bluuebunny/crossref_metadata_2025 huggingface dataset:
Overview of CAST project
Authors: Norris Simon , Capouet Manuel
Published: January 2019

The European Commission CAST project (CArbon-14 Source Term) aimed to develop understanding of the potential release mechanisms of carbon-14 (radiocarbon, 14C) from radioactive waste materials under conditions relevant to waste packaging and disposal to underground geological disposal facilities. The project focused on the release of carbon-14 as dissolved and gaseous species from irradiated metals (steels, Zircaloys), from spent ion-exchange materials and from irradiated graphites. This paper provides an overview of the CAST project and its output. It also acts as an introduction and scene-setter to the other papers in this special edition of Radiocarbon.
PRIVATE INTERNATIONAL LAW IMPLICATIONS OF ‘EQUAL CIVIL PARTNERSHIPS’
Authors: Ní Shúilleabháin Máire
Published: January 2019

The Steinfeld and Keidan campaign for ‘equal civil partnerships’ is focussed on English domestic law. However, it also has profound implications from a private international law perspective. If the UK parliament extends civil partnership to include different-sex couples, this will close a long-standing gap in English private international law. If, on the other hand, it was decided to abolish civil partnership, this would extend the existing lacuna in English private international law, and might generate further collisions with human rights norms. This article explores these lacunae and associated human rights concerns—and suggests possible solutions.
Effects of palm kernel cake (Elaeis guineensis) on intake, digestibility, performance, ingestive behaviour and carcass traits in Nellore bulls
Authors: Cruz Claudia H. , Silva Thadeu M. , Santana Filho Nivaldo B. , Leão André G. , Ribeiro Ossival L. , Carvalho Gleidson G. P. , Bezerra Leilson R. , Oliveira Ronaldo L.
Published: January 2019

The objective of the current experiment was to determine the effects of increasing levels of palm kernel cake in a finishing diet on feed intake, digestibility, performance, ingestive behaviour and carcass traits in zebu bulls. Thirty-two Nellore bulls (420 ± 25.0 kg initial body weight [BW] and 24-months-old), were assigned randomly to individual pens with four treatments (0, 70, 140 and 210 g/kg of palm kernel cake by total dry matter [DM]) and eight replicates per treatment. The inclusion of palm kernel cake linearly decreased DM, crude protein and non-fibrous carbohydrate intake and increased ether extraction intake and digestibility. There was a linear decrease in final BW and hot carcass weight (HCW) associated with palm kernel cake inclusion in the bull diet. However, the gain : feed ratio was similar among the diets. Eating and rumination rates (g DM or neutral detergent fibre/h) were reduced, whereas the total chewing time and idling (min/day) were not affected by palm kernel cake inclusion. There were no effects of palm kernel cake inclusion on most quantitative carcass characteristics and qualitative carcass attributes (subcutaneous fat thickness, longissimus muscle area, colour, texture and marbling). The inclusion of palm kernel cake (up to 210 g/kg total DM) in beef cattle finishing diets decreased eating and rumination rates, thereby decreasing average daily gain and, consequently, final BW and HCW. However, qualitative carcass attributes were not affected by the use of palm kernel cake.
Nutrition from a climate change perspective
Authors: Macdiarmid J. I. , Whybrow S.
Published: January 2019

Climate change is threatening future global food and nutrition security. Limiting the increase in global temperature to 1·5 °C set out in The Paris Agreement (2015) while achieving nutrient security means overhauling the current food system to create one that can deliver healthy and sustainable diets. To attain this, it is critical to understand the implications for nutrition of actions to mitigate climate change as well as the impacts of climate change on food production and the nutrient composition of foods. It is widely recognised that livestock production has a much greater environmental burden than crop production, and therefore advice is to reduce meat consumption. This has triggered concern in some sectors about a lack of protein in diets, which hence is driving efforts to find protein replacements. However, in most high- and middle-income countries, protein intakes far exceed dietary requirements and it would even if all meat were removed from diets. Reduction in micronutrients should be given more attention when reducing meat. Simply eating less meat does not guarantee healthier or more sustainable diets. Climate change will also affect the type, amount and nutrient quality of food that can be produced. Studies have shown that increased temperature and elevated CO2 levels can reduce the nutrient density of some staple crops, which is of particular concern in low-income countries. Nutrition from a climate change perspective means considering the potential consequences of any climate action on food and nutrition security. In this paper, we discuss these issues from an interdisciplinary perspective.
Associations of antenatal glucocorticoid exposure with mental health in children
Authors: Wolford Elina , Lahti-Pulkkinen Marius , Girchenko Polina , Lipsanen Jari , Tuovinen Soile , Lahti Jari , Heinonen Kati , Hämäläinen Esa , Kajantie Eero , Pesonen Anu-Katriina , Villa Pia M. , Laivuori Hannele , Reynolds Rebecca M. , Räikkönen Katri
Published: January 2019

