based training could improve reading in children with visual reading problems. The participants were 24 male primary school students aged between 9–11 (Mean = 9.76, SD = 0.59) with specific reading difficulty. Experimental and control groups were matched for age, sex, educational level, IQ, reading abilities (measured by APRA), magnocellular performance as assessed by a random dot kinematogram (RDK) paradigm and recordings of their saccadic eye movements. The experimental group received twelve magnocellular based visual motion training sessions, twice a week over 6 weeks. During the same period, the control group played a video game with the help of a practitioner. All measures were made just prior to the training and were repeated at the 6th, 12th training session and one month later. The experimental group showed significant improvements in magnocellular function, visual errors and reading accuracy during the course of intervention. Follow-up assessment confirmed that these effects persisted one month later. Impaired magnocellular functioning appeared to be an important cause of poor reading in Persian. Hence magnocellular based training could help many children with specific reading difficulties. Also testing magnocellular function could be used as screening tool for detecting dyslexia before a child begins to fail at school.
Gadoxetic Acid-Enhanced Hepatobiliary-Phase Magnetic Resonance Imaging for Pyrrolizidine Alkaloid-Induced Hepatic Sinusoidal Obstruction Syndrome and Association with Liver Function
Authors: Guo Tingting , Li Xin , Yang Xiaoqian , Kong Xiangquan , Liu Hui , Bai Tao , Xu Keshu , Ye Jin , Song Yuhu
Published: February 2019

Hepatic sinusoidal obstruction syndrome (HSOS) can be caused by pyrrolizidine alkaloids(PAs)-containing herbals. In this study, the aim of our study was to investigate the imaging features of PAs-induced HSOS on gadoxetic acid-enhanced magnetic resonance imaging (MRI), susceptibility-weighted imaging(SWI) and T2* weighted imaging (T2* WI). We analyzed medical records and MR images of 28 PAs-induced HSOS patients enrolled from Feb, 2013, to Apr, 2017. Abnormal liver function was observed in most of the PAs-induced HSOS patients. Heterogeneity of liver parenchyma in hepatobillary phase (HBP) of gadoxetic acid-enhanced MR scan was observed in 100% of the PAs-induced HSOS patients. Distributional patterns of heterogeneous hypointensity were multifocal distribution (mild) in 4 patients (14.29%), multifocal distribution (severe) in 15 cases (53.57%), and diffuse distribution in 9 patients (32.14%). Hypointense in SWI and T2*WI was observed in the patients of PAs-induced HSOS, and the distribution of hypointense in SWI and T2*WI was similar to that of portal-venous phase of MR scan. The severity of heterogeneous hypointensity scored by volume fraction in hepatobillary phase of gadoxetic acid-enhanced MRI was positively correlated with PT and INR, the severity of hypointensity in HBP was a risk factor of death events. In conclusion: Heterogenous hypointensity of liver parenchyma was an imaging sign of hepatobillary phase in gadoxetic acid-enhanced MRI; thus, it will provide evidences for the diagnosis of PA-induced HSOS.
A genetic model of CEDNIK syndrome in zebrafish highlights the role of the SNARE protein Snap29 in neuromotor and epidermal development
Authors: Mastrodonato Valeria , Beznoussenko Galina , Mironov Alexandre , Ferrari Laura , Deflorian Gianluca , Vaccari Thomas
Published: February 2019

Homozygous mutations in SNAP29, encoding a SNARE protein mainly involved in membrane fusion, cause CEDNIK (Cerebral Dysgenesis, Neuropathy, Ichthyosis and Keratoderma), a rare congenital neurocutaneous syndrome associated with short life expectancy, whose pathogenesis is unclear. Here, we report the analysis of the first genetic model of CEDNIK in zebrafish. Strikingly, homozygous snap29 mutant larvae display CEDNIK-like features, such as microcephaly and skin defects. Consistent with Snap29 role in membrane fusion during autophagy, we observe accumulation of the autophagy markers p62 and LC3, and formation of aberrant multilamellar organelles and mitochondria. Importantly, we find high levels of apoptotic cell death during early development that might play a yet uncharacterized role in CEDNIK pathogenesis. Mutant larvae also display mouth opening problems, feeding impairment and swimming difficulties. These alterations correlate with defective trigeminal nerve formation and excess axonal branching. Since the paralog Snap25 is known to promote axonal branching, Snap29 might act in opposition with, or modulate Snap25 activity during neurodevelopment. Our vertebrate genetic model of CEDNIK extends the description in vivo of the multisystem defects due to loss of Snap29 and could provide the base to test compounds that might ameliorate traits of the disease.
Using the NoiSee workflow to measure signal-to-noise ratios of confocal microscopes
Authors: Ferrand Alexia , Schleicher Kai D. , Ehrenfeuchter Nikolaus , Heusermann Wolf , Biehlmaier Oliver
Published: February 2019

