bluuebunny/crossref_metadata_2025 huggingface dataset:
Multicomponent Ionic Transport Modeling in Physically and Electrostatically Heterogeneous Porous Media With PhreeqcRM Coupling for Geochemical Reactions
Authors: Muniruzzaman Muhammad , Rolle Massimo
Published: December 2019

Low‐permeability aquitards, such as clay layers and inclusions, are of utmost importance for contaminant transport in groundwater systems. Although most dissolved species, contaminants, and clay surfaces are charged, the role of electrostatic interactions in subsurface flow‐through systems has not been extensively investigated. This study presents a two‐dimensional multicomponent reactive transport investigation of diffusive/dispersive and electrostatic processes in homogeneous and heterogeneous clay systems. The proposed approach is based on multiple continua and is capable to accurately describe charge interactions during ionic transport in the free water, diffuse layer, and interlayer water of charged porous media. The diffuse layer composition is simulated by considering a mean electrostatic potential following Donnan approach, whereas the interlayer composition is calculated by adopting the Gaines‐Thomas convention. Diffusive/dispersive fluxes within each subcontinuum (free water, diffuse layer, and interlayer) are calculated solving the Nernst‐Planck equation while maintaining a net zero‐charge flux. Furthermore, the multidimensional flow and transport model is coupled with the geochemical code PHREEQC, by utilizing the PhreeqcRM module, thus enabling great flexibility to access all PHREEQC's reaction capabilities. The code is benchmarked in 1‐D systems against other software and previously published experimental data. Successively, reactive transport simulations are performed in 2‐D clayey‐sandy flow‐through domains with spatially variable physical and electrostatic properties at both laboratory and field scales. The results reveal that different properties of surface charge, diffuse layer, and Coulombic interactions impact the transport of charged species and lead to distinct spatial distribution of the ions in the different subcontinua and to significantly different breakthrough curves.
Stable and Radioisotope Systematics Reveal Fossil Water as Fundamental Characteristic of Arid Orogenic‐Scale Groundwater Systems
Authors: Moran Brendan J. , Boutt David F. , Munk Lee Ann
Published: December 2019

In arid and semiarid regions, persistent hydrological imbalances illuminate the considerable gaps in our spatiotemporal understanding of fundamental catchment‐scale governing mechanisms. The Salar de Atacama basin is the most extreme example of groundwater‐dominated continental basins and therefore is an ideal place to probe these unresolved questions. Geochemical and hydrophysical observations indicate that groundwaters discharging into the basin reflect a large regional system integrated over 102–104 year timescales. The groundwater here, as in other arid regions, is a critical freshwater resource subject to substantial demand from competing interests, particularly as development of its world‐class lithium brine deposit expands. Utilizing a uniquely large and comprehensive set of H and O isotopes in water, we demonstrate that much of the presumed recharge area on the Altiplano‐Puna plateau exhibits isotopic signatures quite distinct from waters presently discharging within the endorheic Salar de Atacama watershed. δ18O values of predicted inflow source waters are 3.6‰ to 5.6‰ higher than modern plateau waters, and 3H data from 87 discrete samples indicate that nearly all of this inflow is composed of premodern recharge (i.e., fossil water). Under plausible conditions, these distinctions cannot be explained solely by natural variability in modern meteoric inputs or by steady state groundwater flow. We present a conceptual model revealing the extensive influence of transient draining of fossil groundwater storage augmented by regional interbasin flow from the Andes. Our analysis provides robust constraints on fundamental mechanisms governing this arid continental groundwater system and a framework within which to address persistent uncertainties in similar systems worldwide.
Autophagy-activating strategies to promote innate defense against mycobacteria
Authors: Kim Yi Sak , Silwal Prashanta , Kim Soo Yeon , Yoshimori Tamotsu , Jo Eun-Kyeong
Published: December 2019

Mycobacterium tuberculosis(Mtb) is a major causal pathogen of human tuberculosis (TB), which is a serious health burden worldwide. The demand for the development of an innovative therapeutic strategy to treat TB is high due to drug-resistant forms of TB. Autophagy is a cell-autonomous host defense mechanism by which intracytoplasmic cargos can be delivered and then destroyed in lysosomes. Previous studies have reported that autophagy-activating agents and small molecules may be beneficial in restricting intracellular Mtb infection, even with multidrug-resistant Mtb strains. Recent studies have revealed the essential roles of host nuclear receptors (NRs) in the activation of the host defense through antibacterial autophagy against Mtb infection. In particular, we discuss the function of estrogen-related receptor (ERR) α and peroxisome proliferator-activated receptor (PPAR) α in autophagy regulation to improve host defenses against Mtb infection. Despite promising findings relating to the antitubercular effects of various agents, our understanding of the molecular mechanism by which autophagy-activating agents suppress intracellular Mtb in vitro and in vivo is lacking. An improved understanding of the antibacterial autophagic mechanisms in the innate host defense will eventually lead to the development of new therapeutic strategies for human TB.
Bacteria-cancer interactions: bacteria-based cancer therapy
Authors: Duong Mai Thi-Quynh , Qin Yeshan , You Sung-Hwan , Min Jung-Joon
Published: December 2019

Recent advances in cancer therapeutics, such as targeted therapy and immunotherapy, have raised the hope for cures for many cancer types. However, there are still ongoing challenges to the pursuit of novel therapeutic approaches, including high toxicity to normal tissue and cells, difficulties in treating deep tumor tissue, and the possibility of drug resistance in tumor cells. The use of live tumor-targeting bacteria provides a unique therapeutic option that meets these challenges. Compared with most other therapeutics, tumor-targeting bacteria have versatile capabilities for suppressing cancer. Bacteria preferentially accumulate and proliferate within tumors, where they can initiate antitumor immune responses. Bacteria can be further programmed via simple genetic manipulation or sophisticated synthetic bioengineering to produce and deliver anticancer agents based on clinical needs. Therapeutic approaches using live tumor-targeting bacteria can be applied either as a monotherapy or in combination with other anticancer therapies to achieve better clinical outcomes. In this review, we introduce and summarize the potential benefits and challenges of this anticancer approach. We further discuss how live bacteria interact with tumor microenvironments to induce tumor regression. We also provide examples of different methods for engineering bacteria to improve efficacy and safety. Finally, we introduce past and ongoing clinical trials involving tumor-targeting bacteria.
The activation of bystander CD8+ T cells and their roles in viral infection
Authors: Kim Tae-Shin , Shin Eui-Cheol
Published: December 2019

During viral infections, significant numbers of T cells are activated in a T cell receptor-independent and cytokine-dependent manner, a phenomenon referred to as “bystander activation.” Cytokines, including type I interferons, interleukin-18, and interleukin-15, are the most important factors that induce bystander activation of T cells, each of which plays a somewhat different role. Bystander T cells lack specificity for the pathogen, but can nevertheless impact the course of the immune response to the infection. For example, bystander-activated CD8+T cells can participate in protective immunity by secreting cytokines, such as interferon-γ. They also mediate host injury by exerting cytotoxicity that is facilitated by natural killer cell-activating receptors, such as NKG2D, and cytolytic molecules, such as granzyme B. Interestingly, it has been recently reported that there is a strong association between the cytolytic function of bystander-activated CD8+T cells and host tissue injury in patients with acute hepatitis A virus infection. The current review addresses the induction of bystander CD8+T cells, their effector functions, and their potential roles in immunity to infection, immunopathology, and autoimmunity.
Innate, adaptive, and cell-autonomous immunity against Toxoplasma gondii infection
Authors: Sasai Miwa , Yamamoto Masahiro
Published: December 2019

Hosts have been fighting pathogens throughout the evolution of all infectious diseases.Toxoplasma gondiiis one of the most common infectious agents in humans but causes only opportunistic infection in healthy individuals. Similar to antimicrobial immunity against other organisms, the immune response againstT. gondiiactivates innate immunity and in turn induces acquired immune responses. After activation of acquired immunity, host immune cells robustly produce the proinflammatory cytokine interferon-γ (IFN-γ), which activates a set of IFN-γ-inducible proteins, including GTPases. IFN-inducible GTPases are essential for cell-autonomous immunity and are specialized for effective clearance and growth inhibition ofT. gondiiby accumulating in parasitophorous vacuole membranes. Recent studies suggest that the cell-autonomous immune response plays a protective role in host defense against not onlyT. gondiibut also various intracellular bacteria. Moreover, the negative regulatory mechanisms of such strong immune responses are also important for host survival after infection. In this review, we will discuss in detail recent advances in the understanding of host defenses againstT. gondiiand the roles played by cell-autonomous immune responses.
Bond-selective transient phase imaging via sensing of the infrared photothermal effect
Authors: Zhang Delong , Lan Lu , Bai Yeran , Majeed Hassaan , Kandel Mikhail E. , Popescu Gabriel , Cheng Ji-Xin
Published: December 2019

Phase-contrast microscopy converts the phase shift of light passing through a transparent specimen, e.g., a biological cell, into brightness variations in an image. This ability to observe structures without destructive fixation or staining has been widely utilized for applications in materials and life sciences. Despite these advantages, phase-contrast microscopy lacks the ability to reveal molecular information. To address this gap, we developed a bond-selective transient phase (BSTP) imaging technique that excites molecular vibrations by infrared light, resulting in a transient change in phase shift that can be detected by a diffraction phase microscope. By developing a time-gated pump–probe camera system, we demonstrate BSTP imaging of live cells at a 50 Hz frame rate with high spectral fidelity, sub-microsecond temporal resolution, and sub-micron spatial resolution. Our approach paves a new way for spectroscopic imaging investigation in biology and materials science.
Optical microscopy approaches angstrom precision, in 3D!
Authors: Chu Shi-Wei
Published: December 2019

By coupling dye molecules with a graphene layer and localizing the molecules through quantification of fluorescence lifetime quenching, a novel imaging system offers unprecedented 1-nm resolution with angstrom precision in the axial dimension.
Cooperative interactions between nano-antennas in a high-Q cavity for unidirectional light sources
Authors: Cognée Kévin G. , Doeleman Hugo M. , Lalanne Philippe , Koenderink A. F.
Published: December 2019

We analyse the resonant mode structure and local density of states in high-Q hybrid plasmonic-photonic resonators composed of dielectric microdisks hybridized with pairs of plasmon antennas that are systematically swept in position through the cavity mode. On the one hand, this system is a classical realization of the cooperative resonant dipole–dipole interaction through a cavity mode, as is evident through predicted and measured resonance linewidths and shifts. At the same time, our work introduces the notion of ‘phased array’ antenna physics into plasmonic-photonic resonators. We predict that one may construct large local density of states (LDOS) enhancements exceeding those given by a single antenna, which are ‘chiral’ in the sense of correlating with the unidirectional injection of fluorescence into the cavity. We report an experiment probing the resonances of silicon nitride microdisks decorated with aluminium antenna dimers. Measurements directly confirm the predicted cooperative effects of the coupled dipole antennas as a function of the antenna spacing on the hybrid mode quality factors and resonance conditions.
First salvage treatment with bendamustine and brentuximab vedotin in Hodgkin lymphoma: a phase 2 study of the Fondazione Italiana Linfomi
Authors: Broccoli A. , Argnani L. , Botto B. , Corradini P. , Pinto A. , Re A. , Vitolo U. , Fanti S. , Stefoni V. , Zinzani P. L. ,   on behalf of Fondazione Italiana Linfomi ONLUS
Published: December 2019

Effective salvage options inducing high complete metabolic response (CMR) rates without significant toxicity are needed for Hodgkin lymphoma (HL) patients failing induction treatment and who are candidate to autologous stem cell transplantation (ASCT). Brentuximab vedotin (BV) and bendamustine are active monotherapies in the relapsed/refractory setting and their combination (the BBV regimen) possibly enhances their activity. This single-arm multicenter phase 2 study investigated the efficacy and safety of BBV as first salvage therapy in 40 patients with relapsed/refractory HL. Thirty-eight patients were evaluable for efficacy: 30 (78.9%) had a CMR and 2 (5.3%) a partial response, leading to an overall response rate (ORR) of 84.2%. The ORR in the primary refractory subset was 75.0%, among relapsed patients it was 94.4%. Thirty-five patients could mobilize peripheral blood stem cells and 33 underwent ASCT. At a median follow-up of 23 months, the estimated 3-year overall survival and progression-free survival are 88.1% and 67.3%. During therapy, only 3 grade IV cases of neutropenia occurred and resolved within a week. No grade 4 extrahematologic toxicities were reported; skin reactions were however rather frequent (65%). These results suggest that the BBV regimen exhibits promising efficacy and a manageable toxicity in a challenging subpopulation of HL patients.
Transcription factor NFAT5 contributes to the glycolytic phenotype rewiring and pancreatic cancer progression via transcription of PGK1
Authors: Jiang Yongsheng , He Ruizhe , Jiang Yuhong , Liu Dejun , Tao Lingye , Yang Minwei , Lin Chaoyi , Shen Yang , Fu Xueliang , Yang Jianyu , Li Jiao , Huo Yanmiao , Hua Rong , Liu Wei , Zhang Junfeng , Shen Baiyong , Zhang Zhigang , Sun Yongwei
Published: December 2019

Hypoxia and the hypovascular tumor microenvironment are major hallmarks of pancreatic ductal adenocarcinoma (PDAC), in which glycolysis is of great importance to tumor survival and proliferation. There is little research regarding the role of Nuclear Factor of Activated T Cells 5 (NFAT5) in relation to carcinoma. Here, we explored the impact of NFAT5 on the biological behavior of PDAC and the underlying mechanism. We demonstrated that NFAT5 was highly expressed in PDAC and was related to poorer prognosis. Knockdown of NFAT5 lead to impaired proliferation of tumor cells caused by an aberrant Warburg effect. Mechanically, phosphoglycerate kinase 1 (PGK-1), which is the first enzyme generating ATP in glycolysis, was verified as a target gene of NFAT5. Over-expression of PGK1 compromised the aberrant oncological behavior caused by knockdown of NFAT5 both in vitro and in vivo. Clinical samples underwent positron emission tomography-computed tomography (PET-CT) examination and KrasG12D/+/Trp53R172H/+/Pdx1-Cre (KPC) mice were collected to support our conclusion.
Flagellin-elicited adaptive immunity suppresses flagellated microbiota and vaccinates against chronic inflammatory diseases
Authors: Tran Hao Q. , Ley Ruth E. , Gewirtz Andrew T. , Chassaing Benoit
Published: December 2019

Alterations in gut microbiota composition are associated with metabolic syndrome and chronic inflammatory diseases such as inflammatory bowel disease. One feature of inflammation-associated gut microbiotas is enrichment of motile bacteria, which can facilitate microbiota encroachment into the mucosa and activate pro-inflammatory gene expression. Here, we set out to investigate whether elicitation of mucosal anti-flagellin antibodies by direct administration of purified flagellin might serve as a general vaccine against subsequent development of chronic gut inflammation. We show, in mice, that repeated injection of flagellin elicits increases in fecal anti-flagellin IgA and alterations in microbiota composition, reduces fecal flagellin concentration, prevents microbiota encroachment, protects against IL-10 deficiency-induced colitis, and ameliorates diet-induced obesity. Flagellin’s impact on the microbiota is B-lymphocyte dependent and, in humans, obese subjects exhibit increased levels of fecal flagellin and reduced levels of fecal flagellin-specific IgA, relative to normal weight subjects. Thus, administration of flagellin, and perhaps other pathobiont antigens, may confer some protection against chronic inflammatory diseases.
Safety and feasibility of laparoscopy technology in right hemihepatectomy
Authors: Yu Xin , Luo Dilai , Tang Yupeng , Huang Mingwen , Huang Yong
Published: December 2019

Laparoscopic hepatectomy (LH) has been accepted widely owing to its advantages as a minimally invasive surgery; however, laparoscopic right hemihepatectomy (LRH) has rarely been reported. We aimed to compare the benefits and drawbacks of LRH and open approaches. Between January 2014 and October 2017, 85 patients with tumor and hepatolithiasis who underwent LRH (n = 30) and open right hemihepatectomy (ORH) (n = 55) were enrolled in this study. For tumors, LRH showed significantly better results with respect to blood loss (P = 0.024) and duration of hospital stay (P = 0.008) than ORH, while hospital expenses (P = 0.031) and bile leakage rate (P = 0.012) were higher with LRH. However, the operative time and rate of other complications were not significantly different between the two groups. However, for hepatolithiasis, there was less blood loss (P = 0.015) and longer operative time (P = 0.036) with LRH than with ORH. There were no significant difference between LRH and ORH in terms of hospital stay, hospital expenses, and complication rate (P > 0.05). Moreover, the postoperative white blood cell count, alanine aminotransferase level, aspartate aminotransferase level, and total bilirubin were not significantly different in both types of patients (P > 0.05). Our results suggest the safety and feasibility of laparoscopy technology for right hemihepatectomy in both tumor and hepatolithiasis patients.
Unanticipated Side Effects of Stratospheric Albedo Modification Proposals Due to Aerosol Composition and Phase
Authors: Cziczo Daniel J. , Wolf Martin J. , Gasparini Blaž , Münch Steffen , Lohmann Ulrike
Published: December 2019

The Earth has now warmed ~1.0 °C since the period 1850–1900, due in large part to the anthropogenic addition of greenhouse gases to the atmosphere. Most strategies to address this warming have called for a reduction of emissions and, often, accompanying removal of greenhouse gases. Other proposals suggest masking the increased radiative forcing by an increase in particles and/or clouds to increase scattering of incoming solar radiation. Two related recent proposals have suggested addition of calcite particles to the stratosphere, which one model suggests may enhance ozone. Here we show that the interaction of calcite with acidic materials in the stratosphere results in a more complex aerosol than has been previously considered, including aqueous and hydrate phases that can lead to ozone loss. Our study suggests particle addition to the stratosphere could also perturb global radiative balance by affecting high altitude cloud formation and properties. Experimental and modeling results suggest particles will act as the nucleation sites for polar stratospheric cloud ice and, after sedimentation into the troposphere, impact cirrus clouds in the absence of other efficient ice nucleating particles. These results show that an overly simplistic set of assumptions regarding intentional particle emissions to the atmosphere can lead to incorrect estimates of the radiative effect and fail to identify unintended consequences.
Long-term patterns of abundance, residency and movements of bull sharks (Carcharhinus leucas) in Sydney Harbour, Australia
Authors: Smoothey Amy F. , Lee Kate A. , Peddemors Victor M.
Published: December 2019

Bull sharks (Carcharhinus leucas) are known to frequent nearshore environments, particularly estuaries, resulting in interactions with humans. Knowledge of the behaviour of large individuals in temperate, estuarine environments is limited. This acoustic telemetry study reports on residency and movement patterns of 40 sub-adult and adult bull sharks in Sydney Harbour, a large temperate estuary, over seven years. Bull sharks exhibited clear seasonal patterns in their occurrence during the austral summer and autumn, with abundance peaking in January and February. This pattern was consistent between sexes and across all sizes. Bull sharks displayed weak diel differences in their spatial distribution, with individuals using areas further from the Harbour entrance more frequently during the day and at low tides. A diel pattern in depth use was apparent, with sharks utilising deeper water during daytime and moving shallower at night. Bull sharks had high individual inter-annual variability in their spatial distribution, however, when data were aggregated among all individuals and years, two locations of increased use were identified. Water temperature was the key predictor for seasonal movements and return behaviour to this estuary, suggesting that increasing water temperatures as a result of climate change may lead to higher shark abundance and possibly longer periods of residency in Sydney Harbour. Understanding the drivers for bull shark abundance and distribution will hopefully facilitate better education and shark smart behaviour by estuarine water-users, especially during summer and autumn months.
Colletotrichum species associated with mango in southern China
Authors: Li Qili , Bu Junyan , Shu Juan , Yu Zhihe , Tang Lihua , Huang Suiping , Guo Tangxun , Mo Jianyou , Luo Shuming , Solangi Ghulam Sarwar , Hsiang Tom
Published: December 2019

Mango (Mangifera indica L.) is an economically significant fruit crop in provinces of southern China including Hainan, Yunnan, Sichuan, Guizhou, Guangdong and Fujian. The objective of this study was to examine the diversity of Colletotrichum species infecting mango cultivars in major growing areas in China, using morphological and molecular techniques together with pathogenicity tests on detached leaves and fruits. Over 200 Colletotrichum isolates were obtained across all mango orchards investigated, and 128 of them were selected for sequencing and analyses of actin (ACT), chitin synthase (CHS-1), glyceraldehyde-3-phosphate dehydrogenase (GAPDH), the internal transcribed spacer (ITS) region, β-tubulin (TUB2) genomic regions. Our results showed that the most common fungal isolates associated with mango in southern China involved 13 species: Colletotrichum asianum, C. cliviicola, C. cordylinicola, C. endophytica, C. fructicola, C. gigasporum, C. gloeosporioides, C. karstii, C. liaoningense, C. musae, C. scovillei, C. siamense and C. tropicale. The dominant species were C. asianum and C. siamense each accounting for 30%, and C. fructicola for 25%. Only C. asianum, C. fructicola, C. scovillei and C. siamense have previously been reported on mango, while the other nine Colletotrichum species listed above were first reports associated with mango in China. From this study, five Colletotrichum species, namely C. cordylinicola, C. endophytica, C. gigasporum, C. liaoningense and C. musae were the first report on mango worldwide. Pathogenicity tests revealed that all 13 species caused symptoms on artificially wounded mango fruit and leaves (cv. Tainong). There was no obvious relationship between aggressiveness and the geographic origin of the isolates. These findings will help in mango disease management and future disease resistance breeding.
Novel Zeff imaging method for deep internal areas using back-scattered X-rays
Authors: Yoneyama Akio , Kawamoto Masahide , Baba Rika
Published: December 2019

Elemental kinds, composition ratios, effective atomic number (Zeff), and spatial distributions are the most basic information on materials and determine the physical and chemical properties of materials. X-ray fluorescence analysis have conventionally been used for elemental mapping, however maps on deep internal areas cannot be obtained because the escape depth of fluorescence X-rays is limited to a few mm from the surface of samples. Herein, we present a novel Zeff imaging method that uses back-scattered X-rays. The intensity ratio of elastic and inelastic back-scattered X-rays depends on the atomic number (Z) of a single-element sample (Zeff for a plural-element sample), and so Zeff maps in deep areas can be obtained by spectrum analysis of the scattered high-energy incident X-rays. We demonstrated the feasibility of observing a phantom covered by an aluminum plate by using synchrotron radiation X-ray. A fine Zeff map that can be used to identify materials was obtained from only front-side observation. The novel method opens up a new way for Zeff mapping of deep areas of thick samples from front-side observation.
Stochastic multicellular modeling of x-ray irradiation, DNA damage induction, DNA free-end misrejoining and cell death
Authors: Forster Jake C. , Douglass Michael J. J. , Phillips Wendy M. , Bezak Eva
Published: December 2019

The repair or misrepair of DNA double-strand breaks (DSBs) largely determines whether a cell will survive radiation insult or die. A new computational model of multicellular, track structure-based and pO2-dependent radiation-induced cell death was developed and used to investigate the contribution to cell killing by the mechanism of DNA free-end misrejoining for low-LET radiation. A simulated tumor of 1224 squamous cells was irradiated with 6 MV x-rays using the Monte Carlo toolkit Geant4 with low-energy Geant4-DNA physics and chemistry modules up to a uniform dose of 1 Gy. DNA damage including DSBs were simulated from ionizations, excitations and hydroxyl radical interactions along track segments through cell nuclei, with a higher cellular pO2 enhancing the conversion of DNA radicals to strand breaks. DNA free-ends produced by complex DSBs (cDSBs) were able to misrejoin and produce exchange-type chromosome aberrations, some of which were asymmetric and lethal. A sensitivity analysis was performed and conditions of full oxia and anoxia were simulated. The linear component of cell killing from misrejoining was consistently small compared to values in the literature for the linear component of cell killing for head and neck squamous cell carcinoma (HNSCC). This indicated that misrejoinings involving DSBs from the same x-ray (including all associated secondary electrons) were rare and that other mechanisms (e.g. unrejoined ends) may be important. Ignoring the contribution by the indirect effect toward DNA damage caused the DSB yield to drop to a third of its original value and the cDSB yield to drop to a tenth of its original value. Track structure-based cell killing was simulated in all 135306 viable cells of a 1 mm3 hypoxic HNSCC tumor for a uniform dose of 1 Gy.
Induction of specific adaptive immune responses by immunization with newly designed artificial glycosphingolipids
Authors: Okuda Tetsuya , Shimizu Kayoko , Hasaba Satoshi , Date Mutsuhiro
Published: December 2019

We previously found that artificial glycosphingolipids (artGSLs) containing very-long-chain fatty acids behave as strong immunogens in mice and promote the production of antibodies recognizing the oligosaccharide portion of artGSLs as the epitope. Here, we report that the oligosaccharide structure of artGSLs influences these immunogenic properties. We evaluated the antibody-inducing activity of artGSLs with different oligosaccharide structures in mice and found strong IgG-inducing activity only with an artGSL containing a core-fucosylated tetraoligosaccharide (Manβ1,4GlcNAcβ1,4[Fucα1,6]GlcNAc). To characterize the immunogenic properties of this artGSL, we analyzed various derivatives and found that the non-reducing terminal mannose structure was critical for the antibody-inducing activity. These artGSLs also exhibited IgG-inducing activity dependent on co-administration of lipid A adjuvant, but no cytokine-inducing activity similar to α-galactosylceramide was detected. Furthermore, repetitive immunization with the artGSL promoted the production of antibodies against a core-fucosylated α-fetoprotein isoform (AFP-L3) known as a hepatocellular carcinoma–specific antigen. These results indicate that the newly designed artGSLs specifically induce adaptive immune responses and promote antibody production by B cells, which can be utilized to develop anti-glycoconjugate antibodies and cancer vaccines targeting tumor-associated carbohydrate antigens.
Loss of Ikbkap/Elp1 in mouse oocytes causes spindle disorganization, developmental defects in preimplantation embryos and impaired female fertility
Authors: Yang Kuo-Tai , Inoue Azusa , Lee Yi-Jing , Jiang Chung-Lin , Lin Fu-Jung
Published: December 2019

Elongator complexes are well known to be involved in a wide variety of cellular processes; however, their functions in mammalian oocytes have not been characterized. Here, we demonstrated in mice that specific deletion of one of the core subunits,Ikbkap/Elp1, in oocytes resulted in spindle defects and chromosome disorganization without affecting folliculogenesis. In accordance with these findings, we observed thatIkbkapmutant female mice are subfertile. Further analyses uncovered that kinetochore–microtubule attachments are severely compromised inIkbkap-deficient oocytes. Moreover, we revealed thatIkbkapmodulates the acetylation status of α-tubulin in oocytes, which may at least in part mediate the meiotic phenotypes described above by affecting microtubule dynamics and kinetochore function. Finally, we showed that embryos derived fromIkbkap-deficient oocytes exhibit an increased frequency of aneuploidy, digyny, progressive delays in preimplantation development, and severe degeneration before reaching the blastocyst stage. In summary, we identifyIkbkapas an important player in regulating oocyte meiosis by modulating tubulin acetylation for chromosome/spindle organization.
Chromosomal dynamics in space and time: evolutionary history of Mycetophylax ants across past climatic changes in the Brazilian Atlantic coast
Authors: Micolino Ricardo , Cristiano Maykon Passos , Travenzoli Natália Martins , Lopes Denilce Meneses , Cardoso Danon Clemes
Published: December 2019

Fungus-farming ants of the genusMycetophylaxexhibit intra and interspecific chromosome variability, which makes them suitable for testing hypotheses about possible chromosomal rearrangements that endure lineage diversification. We combined cytogenetic and molecular data fromMycetophylaxpopulations from coastal environments to trace the evolutionary history of the clade in light of chromosomal changes under a historical and geographic context. Our cytogenetic analyses revealed chromosomal differences within and among species.M.morschiexhibited three distinct karyotypes and considerable variability in the localization of 45S rDNA clusters. The molecular phylogeny was congruent with our cytogenetic findings. Biogeographical and divergence time dating analyses estimated that the most recent common ancestor ofMycetophylaxwould have originated at about 30 Ma in an area including the Amazon and Southern Grasslands, and several dispersion and vicariance events may have occurred before the colonization of the Brazilian Atlantic coast. Diversification of the psammophilousMycetophylaxfirst took place in the Middle Miocene (ca. 18–10 Ma) in the South Atlantic coast, while “M.morschi” lineages diversified during the Pliocene-Pleistocene transition (ca. 3–2 Ma) through founder-event dispersal for the Northern coastal regions. PsammophilousMycetophylaxdiversification fits into the major global climatic events that have had a direct impact on the changes in sea level as well as deep ecological impact throughout South America. We assume therefore that putative chromosomal rearrangements correlated with increased ecological stress during the past climatic transitions could have intensified and/or accompanied the divergence of the psammophilousMycetophylax. We further reiterate that “M.morschi” comprises a complex of at least three well-defined lineages, and we emphasize the role of this integrative approach for the identification and delimitation of evolutionary lineages.
From prodigious volcanic degassing to caldera subsidence and quiescence at Ambrym (Vanuatu): the influence of regional tectonics
Authors: Shreve Tara , Grandin Raphaël , Boichu Marie , Garaebiti Esline , Moussallam Yves , Ballu Valérie , Delgado Francisco , Leclerc Frédérique , Vallée Martin , Henriot Nicolas , Cevuard Sandrine , Tari Dan , Lebellegard Pierre , Pelletier Bernard
Published: December 2019

Eruptive activity shapes volcanic edifices. The formation of broad caldera depressions is often associated with major collapse events, emplacing conspicuous pyroclastic deposits. However, caldera subsidence may also proceed silently by magma withdrawal at depth, more difficult to detect. Ambrym, a basaltic volcanic island, hosts a 12-km wide caldera and several intensely-degassing lava lakes confined to intra-caldera cones. Using satellite remote sensing of deformation, gas emissions and thermal anomalies, combined with seismicity and ground observations, we show that in December 2018 an intra-caldera eruption at Ambrym preceded normal faulting with >2 m of associated uplift along the eastern rift zone and 2.5 m of caldera-wide subsidence. Deformation was caused by lateral migration of >0.4 cubic kilometers of magma into the rift zone, extinguishing the lava lakes, and feeding a submarine eruption in the rift edge. Recurring rifting episodes, favored by stress induced by the D’Entrecasteaux Ridge collision against the New Hebrides arc, lead to progressive subsidence of Ambrym’s caldera and concurrent draining of the lava lakes. Although counterintuitive, convergent margin systems can induce rift zone volcanism and subsequent caldera subsidence.
Fe(III) doped carbon nanodots with intense green photoluminescence and dispersion medium dependent emission
Authors: Stan Corneliu Sergiu , Coroabă Adina , Ursu Elena Laura , Secula Marius Sebastian , Simionescu Bogdan C.
Published: December 2019

The preparation and investigation of Fe(III) doped carbon nanodots (CNDs) with intense green photoluminescence and emission dependence on the dispersion medium are reported. Their unusual photoluminescence is especially highlighted in water where the initial blue emission is gradually shifted to intense deep green, while in other common solvents (chloroform, acetone etc.) this behavior has not been observed. Through embedding in a polymer matrix (e.g., PVA) the color transition becomes reversible and dependent on water content, ranging from a full blue emission, when completely dried, to an intense green emission, when wetted. The preparation path of the Fe(III) doped CNDs undergoes two main stages involving the initial obtaining of Fe(III)–N–Hydroxyphthalimide complex and then a thermal processing through controlled pyrolysis. Morphostructural investigations of the prepared Fe(III) doped CNDs were performed through TG, FT-IR, XPS, DLS, TEM and AFM techniques whereas absolute PLQY, steady state and lifetime fluorescence were used to highlight their luminescence properties. The results issued from structural and fluorescence investigations bring new insights on the particular mechanisms involved in CNDs photoluminescence, a topic still open to debate.
Characterization of A Bifunctional Synthetic RNA Aptamer and A Truncated Form for Ability to Inhibit Growth of Non-Small Cell Lung Cancer
Authors: Wang Hanlu , Qin Meng , Liu Rihe , Ding Xinxin , Chen Irvin S. Y. , Jiang Yongping
Published: December 2019

An in vitro-transcribed RNA aptamer (trans-RA16) that targets non-small cell lung cancer (NSCLC) was previously identified through in vivo SELEX. Trans-RA16 can specifically target and inhibit human NCI-H460 cells in vitro and xenograft tumors in vivo. Here, in a follow-up study, we obtained a chemically-synthesized version of this RNA aptamer (syn-RA16) and a truncated form, and compared them to trans-RA16 for abilities to target and inhibit NCI-H460 cells. The syn-RA16, preferred for drug development, was by design to differ from trans-RA16 in the extents of RNA modifications by biotin, which may affect RA16’s anti-tumor effects. We observed aptamer binding to NCI-H460 cells with KD values of 24.75 ± 2.28 nM and 12.14 ± 1.46 nM for syn-RA16 and trans-RA16, respectively. Similar to trans-RA16, syn-RA16 was capable of inhibiting NCI-H460 cell viability in a dose-dependent manner. IC50 values were 118.4 nM (n = 4) for syn-RA16 and 105.7 nM (n = 4) for trans-RA16. Further studies using syn-RA16 demonstrated its internalization into NCI-H460 cells and inhibition of NCI-H460 cell growth. Moreover, in vivo imaging demonstrated the gradual accumulation of both syn-RA16 and trans-RA16 at the grafted tumor site, and qRT-PCR showed high retention of syn-RA16 in tumor tissues. In addition, a truncated fragment of trans-RA16 (S3) was identified, which exhibited binding affinity for NCI-H460 cells with a KD value of 63.20 ± 0.91 nM and inhibited NCI-H460 cell growth by 39.32 ± 3.25% at 150 nM. These features of the syn-RA16 and S3 aptamers should facilitate the development of a novel diagnostic or treatment approach for NSCLC in clinical settings.
Differential remodeling of the electron transport chain is required to support TLR3 and TLR4 signaling and cytokine production in macrophages
Authors: Ahmed Duale , Roy David , Jaworski Allison , Edwards Alexander , Abizaid Alfonso , Kumar Ashok , Golshani Ashkan , Cassol Edana
Published: December 2019

Increasing evidence suggests that mitochondria play a critical role in driving innate immune responses against bacteria and viruses. However, it is unclear if differential reprogramming of mitochondrial function contributes to the fine tuning of pathogen specific immune responses. Here, we found that TLR3 and TLR4 engagement on murine bone marrow derived macrophages was associated with differential remodeling of electron transport chain complex expression. This remodeling was associated with differential accumulation of mitochondrial and cytosolic ROS, which were required to support ligand specific inflammatory and antiviral cytokine production. We also found that the magnitude of TLR3, but not TLR4, responses were modulated by glucose availability. Under conditions of low glucose, TLR3 engagement was associated with increased ETC complex III expression, increased mitochondrial and cytosolic ROS and increased inflammatory and antiviral cytokine production. This amplification was selectively reversed by targeting superoxide production from the outer Q-binding site of the ETC complex III. These results suggest that ligand specific modulation of the ETC may act as a rheostat that fine tunes innate immune responses via mitochondrial ROS production. Modulation of these processes may represent a novel mechanism to modulate the nature as well as the magnitude of antiviral vs. inflammatory immune responses.
Climate change over the Mediterranean and current destruction of marine ecosystem
Authors: Kim Go-Un , Seo Kyong-Hwan , Chen Deliang
Published: December 2019

The Mediterranean is one of the most vulnerable regions to climate change and its summer climate is known to be affected by the South Asian summer monsoon (SASM) through the monsoon–desert teleconnection. In future, rainfall is expected to increase not only over the SASM area but also over the East Asian summer monsoon (EASM) and equatorial Atlantic regions. Here we show that the remote forcing regions affect the Mediterranean climate in the future. A subset of CMIP5 climate simulations exhibits an increase in the descending motion over the Western Mediterranean in the future. This strengthened subsidence comes from the SASM, EASM, and Atlantic forcings: the SASM and EASM heating induces the Gill-type Rossby wave response, and the Atlantic forcing causes the northeastward wave energy propagation. The sea surface temperature change over the Western Mediterranean is consistent with the subsidence change both in the future and in the recent decades. The chlorophyll-a concentration and fisheries landings have decreased in the recent period along with sea surface temperature warming. Our results suggest that special attention is required to conserve the marine ecosystem in the Mediterranean as climate warms.
Antioxidant, Anticancer Activity and Phytochemical Analysis of Green Algae, Chaetomorpha Collected from the Arabian Gulf
Authors: Haq Samina Hyder , Al-Ruwaished Ghaida , Al-Mutlaq Moudhi Abdullah , Naji Sundus Ali , Al-Mogren Maha , Al-Rashed Sarah , Ain Qura Tul , Al-Amro Abir Abdullah , Al-Mussallam Adnan
Published: December 2019

Seaweeds are a group of marine multicellular algae; the presence of antioxidant phytochemical constituents in Seaweed Chaetomorpha sp. extracts has received attention for their role in the prevention of human diseases. This study explores the phytochemical constituents, antioxidant, and anticancer properties of the Cladophoraceae, Chaetomorpha sp. Energy dispersive x-ray spectroscopy (EDX), and Gas chromatography-mass spectrometry (GC/MS) were performed to study the chemical structure and chemical formula. Different concentrations of ethanol and aqueous extracts of Chaetomorpha were used to estimate antioxidant activity by 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging activity and total flavonoid, phenolic, and tannins content assays. Anti-tumor activity against breast cancer cell lines (MCF-7 and MDA-MB-231) was assessed by 3-(4,5-Dimethylthiazol-2-cyl)-2,5-Diphenyltetrazolium Bromide (MTT) assay. The EDX analysis indicated the presence of oxygen, silicon, and calcium as dominant elements. Antioxidant assays indicated that the ethanol extracts of Chaetomorpha consisted of a total of 189.14 ± 0.99 mg QE/g flavonoid content, 21.92 ± 0.43 mg GAE/g phenolic content and 21.81 ± 0.04 mg GAE/g tannins content. The DPPH radical scavenging assay exhibited higher antioxidant activity IC50 (9.41 ± 0.54 mg/mL) in the ethanol extract. Moreover, it showed high anticancer activity by growth inhibition in the MDA-MB-231 breast cancer cell line and low IC50 (225.18 ± 0.61 µg/mL). GC/MS analysis revealed the presence of Dichloracetic acid (DCA) as the active antitumor constituent of Chaetomorpha sp.; other anticancer compounds identified were Oximes and L-α-Terpinol. The results revealed that the type of Chaetomorpha sp. studied here possesses very unique and novel constituents and active potent antitumor chemical constituents and it can act as a promising antioxidant and anticancer agent for future applications in pharmaceutical industries.
Population reference and healthy standard blood pressure range charts in pregnancy: findings from the Born in Bradford cohort study
Authors: Santorelli Gillian , Lawlor Debbie A. , West Jane , Tuffnell Derek , Farrar Diane
Published: December 2019

Women who develop gestational hypertension are at increased risk of adverse perinatal and longer-term outcomes. Reference charts may aid early detection of raised blood pressure (BP) and in doing so reduce adverse outcome risk. We used repeated BP measurements to produce ‘reference’ (whole population) and ‘standard’ (healthy pregnancies only) gestational-age-specific BP charts for all pregnant women (irrespective of ethnicity) and for White British (WB) and Pakistani (P) women. We included 9218 women recruited to the Born in Bradford study with 74,770 BPs. 19% of the whole population, 11% and 25% of WB and P women respectively were defined as healthy pregnancies. For reference and standard charts, for all women and each ethnic group, SBP/DBP at 12 and 20 weeks gestation was similar before rising at 37 weeks. DBP/SBP of reference charts for all women and for each ethnic group were higher than those of the corresponding standard charts. Compared to WB, P women had lower SBP/DBP at 12, 20 and 37 weeks gestation. To conclude; maternal population BP reference charts are higher compared to standard charts (healthy pregnancies) and are influenced by ethnicity.
Tempo and mode of allopatric divergence in the weakly electric fish Sternopygus dariensis in the Isthmus of Panama
Authors: Aguilar Celestino , Miller Matthew J. , Loaiza Jose R. , González Rigoberto , Krahe Rüdiger , De León Luis F.
Published: December 2019

Spatial isolation is one of the main drivers of allopatric speciation, but the extent to which spatially-segregated populations accumulate genetic differences relevant to speciation is not always clear. We used data from ultraconserved elements (UCEs) and whole mitochondrial genomes (i.e., mitogenomes) to explore genetic variation among allopatric populations of the weakly electric fish Sternopygus dariensis across the Isthmus of Panama. We found strong genetic divergence between eastern and western populations of S. dariensis. Over 77% of the UCE loci examined were differentially fixed between populations, and these loci appear to be distributed across the species’ genome. Population divergence occurred within the last 1.1 million years, perhaps due to global glaciation oscillations during the Pleistocene. Our results are consistent with a pattern of genetic differentiation under strict geographic isolation, and suggest the presence of incipient allopatric species within S. dariensis. Genetic divergence in S. dariensis likely occurred in situ, long after the closure of the Isthmus of Panama. Our study highlights the contribution of spatial isolation and vicariance to promoting rapid diversification in Neotropical freshwater fishes. The study of spatially-segregated populations within the Isthmus of Panama could reveal how genetic differences accumulate as allopatric speciation proceeds.
Sample Size Requirements of Glaucoma Clinical Trials When Using Combined Optical Coherence Tomography and Visual Field Endpoints
Authors: Wu Zhichao , Medeiros Felipe A.
Published: December 2019

Glaucoma clinical trials using visual field (VF) endpoints currently require large sample sizes because of the slowly-progressive nature of this disease. We sought to examine whether the combined use of VF testing and non-invasive optical coherence tomography (OCT) imaging of the neuroretinal tissue could improve the feasibility of such trials. To examine this, we included 192 eyes of 121 glaucoma participants seen at ≥5 visits over a 2-year period to extract real-world estimates of the rates of change and variability of VF and OCT imaging measurements for computer simulations to obtain sample size estimates. We observed that the combined use of VF and OCT endpoints led to a 31–33% reduction in sample size requirements compared to using VF endpoints alone for various treatment effect sizes. For example, 189 participants would be required per group to detect a 30% treatment effect with 90% power with combined VF and OCT endpoints, whilst 276 and 285 participants would be required when using VF and OCT endpoints alone respectively. The combined use of OCT and VF endpoints thus has the potential to effectively improve the feasibility of future glaucoma clinical trials.