Background

Synthetic glucocorticoids, to enhance fetal maturation, are a standard treatment when preterm birth before 34 gestational weeks is imminent. While morbidity- and mortality-related benefits may outweigh potential neurodevelopmental harms in children born preterm (<37 gestational weeks), this may not hold true when pregnancy continues to term (⩾37 gestational weeks). We studied the association of antenatal betamethasone exposure on child mental health in preterm and term children.

Methods

We included 4708 women and their children, born 2006–2010, from the Prediction and Prevention of Pre-eclampsia and Intrauterine Growth Restriction Study with information on both antenatal betamethasone treatment and child mental and behavioral disorders from the Finnish Hospital Discharge Register from the child's birth to 31 December 2016. Additional follow-up data on mother-reported psychiatric problems and developmental milestones were available for 2640 children at 3.5 (s.d. = 0.07) years-of-age.

Results

Of the children, 187 were born preterm (61 betamethasone-exposed) and 4521 at term (56 betamethasone-exposed). The prevalence of any mental and behavioral, psychological development, emotional and behavioral, and comorbid disorders was higher in the betamethasone-exposed, compared to non-exposed children [odds ratio 2.76 (95% confidence interval 1.76–4.32), 3.61 (2.19–5.95), 3.29 (1.86–5.82), and 6.04 (3.25–11.27), respectively]. Levels of psychiatric problems and prevalence of failure to meet the age-appropriate development in personal-social skills were also higher in mother-reports of betamethasone-exposed children. These associations did not vary significantly between preterm and term children.

Conclusions

Antenatal betamethasone exposure may be associated with mental health problems in children born preterm and in those who end up being born at term.
Trapped in Precariousness: Migrant Agency Workers in China's State-owned Enterprises
Authors: Feng Xiaojun
Published: January 2019

This article develops an integrated perspective to study whether formalization can significantly reduce precariousness for informal workers. This perspective combines the analysis of employment dualism with that of rural–urban dualism and the analysis of the production sphere with that of the social reproduction sphere. By applying this integrated framework to the case of a state-owned enterprise (SOE) in China, this article finds that formalization does little to reduce precariousness for the migrant agency workers there. Migrant agency workers in China are in a precarious position not only because of their employment status but also because of their incomplete citizenship and the commodification of social reproduction materials. With the compensation gap between formal and agency workers narrowed primarily owing to the deterioration of formal employment, formalization has little effect on increasing the income of agency workers or alleviating the financial pressure upon them in the sphere of social reproduction; neither can formalization raise migrants up to full citizenship or reduce related precariousness.
Robust Initial Satellite Orbit Determination method using a Modified Kalman Filter
Authors: Potu Shirish , Anand S.K. , Raha Soumyendu
Published: January 2019

The control segment in satellite navigation systems is responsible for estimating satellite orbit and clock bias which is required for a reliable Position, Navigation and Timing (PNT) user service. Initial orbit determination is a crucial step which accounts for all unknowns/anomalous parameters such as satellite orbit manoeuvres, on board and receiver clock frequency variations and environmental effects. It is vital that the estimates of the orbits and clock are insensitive to these factors. In this paper, an initial orbit determination method is presented using existing robust methodology for estimation of initial satellite position and its propagation using a variant of the Kalman Filter (KF) which allows the initial position determination process to be independent of satellite and receiver anomalies. The derivation of this KF variant is presented. Preliminary results obtained from simulated data are shown. The said method is checked for robustness by comparing results obtained for a given satellite position data set with that from the conventional Kalman Filter. The conventional KF exhibits divergence due to anomalies which are eliminated by the use of the method presented in this paper.
“Back into the Days of Slavery”: Freedom, Citizenship, and the Black Family in the Reconstruction-Era Courtroom
Authors: Perrone Giuliana
Published: January 2019

This article analyses domestic law cases brought by former slaves during the decade following the Civil War. It argues that ending slavery was a long and complex process that included not only granting rights to freedpeople, but also subtracting the incapacities previously imposed by bondage and applying certain rights retroactively. Reconstruction-era judges, throughout the era and across the South, overlooked the realities of slavery as a lived institution. Instead, they reimagined slavery as a collection of legal disabilities that could simply be subtracted and summarily resolved. This is how they would carry out abolition. The notion that slavery had to be undone stands in contrast to prevailing scholarship that emphasizes the acquisition and exercise of rights as demonstrative of consummate freedom. Instead, this article shows that even when positive law and judicial rulings were used to deconstruct the peculiar institution, slavery, as a legal construct, could not be fully demolished. Judges and freedpeople alike were left to face troubling legacies for which there was no remedy. No performance of legal acrobatics could alter, undo, or fully resolve the myriad ways slavery continued to affect many former slaves and influence the direction of their free lives. Abolition would remain incomplete.
Balloon atrial septostomy at the bedside versus the catheterisation laboratory
Authors: Gopalakrishnan Arun , Krishnamoorthy Kavassery Mahadevan , Sivasubramonian Sivasankaran
Published: January 2019

A shorter umbilical venous approach provides an opportunity for balloon atrial septostomy in the younger neonate as opposed to those who present at the end of first week of life. However, the ideal choice of access for a bedside balloon atrial septostomy is not well established. Wouldn’t prostaglandin infusion be a safer option for transport of babies with dextro-transposition in the neonatal period, when the arterial duct can be kept open? A prenatal diagnosis of dextro-transposition facilitates monitoring and planning of septostomy in the early neonatal period explaining why babies underwent bedside procedures more often.
Properties of Whistler Mode Waves in Earth's Plasmasphere and Plumes
Authors: Shi Run , Li Wen , Ma Qianli , Green Alex , Kletzing Craig A. , Kurth William S. , Hospodarsky George B. , Claudepierre Seth G. , Spence Harlan E. , Reeves Geoff D.
Published: January 2019

Whistler mode wave properties inside the plasmasphere and plumes are systematically investigated using 5‐year data from Van Allen Probes. The occurrence and intensity of whistler mode waves in the plasmasphere and plumes exhibit dependences on magnetic local time, L, and AE. Based on the dependence of the wave normal angle and Poynting flux direction on L shell and normalized wave frequency to electron cyclotron frequency (fce), whistler mode waves are categorized into four types. Type I: ~0.5 fce with oblique wave normal angles mostly in plumes; Type II: 0.01–0.5 fce with small wave normal angles in the outer plasmasphere or inside plumes; Type III: <0.01 fce with oblique wave normal angles mostly within the plasmasphere or plumes; Type IV: 0.05–0.5 fce with oblique wave normal angles deep inside the plasmasphere. The Poynting fluxes of Type I and II waves are mostly directed away from the equator, suggesting local amplification, whereas the Poynting fluxes of Type III and IV are directed either away from or toward the equator, and may originate from other source regions. Whistler mode waves in plumes have relatively small wave normal angles with Poynting flux mostly directed away from the equator and are associated with high electron fluxes from ~30 keV to hundreds of keV, all of which support local amplification. Whistler mode wave amplitudes in plumes can be stronger than typical plasmaspheric hiss, particularly during active times. Our results provide critical insights into understanding whistler mode wave generation inside the plasmasphere and plumes.
Correction to: NFATc2 is an intrinsic regulator of melanoma dedifferentiation
Authors: Perotti V. , Baldassari P. , Molla A. , Vegetti C. , Bersani I. , Maurichi A. , Santinami M. , Anichini A. , Mortarini R.
Published: January 2019

In Fig. 6e, the authors noticed that wrong blots for MITF, MART-1 expression/modulation, and for β-actin were presented, due to the similarity with experiments shown in Figure 5c. Correct MITF, MART-1, and β-actin blots were added to the revised Fig. 6 shown in the associated Correction. The meaning of the results shown in Fig.6e, as well as the conclusions of this paper were not affected, and the authors regret for this error. These errors have not been fixed in the original Article.
Nimbolide protects against endotoxin-induced acute respiratory distress syndrome by inhibiting TNF-α mediated NF-κB and HDAC-3 nuclear translocation
Authors: Pooladanda Venkatesh , Thatikonda Sowjanya , Bale Swarna , Pattnaik Bijay , Sigalapalli Dilep Kumar , Bathini Nagendra Babu , Singh Shashi Bala , Godugu Chandraiah
Published: January 2019

Acute respiratory distress syndrome (ARDS) is characterized by an excessive acute inflammatory response in lung parenchyma, which ultimately leads to refractory hypoxemia. One of the earliest abnormalities seen in lung injury is the elevated levels of inflammatory cytokines, among them, the soluble tumor necrosis factor (TNF-α) has a key role, which exerts cytotoxicity in epithelial and endothelial cells thus exacerbates edema. The bacterial lipopolysaccharide (LPS) was used both in vitro (RAW 264.7, THP-1, MLE-12, A549, and BEAS-2B) and in vivo (C57BL/6 mice), as it activates a plethora of overlapping inflammatory signaling pathways involved in ARDS. Nimbolide is a chemical constituent of Azadirachta indica, which contains multiple biological properties, while its role in ARDS is elusive. Herein, we have investigated the protective effects of nimbolide in abrogating the complications associated with ARDS. We showed that nimbolide markedly suppressed the nitrosative-oxidative stress, inflammatory cytokines, and chemokines expression by suppressing iNOS, myeloperoxidase, and nitrotyrosine expression. Moreover, nimbolide mitigated the migration of neutrophils and mast cells whilst normalizing the LPS-induced hypothermia. Also, nimbolide modulated the expression of epigenetic regulators with multiple HDAC inhibitory activity by suppressing the nuclear translocation of NF-κB and HDAC-3. We extended our studies using molecular docking studies, which demonstrated a strong interaction between nimbolide and TNF-α. Additionally, we showed that treatment with nimbolide increased GSH, Nrf-2, SOD-1, and HO-1 protein expression; concomitantly abrogated the LPS-triggered TNF-α, p38 MAPK, mTOR, and GSK-3β protein expression. Collectively, these results indicate that TNF-α-regulated NF-κB and HDAC-3 crosstalk was ameliorated by nimbolide with promising anti-nitrosative, antioxidant, and anti-inflammatory properties in LPS-induced ARDS.
Selective inhibition of mitochondrial sodium-calcium exchanger protects striatal neurons from α-synuclein plus rotenone induced toxicity
Authors: Bastioli Guendalina , Piccirillo Silvia , Castaldo Pasqualina , Magi Simona , Tozzi Alessandro , Amoroso Salvatore , Calabresi Paolo
Published: January 2019

Progressive accumulation of α-synuclein (α-syn) and exposure to environmental toxins are risk factors that may both concur to Parkinson’s disease (PD) pathogenesis. Electrophysiological recordings of field postsynaptic potentials (fEPSPs) and Ca2+measures in striatal brain slices and differentiated SH-SY5Y cells showed that co-application of α-syn and the neurotoxic pesticide rotenone (Rot) induced Ca2+dysregulation and alteration of both synaptic transmission and cell function. Interestingly, the presence of the mitochondrial NCX inhibitor CGP-37157 prevented these alterations. The specific involvement of the mitochondrial NCX was confirmed by the inability of the plasma membrane inhibitor SN-6 to counteract such phenomenon. Of note, using a siRNA approach, we found that NCX1 was the isoform specifically involved. These findings suggested that NCX1, operating on the mitochondrial membrane, may have a critical role in the maintenance of ionic Ca2+homeostasis in PD and that its inhibition most likely exerts a protective effect in the toxicity induced by α-syn and Rot.
Author Correction: Alpha-fetoprotein inhibits autophagy to promote malignant behaviour in hepatocellular carcinoma cells by activating PI3K/AKT/mTOR signalling
Authors: Wang Shanshan , Zhu Mingyue , Wang Qiaoyun , Hou Yuli , Li Lei , Weng Honglei , Zhao Yan , Chen Dexi , Ding Huiguo , Guo Junli , Li Mengsen
Published: January 2019

The correct ordering and designations for corresponding/first authors are as follows: Shanshan Wang1,2*, Mingyue Zhu3, Qiaoyun Wang3, Yuli Hou4, Lei Li5, Honglei Weng6, Yan Zhao4, Dexi Chen1,2, Junli Guo3, Huiguo Ding#5, Mengsen Li#3
Decreased IL-17RB expression impairs CD11b+CD11c− myeloid cell accumulation in gastric mucosa and host defense during the early-phase of Helicobacter pylori infection
Authors: Teng Yong-sheng , Liu Yu-gang , Chen Xian-hua , Wang Ting-ting , Cheng Ping , Lv Yi-pin , Kong Hui , Mao Fang-yuan , Hao Chuan-jie , Yang Shi-ming , Chen Weisan , Zhang Jin-yu , Peng Liu-sheng , Han Bin , Ma Qiang , Han Jia , Zou Quan-ming , Zhuang Yuan
Published: January 2019

Interleukin-17 receptor B (IL-17RB), a member of the IL-17 receptor family activated by IL-17B/IL-17E, has been shown to be involved in inflammatory diseases. However, the regulation and function of IL-17RB in Helicobacter pylori (H. pylori) infection, especially in the early-phase is still unknown. Here, we found that gastric IL-17RB mRNA and protein were decreased in gastric mucosa of both patients and mice infected with H. pylori. In vitro experiments show that IL-17RB expression was down regulated via PI3K/AKT pathway on gastric epithelial cells (GECs) stimulated with H. pylori in a cagA-involved manner, while in vivo studies showed that the effect was partially dependent on cagA expression. IL-17E was also decreased during the early-phase of H. pylori infection, and provision of exogenous IL-17E resulted in increased CD11b+CD11c− myeloid cells accumulation and decreased bacteria colonization within the gastric mucosa. In the early-phase of H. pylori infection, IL-17E-IL-17RB promoted gastric epithelial cell-derived CXCL1/2/5/6 to attract CD11b+CD11c− myeloid cells, and also contributed to host defense by promoting the production of antibacterial protein Reg3a. This study defines a negative regulatory network involving IL-17E, GECs, IL-17RB, CD11b+CD11c− myeloid cells, and Reg3a in the early-phase of H. pylori infection, which results in an impaired host defense within the gastric microenvironment, suggesting IL-17RB as a potential early intervening target in H. pylori infection.
Induction of 3-hydroxy-3-methylglutaryl-CoA reductase mediates statin resistance in breast cancer cells
Authors: Göbel Andy , Breining Dorit , Rauner Martina , Hofbauer Lorenz C. , Rachner Tilman D.
Published: January 2019

The mevalonate pathway has emerged as a promising target for several solid tumors. Statins are inhibitors of the 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR), the rate-limiting enzyme of this pathway, and are commonly used to treat patients with hypercholesterolemia. Pleiotropic antitumor mechanisms of statins have been demonstrated for several human cancer types. However, cancer cells differ in their individual statin sensitivity and some cell lines have shown relative resistance. In this study we demonstrate, that the human breast cancer cell lines MDA-MB-231, MDA-MB-468, MCF-7, and T47D are differentially affected by statins. Whereas the vitality of MDA-MB-231 and MDA-MB-468 cells was reduced by up to 60% using atorvastatin, simvastatin, or rosuvastatin (p < 0.001), only marginal effects were seen in T47D and MCF-7 cells following exposure to statins. Statin treatment led to an upregulation of HMGCR mRNA and protein expression by up to sixfolds in the statin-resistant cells lines (p < 0.001), but no alterations of HMGCR were observed in the statin-sensitive MDA-MB-231 and MDA-MB-468 cells. The knockdown of HMGCR prior to statin treatment sensitized the resistant cell lines, reflected by a 70% reduction in vitality, increased apoptotic DNA fragmentation (sixfold) and by accumulation of the apoptosis marker cleaved poly-ADP ribose polymerase. Statins induced a cleavage of the sterol-regulatory element-binding protein (SREBP)-2, a transcriptional activator of the HMGCR, in T47D and MCF-7 cells. The inhibition of SREBP-2 activation by co-administration of dipyridamole sensitized MCF-7 and T47D cells for statins (loss of vitality by 80%; p < 0.001). Furthermore, assessment of a statin-resistant MDA-MB-231 clone, generated by long-term sublethal statin exposure, revealed a significant induction of HMGCR expression by up to 12-folds (p < 0.001). Knockdown of HMGCR restored statin sensitivity back to levels of the parental cells. In conclusion, these results indicate a resistance of cancer cells against statins, which is in part due to the induction of HMGCR.
Amide nitrogen pyramidalization changes lactam amide spinning
Authors: Otani Yuko , Liu Xin , Ohno Hisashi , Wang Siyuan , Zhai Luhan , Su Aoze , Kawahata Masatoshi , Yamaguchi Kentaro , Ohwada Tomohiko
Published: January 2019

Although cis-trans lactam amide rotation is fundamentally important, it has been little studied, except for a report on peptide-based lactams. Here, we find a consistent relationship between the lactam amide cis/trans ratios and the rotation rates between the trans and cis lactam amides upon the lactam chain length of the stapling side-chain of two 7-azabicyclo[2.2.1]heptane bicyclic units, linked through a non-planar amide bond. That is, as the chain length increased, the rotational rate of trans to cis lactam amide was decreased, and consequently the trans ratio was increased. This chain length-dependency of the lactam amide isomerization and our simulation studies support the idea that the present lactam amides can spin through 360 degrees as in open-chain amides, due to the occurrence of nitrogen pyramidalization. The tilting direction of the pyramidal amide nitrogen atom of the bicyclic systems is synchronized with the direction of the semicircle-rotation of the amide.
Venous identity requires BMP signalling through ALK3
Authors: Neal Alice , Nornes Svanhild , Payne Sophie , Wallace Marsha D. , Fritzsche Martin , Louphrasitthiphol Pakavarin , Wilkinson Robert N. , Chouliaras Kira M. , Liu Ke , Plant Karen , Sholapurkar Radhika , Ratnayaka Indrika , Herzog Wiebke , Bond Gareth , Chico Tim , Bou-Gharios George , De Val Sarah
Published: January 2019

Venous endothelial cells are molecularly and functionally distinct from their arterial counterparts. Although veins are often considered the default endothelial state, genetic manipulations can modulate both acquisition and loss of venous fate, suggesting that venous identity is the result of active transcriptional regulation. However, little is known about this process. Here we show that BMP signalling controls venous identity via the ALK3/BMPR1A receptor and SMAD1/SMAD5. Perturbations to TGF-β and BMP signalling in mice and zebrafish result in aberrant vein formation and loss of expression of the venous-specific gene Ephb4, with no effect on arterial identity. Analysis of a venous endothelium-specific enhancer for Ephb4 shows enriched binding of SMAD1/5 and a requirement for SMAD binding motifs. Further, our results demonstrate that BMP/SMAD-mediated Ephb4 expression requires the venous-enriched BMP type I receptor ALK3/BMPR1A. Together, our analysis demonstrates a requirement for BMP signalling in the establishment of Ephb4 expression and the venous vasculature.
High-flux ultrafast extreme-ultraviolet photoemission spectroscopy at 18.4 MHz pulse repetition rate
Authors: Saule T. , Heinrich S. , Schötz J. , Lilienfein N. , Högner M. , deVries O. , Plötner M. , