bluuebunny/crossref_metadata_2025 huggingface dataset:
Insights Into the Origins and Compositions of Mantle Plumes: A Comparison of Galápagos and Hawai'i
Authors: Harpp Karen S. , Weis Dominique
Published: June 2020

The Galápagos and Hawai'i archipelagos are formed by mantle plumes originating at the large low shear velocity province (LLSVP) boundary. We report new high‐precision Pb, Sr, Nd, and Hf isotopic analyses on 83 Galápagos samples and compare them with those of Hawai'i. The data confirm that like Hawai'i, Galápagos is a bilaterally asymmetric plume whose compositional boundary trends NW‐SE. On their northeast sides, the plumes share a common source, Pacific lower mantle, whose intermediate isotopic signature may be common to many plumes. The Hawaiian and Galápagos plumes' southwestern sides are anchored in the Pacific LLSVP and are compositionally distinct; in Hawai'i, Loa trend lavas reflect contributions from the EM1 mantle end‐member, whereas in Galápagos, HIMU is dominant, suggesting that the Pacific LLSVP is compositionally heterogeneous and includes different types of recycled material. Furthermore, the surficial expression of a bilaterally asymmetric plume is strongly influenced by its tectonic setting: (a) Thick Hawaiian lithosphere supports a volcano evolution process, including rejuvenated volcanism, whereas the thin Galápagos lithosphere inhibits Hawai'i‐style rejuvenated‐stage eruptive activity, instead causing extended, widespread volcanism; (b) the proximity of the Galápagos to a mid‐ocean ridge causes entrainment of the depleted upper mantle, overwhelming depleted material intrinsic to the plume and affecting volcanoes' magmatic architecture; and (c) the geometric relationship between the LLSVP boundary and plate motion influences geochemical patterns at the surface. Thus, despite striking differences in surficial expression of the Galápagos and Hawai'i plumes, they share a common generation mechanism, supplied by the Pacific LLSVP and the lower mantle.
Modeling the Dynamics of Small‐Scale River and Creek Plumes in Tidal Waters
Authors: Basdurak N. B. , Largier J. L. , Nidzieko N. J.
Published: June 2020

The fate of discharges from small rivers and mountainous streams are little studied relative to the dynamics of large river plumes. Flows from small watersheds are episodic, forming transient low‐salinity surface plumes that vary tidally due to interaction of outflow inertia with buoyancy and ambient tidal currents. An implementation of the Regional Ocean Modeling System (ROMS v3.0), a three‐dimensional, free‐surface, terrain‐following numerical model, is applied to small river outflows (≤10 m3 s−1) entering a tidal ocean, where they form small plumes of scale ~103 m or smaller. Analysis of the momentum balance points to three distinct zones: (i) an inertia‐driven near field, where advection, pressure gradient, and vertical stress divergence control the plume dynamics, (ii) a buoyancy‐driven midfield, where pressure gradient, lateral stress divergence, and rotational accelerations are dominant, and (iii) an advective far field, where local accelerations induced by ambient tidal currents determine the fate of the river/estuarine discharge. The response of these small tidal plumes to different buoyancy forcing and outflow rate is explored. With increasing buoyancy, plumes change from narrow/elongated, bottom‐attached flows to radially expanding, surface‐layer flows. Weak outflow promotes stratification within the plume layer, and with stronger outflow, the plume layer becomes thinner and well‐mixed. When compared with prototypical large‐river plumes in which Coriolis effects are important, (i) in these small plumes, there is no bulge and no coastal buoyancy current, that is, shore contact is mostly absent, and (ii) the plume is strongly influenced by ambient tidal currents, forming a tidal plume that is deflected upcoast/downcoast from the river mouth.
Quaternary Volcanism in Myanmar: A Record of Indian Slab Tearing in a Transition Zone From Oceanic to Continental Subduction
Authors: Zhang L. Y. , Fan W. M. , Ding L. , Ducea M. N. , Pullen A. , Li J. X. , Sun Y. L. , Yue Y. H. , Cai F. L. , Wang C. , Peng T. P. , Sein Kyaing
Published: June 2020

Magmatic processes that occur during the transition from oceanic to continental subduction and collision in orogens are critical and still poorly resolved. Oceanic slab detachment in particular is hypothesized to mark a fundamental change in magmatism and deformation within an orogen. Here, we report on two Quaternary volcanic centers of Myanmar that may help us better understand the process of slab detachment. The Monywa volcanic rocks are composed of low‐K tholeiitic, medium‐K calk‐alkaline, and high‐K to shoshonitic basalts with arc signatures, while the Singu volcanic rocks show geochemical characteristics similar to asthenosphere‐derived magmas. These volcanic rocks have low Os concentrations but extremely high 187Os/186Osi ratios (0.1498 to 0.3824) due to minor (<4%) crustal contamination. The Monywa arc‐like rocks were generated by small degrees of partial melting of subduction‐modified asthenospheric mantle at variable depths from the spinel to garnet stability fields. Distinct from the Monywa arc‐like rocks (87Sr/86Sri = 0.7043 to 0.7047; εNdi = +2.3 to +4.7), the Singu OIB‐like rocks exhibit higher 87Sr/86Sri (0.7056 to 0.7064) and lower εNdi (+0.8 to +1.6) values. These isotopic characteristics indicate a large contribution of an isotopically enriched asthenosphere layer beneath the Burmese microplate, which possibly flowed from SE Tibet. We interpret that this short‐lived, small‐scale, and low‐degree melting Quaternary volcanism in Myanmar was triggered by its position above a slab window resulting from the tearing of the oceanic lithosphere from buoyant continental lithosphere of the Indian plate.
Tungsten Isotope Composition of Archean Crustal Reservoirs and Implications for Terrestrial μ182W Evolution
Authors: Reimink Jesse R. , Mundl‐Petermeier Andrea , Carlson Richard W. , Shirey Steven B. , Walker Richard J. , Pearson D. Graham
Published: June 2020

The evolution of Earth's major geochemical reservoirs over ~4.5 × 109 years remains a matter of intense study. Geochemical tools in the form of short‐lived radionuclide isotope ratios (142Nd/144Nd and 182W/184W) have expanded our understanding of the geochemical variability in both the modern and ancient Earth. Here, we present 142Nd/144Nd and 182W/184W data from a suite of rocks from the Slave craton that formed over a 1.1 × 109 year time span in the Archean. The rocks have consistently high 182W/184W, yet 142Nd/144Nd that is lower than bulk mantle and increased over time. The declining variability in 142Nd/144Nd with time likely reflects the homogenization of compositional heterogeneities in the silicate Earth that were initially created by differentiation events that occurred prior to 4.2 Ga. The elevated 182W/184W recorded in the Slave samples help refine models for the broader W‐isotope evolution of the silicate Earth. Globally, the Archean mantle that formed continental crust was dominated by 182W/184W elevated by some 10–15 ppm compared to the value for the modern upper mantle. The Slave craton lacks significant volumes of komatiite yet has elevated 182W/184W until 2.9 Ga. This observation, combined with the presence of other komatiite suites that have low 182W/184W, suggests that deep‐seated sources contributed low 182W/184W in the Archean Earth. The regional variability in 182W/184W may be explained by invoking chemical and/or isotopic exchange between a well‐mixed silicate Earth and the core or a portion of the lower mantle whose W‐isotope composition has been influenced by interaction with the core.
Impact of Shoaling Ocean Surface Waves on Wind Stress and Drag Coefficient in Coastal Waters: 2. Tropical Cyclones
Authors: Chen Xuanyu , Ginis Isaac , Hara Tetsu
Published: June 2020

This study investigates the impacts of shoaling waves on the wind stress and drag coefficient (Cd) in coastal waters during tropical cyclone (TC) landfall. Numerical experiments are conducted using idealized TCs with two intensities, Category 1 and 5, and two translation speeds, 5 and 10 m/s, propagating toward and normal to the shoreline over two bottom slopes, 1:200 and 1:2000. The wave spectra are simulated using the WAVEWATCH III wave model. The unresolved high‐frequency spectral tail is parameterized as a function of wind speed, and the full wave spectrum is used to calculate the wind stress and drag coefficient. Our results show that the sea state dependence of wind stress magnitude (or Cd) is significantly increased in shallow water at a given wind speed. Compared to its deep‐water value, Cd is enhanced in the right (due to shoaling fetch‐dependent waves) and in the left (due to shoaling opposing‐wind swells) TC quadrants. However, Cd is reduced in the front/rear quadrants due to weaker wind seas. The misalignment between the wind stress and wind speed directions is enhanced in shallow water. In general, the shoaling wave effects on the wind stress and Cd are much stronger on steeper bottom slopes and in faster moving storms.
Radiotherapy targeting cancer stem cells “awakens” them to induce tumour relapse and metastasis in oral cancer
Authors: Liu Yangfan , Yang Miao , Luo Jingjing , Zhou Hongmei
Published: June 2020

Radiotherapy is one of the most common treatments for oral cancer. However, in the clinic, recurrence and metastasis of oral cancer occur after radiotherapy, and the underlying mechanism remains unclear. Cancer stem cells (CSCs), considered the “seeds” of cancer, have been confirmed to be in a quiescent state in most established tumours, with their innate radioresistance helping them survive more easily when exposed to radiation than differentiated cancer cells. There is increasing evidence that CSCs play an important role in recurrence and metastasis post-radiotherapy in many cancers. However, little is known about how oral CSCs cause tumour recurrence and metastasis post-radiotherapy. In this review article, we will first summarise methods for the identification of oral CSCs and then focus on the characteristics of a CSC subpopulation induced by radiation, hereafter referred to as “awakened” CSCs, to highlight their response to radiotherapy and potential role in tumour recurrence and metastasis post-radiotherapy as well as potential therapeutics targeting CSCs. In addition, we explore potential therapeutic strategies targeting these “awakened” CSCs to solve the serious clinical challenges of recurrence and metastasis in oral cancer after radiotherapy.
Elevated FMR1-mRNA and lowered FMRP – A double-hit mechanism for psychiatric features in men with FMR1 premutations
Authors: Schneider Andrea , Winarni Tri Indah , Cabal-Herrera Ana María , Bacalman Susan , Gane Louise , Hagerman Paul , Tassone Flora , Hagerman Randi
Published: June 2020

Fragile X syndrome (FXS) is caused by a full mutation of the FMR1 gene (>200 CGG repeats and subsequent methylation), such that there is little or no FMR1 protein (FMRP) produced, leading to intellectual disability (ID). Individuals with the premutation allele (55–200 CGG repeats, generally unmethylated) have elevated FMR1 mRNA levels, a consequence of enhanced transcription, resulting in neuronal toxicity and a spectrum of premutation-associated disorders, including the neurodegenerative disorder fragile X-associated tremor/ataxia syndrome (FXTAS). Here we described 14 patients who had both lowered FMRP and elevated FMR1 mRNA levels, representing dual mechanisms of clinical involvement, which may combine features of both FXS and FXTAS. In addition, the majority of these cases show psychiatric symptoms, including bipolar disorder, and/or psychotic features, which are rarely seen in those with just FXS.
Optimization of adeno-associated viral vector-mediated transduction of the corticospinal tract: comparison of four promoters
Authors: Nieuwenhuis Bart , Haenzi Barbara , Hilton Sam , Carnicer-Lombarte Alejandro , Hobo Barbara , Verhaagen Joost , Fawcett James W.
Published: June 2020

Adeno-associated viral vectors are widely used as vehicles for gene transfer to the nervous system. The promoter and viral vector serotype are two key factors that determine the expression dynamics of the transgene. A previous comparative study has demonstrated that AAV1 displays efficient transduction of layer V corticospinal neurons, but the optimal promoter for transgene expression in corticospinal neurons has not been determined yet. In this paper, we report a side-by-side comparison between four commonly used promoters: the short CMV early enhancer/chicken β actin (sCAG), human cytomegalovirus (hCMV), mouse phosphoglycerate kinase (mPGK) and human synapsin (hSYN) promoter. Reporter constructs with each of these promoters were packaged in AAV1, and were injected in the sensorimotor cortex of rats and mice in order to transduce the corticospinal tract. Transgene expression levels and the cellular transduction profile were examined after 6 weeks. The AAV1 vectors harbouring the hCMV and sCAG promoters resulted in transgene expression in neurons, astrocytes and oligodendrocytes. The mPGK and hSYN promoters directed the strongest transgene expression. The mPGK promoter did drive expression in cortical neurons and oligodendrocytes, while transduction with AAV harbouring the hSYN promoter resulted in neuron-specific expression, including perineuronal net expressing interneurons and layer V corticospinal neurons. This promoter comparison study contributes to improve transgene delivery into the brain and spinal cord. The optimized transduction of the corticospinal tract will be beneficial for spinal cord injury research.
Fasting mimicking diet as an adjunct to neoadjuvant chemotherapy for breast cancer in the multicentre randomized phase 2 DIRECT trial
Authors: de Groot Stefanie , Lugtenberg Rieneke T. , Cohen Danielle , Welters Marij J. P. , Ehsan Ilina , Vreeswijk Maaike P. G. , Smit Vincent T. H. B. M. , de Graaf Hiltje , Heijns Joan B. , Portielje Johanneke E. A. , van de Wouw Agnes J. , Imholz Alex L. T. , Kessels Lonneke W. , Vrijaldenhoven Suzan , Baars Arnold , Kranenbarg Elma Meershoek-Klein , Carpentier Marjolijn Duijm-de , Putter Hein , van der Hoeven Jacobus J. M. , Nortier Johan W. R. , Longo Valter D. , Pijl Hanno , Kroep Judith R. ,   Dutch Breast Cancer Research Group (BOOG), de Graaf Hiltje , Heijns Joan B. , Portielje Johanneke E. A. , van de Wouw Agnes J. , Imholz Alex L. T. , Kessels Lonneke W. , Vrijaldenhoven Suzan , Baars Arnold , Göker Emine , Pas Anke J. M. , Honkoop Aafke H. , van Leeuwen-Stok A. Elise , Kroep Judith R.
Published: June 2020

Short-term fasting protects tumor-bearing mice against the toxic effects of chemotherapy while enhancing therapeutic efficacy. We randomized 131 patients with HER2-negative stage II/III breast cancer, without diabetes and a BMI over 18 kg m−2, to receive either a fasting mimicking diet (FMD) or their regular diet for 3 days prior to and during neoadjuvant chemotherapy. Here we show that there was no difference in toxicity between both groups, despite the fact that dexamethasone was omitted in the FMD group. A radiologically complete or partial response occurs more often in patients using the FMD (OR 3.168, P = 0.039). Moreover, per-protocol analysis reveals that the Miller&Payne 4/5 pathological response, indicating 90–100% tumor-cell loss, is more likely to occur in patients using the FMD (OR 4.109, P = 0.016). Also, the FMD significantly curtails chemotherapy-induced DNA damage in T-lymphocytes. These positive findings encourage further exploration of the benefits of fasting/FMD in cancer therapy. Trial number: NCT02126449.
Efficient self-assembly of heterometallic triangular necklace with strong antibacterial activity
Authors: Wu Gui-Yuan , Shi Xueliang , Phan Hoa , Qu Hang , Hu Yi-Xiong , Yin Guang-Qiang , Zhao Xiao-Li , Li Xiaopeng , Xu Lin , Yu Qilin , Yang Hai-Bo
Published: June 2020

Sophisticated mechanically interlocked molecules (MIMs) with interesting structures, properties and applications have attracted great interest in the field of supramolecular chemistry. We herein report a highly efficient self-assembly of heterometallic triangular necklace 1 containing Cu and Pt metals with strong antibacterial activity. Single-crystal X-ray analysis shows that the finely arranged triangular necklace 1 has two racemic enantiomers in its solid state with intriguing packing motif. The superior antibacterial activity of necklace 1 against both standard and clinically drug-resistant pathogens implies that the presence of Cu(I) center and platinum(II) significantly enhance the bacterium-binding/damaging activity, which is mainly attributed to the highly positively charged nature, the possible synergistic effect of heterometals in the necklace, and the improved stability in culture media. This work clearly discloses the structure-property relationships that the existence of two different metal centers not only facilitates successful construction of heterometallic triangular necklace but also endows it with superior nuclease properties and antibacterial activities.
Single-particle imaging of stress-promoters induction reveals the interplay between MAPK signaling, chromatin and transcription factors
Authors: Wosika Victoria , Pelet Serge
Published: June 2020

Precise regulation of gene expression in response to environmental changes is crucial for cell survival, adaptation and proliferation. In eukaryotic cells, extracellular signal integration is often carried out by Mitogen-Activated Protein Kinases (MAPK). Despite a robust MAPK signaling activity, downstream gene expression can display a great variability between single cells. Using a live mRNA reporter, here we monitor the dynamics of transcription in Saccharomyces cerevisiae upon hyper-osmotic shock. We find that the transient activity of the MAPK Hog1 opens a temporal window where stress-response genes can be activated. We show that the first minutes of Hog1 activity are essential to control the activation of a promoter. Chromatin repression on a locus slows down this transition and contributes to the variability in gene expression, while binding of transcription factors increases the level of transcription. However, soon after Hog1 activity peaks, negative regulators promote chromatin closure of the locus and transcription progressively stops.
Semiconductive microporous hydrogen-bonded organophosphonic acid frameworks
Authors: Tholen Patrik , Peeples Craig A. , Schaper Raoul , Bayraktar Ceyda , Erkal Turan Selman , Ayhan Mehmet Menaf , Çoşut Bünyemin , Beckmann Jens , Yazaydin A. Ozgur , Wark Michael , Hanna Gabriel , Zorlu Yunus , Yücesan Gündoğ
Published: June 2020

Herein, we report a semiconductive, proton-conductive, microporous hydrogen-bonded organic framework (HOF) derived from phenylphosphonic acid and 5,10,15,20‐tetrakis[p‐phenylphosphonic acid] porphyrin (GTUB5). The structure of GTUB5 was characterized using single crystal X-ray diffraction. A narrow band gap of 1.56 eV was extracted from a UV-Vis spectrum of pure GTUB5 crystals, in excellent agreement with the 1.65 eV band gap obtained from DFT calculations. The same band gap was also measured for GTUB5 in DMSO. The proton conductivity of GTUB5 was measured to be 3.00 × 10−6 S cm−1at 75 °C and 75% relative humidity. The surface area was estimated to be 422 m2 g−1from grand canonical Monte Carlo simulations. XRD showed that GTUB5 is thermally stable under relative humidities of up to 90% at 90 °C. These findings pave the way for a new family of organic, microporous, and semiconducting materials with high surface areas and high thermal stabilities.
Evidence of shock-compressed stishovite above 300 GPa
Authors: Schoelmerich Markus O. , Tschentscher Thomas , Bhat Shrikant , Bolme Cindy A. , Cunningham Eric , Farla Robert , Galtier Eric , Gleason Arianna E. , Harmand Marion , Inubushi Yuichi , Katagiri Kento , Miyanishi Kohei , Nagler Bob , Ozaki Norimasa , Preston Thomas R. , Redmer Ronald , Smith Ray F. , Tobase Tsubasa , Togashi Tadashi , Tracy Sally J. , Umeda Yuhei , Wollenweber Lennart , Yabuuchi Toshinori , Zastrau Ulf , Appel Karen
Published: June 2020

SiO2 is one of the most fundamental constituents in planetary bodies, being an essential building block of major mineral phases in the crust and mantle of terrestrial planets (1–10 ME). Silica at depths greater than 300 km may be present in the form of the rutile-type, high pressure polymorph stishovite (P42/mnm) and its thermodynamic stability is of great interest for understanding the seismic and dynamic structure of planetary interiors. Previous studies on stishovite via static and dynamic (shock) compression techniques are contradictory and the observed differences in the lattice-level response is still not clearly understood. Here, laser-induced shock compression experiments at the LCLS- and SACLA XFEL light-sources elucidate the high-pressure behavior of stishovite on the lattice-level under in situ conditions on the Hugoniot to pressures above 300 GPa. We find stishovite is still (meta-)stable at these conditions, and does not undergo any phase transitions. This contradicts static experiments showing structural transformations to the CaCl2, α-PbO2 and pyrite-type structures. However, rate-limited kinetic hindrance may explain our observations. These results are important to our understanding into the validity of EOS data from nanosecond experiments for geophysical applications.
Risk factors for African swine fever incursion in Romanian domestic farms during 2019
Authors: Boklund A. , Dhollander S. , Chesnoiu Vasile T. , Abrahantes J. C. , Bøtner A. , Gogin A. , Gonzalez Villeta L. C. , Gortázar C. , More S. J. , Papanikolaou A. , Roberts H. , Stegeman A. , Ståhl K. , Thulke H. H. , Viltrop A. , Van der Stede Y. , Mortensen S.
Published: June 2020

African swine fever (ASF) entered Georgia in 2007 and the EU in 2014. In the EU, the virus primarily spread in wild boar (Sus scrofa) in the period from 2014–2018. However, from the summer 2018, numerous domestic pig farms in Romania were affected by ASF. In contrast to the existing knowledge on ASF transmission routes, the understanding of risk factors and the importance of different transmission routes is still limited. In the period from May to September 2019, 655 Romanian pig farms were included in a matched case-control study investigating possible risk factors for ASF incursion in commercial and backyard pig farms. The results showed that close proximity to outbreaks in domestic farms was a risk factor in commercial as well as backyard farms. Furthermore, in backyard farms, herd size, wild boar abundance around the farm, number of domestic outbreaks within 2 km around farms, short distance to wild boar cases and visits of professionals working on farms were statistically significant risk factors. Additionally, growing crops around the farm, which could potentially attract wild boar, and feeding forage from ASF affected areas to the pigs were risk factors for ASF incursion in backyard farms.
Hyaloid vasculature and mmp2 activity play a role during optic fissure fusion in zebrafish
Authors: Weaver Megan L. , Piedade Warlen P. , Meshram Nishita N. , Famulski Jakub K.
Published: June 2020

Vertebrate retinal development requires timely and precise fusion of the optic fissure (OF). Failure of this event leads to congenital vision impairment in the form of coloboma. Recent studies have suggested hyaloid vasculature to be involved in OF fusion. In order to examine this link, we analyzed OF fusion and hyaloid vasculogenesis in the zebrafish pax2a noi mutant line. We first determined that pax2a−/− embryos fail to accumulate F-actin in the OF prior to basement membrane (BM) degradation. Furthermore, using 3D and live imaging we observed reduced OF hyaloid vascularization in pax2a−/− embryos. When examining the connection between pax2a loss of function and hyaloid vasculature, we observed significant reduction of talin1 expression, a regulator of hyaloid vasculature. In addition, cranial VEGF expression was found to be reduced in pax2a−/− embryos. Pharmacological inhibition of VEGF signaling phenocopied the pax2a−/− vasculature, F-actin and BM degradation phenotypes. Lastly, we determined that OF associated hyaloid vasculature is a source of mmp2, mmp14a and mmp14b expression and showed that mmp2 is functionally necessary for degradation of OF BM. Taken together we propose a pax2a driven mechanism that ensures proper and timely hyaloid vasculature invasion of the OF in order to facilitate availability of the BM remodeler mmp2.
Conditioning of Superconductive Properties in Graph-Shaped Reticles
Authors: Lucci M. , Cassi D. , Merlo V. , Russo R. , Salina G. , Cirillo M.
Published: June 2020

We report on phenomena observed in planar integrated networks obtained connecting superconducting island by Josephson tunnel junctions. These networks, identifiable as tree-like graphs, have branches consisting of series arrays of Josephson junctions which can be individually current biased and characterized. Both Josephson supercurrents and gap parameters of the arrays embedded in the graph structures display properties significantly different from those of “reference” arrays fabricated on the same chips and having identical geometrical shape. The temperature and magnetic field dependencies of the Josephson current of the embedded arrays both show a singular behavior when a critical value is reached by the Josephson characteristic energy. The gap parameter of the junctions generating the embedded arrays is higher than that of the junctions forming the reference geometrical arrays.
Asymmetry between Activators and Deactivators in Functional Protein Networks
Authors: Tareen Ammar , Wingreen Ned S. , Mukhopadhyay Ranjan
Published: June 2020

Are “turn-on” and “turn-off” functions in protein-protein interaction networks exact opposites of each other? To answer this question, we implement a minimal model for the evolution of functional protein-interaction networks using a sequence-based mutational algorithm, and apply the model to study neutral drift in networks that yield oscillatory dynamics. We study the roles of activators and deactivators, two core components of oscillatory protein interaction networks, and find a striking asymmetry in the roles of activating and deactivating proteins, where activating proteins tend to be synergistic and deactivating proteins tend to be competitive.
Heritability and genome-wide association of swine gut microbiome features with growth and fatness parameters
Authors: Bergamaschi Matteo , Maltecca Christian , Schillebeeckx Constantino , McNulty Nathan P. , Schwab Clint , Shull Caleb , Fix Justin , Tiezzi Francesco
Published: June 2020

Despite recent efforts to characterize longitudinal variation in the swine gut microbiome, the extent to which a host’s genome impacts the composition of its gut microbiome is not yet well understood in pigs. The objectives of this study were: i) to identify pig gut microbiome features associated with growth and fatness, ii) to estimate the heritability of those features, and, iii) to conduct a genome-wide association study exploring the relationship between those features and single nucleotide polymorphisms (SNP) in the pig genome. A total of 1,028 pigs were characterized. Animals were genotyped with the Illumina PorcineSNP60 Beadchip. Microbiome samples from fecal swabs were obtained at weaning (Wean), at mid-test during the growth trial (MidTest), and at the end of the growth trial (OffTest). Average daily gain was calculated from birth to week 14 of the growth trial, from weaning to week 14, from week 14 to week 22, and from week 14 to harvest. Backfat and loin depth were also measured at weeks 14 and 22. Heritability estimates (±SE) of Operational Taxonomic Units ranged from 0.025 (±0.0002) to 0.139 (±0.003), from 0.029 (±0.003) to 0.289 (±0.004), and from 0.025 (±0.003) to 0.545 (±0.034) at Wean, MidTest, and OffTest, respectively. Several SNP were significantly associated with taxa at the three time points. These SNP were located in genomic regions containing a total of 68 genes. This study provides new evidence linking gut microbiome composition with growth and carcass traits in swine, while also identifying putative host genetic markers associated with significant differences in the abundance of several prevalent microbiome features.
State-space models reveal a continuing elephant poaching problem in most of Africa
Authors: Schlossberg Scott , Chase Michael J. , Gobush Kathleen S. , Wasser Samuel K. , Lindsay Keith
Published: June 2020

The most comprehensive data on poaching of African elephants comes from the Monitoring the Illegal Killing of Elephants (MIKE) program, which reports numbers of illegally killed carcasses encountered by rangers. Recent studies utilizing MIKE data have reported that poaching of African elephants peaked in 2011 and has been decreasing through 2018. Closer examination of these studies, however, raises questions about the conclusion that poaching is decreasing throughout the continent. To provide more accurate information on trends in elephant poaching, we analyzed MIKE data using state-space models. State-space models account for missing data and the error inherent when sampling carcasses. Using the state-space model, for 2011–2018, we found no significant temporal trends in rates of illegal killing for Southern, Central and Western Africa. Only in Eastern Africa have poaching rates decreased substantially since 2011. For Africa as a whole, poaching did decline for 2011–2018, but the decline was entirely due to Eastern African sites. Our results suggest that poaching for ivory has not diminished across most of Africa since 2011. Continued vigilance and anti-poaching efforts will be necessary to combat poaching and to conserve African elephants.
FACS-Based Functional Protein Screening via Microfluidic Co-encapsulation of Yeast Secretor and Mammalian Reporter Cells
Authors: Yanakieva Desislava , Elter Adrian , Bratsch Jens , Friedrich Karlheinz , Becker Stefan , Kolmar Harald
Published: June 2020

In this study, we present a straightforward approach for functional cell-based screening by co-encapsulation of secretor yeast cells and reporter mammalian cells in millions of individual agarose-containing microdroplets. Our system is compatible with ultra-high-throughput selection utilizing standard fluorescence-activated cell sorters (FACS) without need of extensive adaptation and optimization. In a model study we co-encapsulated murine interleukin 3 (mIL-3)-secreting S. cerevisiae cells with murine Ba/F3 reporter cells, which express green fluorescent protein (GFP) upon stimulation with mIL-3, and could observe specific and robust induction of fluorescence signal compared to a control with yeast cells secreting a non-functional mIL-3 mutant. We demonstrate the successful enrichment of activating mIL-3 wt-secreting yeast cells from a 1:10,000 dilution in cells expressing the inactive cytokine variant by two consecutive cycles of co-encapsulation and FACS. This indicates the suitability of the presented strategy for functional screening of high-diversity yeast-based libraries and demonstrates its potential for the efficient isolation of clones secreting bioactive recombinant proteins.
β-carboline chemical signals induce reveromycin production through a LuxR family regulator in Streptomyces sp. SN-593
Authors: Panthee Suresh , Kito Naoko , Hayashi Teruo , Shimizu Takeshi , Ishikawa Jun , Hamamoto Hiroshi , Osada Hiroyuki , Takahashi Shunji
Published: June 2020

Actinomycetes bacteria produce diverse bioactive molecules that are useful as drug seeds. To improve their yield, researchers often optimize the fermentation medium. However, exactly how the extracellular chemicals present in the medium activate secondary metabolite gene clusters remains unresolved. BR-1, a β-carboline compound, was recently identified as a chemical signal that enhanced reveromycin A production in Streptomyces sp. SN-593. Here we show that BR-1 specifically bound to the transcriptional regulator protein RevU in the reveromycin A biosynthetic gene cluster, and enhanced RevU binding to its promoter. RevU belongs to the LuxR family regulator that is widely found in bacteria. Interestingly, BR-1 and its derivatives also enhanced the production of secondary metabolites in other Streptomyces species. Although LuxR-N-acyl homoserine lactone systems have been characterized in Gram-negative bacteria, we revealed LuxR-β-carboline system in Streptomyces sp. SN-593 for the production of secondary metabolites. This study might aid in understanding hidden chemical communication by β-carbolines.
Bee venom-derived antimicrobial peptide melectin has broad-spectrum potency, cell selectivity, and salt-resistant properties
Authors: Ko Su Jin , Park Eunji , Asandei Alina , Choi Jee-Young , Lee Seung-Chul , Seo Chang Ho , Luchian Tudor , Park Yoonkyung
Published: June 2020

Antimicrobial peptides have attracted attention as alternatives to conventional antibiotics. Previously, a novel antimicrobial peptide, melectin, consisting of 18 amino acids was isolated from the venom of a bee, Melecta albifrons. Here, we investigated the antibacterial activity of melectin against drug-resistant bacteria. Melectin showed broad-spectrum antimicrobial activity but low cytotoxicity and no hemolytic activity. Melectin maintained its antimicrobial activity at physiological salt concentrations. Melectin is an α-helical structure that binds to the bacterial membrane via electrostatic interactions and kills bacteria in a short time by bacterial membrane targeting. Collectively, our results suggest that melectin has antibacterial activity and anti-inflammatory activity.
Author Correction: Kinesiologist-guided functional exercise in addition to intradialytic cycling program in end-stage kidney disease patients: a randomised controlled trial
Authors: Bogataj Špela , Pajek Jernej , Ponikvar Jadranka Buturović , Hadžić Vedran , Pajek Maja
Published: June 2020

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
Evaluation of deep convolutional neural networks for automatic classification of common maternal fetal ultrasound planes
Authors: Burgos-Artizzu Xavier P. , Coronado-Gutiérrez David , Valenzuela-Alcaraz Brenda , Bonet-Carne Elisenda , Eixarch Elisenda , Crispi Fatima , Gratacós Eduard
Published: June 2020

The goal of this study was to evaluate the maturity of current Deep Learning classification techniques for their application in a real maternal-fetal clinical environment. A large dataset of routinely acquired maternal-fetal screening ultrasound images (which will be made publicly available) was collected from two different hospitals by several operators and ultrasound machines. All images were manually labeled by an expert maternal fetal clinician. Images were divided into 6 classes: four of the most widely used fetal anatomical planes (Abdomen, Brain, Femur and Thorax), the mother’s cervix (widely used for prematurity screening) and a general category to include any other less common image plane. Fetal brain images were further categorized into the 3 most common fetal brain planes (Trans-thalamic, Trans-cerebellum, Trans-ventricular) to judge fine grain categorization performance. The final dataset is comprised of over 12,400 images from 1,792 patients, making it the largest ultrasound dataset to date. We then evaluated a wide variety of state-of-the-art deep Convolutional Neural Networks on this dataset and analyzed results in depth, comparing the computational models to research technicians, which are the ones currently performing the task daily. Results indicate for the first time that computational models have similar performance compared to humans when classifying common planes in human fetal examination. However, the dataset leaves the door open on future research to further improve results, especially on fine-grained plane categorization.
Orientation control of ideal blue phase photonic crystals
Authors: Otón Eva , Yoshida Hiroyuki , Morawiak Przemysław , Strzeżysz Olga , Kula Przemysław , Ozaki Masanori , Piecek Wiktor
Published: June 2020

Three-dimensional (3D) photonic crystals like Blue Phases, self-assemble in highly organized structures with a sub-micrometer range periodicity, producing selective Bragg reflections in narrow bands. Current fabrication techniques are emerging at a fast pace, however, manufacturing large 3D monocrystals still remains a challenge, and controlling the crystal orientation of large crystals has not yet been achieved. In this work, we prepared ideal 3D Blue Phase macrocrystals with a controlled crystal orientation. We designed a method to obtain large monocrystals at a desired orientation and lattice size (or reflection wavelength) by adjusting the precursor materials formulation and a simple surface treatment. Moreover, using the same method, it is possible to predict unknown lattice orientations of Blue Phases without resorting to Kossel analysis. Producing large 3D photonic crystals that are also functional tunable structures is likely to have a direct impact on new photonic applications, like microcavity lasers, displays, 3D lasers, or biosensors.
Predictive value of heart rate deceleration capacity on coronary artery lesion in acute phase of Kawasaki disease
Authors: Lu Yaheng , Guo Yonghong , Si Feifei , Chen Tingting , Jin Mei , Wen Yizhou , Wang Xianmin
Published: June 2020

This study was to investigate the correlation of vagal activity with coronary artery lesion (CAL) in Kawasaki disease (KD) children, and assess the predictive value of heart rate deceleration capacity (DC) for CAL in acute phase of KD.50 KD children with CAL, 130 KD children without CAL, 30 children with acute upper respiratory infection and 100 healthy children were recruited and indicators reflecting vagal activity including DC were measstuogram. KD children with CAL showed decreased vagal activity with significantly lower values of DC. DC was negatively correlated with levels of N-terminal pro-brain natriuretic peptide (NT-proBNP) and C-reactive protein (CRP) in KD children. DC was a usable cardiac electrophysiological index to predict CAL in children with KD, with an area under the receiver operating characteristic curve (AUC) of 0.741. The cut-off value of DC for predicting CAL in KD children was 4.37 ms. DC was an independent predictor of CAL in children with KD, evaluated by multiple logistic regression analysis, KD children with DC ≤ 4.37 ms had an increased risk of CAL, with odds ratios (OR) of 5.94. Our study illustrates DC could be used to predict CAL in acute phase of KD.
CD47 is a negative regulator of intestinal epithelial cell self-renewal following DSS-induced experimental colitis
Authors: He Yueqin , Sun Xinlei , Rong Weiwei , Yang Rong , Liang Hongwei , Qi Ying , Li Limin , Zen Ke
Published: June 2020

CD47 deficient mice are resistant to dextran sulfate sodium (DSS)-induced experimental colitis. The underlying mechanism, however, remains incompletely understood. In this study, we characterized the role of CD47 in modulating homeostasis of gastrointestinal tract. We found that CD47 expression in both human and mouse intestinal epithelium was upregulated in colitic condition compared to that under normal condition. In line with this, CD47 deficiency protected mice from DSS-induced colitis. Analysis based on both intestinal organoid and cultured cell assays showed that CD47 deficiency accelerated intestinal epithelial cell proliferation and migration. Mechanistically, western blot and functional assays indicated that CD47 deficiency promoting mouse intestinal epithelial cell proliferation and migration follow cell injury is likely through upregulating expression of four Yamanaka transcriptional factors Oct4, Sox2, Klf4 and c-Myc (OSKM in abbreviation). Our studies thus reveal CD47 as a negative regulator in intestinal epithelial cell renewal during colitis through downregulating OSKM transcriptional factors.
Author Correction: Calcium mishandling in absence of primary mitochondrial dysfunction drives cellular pathology in Wolfram Syndrome
Authors: La Morgia Chiara , Maresca Alessandra , Amore Giulia , Gramegna Laura Ludovica , Carbonelli Michele , Scimonelli Emanuela , Danese Alberto , Patergnani Simone , Caporali Leonardo , Tagliavini Francesca , Del Dotto Valentina , Capristo Mariantonietta , Sadun Federico , Barboni Piero , Savini Giacomo , Evangelisti Stefania , Bianchini Claudio , Valentino Maria Lucia , Liguori Rocco , Tonon Caterina , Giorgi Carlotta , Pinton Paolo , Lodi Raffaele , Carelli Valerio
Published: June 2020

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
Vaccination of koalas during antibiotic treatment for Chlamydia-induced cystitis induces an improved antibody response to Chlamydia pecorum
Authors: Phillips Samuel , Quigley Bonnie L , Olagoke Olusola , Booth Rosemary , Pyne Michael , Timms Peter
Published: June 2020

Chlamydia infection and disease are endemic in free-ranging koalas. Antibiotics remain the front line treatment for Chlamydia in koalas, despite their rates of treatment failure and adverse gut dysbiosis outcomes. A Chlamydia vaccine for koalas has shown promise for replacing antibiotic treatment in mild ocular Chlamydia disease. In more severe disease presentations that require antibiotic intervention, the effect of vaccinating during antibiotic use is not currently known. This study investigated whether a productive immune response could be induced by vaccinating koalas during antibiotic treatment for Chlamydia-induced cystitis. Plasma IgG antibody levels against the C. pecorum major outer membrane protein (MOMP) dropped during antibiotic treatment in both vaccinated and unvaccinated koalas. Post-treatment, IgG levels recovered. The IgG antibodies from naturally-infected, vaccinated koalas recognised a greater proportion of the MOMP protein compared to their naturally-infected, unvaccinated counterparts. Furthermore, peripheral blood mononuclear cell gene expression revealed an up-regulation in genes related to neutrophil degranulation in vaccinated koalas during the first month post-vaccination. These findings show that vaccination of koalas while they are being treated with antibiotics for cystitis can result in the generation of a productive immune response, in the form of increased and expanded IgG production and host response through neutrophil degranulation.
Differences in risk factors for biochemical recurrence after radical prostatectomy stratified by the degree of obesity: Focused on surgical methods
Authors: Suh Jungyo , Yoo Sangjun , Park Juhyun , Cho Min Chul , Jeong Chang Wook , Ku Ja Hyeon , Kwak Cheol , Kim Hyeon Hoe , Jeong Hyeon
Published: June 2020

This study aims to evaluate differences in the risk factors for biochemical recurrence (BCR) for radical prostatectomy stratified by degree of obesity, focusing on the surgical method used. All 3099 patients who underwent radical prostatectomy in two medical centres from January 2008 to March 2018 were retrospectively reviewed. Patients were divided into three groups based on body mass index: ‘normal’, ‘overweight’, and ‘obese’. Risk factors associated with biochemical recurrence were compared between different degrees of obesity. We analysed the contributing risk factors of BCR-free survival using univariate and multivariable Cox hazard models. There were 378 (12.2%) and 1815 (58.6%) patients in the ‘obese’ and ‘overweight’ groups, respectively. Accordingly, 1324 patients underwent retropubic radical prostatectomy (RRP), and 1775 underwent robotic-assisted laparoscopic prostatectomy (RALP). Multivariable analysis showed that patients who underwent RALP had significantly lower BCR free survival in the ‘overweight’ and ‘obese’ groups than those who underwent RRP, with adjusted hazard ratios of 0.75 (95% CI 0.59–0.95, p-value = 0.01) and 0.55 (95% CI 0.33–0.90, p-value = 0.02), respectively. The degree of obesity was not directly associated with BCR-free survival. Robotic prostatectomy showed greater benefits in BCR-free survival than open prostatectomy in the ‘overweight’ and ‘obese’ groups.
High expression of spliced X-Box Binding Protein 1 in lung tumors is associated with cancer aggressiveness and epithelial-to-mesenchymal transition
Authors: Tavernier Quentin , Legras Antoine , Didelot Audrey , Normand Corinne , Gibault Laure , Badoual Cécile , Le Pimpec-Barthes Françoise , Puig Pierre Laurent , Blons Hélène , Pallet Nicolas
Published: June 2020

Proteostasis imbalance is emerging as a major hallmark of cancer, driving tumor growth and aggressiveness. Endoplasmic Reticulum (ER) stress has been documented in most major cancers, and the ability to tolerate persistent ER stress through an effective unfolded protein response enhances cancer cell survival, angiogenesis, metastasis, drug resistance and immunosuppression. The ER stress sensor IRE1α contributes to tumor progression through XBP1 mRNA splicing and regulated IRE1α-dependent decay of mRNA and miRNA. The aim of this study was to perform a molecular characterization of series of tumor samples to explore the impact of intratumoral IRE1 signaling in non-small cell lung cancer characteristics. To monitor IRE1 splicing activity, we adopted a fragment length analysis to detect changes in the length of the XBP1 mRNA before and after splicing as a method for measuring sXBP1 mRNA levels in tumors because sXBP1 mRNA is not probed by standard transcriptomic analyses. We demonstrate for the first time that XBP1 splicing is a valuable marker of lung cancer aggressiveness, and our results support a model in which IRE1 downstream signaling could act as a regulator of Epithelial to Mesenchymal Transition (EMT). Our findings study highlights the role of IRE1α downstream signaling in non-small cell lung cancer and opens a conceptual framework to determine how IRE1α endoribonuclease activity shapes the EMT program.
Metallurgical and Electrochemical Properties of Super Duplex Stainless Steel Clads on Low Carbon Steel Substrate produced with Laser Powder Bed Fusion
Authors: Murkute Pratik , Pasebani Somayeh , Burkan Isgor O.
Published: June 2020

This study aims to improve the corrosion resistance of the low carbon steel by cladding it with super duplex stainless steel using laser powder bed fusion process. Critical process parameters such as laser power, laser scan speed, hatch spacing, and powder layer thickness were optimized to achieve the best possible metallurgical bonding between the clad and the substrate. The evaporative losses experienced during the laser melting process resulted in clad layers with lower chromium content (12–25 wt. %) as compared to 26 wt. % of the feedstock powder. A clad thickness of 65.8 µm was achieved after melting ten 50 µm thick powder layers. The higher cooling rates associated with laser powder bed fusion resulted in fine high aspect ratio columnar grain structures with predominantly ferrite grains; however, widmanstätten austenite needles were observed with increasing laser scan speeds. Increasing scan speed had a negative impact on the thickness, corrosion resistance, and the pitting potential of the clads exposed to 3.5 wt.% NaCl aqueous solution. Clads produced at the lowest scan speeds showed comparable corrosion resistance to rolled and annealed super duplex stainless steel.
Facile synthesis of nanostructured cobalt pigments by Co- A zeolite thermal conversion and its application in porcelain manufacture
Authors: Campanile Assunta , Liguori Barbara , Marino Ottavio , Cavaliere Gennaro , De Bartolomeis Valter Luca , Caputo Domenico
Published: June 2020

An innovative and facile synthesis of cobalt based inorganic pigment was carried out by means of a low energy thermal conversion of a cobalt-exchanged zeolite. The Na-A [LTA] zeolite was used, since it is a low cost and easily available raw material. The ion exchange mechanism allowed to control, at microscopic level, the composition of the zeolitic precursor. Several chromatic effects could be obtained by varying the treatment temperature and/or the cobalt concentration in the contact solution. The reliability of these new zeolite-based pigments was tested in porcelain manufacture, in collaboration with the Institute for the Capodimonte porcelain “Giovanni Caselli”. The developed cobalt pigments were successfully tested either in the porcelain mixture to obtain a coloured product or in the decoration step (such as ingobbio, colored glazes and “third fire decoration”).