bluuebunny/crossref_metadata_2025 huggingface dataset:
Large Gas Reservoir Along the Rift Axis of a Continental Back‐Arc Basin Revealed by Automated Seismic Velocity Analysis in the Okinawa Trough
Authors: Mukumoto Kota , Tsuji Takeshi , Hendriyana Andri
Published: August 2019

In the Okinawa Trough off southwestern Japan, hydrothermal circulation due to back‐arc rifting is active. Biogenic CH4 in discharging hydrothermal fluids at the Iheya North Knoll is derived from outside the knoll; however, the location of the gas reservoir has not been identified. Here, we applied automated velocity analysis to seismic reflection data to obtain a P wave velocity structure in high spatial resolution. The resulting profiles reveal large gas reservoirs as low‐velocity zones along the rifting axis (>5 km for axis direction) around the Iheya North Knoll. The main gaseous components in the reservoir could be CO2 and CH4. The heat flow inferred from seismic profiles (i.e., depth of reflector) indicates that CH4 hydrate could be trapping the gas. Furthermore, the heat flow is higher at the rifting axis and close to the knoll, reflecting the large gas reservoir feeding the hydrothermal fluids in the discharging area at the knoll.
Residual Trapping of CO2 in an Oil‐Filled, Oil‐Wet Sandstone Core: Results of Three‐Phase Pore‐Scale Imaging
Authors: Iglauer Stefan , Paluszny Adriana , Rahman Taufiq , Zhang Yihuai , Wülling Wolfgang , Lebedev Maxim
Published: August 2019

CO2 geosequestration in oil reservoirs is an economically attractive solution as it can be combined with enhanced oil recovery (CO2‐EOR). However, the effectiveness of the associated three‐phase displacement processes has not been tested at the micrometer pore scale, which determines the overall reservoir‐scale fluid dynamics and thus CO2‐EOR project success. We thus imaged such displacement processes in situ in 3‐D with X‐ray microcomputed tomography at high resolution at reservoir conditions and found that oil extraction was enhanced substantially, while a significant residual CO2 saturation (13.5%) could be achieved in oil‐wet rock. Statistics of the residual CO2 and oil clusters are also provided; they are similar to what is found in analogue two‐phase systems although some details are different, and displacement processes are significantly more complex.
Tropical Cyclone Cold Wake Size and Its Applications to Power Dissipation and Ocean Heat Uptake Estimates
Authors: Zhang Jishi , Lin Yanluan , Chavas Daniel R. , Mei Wei
Published: August 2019

Mixing of the upper ocean by the wind field associated with tropical cyclones (TCs) creates observable cold wakes in sea surface temperature and may potentially influence ocean heat uptake. The relationship between cold wake size and storm size, however, has yet to be explored. Here we apply two objective methods to observed daily sea surface temperature data to quantify the size of TC‐induced cold wakes. The obtained cold wake sizes agree well with the TC sizes estimated from the QuikSCAT‐R wind field database with a correlation coefficient of 0.51 and 0.59, respectively. Furthermore, our new estimate of the total cooling that incorporates the variations in the cold wake size provides improved estimates of TC power dissipation and TC‐induced ocean heat uptake. This study thus highlights the importance of cold wake size in evaluating the climatological effects of TCs.
Robust Solar Signature in Late Winter Precipitation Over Southern China
Authors: Ma Hedi , Chen Haishan , Lai Anwei , Li Xing , Wang Ruili , Gao Chujie
Published: August 2019

The 11‐year solar cycle (SC) has been widely recognized as a potential source of regional climate variability in the Northern Hemisphere winter. However, whether an SC signal exists in the southern China winter precipitation remains unclear. By analyzing land surface precipitation and sunspot number data from 1901 to 2010 in this study, evidence of a robust positive precipitation response that is synchronous with the SC in late winter (January–March) over southern China is provided, and the most statistically significant signals (p < 0.01) are detected over the middle Yangtze River basin. In early winter (October–December), there are only nonsignificant negative responses. The late winter SC‐precipitation relationship persists over time and appears to largely result from a solar‐associated Rossby wave train originating from the North Atlantic/European region. Our results indicate an enhanced predictability of late winter precipitation over southern China.
Seasonal Predictability of the Winter North Atlantic Oscillation From a Jet Stream Perspective
Authors: Parker Tess , Woollings Tim , Weisheimer Antje , O'Reilly Chris , Baker Laura , Shaffrey Len
Published: August 2019

The winter North Atlantic Oscillation (NAO) has varied on interannual and decadal timescales over the last century, associated with variations in the speed and latitude of the eddy‐driven jet stream. This paper uses hindcasts from two operational seasonal forecast systems (the European Centre for Medium‐range Weather Forecasts's seasonal forecast system, and the U.K. Met Office global seasonal forecast system) and a century‐long atmosphere‐only experiment (using the European Centre for Medium‐range Weather Forecasts's Integrated Forecasting System model) to relate seasonal prediction skill in the NAO to these aspects of jet variability. This shows that the NAO skill realized so far arises from interannual variations in the jet, largely associated with its latitude rather than speed. There likely remains further potential for predictability on longer, decadal timescales. In the small sample of models analyzed here, improved representation of the structure of jet variability does not translate to enhanced seasonal forecast skill.
Mineral Abundances Inferred From In Situ Reflectance Measurements of Chang'E‐4 Landing Site in South Pole‐Aitken Basin
Authors: Hu Xiaoyi , Ma Pei , Yang Yazhou , Zhu Meng‐Hua , Jiang Te , Lucey Paul G. , Sun Lingzhi , Zhang Hao , Li Chunlai , Xu Rui , He Zhiping , Lin Hongyu , Huang Changning , Sun Yuxue
Published: August 2019

During its first two lunar day measurements, the visible and near‐infrared spectrometer on board the Yutu‐2 Rover of the Chang'E‐4 mission acquired six in situ reflectance spectra from the floor of Von Kármán crater within the South Pole‐Aitken basin. A spectral lookup table search has shown that the regolith at the landing site contains 56–72% plagioclase, 9–28% orthopyroxene, 4–19% clinopyroxene, and 2–12% olivine, in relative abundance, in agreement with the results from Kaguya Multiband Imager mineral mapping. A mineral composition analysis using measurements made by the Moon Mineralogy Mapper and the Multiband Imager has shown that the surface materials of the landing site may have been ejected from the nearby Finsen crater. This result is also supported by principal component analysis which shows a strong correlation between the compositions of the landing area and Finsen crater.
Disentangling the Drivers of the Summertime Ozone‐Temperature Relationship Over the United States
Authors: Kerr Gaige Hunter , Waugh Darryn W. , Strode Sarah A. , Steenrod Stephen D. , Oman Luke D. , Strahan Susan E.
Published: August 2019

Summertime surface‐level ozone (O3) is known to vary with temperature, but the relative roles of different processes responsible for causing the O3‐temperature relationship are not well quantified. In this study we use simulations of NASA's Global Modeling Initiative chemical transport model to isolate and assess the relative impact of atmospheric transport, chemistry, and emissions on large‐scale O3variability, events, and and the covariance of O3with temperature. Using observations from the Clean Air Status and Trends Network in the contiguous United States, we show that the Global Modeling Initiative chemical transport model reproduces the spatiotemporal variability of O3and its relationship with temperature during the summer. We use the change in O3given a change in temperature (dO3/dT) along with other metrics to understand differences between our simulations. In regions with moderate to strong positive correlations between temperature and O3such as the northeast, Great Lakes, and Great Plains, temperature's association with transport yields a majority of the total O3‐temperature relationship (∼60%), while temperature‐dependent chemistry and anthropogenic NO emissions play smaller roles (∼30% and ∼10%, respectively). There are regions, however, with insignificant correlations between temperature and O3, and our findings suggest that transport is still an important driver of O3variability in these regions, albeit not correlated with temperature. Transport is not directly dependent on temperature but rather is linked through an indirect association, and it is therefore important to understand the exact mechanisms that link transport to O3and how these mechanisms will change in a warming world.
Regulating autophagy facilitated therapeutic efficacy of the sonic Hedgehog pathway inhibition on lung adenocarcinoma through GLI2 suppression and ROS production
Authors: Fan Jiajun , Zhang Xuyao , Wang Shaofei , Chen Wei , Li Yubin , Zeng Xian , Wang Yichen , Luan Jingyun , Li Li , Wang Ziyu , Sun Xilin , Shen Baozhong , Ju Dianwen
Published: August 2019

Lung adenocarcinoma (LUAD), which comprises over 50% of all cases of non-small-cell lung cancer, has a poor prognosis and requires novel therapeutic approaches. The sonic Hedgehog (Shh) pathway, which plays a crucial role in differentiation, proliferation, and survival of cancer cells, is likely to be activated in LUADs, suggesting the Shh pathway as a potential therapeutic target for LUAD treatment. In this study, we reported that vismodegib, an inhibitor of the Shh pathway, only elicited minor antitumor efficacy in A549 and NCI-H1975 LUAD cells as well as in the xenograft tumors, with overexpressed GLI2 and increased autophagic activity. The aberrant autophagy in LUAD cells was further confirmed by the three main stages of autophagic flux, including the formation of autophagosomes, the fusion of autophagosomes with lysosomes, and degradation of autophagosomes in lysosomes. Furthermore, inhibition of autophagy by siRNA against ATG5 or ATG7 rescued the sensitivity of A549 and NCI-H1975 LUAD cells to vismodegib in vitro. Meanwhile, administration of the pharmaceutical inhibitor of autophagy, chloroquine, contributed to the enhanced anti-LUAD efficacy of vismodegib in vivo, probably through overproduction of ROS, acceleration of apoptosis, and suppression of GLI2 in LUAD tissues. In summary, our research revealed that downregulating autophagy facilitated the anti-LUAD efficacy of the Shh pathway suppression, thus highlighting a potential approach for LUAD therapy via simultaneously targeting the Shh signaling and autophagy pathway.
NudC-like protein 2 restrains centriole amplification by stabilizing HERC2
Authors: Li Min , Xu Xiaoyang , Zhang Jun , Liu Min , Wang Wei , Gao Ya , Sun Qiang , Zhang Jiayu , Lu Yunkun , Wang Fangwei , Liu Wei , Zhou Tianhua , Yang Yuehong
Published: August 2019