Confocal microscopy is used today on a daily basis in life science labs. This “routine” technique contributes to the progress of scientific projects across many fields by revealing structural details and molecular localization, but researchers need to be aware that detection efficiency and emission light path performance is of major influence in the confocal image quality. By design, a large portion of the signal is discarded in confocal imaging, leading to a decreased signal-to-noise ratio (SNR) which in turn limits resolution. A well-aligned system and high performance detectors are needed in order to generate an image of best quality. However, a convenient method to address system status and performance on the emission side is still lacking. Here, we present a complete method to assess microscope and emission light path performance in terms of SNR, with a comprehensive protocol alongside NoiSee, an easy-to-use macro for Fiji (available via the corresponding update site). We used this method to compare several confocal systems in our facility on biological samples under typical imaging conditions. Our method reveals differences in microscope performance and highlights the various detector types used (multialkali photomultiplier tube (PMT), gallium arsenide phosphide (GaAsP) PMT, and Hybrid detector). Altogether, our method will provide useful information to research groups and facilities to diagnose their confocal microscopes.
Cationic Amphipathic Triazines with Potent Anti-bacterial, Anti-inflammatory and Anti-atopic Dermatitis Properties
Authors: Gunasekaran Pethaiah , Rajasekaran Ganesan , Han Eun Hee , Chung Young-Ho , Choi Young-Jin , Yang Yu Jin , Lee Ji Eun , Kim Hak Nam , Lee Kiram , Kim Jin-Seok , Lee Hyun-Jun , Choi Eun-Ju , Kim Eun-Kyung , Shin Song Yub , Bang Jeong Kyu
Published: February 2019

The emergence of multi-drug resistant bacteria forces the therapeutic world into a position, where the development of new and alternative kind of antibiotics is highly important. Herein, we report the development of triazine-based amphiphilic small molecular antibacterial agents as mimics of lysine- and arginine-based cationic peptide antibiotics (CPAs). These compounds were screened against a panel of both Gram-positive and Gram-negative bacterial strains. Further, anti-inflammatory evaluation of these compounds led to the identification of four efficient compounds, DG-5, DG-6, DL-5, and DL-6. These compounds displayed significant potency against drug-resistant bacteria, including methicillin-resistantS.aureus(MRSA), multidrug-resistantP.aeruginosa(MDRPA), and vancomycin-resistantE.faecium(VREF). Mechanistic studies, including cytoplasmic membrane depolarization, confocal imaging and flow cytometry suggest that DG-5, DG-6, and DL-5 kill bacteria by targeting bacterial membrane, while DL-6 follows intracellular targeting mechanism. We also demonstrate that these molecules have therapeutic potential by showing the efficiency of DG-5 in preventing the lung inflammation of lipopolysaccharide (LPS)-induced acute lung injury (ALI) mouse model. More interestingly, DL-6 exhibited impressive potency on atopic dermatitis (AD)-like skin lesions in BALB/c mice model by suppressing pro-inflammatory cytokines. Collectively, these results suggest that they can serve a new class of antimicrobial, anti-inflammatory and anti-atopic agents with promising therapeutic potential.
Diversified secondary metabolite biosynthesis gene repertoire revealed in symbiotic dinoflagellates
Authors: Beedessee Girish , Hisata Kanako , Roy Michael C. , Van Dolah Frances M. , Satoh Noriyuki , Shoguchi Eiichi
Published: February 2019

Symbiodiniaceae dinoflagellates possess smaller nuclear genomes than other dinoflagellates and produce structurally specialized, biologically active, secondary metabolites. Till date, little is known about the evolution of secondary metabolism in dinoflagellates as comparative genomic approaches have been hampered by their large genome sizes. Here, we overcome this challenge by combining genomic and metabolomics approaches to investigate how chemical diversity arises in three decoded Symbiodiniaceae genomes (clades A3, B1 and C). Our analyses identify extensive diversification of polyketide synthase and non-ribosomal peptide synthetase genes from two newly decoded genomes of Symbiodinium tridacnidorum (A3) and Cladocopium sp. (C). Phylogenetic analyses indicate that almost all the gene families are derived from lineage-specific gene duplications in all three clades, suggesting divergence for environmental adaptation. Few metabolic pathways are conserved among the three clades and we detect metabolic similarity only in the recently diverged clades, B1 and C. We establish that secondary metabolism protein architecture guides substrate specificity and that gene duplication and domain shuffling have resulted in diversification of secondary metabolism genes.
CdsA is involved in biosynthesis of glycolipid MPIase essential for membrane protein integration in vivo
Authors: Sawasato Katsuhiro , Sato Ryo , Nishikawa Hanako , Iimura Naoki , Kamemoto Yuki , Fujikawa Kohki , Yamaguchi Toshiyuki , Kuruma Yutetsu , Tamura Yasushi , Endo Toshiya , Ueda Takuya , Shimamoto Keiko , Nishiyama Ken-ichi
Published: February 2019

MPIase is a glycolipid that is involved in membrane protein integration. Despite evaluation of its functions in vitro, the lack of information on MPIase biosynthesis hampered verification of its involvement in vivo. In this study, we found that depletion of CdsA, a CDP-diacylglycerol synthase, caused not only a defect in phospholipid biosynthesis but also MPIase depletion with accumulation of the precursors of both membrane protein M13 coat protein and secretory protein OmpA. Yeast Tam41p, a mitochondrial CDP-diacylglycerol synthase, suppressed the defect in phospholipid biosynthesis, but restored neither MPIase biosynthesis, precursor processing, nor cell growth, indicating that MPIase is essential for membrane protein integration and therefore for cell growth. Consistently, we observed a severe defect in protein integration into MPIase-depleted membrane vesicles in vitro. Thus, the function of MPIase as a factor involved in protein integration was proven in vivo as well as in vitro. Moreover, Cds1p, a eukaryotic CdsA homologue, showed a potential for MPIase biosynthesis. From these results, we speculate the presence of a eukaryotic MPIase homologue.
Forest type and height are important in shaping the altitudinal change of radial growth response to climate change
Authors: Liang Penghong , Wang Xiangping , Sun Han , Fan Yanwen , Wu Yulian , Lin Xin , Chang Jinfeng
Published: February 2019

Tree radial growth is widely found to respond differently to climate change across altitudinal gradients, but the relative roles of biotic factors (e.g. forest type, height and density) vs. climate gradient remain unclear. We sampled tree rings from 15 plots along a large altitudinal gradient in northeast China, and examined how climate gradient, forest type, height, tree size and density affect: (1) temporal growth variability [mean sensitivity (MS) and standard deviation (SD) of the chronologies], and (2) the relationship of ring width indices (RWI) with historical climate. We used BIC based model selection and variable importance to explore the major drivers of their altitudinal patterns. The results showed that: both growth variability and RWI-climate relationships changed significantly with altitude. Forest height was the most important predictor for altitudinal changes of MS and SD. For RWI-climate relationships, forest type was more important than climate gradient, while height and stem density were weak but necessary predictors. We showed that the altitudinal difference in growth response to climate change cannot be explained by climate gradient alone, and highlight the necessity to examine the influence of biotic factors (which covary with climate across geographic gradient) to better understand forest response to climate change.
Operation mode of a step-feed anoxic/oxic process with distribution of carbon source from anaerobic zone on nutrient removal and microbial properties
Authors: Shen Yijun , Yang Dianhai , Wu Yang , Zhang Hao , Zhang Xinxi
Published: February 2019

This study investigated the operation mode of a step-feed anoxic/oxic (A/O) process with distribution of the carbon source from the anaerobic zone in terms of the treatment effects on sewage with low carbon and high nitrogen and phosphorus. After seven phases of operation, an optimal flow distribution ratio of 75%:25% was obtained from the anaerobic zone, and the concentrations of chemical oxygen demand, ammonia nitrogen, total nitrogen, and total phosphorous in the effluent were 20.8, 0.64, 14.2, and 0.89 mg/L, respectively. The presence of an internal reflux system in the deaeration zone improved the treatment. 16S rRNA high-throughput sequencing revealed that the microbial communities in aerobic zone I(O1) of the first-step A/O sludge were different from those in aerobic zone I (O2) of the second-step A/O sludge, whereas microbial communities of the seed sludge were similar to those in O2 of the second-step A/O sludge. The richness and diversity of microbial communities in O1 of the first-step A/O sludge samples were higher than those in O2 of the second-step A/O and seed sludge. At the optimal flow distribution ratio, the microbial abundance and treatment removal efficiency were the highest.
Magnetic phase diagram of K2Cr8O16 clarified by high-pressure muon spin spectroscopy
Authors: Forslund Ola Kenji , Andreica Daniel , Sassa Yasmine , Nozaki Hiroshi , Umegaki Izumi , Nocerino Elisabetta , Jonsson Viktor , Tjernberg Oscar , Guguchia Zurab , Shermadini Zurab , Khasanov Rustem , Isobe Masahiko , Takagi Hidenori , Ueda Yutaka , Sugiyama Jun , Månsson Martin
Published: February 2019

The K2Cr8O16 compound belongs to a series of quasi-1D compounds with intriguing magnetic properties that are stabilized through a high-pressure synthesis technique. In this study, a muon spin rotation, relaxation and resonance (μ+SR) technique is used to investigate the pressure dependent magnetic properties up to 25 kbar. μ+SR allows for measurements in true zero applied field and hereby access the true intrinsic material properties. As a result, a refined temperature/pressure phase diagram is presented revealing a novel low temperature/high pressure (pC1 = 21 kbar) transition from a ferromagnetic insulating to a high-pressure antiferromagnetic insulator. Finally, the current study also indicates the possible presence of a quantum critical point at pC2 ~ 33 kbar where the magnetic order in K2Cr8O16 is expected to be fully suppressed even at T = 0 K.
Deformation Induced Hierarchical Twinning Coupled with Omega Transformation in a Metastable β-Ti Alloy
Authors: Mantri S. A. , Sun F. , Choudhuri D. , Alam T. , Gwalani B. , Prima F. , Banerjee R.
Published: February 2019

Hierarchical twinning, at multiple length scales, was noted in a metastable body-centered cubic (bcc) β-titanium alloy on tensile deformation. Site-specific characterization within the deformation bands, carried out using EBSD and TEM, revealed {332} <113> type primary bcc twins, containing different variants of secondary and tertiary twins, as well as the formation of stress-induced martensite (α”). Within the primary {332} <113> type twin, “destruction” of the prior quenched-in athermal ω phase was observed, while a stress-induced ω phase reforms within the tertiary twins, revealing the intricate nature of coupling between deformation twinning and displacive ω transformation.
Jet and Shock Wave from Collapse of Two Cavitation Bubbles
Authors: Luo Jing , Niu Zhipan
Published: February 2019

As a common hydrodynamic phenomenon, multi-cavitation dynamics is widely found in many industries such as hydraulic engineering, shipping industry and chemical industry. The jet and shock wave phenomenon in the interaction of two cavitation bubbles are the basis of multi-cavitation bubbles interaction research. By respectively inducing two cavitation bubbles through laser and underwater low-voltage discharge, this paper tested the jet and shock wave resulting from the collapse of the two cavitation bubbles, and the following conclusions are obtained: (1) If the two cavitation bubbles are synchronously generated but in different size, as the distance between the two cavitation bubbles increases or the maximum radius of the smaller cavitation bubble increases, the effect of the small cavitation bubble on the larger one gradually changes from the surface wave phenomenon to jet that breaks through the larger bubble. When the two bubble center lines are parallel to the wall surface, this jet suppresses the formation of the jet to the wall surface when the large cavitation bubble collapses; if the two cavitation bubbles are generated at the same time with same size, as the initial distance of the two cavitation bubbles gradually decreases, the two bubbles are more likely to form a face-to-face collapse, and the smaller the distance between the two, the easier it is to fuse. (2) The impact of the initial moment of the cavitation bubble on the structure of the collapse shock wave is as follows: for two bubbles of different sizes formed synchronously, the shock wave propagates to the periphery in the form of a number of consecutive waves appearing in the larger bubble, while for the unsynchronized ones, shock waves appeared in both cavitation collapses, and a number of consecutive waves appear in the late-formed cavitation bubble. And multiple consecutive shock waves may overlap in some areas of the space. These conclusions have obvious implications for preventing cavitation damage and utilization of cavitation.
Decreased dopamine in striatum and difficult locomotor recovery from MPTP insult after exposure to radiofrequency electromagnetic fields
Authors: Kim Ju Hwan , Lee Choong-Hyun , Kim Hyung-Gun , Kim Hak Rim
Published: February 2019

Concern is growing about possible neuronal effects of human exposure to radiofrequency electromagnetic fields because of the increasing usage of cell phones and the close proximity of these devices to the brain when in use. We found that exposure to a radiofrequency electromagnetic field (RF-EMF) of 835 MHz (4.0 W/kg specific absorption rate [SAR] for 5 h/day for 12 weeks) affects striatal neurons in C57BL/6 mice. The number of synaptic vesicles (SVs) in striatal presynaptic boutons was significantly decreased after RF-EMF exposure. The expression levels of synapsin I and II were also significantly decreased in the striatum of the RF-EMF-exposed group. RF-EMF exposure led to a reduction in dopamine concentration in the striatum and also to a decrease in the expression of tyrosine hydroxylase in striatal neurons. Furthermore, in behavioral tests, exposure to RF-EMF impeded the recovery of locomotor activities after repeated treatments with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). These results suggest that the observed decrease in dopamine concentration in the striatum was caused by both a reduction in the number of dopaminergic neurons and a decline in the number of SVs. The decreased dopamine neuron numbers and concentration seen after RF-EMF exposure would have caused the difficult recovery after MPTP treatment. In summary, our results strongly suggest that exposing the brain to RF-EMF can decrease the number of SVs and dopaminergic neurons in the striatum. These primary changes impair the recovery of locomotor activities following MPTP damage to the striatum.
Prenatal Betamethasone interferes with immune system development and alters target cells in autoimmune diabetes
Authors: Perna-Barrull David , Rodriguez-Fernandez Silvia , Pujol-Autonell Irma , Gieras Anna , Ampudia-Carrasco Rosa M. , Villalba Adrian , Glau Laura , Tolosa Eva , Vives-Pi Marta
Published: February 2019

Non-genetic factors are crucial in the pathogenesis of type 1 diabetes (T1D), a disease caused by autoimmunity against insulin-producing β-cells. Exposure to medications in the prenatal period may influence the immune system maturation, thus altering self-tolerance. Prenatal administration of betamethasone –a synthetic glucocorticoid given to women at risk of preterm delivery– may affect the development of T1D. It has been previously demonstrated that prenatal betamethasone administration protects offspring from T1D development in nonobese diabetic (NOD) mice. The direct effect of betamethasone on the immature and mature immune system of NOD mice and on target β-cells is analysed in this paper. In vitro, betamethasone decreased lymphocyte viability and induced maturation-resistant dendritic cells, which in turn impaired γδ T cell proliferation and decreased IL-17 production. Prenatal betamethasone exposure caused thymus hypotrophy in newborn mice as well as alterations in immune cells subsets. Furthermore, betamethasone decreased β-cell growth, reduced C-peptide secretion and altered the expression of genes related to autoimmunity, metabolism and islet mass in T1D target tissue. These results support the protection against T1D in the betamethasone-treated offspring and demonstrate that this drug alters the developing immune system and β-cells. Understanding how betamethasone generates self-tolerance could have potential clinical relevance in T1D.
Observation of Wavelength-Dependent Quantum Plasmon Tunneling with Varying the Thickness of Graphene Spacer
Authors: Lee Khang June , Kim Shinho , Hong Woonggi , Park Hamin , Jang Min Seok , Yu Kyoungsik , Choi Sung-Yool
Published: February 2019

Plasmonic coupling provides a highly localized electromagnetic field in the gap of noble metals when illuminated by a light. The plasmonic field enhancement is generally known to be inversely proportional to the gap distance. Given such a relation, reducing the gap distance appears to be necessary to achieve the highest possible field enhancement. At the sub-nanometer scale, however, quantum mechanical effects have to be considered in relation to plasmonic coupling. Here, we use graphene as a spacer to observe plasmonic field enhancement in sub-nanometer gap. The gap distance is precisely controlled by the number of stacked graphene layers. We propose that the sudden drop of field enhancement for the single layer spacer is originated from the plasmon tunneling through the thin spacer. Numerical simulation which incorporates quantum tunneling is also performed to support the experimental results. From the fact that field enhancement with respect to the number of graphene layers exhibits different behavior in two wavelengths corresponding to on- and off-resonance conditions, tunneling phenomenon is thought to destroy the resonance conditions of plasmonic coupling.
A transcription factor PU.1 is critical for Ccl22 gene expression in dendritic cells and macrophages
Authors: Yashiro Takuya , Nakano Shiori , Nomura Kurumi , Uchida Yuna , Kasakura Kazumi , Nishiyama Chiharu
Published: February 2019

The chemokine CCL22 is predominantly produced by dendritic cells (DCs) and macrophages. CCL22 acts on CCR4-expressing cells including Th2 and Treg. Although a correlation between the CCL22-CCR4 axis and allergic diseases has been established, the mechanism of monocyte lineage-specific Ccl22 gene expression is largely unknown. In the current study, we investigated transcriptional regulation of the Ccl22 gene in DCs and macrophages. Using reporter assays, we identified the critical cis-enhancing elements at 21/−18 and −10/−4 in the Ccl22 promoter. Electrophoretic mobility shift assays proved that transcription factor PU.1 directly binds to the cis-elements. Knockdown of PU.1 markedly decreased Ccl22 expression in bone marrow-derived DCs (BMDCs) and BM macrophages (BMDMs). Chromatin immunoprecipitation assays revealed that PU.1 bound to the Ccl22 promoter in not only BMDCs and BMDMs, but also splenic DCs and peritoneal macrophages. LPS stimulation increased the amount of PU.1 recruited to the promoter, accompanied by upregulation of the Ccl22 mRNA level, which was diminished by Spi1 knockdown. We identified similar cis-elements on the human CCL22 promoter, which were bound with PU.1 in human monocytes. Taken together, these findings indicate that PU.1 transactivates the Ccl22 gene in DCs and macrophages by directly binding to the two elements in the promoter.
Oil-Spill Triggered Shift in Indigenous Microbial Structure and Functional Dynamics in Different Marine Environmental Matrices
Authors: Neethu C. S. , Saravanakumar C. , Purvaja R. , Robin R. S. , Ramesh R.
Published: February 2019

Microbial degradation has long been recognized as the key rescue mechanism in shaping the oil polluted marine environments and the role of indigenous populations or their functional genomics have never been explored from Indian marine environments, post an oil spill event. In the current study, high throughput metagenomic analysis, PLFA profiling and mass spectrophotometric analysis was performed in combination with metabolomics to capture signature variations among the microbial communities in sediment, water and laboratory enrichments. Contrary to the previous reports, the bloom of Pseudomonadales (specifically genus Acinetobacter) in oiled sediment and Methylococcales in oiled water outnumbered the relative abundance of Alcanivorax in response to hydrocarbon contamination. Overall enhancement of xenobiotic degradation was suggested by metabolomic analysis in sediment and water post the spill event and varying quantitative assemblage of enzymes were found to be involved in hydrocarbon utilization. Laboratory enrichments revealed the competitive advantage of sediment communities over the water communities although unique taxa belonging to the later were also found to be enriched under in vitro conditions. Simultaneous analysis of sediment and water in the study provided explicit evidences on existence of differential microbial community dynamics, offering insight into possibilities of formulating nature identical solutions for hydrocarbon pollution.
Deep Neural Network Inverse Design of Integrated Photonic Power Splitters
Authors: Tahersima Mohammad H. , Kojima Keisuke , Koike-Akino Toshiaki , Jha Devesh , Wang Bingnan , Lin Chungwei , Parsons Kieran
Published: February 2019

Predicting physical response of an artificially structured material is of particular interest for scientific and engineering applications. Here we use deep learning to predict optical response of artificially engineered nanophotonic devices. In addition to predicting forward approximation of transmission response for any given topology, this approach allows us to inversely approximate designs for a targeted optical response. Our Deep Neural Network (DNN) could design compact (2.6 × 2.6 μm2) silicon-on-insulator (SOI)-based 1 × 2 power splitters with various target splitting ratios in a fraction of a second. This model is trained to minimize the reflection (to smaller than ~ −20 dB) while achieving maximum transmission efficiency above 90% and target splitting specifications. This approach paves the way for rapid design of integrated photonic components relying on complex nanostructures.
Interhemispheric field-aligned currents at the edges of equatorial plasma depletions
Authors: Rodríguez-Zuluaga Juan , Stolle Claudia
Published: February 2019

A comprehensive description of electromagnetic processes related to equatorial plasma depletions (EPDs) is essential for understanding their evolution and day-to-day variability. Recently, field-aligned currents (FACs) flowing at both western and eastern edges of EPDs were observed to be interhemispheric rather than anti-parallel about the dip equator, as suggested by previous theoretical studies. In this paper, we investigate the spatial and temporal variability of the FACs orientation using simultaneous measurements of electron density and magnetic field gathered by ESA’s Swarm constellation mission. By using empirical models, we assess the role of the Pedersen conductance in the preference of the FACs to close either in the northern or southern magnetic hemisphere. Here we show that the closure of the FACs agrees with an electrostatic regime determined by a hemispherical asymmetry of the Pedersen conductance. That is, the EPD-related FACs close at lower altitudes in the hemisphere with the highest conductivity. The evidence of this conclusion stands on the general agreement between the longitudinal and seasonal variability of both the conductivity and the FACs orientation.
pH-driven conformational switch between non-canonical DNA structures in a C-rich domain of EGFR promoter
Authors: Cristofari Camilla , Rigo Riccardo , Greco Maria Laura , Ghezzo Michele , Sissi Claudia
Published: February 2019

EGFR is an oncogene that encodes for a trans-membrane tyrosine kinase receptor. Its mis-regulation is associated to several human cancers that, consistently, can be treated by selective tyrosine kinase inhibitors. The proximal promoter of EGFR contains a G-rich domain located at 272 bases upstream the transcription start site. We previously proved it folds into two main interchanging G-quadruplex structures, one of parallel and one of hybrid topology. Here we present the first evidences supporting the ability of the complementary C-rich strand (EGFR-272_C) to assume an intramolecular i-Motif (iM) structure that, according to the experimental conditions (pH, presence of co-solvent and salts), can coexist with a different arrangement we referred to as a hairpin. The herein identified iM efficiently competes with the canonical pairing of the two complementary strands, indicating it as a potential novel target for anticancer therapies. A preliminary screening for potential binders identified some phenanthroline derivatives as able to target EGFR-272_C at multiple binding sites when it is folded into an iM.
Recurrent speciation of a tomato yellow leaf curl geminivirus in Portugal by recombination
Authors: Fiallo-Olivé Elvira , Trenado Helena P. , Louro Diamantina , Navas-Castillo Jesús
Published: February 2019

Recurrent evolution can involve interspecific interactions, recognized to play a primary role in the diversification and organization of life. Both in the plant and animal kingdoms, the recurrent formation of allopolyploid species has been described. In the virosphere, recombination between isolates of different species has been shown to be a source of speciation. In this work, complete genome analysis showed that speciation through recombination of an emergent DNA plant virus, tomato yellow leaf curl Malaga virus (genusBegomovirus, familyGeminiviridae), has occurred independently in Portugal and Spain, confirming previous observations with tomato yellow leaf curl Axarquia virus, also originated independently in Spain and Italy. These results will guide future research to discover new cases of recurrent emergence of recombinant virus species in geographical areas where the putative parents co-exist or can be introduced. This will reveal the role that recurrent speciation through recombination plays in the evolution of the virosphere and will help to understand the consequences of this phenomenon on the diversification of life.
Modulation of salt tolerance in Thai jasmine rice (Oryza sativa L. cv. KDML105) by Streptomyces venezuelae ATCC 10712 expressing ACC deaminase
Authors: Yoolong Suranan , Kruasuwan Worarat , Thanh Phạm Huyền Thị , Jaemsaeng Ratchaniwan , Jantasuriyarat Chatchawan , Thamchaipenet Arinthip
Published: February 2019

1-Aminocyclopropane-1-carboxylate (ACC) deaminase is a plant growth promoting (PGP) trait found in beneficial bacteria including streptomycetes and responsible for stress modulation. The ACC deaminase gene, acdS, of S. venezuelae ATCC 10712 was cloned into an expression plasmid, pIJ86, to generate S. venezuelae/pIJ86-acdS. Expression of acdS and production of ACC deaminase of S. venezuelae/pIJ86-acdS were significantly higher than the unmodified strain. The ACC deaminase-overexpressing mutant and the wild type control were inoculated into Thai jasmine rice (Oryza sativa L. cv. KDML105) under salt stress conditions. S. venezuelae on its own augmented rice growth and significantly increased more tolerance to salinity by reduction of ethylene, reactive oxygen species (ROS) and Na+ contents, while accumulating more proline, total chlorophyll, relative water content (RWC), malondialdehyde (MDA), and K+ than those of uninoculated controls. The overproducer did not alter chlorophyll, RWC, or MDA further–while it did boost more shoot weight and elongation, and significantly regulated salt tolerance of rice by increasing proline and reducing ethylene and Na+ contents further than that of the wild type. This work is the first illustration of the beneficial roles of S. venezuelae to enhance plant fitness endophytically by promotion of growth and salt tolerance of rice.
The Cyclin-Dependent Kinase 5 Inhibitor Peptide Inhibits Herpes Simplex Virus Type 1 Replication
Authors: Man Adrian , Slevin Mark , Petcu Eugen , Fraefel Cornel
Published: February 2019

In order to evaluate the influence of CDK5 inhibitory peptide (CIP) on Human alphaherpesvirus 1 (HSV-1) replication, we constructed two recombinant adeno-associated-virus 2 (rAAV2) vectors encoding CIP fused with cyan-fluorescent-protein (CFP), with or without nuclear localization signal. A third vector encoding non-fused CIP and CFP was also constructed. HeLa and HEK 293T cells were infected with the rAAV-CIP vectors at multiplicity of infection (MOI) of 5000, in the absence or presence of a recombinant HSV-1 that encodes a yellow-fluorescent-protein (rHSV48Y; MOI = 1). Cells co-infected with rHSV48Y and rAAV vectors that did not express the CIP gene (rAAV-CFP-Neo) served as controls. At 24 h after infection, the effect of CIP on rHSV48Y replication was assessed by PCR, qRT-PCR, Western-blot, flow-cytometry, epifluorescence and confocal microscopy. We show that in cultures co-infected with rAAV-CFP-Neo, 27% of the CFP-positive cells present rHSV48Y replication compartments. By contrast, in cultures co-infected with CIP-encoding rAAV2 vectors and rHSV48Y only 6–20% of the cells positive for CIP showed rHSV48Y replication compartments, depending on the CIP variant. Flow-cytometry showed that less than 40% of the rHSV48Y/rAAV-CIP, and more than 75% of rHSV48Y/rAAV-CFP-Neo co-infected cells were positive for both transgene products. The microscopy and flow-cytometry data support the hypothesis that CIP is inhibiting HSV-1 replication.
Molecular genetic analysis using targeted NGS analysis of 677 individuals with retinal dystrophy
Authors: Jespersgaard Cathrine , Fang Mingyan , Bertelsen Mette , Dang Xiao , Jensen Hanne , Chen Yulan , Bech Niels , Dai Lanlan , Rosenberg Thomas , Zhang Jianguo , Møller Lisbeth Birk , Tümer Zeynep , Brøndum-Nielsen Karen , Grønskov Karen
Published: February 2019

Inherited retinal diseases (IRDs) are a common cause of visual impairment. IRD covers a set of genetically highly heterogeneous disorders with more than 150 genes associated with one or more clinical forms of IRD. Molecular genetic diagnosis has become increasingly important especially due to expanding number of gene therapy strategies under development. Next generation sequencing (NGS) of gene panels has proven a valuable diagnostic tool in IRD. We present the molecular findings of 677 individuals, residing in Denmark, with IRD and report 806 variants of which 187 are novel. We found that deletions and duplications spanning one or more exons can explain 3% of the cases, and thus copy number variation (CNV) analysis is important in molecular genetic diagnostics of IRD. Seven percent of the individuals have variants classified as pathogenic or likely-pathogenic in more than one gene. Possible Danish founder variants in EYS and RP1 are reported. A significant number of variants were classified as variants with unknown significance; reporting of these will hopefully contribute to the elucidation of the actual clinical consequence making the classification less troublesome in the future. In conclusion, this study underlines the relevance of performing targeted sequencing of IRD including CNV analysis as well as the importance of interaction with clinical diagnoses.
Clostridium ramosum regulates enterochromaffin cell development and serotonin release
Authors: Mandić Ana D. , Woting Anni , Jaenicke Tina , Sander Anika , Sabrowski Wiebke , Rolle-Kampcyk Ulrike , von Bergen Martin , Blaut Michael
Published: February 2019

Peripheral serotonin (5-hydroxytryptamine: 5-HT) synthesized in the intestine by enterochromaffin cells (ECs), plays an important role in the regulation of peristaltic of the gut, epithelial secretion and promotes the development and maintenance of the enteric neurons. Recent studies showed that the indigenous gut microbiota modulates 5-HT signalling and that ECs use sensory receptors to detect dietary and microbiota-derived signals from the lumen to subsequently transduce the information to the nervous system. We hypothesized that Clostridium ramosum by increasing gut 5-HT availability consequently contributes to high-fat diet-induced obesity. Using germ-free mice and mice monoassociated with C. ramosum, intestinal cell lines and mouse organoids, we demonstrated that bacterial cell components stimulate host 5-HT secretion and program the differentiation of colonic intestinal stem progenitors toward the secretory 5-HT-producing lineage. An elevated 5-HT level regulates the expression of major proteins involved in intestinal fatty acid absorption in vitro, suggesting that the presence of C. ramosum in the gut promotes 5-HT secretion and thereby could facilitates intestinal lipid absorption and the development of obesity.
High content screening identifies monensin as an EMT-selective cytotoxic compound
Authors: Vanneste Marion , Huang Qin , Li Mengshi , Moose Devon , Zhao Lei , Stamnes Mark A. , Schultz Michael , Wu Meng , Henry Michael D.
Published: February 2019

Epithelial-to-mesenchymal transition (EMT) is implicated in cancer metastasis and drug resistance. Specifically targeting cancer cells in an EMT-like state may have therapeutic value. In this study, we developed a cell imaging-based high-content screening protocol to identify EMT-selective cytotoxic compounds. Among the 2,640 compounds tested, salinomycin and monensin, both monovalent cation ionophores, displayed a potent and selective cytotoxic effect against EMT-like cells. The mechanism of action of monensin was further evaluated. Monensin (10 nM) induced apoptosis, cell cycle arrest, and an increase in reactive oxygen species (ROS) production in TEM 4-18 cells. In addition, monensin rapidly induced swelling of Golgi apparatus and perturbed mitochondrial function. These are previously known effects of monensin, albeit occurring at much higher concentrations in the micromolar range. The cytotoxic effect of monensin was not blocked by inhibitors of ferroptosis. To explore the generality of our findings, we evaluated the toxicity of monensin in 24 human cancer cell lines and classified them as resistant or sensitive based on IC50 cutoff of 100 nM. Gene Set Enrichment Analysis identified EMT as the top enriched gene set in the sensitive group. Importantly, increased monensin sensitivity in EMT-like cells is associated with elevated uptake of 3H-monensin compared to resistant cells.