Centriole duplication is tightly controlled to occur once per cell cycle, and disruption of this synchrony causes centriole amplification, which is frequently observed in many cancers. Our previous work showed that nuclear distribution gene C (NudC)-like protein 2 (NudCL2) localizes to centrosomes; however, little is known about the role of NudCL2 in the regulation of centrosome function. Here, we find that NudCL2 is required for accurate centriole duplication by stabilizing the E3 ligase HECT domain and RCC1-like domain-containing protein 2 (HERC2). Knockout (KO) of NudCL2 using CRISPR/Cas9-based genome editing or depletion of NudCL2 using small interfering RNA causes significant centriole amplification. Overexpression of NudCL2 significantly suppresses hydroxyurea-induced centriole overduplication. Quantitative proteomic analysis reveals that HERC2 is downregulated in NudCL2 KO cells. NudCL2 is shown to interact with and stabilize HERC2. Depletion of HERC2 leads to the similar defects to that in NudCL2-downregulated cells, and ectopic expression of HERC2 effectively rescues the centriole amplification caused by the loss of NudCL2, whereas the defects induced by HERC2 depletion cannot be reversed by exogenous expression of NudCL2. Either loss of NudCL2 or depletion of HERC2 leads to the accumulation of ubiquitin-specific peptidase 33 (USP33), a centrosomal protein that positively regulates centriole duplication. Moreover, knockdown of USP33 reverses centriole amplification in both NudCL2 KO and HERC2-depleted cells. Taken together, our data suggest that NudCL2 plays an important role in maintaining the fidelity of centriole duplication by stabilizing HERC2 to control USP33 protein levels, providing a previously undescribed mechanism restraining centriole amplification.
Tuning the activity and selectivity of electroreduction of CO2 to synthesis gas using bimetallic catalysts
Authors: Lee Ji Hoon , Kattel Shyam , Jiang Zhao , Xie Zhenhua , Yao Siyu , Tackett Brian M. , Xu Wenqian , Marinkovic Nebojsa S. , Chen Jingguang G.
Published: August 2019

The electrochemical carbon dioxide reduction reaction to syngas with controlled CO/H2 ratios has been studied on Pd-based bimetallic hydrides using a combination of in situ characterization and density functional theory calculations. When compared with pure Pd hydride, the bimetallic Pd hydride formation occurs at more negative potentials for Pd-Ag, Pd-Cu, and Pd-Ni. Theoretical calculations show that the choice of the second metal has a more significant effect on the adsorption strength of *H than *HOCO, with the free energies between these two key intermediates (i.e., ΔG(*H)–ΔG(*HOCO)) correlating well with the carbon dioxide reduction reaction activity and selectivity observed in the experiments, and thus can be used as a descriptor to search for other bimetallic catalysts. The results also demonstrate the possibility of alloying Pd with non-precious transition metals to promote the electrochemical conversion of CO2 to syngas.
Comprehensive characterization of RAS mutations in colon and rectal cancers in old and young patients
Authors: Serebriiskii Ilya G. , Connelly Caitlin , Frampton Garrett , Newberg Justin , Cooke Matthew , Miller Vince , Ali Siraj , Ross Jeffrey S. , Handorf Elizabeth , Arora Sanjeevani , Lieu Christopher , Golemis Erica A. , Meyer Joshua E.
Published: August 2019

Colorectal cancer (CRC) is increasingly appreciated as a heterogeneous disease, with factors such as microsatellite instability (MSI), cancer subsite within the colon versus rectum, and age of diagnosis associated with specific disease course and therapeutic response. Activating oncogenic mutations in KRAS and NRAS are common in CRC, driving tumor progression and influencing efficacy of both cytotoxic and targeted therapies. The RAS mutational spectrum differs substantially between tumors arising from distinct tissues. Structure-function analysis of relatively common somatic RAS mutations in G12, Q61, and other codons is characterized by differing potency and modes of action. Here we show the mutational profile of KRAS, NRAS, and the less common HRAS in 13,336 CRC tumors, comparing the frequency of specific mutations based on age of diagnosis, MSI status, and colon versus rectum subsite. We identify mutation hotspots, and unexpected differences in mutation spectrum, based on these clinical parameters.
Modelling the ultra-strongly coupled spin-boson model with unphysical modes
Authors: Lambert Neill , Ahmed Shahnawaz , Cirio Mauro , Nori Franco
Published: August 2019

A quantum system weakly coupled to a zero-temperature environment will relax, via spontaneous emission, to its ground-state. However, when the coupling to the environment is ultra-strong the ground-state is expected to become dressed with virtual excitations. This regime is difficult to capture with some traditional methods because of the explosion in the number of Matsubara frequencies, i.e., exponential terms in the free-bath correlation function. To access this regime we generalize both the hierarchical equations of motion and pseudomode methods, taking into account this explosion using only a biexponential fitting function. We compare these methods to the reaction coordinate mapping, which helps show how these sometimes neglected Matsubara terms are important to regulate detailed balance and prevent the unphysical emission of virtual excitations. For the pseudomode method, we present a general proof of validity for the use of superficially unphysical Matsubara-modes, which mirror the mathematical essence of the Matsubara frequencies.
AAV-ie enables safe and efficient gene transfer to inner ear cells
Authors: Tan Fangzhi , Chu Cenfeng , Qi Jieyu , Li Wenyan , You Dan , Li Ke , Chen Xin , Zhao Weidong , Cheng Cheng , Liu Xiaoyi , Qiao Yunbo , Su Bing , He Shuijin , Zhong Chao , Li Huawei , Chai Renjie , Zhong Guisheng
Published: August 2019

Hearing loss is the most common sensory disorder. While gene therapy has emerged as a promising treatment of inherited diseases like hearing loss, it is dependent on the identification of gene delivery vectors. Adeno-associated virus (AAV) vector-mediated gene therapy has been approved in the US for treating a rare inherited eye disease but no safe and efficient vectors have been identified that can target the diverse types of inner ear cells. Here, we identify an AAV variant, AAV-inner ear (AAV-ie), for gene delivery in mouse inner ear. Our results show that AAV-ie transduces the cochlear supporting cells (SCs) with high efficiency, representing a vast improvement over conventional AAV serotypes. Furthermore, after AAV-ie-mediated transfer of the Atoh1 gene, we find that many SCs trans-differentiated into new HCs. Our results suggest that AAV-ie is a useful tool for the cochlear gene therapy and for investigating the mechanism of HC regeneration.
MICU1 controls cristae junction and spatially anchors mitochondrial Ca2+ uniporter complex
Authors: Gottschalk Benjamin , Klec Christiane , Leitinger Gerd , Bernhart Eva , Rost René , Bischof Helmut , Madreiter-Sokolowski Corina T. , Radulović Snježana , Eroglu Emrah , Sattler Wolfgang , Waldeck-Weiermair Markus , Malli Roland , Graier Wolfgang F.
Published: August 2019

Recently identified core proteins (MICU1, MCU, EMRE) forming the mitochondrial Ca2+ uniporter complex propelled investigations into its physiological workings. Here, we apply structured illumination microscopy to visualize and localize these proteins in living cells. Our data show that MICU1 localizes at the inner boundary membrane (IBM) due to electrostatic interaction of its polybasic domain. Moreover, this exclusive localization of MICU1 is important for the stability of cristae junctions (CJ), cytochrome c release and mitochondrial membrane potential. In contrast to MICU1, MCU and EMRE are homogeneously distributed at the inner mitochondrial membrane under resting conditions. However, upon Ca2+ elevation MCU and EMRE dynamically accumulate at the IBM in a MICU1-dependent manner. Eventually, our findings unveil an essential function of MICU1 in CJ stabilization and provide mechanistic insights of how sophistically MICU1 controls the MCU-Complex while maintaining the structural mitochondrial membrane framework.
Comprehensive analysis of syndromic hearing loss patients in Japan
Authors: Ideura Michie , Nishio Shin-ya , Moteki Hideaki , Takumi Yutaka , Miyagawa Maiko , Sato Teruyuki , Kobayashi Yumiko , Ohyama Kenji , Oda Kiyoshi , Matsui Takamichi , Ito Tsukasa , Suzumura Hiroshi , Nagai Kyoko , Izumi Shuji , Nishiyama Nobuhiro , Komori Manabu , Kumakawa Kozo , Takeda Hidehiko , Kishimoto Yoko , Iwasaki Satoshi , Furutate Sakiko , Ishikawa Kotaro , Fujioka Masato , Nakanishi Hiroshi , Nakayama Jun , Horie Rie , Ohta Yumi , Naito Yasushi , Kakudo Mariko , Sakaguchi Hirofumi , Kataoka Yuko , Sugahara Kazuma , Hato Naohito , Nakagawa Takashi , Tsuchihashi Nana , Kanda Yukihiko , Kihara Chiharu , Tono Tetsuya , Miyanohara Ikuyo , Ganaha Akira , Usami Shin-ichi
Published: August 2019

More than 400 syndromes associated with hearing loss and other symptoms have been described, corresponding to 30% of cases of hereditary hearing loss. In this study we aimed to clarify the mutation spectrum of syndromic hearing loss patients in Japan by using next-generation sequencing analysis with a multiple syndromic targeted resequencing panel (36 target genes). We analyzed single nucleotide variants, small insertions, deletions and copy number variations in the target genes. We enrolled 140 patients with any of 14 syndromes (BOR syndrome, Waardenburg syndrome, osteogenesis imperfecta, spondyloepiphyseal dysplasia congenita, Stickler syndrome, CHARGE syndrome, Jervell and Lange-Nielsen syndrome, Pendred syndrome, Klippel-Feil syndrome, Alport syndrome, Norrie disease, Treacher-Collins syndrome, Perrault syndrome and auditory neuropathy with optic atrophy) and identified the causative variants in 56% of the patients. This analysis could identify the causative variants in syndromic hearing loss patients in a short time with a high diagnostic rate. In addition, it was useful for the analysis of the cases who only partially fulfilled the diagnostic criteria.
Fault stress inversion reveals seismogenic asperity of the 2011 Mw 9.0 Tohoku-Oki earthquake
Authors: Xie Zhoumin , Cai Yongen , Wang Chi-yuen , Yoshioka Shoichi , Tanaka Momo
Published: August 2019

We predict, with a model (earthquake stress model) that inverts the displacements documented at 163 GNSS onshore stations of the GEONET, the change of shear and normal stresses on the megathrust near the Japan Trench over the seven years before the 2011 Mw 9.0 Tohoku-Oki earthquake. We find three areas on the megathrust with greater accumulations of shear and normal stresses before the earthquake, which match the ruptured areas of the mainshock and two largest aftershocks (Mw 7.8 and 7.4) that occurred within half an hour after the mainshock. We also find that the change of normal stress on the fault before the earthquake is not uniform but increases in the up-dip portion (shallower depth) of the fault from the hypocenter and decreases in the down-dip portion. We infer that the occurrence of the giant earthquake at the shallow portion of the megathrust may be attributed to the increase of the normal stress there, which leads to an increase of fault shear strength and allows more elastic strain energy to accumulate to prepare for the next big earthquake. Based on these results we propose a new concept of the seismogenic asperity as the area of greater accumulations of shear and normal stresses. The method presented here may be useful for predicting the rupture zone of future large earthquakes.
Examination of molecular space and feasible structures of bioactive components of humic substances by FTICR MS data mining in ChEMBL database
Authors: Orlov Alexey A. , Zherebker Alexander , Eletskaya Anastasia A. , Chernikov Viktor S. , Kozlovskaya Liubov I. , Zhernov Yury V. , Kostyukevich Yury , Palyulin Vladimir A. , Nikolaev Eugene N. , Osolodkin Dmitry I. , Perminova Irina V.
Published: August 2019

Humic substances (HS) are complex natural mixtures comprising a large variety of compounds produced during decomposition of decaying biomass. The molecular composition of HS is extremely diverse as it was demonstrated with the use of high resolution mass spectrometry. The building blocks of HS are mostly represented by plant-derived biomolecules (lignins, lipids, tannins, carbohydrates, etc.). As a result, HS show a wide spectrum of biological activity. Despite that, HS remain a ‘biological activity black-box’ due to unknown structures of constituents responsible for the interaction with molecular targets. In this study, we investigated the antiviral activity of eight HS fractions isolated from peat and coal, as well as of two synthetic humic-like materials. We determined molecular compositions of the corresponding samples using ultra-high resolution Fourier-transform ion cyclotron resonance mass-spectrometry (FTICR MS). Inhibitory activity of HS was studied with respect to reproduction of tick-borne encephalitis virus (TBEV), which is a representative of Flavivirus genus, and to a panel of enteroviruses (EVs). The samples of natural HS inhibited TBEV reproduction already at a concentration of 1 µg/mL, but they did not inhibit reproduction of EVs. We found that the total relative intensity of FTICR MS formulae within elemental composition range commonly attributed to flavonoid-like structures is correlating with the activity of the samples. In order to surmise on possible active structural components of HS, we mined formulae within FTICR MS assignments in the ChEMBL database. Out of 6502 formulae within FTICR MS assignments, 3852 were found in ChEMBL. There were more than 71 thousand compounds related to these formulae in ChEMBL. To support chemical relevance of these compounds to natural HS we applied the previously developed approach of selective isotopic exchange coupled to FTICR MS to obtain structural information on the individual components of HS. This enabled to propose compounds from ChEMBL, which corroborated the labeling data. The obtained results provide the first insight onto the possible structures, which comprise antiviral components of HS and, respectively, can be used for further disclosure of antiviral activity mechanism of HS.
Regulation of gene expression by altered promoter methylation using a CRISPR/Cas9-mediated epigenetic editing system
Authors: Kang Jeong Gu , Park Jin Suk , Ko Jeong-Heosn , Kim Yong-Sam
Published: August 2019

Despite the increased interest in epigenetic research, its progress has been hampered by a lack of satisfactory tools to control epigenetic factors in specific genomic regions. Until now, many attempts to manipulate DNA methylation have been made using drugs but these drugs are not target-specific and have global effects on the whole genome. However, due to new genome editing technologies, potential epigenetic factors can now possibly be regulated in a site-specific manner. Here, we demonstrate the utility of CRISPR/Cas9 to modulate methylation at specific CpG sites and to elicit gene expression. We targeted the murine Oct4 gene which is transcriptionally locked due to hypermethylation at the promoter region in NIH3T3 cells. To induce site-specific demethylation at the Oct4 promoter region and its gene expression, we used the CRISPR/Cas9 knock-in and CRISPR/dCas9-Tet1 systems. Using these two approaches, we induced site-specific demethylation at the Oct4 promoter and confirmed the up-regulation of Oct4 expression. Furthermore, we confirmed that the synergistic effect of DNA demethylation and other epigenetic regulations increased the expression of Oct4 significantly. Based on our research, we suggest that our proven epigenetic editing methods can selectively modulate epigenetic factors such as DNA methylation and have promise for various applications in epigenetics.
In vitro spleen cell cytokine responses of adult mice immunized with a recombinant PorA (major outer membrane protein [MOMP]) from Campylobacter jejuni
Authors: Albert M. John , Raghupathy Raj , Khan Islam , Azizieh Fawaz Y.
Published: August 2019

There is no information on cytokine profiles for use as markers of protection in Campylobacter jejuni infection. To study this, we used outer membrane protein (MOMP [PorA]) as the vaccine for protection and spleen cell cytokines as markers of protection. We cloned and expressed porA from C. jejuni111 and immunized mice by the intraperitoneal route. Subsequently, mice were orally challenged with live C. jejuni 111. The vaccine induced protection as evidenced by reduced fecal excretion of C. jejuni111. Cytokines were measured in vitro after stimulation of spleen cells with MOMP. The levels of pro-inflammatory cytokines, IL-12, TNF-α, IL-17A and IL-17F were similar in control and test mice. The levels of pro-inflammatory cytokines, IL-2 and IFN-γ were higher in control mice than in test mice, and the levels of pro-inflammatory cytokines, IL-8 and IL-1β were higher in test mice than in control mice. Among the two anti-inflammatory cytokines, the levels were similar for IL-10 but higher for IL-4 in test mice than in control mice. Ratios of pro-inflammatory to anti-inflammatory cytokines showed a bias towards an anti-inflammatory response in favor of antibody production reflecting the role of antibodies in immunity. Cytokine production patterns by spleen cells may be used as markers of protection in the mouse model.
Adsorption of 1,4-phenylene diisothiocyanate onto the graphene oxide sheets functionalized with polydiphenylamine in doped state
Authors: Baibarac M. , Daescu M. , Fejer S. N.
Published: August 2019

Adsorption processes of 1,4-phenylene diisothiocyanate (PDITC) on two new platforms of the type graphene oxide (GO) sheets and GO layers functionalization with polydiphenylamine (PDPA) are studied by Raman scattering and photoluminescence (PL). An interaction in solid state phase of the two constituents, i.e. PDITC and GO sheets, and a deposition of PDITC onto the PDPA functionalized GO layers, respectively, by the drop casting method, were performed. In the first case, it is shown that interaction in solid state phase of GO with PDITC leads to an intercalation of the organic compound between GO sheets simultaneously with the appearance of the o-thiocarbamate groups, that induces: (i) an enhancement of the PDITC Raman lines situated in the 400–800 and 1000–1300 cm−1 spectral ranges, (ii) a change in the ratio between the relative intensities of the two Raman lines peaked at 1585 and 1602 cm−1 accompanied by an up-shift in the case of the second line and (iii) a down-shift of the PDTIC PL band from 502 to 491 nm. Using cyclic voltammetry, an electrochemical functionalization of the GO layers with PDPA doped with H3PMo12O40 heteropolyanions takes place, as demonstrated by Raman scattering and FTIR spectroscopy. The presence of the amine groups in the molecular structure of the doped PDPA functionalized GO layers induces a chemical adsorption of PDITC on this platform, when the thiourea groups appear simultaneously with o-thiocarbamate groups. A chemical mechanism is proposed to take place at the interface of the GO sheets and the doped PDPA functionalized GO layers, respectively, with PDITC.
Tissue-specific progesterone receptor-chromatin binding and the regulation of progesterone-dependent gene expression
Authors: Dinh D. T. , Breen J. , Akison L. K. , DeMayo F. J. , Brown H. M. , Robker R. L. , Russell D. L.
Published: August 2019

Progesterone receptor (PGR) co-ordinately regulates ovulation, fertilisation and embryo implantation through tissue-specific actions, but the mechanisms for divergent PGR action are poorly understood. Here we characterised PGR activity in mouse granulosa cells using combined ChIP-seq for PGR and H3K27ac and gene expression microarray. Comparison of granulosa, uterus and oviduct PGR-dependent genes showed almost complete tissue specificity in PGR target gene profiles. In granulosa cells 82% of identified PGR-regulated genes bound PGR within 3 kb of the gene and PGR binding sites were highly enriched in proximal promoter regions in close proximity to H3K27ac-modified active chromatin. Motif analysis showed highly enriched PGR binding to the PGR response element (GnACAnnnTGTnC), but PGR also interacted significantly with other transcription factor binding motifs. In uterus PGR showed far more tendency to bind intergenic chromatin regions and low evidence of interaction with other transcription factors. This is the first genome-wide description of PGR action in granulosa cells and systematic comparison of diverse PGR action in different reproductive tissues. It clarifies finely-tuned contextual PGR-chromatin interactions with implications for more targeted reproductive medicine.
Electrical stimulation promotes the angiogenic potential of adipose-derived stem cells
Authors: Beugels Jip , Molin Daniel G. M. , Ophelders Daan R. M. G. , Rutten Teun , Kessels Lilian , Kloosterboer Nico , Grzymala Andrzej A. Piatkowski de , Kramer Boris W. W. , van der Hulst René R. W. J. , Wolfs Tim G. A. M.
Published: August 2019

Autologous fat transfer (AFT) is limited by post-operative volume loss due to ischemia-induced cell death in the fat graft. Previous studies have demonstrated that electrical stimulation (ES) promotes angiogenesis in a variety of tissues and cell types. In this study we investigated the effects of ES on the angiogenic potential of adipose-derived stem cells (ASC), important progenitor cells in fat grafts with proven angiogenic potential. Cultured human ASC were electrically stimulated for 72 hours after which the medium of stimulated (ES) and non-stimulated (control) ASC was analysed for angiogenesis-related proteins by protein array and ELISA. The functional effect of ES on angiogenesis was then assessed in vitro and in vivo. Nine angiogenesis-related proteins were detected in the medium of electrically (non-)stimulated ASC and were quantified by ELISA. The pro-angiogenic proteins VEGF and MCP-1 were significantly increased following ES compared to controls, while the anti-angiogenic factor Serpin E1/PAI-1 was significantly decreased. Despite increased levels of anti-angiogenic TSP-1 and TIMP-1, medium of ES-treated ASC significantly increased vessel density, total vessel network length and branching points in chorio-allantoic membrane assays. In conclusion, our proof-of-concept study showed that ES increased the angiogenic potential of ASC both in vitro and in vivo.
Micronutrients decline under long-term tillage and nitrogen fertilization
Authors: Shiwakoti Santosh , Zheljazkov Valtcho D. , Gollany Hero T. , Kleber Markus , Xing Baoshan
Published: August 2019

Tillage and nitrogen (N) fertilization can be expected to alter micronutrient dynamics in the soil and in plants over time. However, quantitative information regarding the effects of tillage and N application rates on micronutrient dynamics is limited. The objectives of this study were (a) to determine the long-term effect of different tillage methods as well as variation in N application rates on the distribution of Mehlich III extractable manganese, copper, zinc, boron, and iron in soils and (b) to assess accumulation of the same nutrients in wheat (Triticum aestivum L.) tissues. The system studied was under a dryland winter wheat-fallow (WW-F) rotation. Tillage methods included moldboard (MP), disk (DP) and sweep (SW), and the N application rates were 0, 45, 90, 135, and 180 kg ha−1. The concentration of soil manganese was greater under DP (131 mg kg−1) than under MP (111 mg kg−1). Inorganic N application reduced extractable soil copper while, it increased manganese accumulation in wheat grain over time. Comparison of micronutrients with adjacent long-term (since 1931) undisturbed grass pasture revealed that the WW-F plots had lost at least 43% and 53% of extractable zinc and copper, respectively, after 75 years of N fertilization and tillage. The results indicate that DP and inorganic N application could reduce the rate of micronutrient decline in soil and winter wheat grain over time compared to MP and no N fertilization.
Optimisation and validation of hydrogel-based brain tissue clearing shows uniform expansion across anatomical regions and spatial scales
Authors: Tyson Adam L. , Akhtar Ayesha M. , Andreae Laura C.
Published: August 2019

Imaging of fixed tissue is routine in experimental neuroscience, but is limited by the depth of tissue that can be imaged using conventional methods. Optical clearing of brain tissue using hydrogel-based methods (e.g. CLARITY) allows imaging of large volumes of tissue and is rapidly becoming commonplace in the field. However, these methods suffer from a lack of standardized protocols and validation of the effect they have upon tissue morphology. We present a simple and reliable protocol for tissue clearing along with a quantitative assessment of the effect of tissue clearing upon morphology. Tissue clearing caused tissue swelling (compared to conventional methods), but this swelling was shown to be similar across spatial scales and the variation was within limits acceptable to the field. The results of many studies rely upon an assumption of uniformity in tissue swelling, and by demonstrating this quantitatively, research using these methods can be interpreted more reliably.
Engineered Dendritic Cell-Directed Concurrent Activation of Multiple T cell Inhibitory Pathways Induces Robust Immune Tolerance
Authors: Gudi Radhika R. , Karumuthil-Melethil Subha , Perez Nicolas , Li Gongbo , Vasu Chenthamarakshan
Published: August 2019

Inhibitory/repressor-receptors are upregulated significantly on activated T cells, and have been the molecules of attention as targets for inducing immune tolerance. Induction of effective antigen specific tolerance depends on concurrent engagement of the TCR and one or more of these inhibitory receptors. Here, we show, for the first time that dendritic cells (DCs) can be efficiently engineered to express multiple T cell inhibitory ligands, and enhanced engagement of T cell inhibitory receptors, upon antigen presentation, by these DCs can induce effective CD4+ T cell tolerance and suppress autoimmunity. Compared to control DCs, antigen presentation by DCs that ectopically express CTLA4, PD1 and BTLA selective ligands (B7.1wa, PD-L1, and HVEM-CRD1 respectively) individually (mono-ligand DCs) or in combination (multi-ligand DCs) causes an inhibition of CD4+ T cell proliferation and pro-inflammatory cytokine response, as well as increase in Foxp3+ Treg frequency and immune regulatory cytokine production. Administration of self-antigen (mouse thyroglobulin; mTg) loaded multi-ligand DCs caused hyporesponsiveness to mTg challenge, suppression of autoantibody production, and amelioration of experimental autoimmune thyroiditis. Overall, this study shows that engineered DC-directed enhanced concurrent activation of multiple T cell coinhibitory pathways is an effective way to induce self-antigen specific T cell tolerance to suppress ongoing autoimmunity.
Enhancing the photovoltaic performance of hybrid heterojunction solar cells by passivation of silicon surface via a simple 1-min annealing process
Authors: Xie Rongbin , Ishijima Naoya , Sugime Hisashi , Noda Suguru
Published: August 2019

Solution-based heterojunction technology is emerging for facile fabrication of silicon (Si)-based solar cells. Surface passivation of Si substrate has been well established to improve the photovoltaic (PV) performance for the conventional bulk Si cells. However, the impact is still not seen for the heterojunction cells. Here, we developed a facile and repeatable method to passivate the Si surface by a simple 1-min annealing process in vacuum, and integrated it into the heterojunction cells with poly(3,4-ethylenedioxythiophene): poly(styrenesulfonate) (PEDOT:PSS) or carbon nanotube (CNT). A thin and dense oxide layer was introduced on the Si surface to provide a high-quality hole transport layer and passivation layer. The layer enhanced the power conversion efficiency from 9.34% to 12.87% (1.38-times enhancement) for the PEDOT:PSS/n-Si cells and from 6.61% to 8.52% (1.29-times enhancement) for the CNT/n-Si cells. The simple passivation is a promising way to enhance the PV performance of the Si cells with various solution-based heterojunctions.
Simultaneous detection of five flavoring agents in chewing gum by ultrasound-microwave synergistic extraction coupled with gas chromatography
Authors: Li Junde , Liu Xiaojuan , Liang Xin , Zhang Manman , Han Lei , Song Jiying
Published: August 2019

So far, the identification and determination of flavor additives in food has gained extensive attention in the area of food safety. However, it remains a big challenge for simultaneous detection of diverse flavor agents. In this work, a novel gas chromatography method coupled with ultrasound-microwave synergistic extraction was developed for simultaneous detection of five flavor compounds, including butyl butyrate, menthol, methyl salicylate, eugenol and vanilline. In this strategy, ultrasound-microwave synergistic extraction was used to extract the five flavoring agents from chewing gum. The effects of extractants, solid-liquid ratio, extraction time and microwave power on extraction yield were researched by using orthogonal test. After the optimization of programme temperature and splitless injection, the five flavoring agents were well separated and simultaneously detected with wide linear ranges, low limits of detection, high accuracy and good repeatability. Therefore, this proposed method would hold great promise for assay application on the food safety.
Unique CdS@MoS2 Core Shell Heterostructure for Efficient Hydrogen Generation Under Natural Sunlight
Authors: Kadam Sunil R. , Gosavi Suresh W. , Kale Bharat B. , Suzuki Norihiro , Terashima Chiaki , Fujishima Akira
Published: August 2019

The hierarchical nanostructured CdS@MoS2 core shell was architectured using template free facile solvothermal technique. More significantly, the typical hexagonal phase of core CdS and shell MoS2 has been obtained. Optical study clearly shows the two steps absorption in the visible region having band gap of 2.4 eV for CdS and 1.77 eV for MoS2. The FESEM of CdS@MoS2 reveals the formation of CdS microsphere (as a core) assemled with 40–50 nm nanoparticles and covered with ultrathin nanosheets of MoS2 (Shell) having size 200–300 nm and the 10–20 nm in thickness. The overall size of the core shell structure is around 8 µm. Intially, there is a formation of CdS microsphre due to high affinity of Cd ions with sulfur and further growth of MoS2 thin sheets on the surface. Considering band gap ideally in visible region, photocatalytic hydrogen evolution using CdS@MoS2 core shell was investigated under natural sunlight. The utmost hydrogen evolution rate achieved for core shell is 416.4 µmole h−1 with apparent quantum yield 35.04%. The photocatalytic activity suggest that an intimate interface contact, extended visible light absorption and effective photo generated charge carrier separation contributed to the photocatalytic enhancement of the CdS@MoS2 core shell. Additional, the enhanced hole trapping process and effective electrons transfer from CdS to MoS2 in CdS@MoS2 core shell heterostructures can significantly contribute for photocatalytic activity. Such core shell heterostructure will also have potential in thin film solar cell and other microelectronic devices.
Blockade of α4 integrins reduces leukocyte–endothelial interactions in cerebral vessels and improves memory in a mouse model of Alzheimer’s disease
Authors: Pietronigro Enrica , Zenaro Elena , Bianca Vittorina Della , Dusi Silvia , Terrabuio Eleonora , Iannoto Giulia , Slanzi Anna , Ghasemi Somayehsadat , Nagarajan Rajasekar , Piacentino Gennj , Tosadori Gabriele , Rossi Barbara , Constantin Gabriela
Published: August 2019

Alzheimer’s disease (AD) is a neurodegenerative disorder characterized by cognitive decline associated with the deposition of amyloid-β (Aβ) plaques, hyperphosphorylation of tau protein, and neuronal loss. Vascular inflammation and leukocyte trafficking may contribute to AD pathogenesis, and a better understanding of these inflammation mechanisms could therefore facilitate the development of new AD therapies. Here we show that T cells extravasate in the proximity of cerebral VCAM-1+vessels in 3xTg-AD transgenic mice, which develop both Aβ and tau pathologies. The counter-ligand of VCAM-1 – α4β1 integrin, also known as very late antigen-4 (VLA-4) – was more abundant on circulating CD4+T cells and was also expressed by a significant proportion of blood CD8+T cells and neutrophils in AD mice. Intravital microscopy of the brain microcirculation revealed that α4 integrins control leukocyte–endothelial interactions in AD mice. Therapeutic targeting of VLA-4 using antibodies that specifically block α4 integrins improved the memory of 3xTg-AD mice compared to an isotype control. These antibodies also reduced neuropathological hallmarks of AD, including microgliosis, Aβ load and tau hyperphosphorylation. Our results demonstrate that α4 integrin-dependent leukocyte trafficking promotes cognitive impairment and AD neuropathology, suggesting that the blockade of α4 integrins may offer a new therapeutic strategy in AD.
Filamentation in Atmospheric Air with Tunable 1100–2400 nm Near-Infrared Femtosecond Laser Source
Authors: O’Connor Sean P. , Marble Christopher B. , Nodurft Dawson T. , Noojin Gary D. , Boretsky Adam R. , Wharmby Andrew W. , Scully Marlan O. , Yakovlev Vladislav V.
Published: August 2019

Intense femtosecond pulse filamentation in open-air has been utilized for long distance optical communication and remote sensing, but it results in nonlinear-effect driven eye hazards which are not addressed by current eye safety standards. A systematic study of filamentation in atmospheric air was performed using a tunable 100 fs near-infrared laser (1100 nm–2400 nm). While undergoing filamentation, each source wavelength was spectrally broadened resulting in supercontinuum and third harmonic generation in the visible and near-IR spectrum. We record the spectra at the center and fringes of the supercontinuum as it is imaged onto a planar surface. In a full beam collection regime, we report the energy of the sub-1000 nm light generation for source wavelengths from 1100 nm to 1600 nm and compare the energy density to the maximum permissible exposure values under the ANSI Z136.1 laser safety standard.
An Efficient New Process for the Selective Production of Odd-Chain Carboxylic Acids by Simple Carbon Elongation Using Megasphaera hexanoica
Authors: Kim Hyunjin , Jeon Byoung Seung , Sang Byoung-In
Published: August 2019

The caproate-producing bacterium, Megasphaera hexanoica, metabolizes fructose to produce C2~C8 carbon-chain carboxylic acids using various electron acceptors. In particular, odd-chain carboxylic acids (OCCAs) such as valerate (C5) and heptanoate (C7), were produced at relatively high concentrations upon propionate supplementation. Using a statistical experimental design method, the optimal culture medium was established for the selective production of OCCAs among the total produced acids. In a medium containing 2.42 g L−1 sodium acetate and 18.91 g L−1 sodium propionate, M. hexanoica produced 9.48 g L−1 valerate, 2.48 g L−1 heptanoate, and 0.12 g L−1 caproate. To clarify the metabolism of the exogenous added propionate for OCCAs production, 13C tracer experiments were performed by supplementing the culture broth with [1,2,3-13C3] propionate. The metabolites analysis based on mass spectrometry showed that the propionate was only used to produce valerate and heptanoate without being participated in other metabolic pathways. Furthermore, the carbon elongation pathway in M. hexanoica was explained by the finding that the incorporation of propionate and acetate in the produced valerate occurred in only one orientation.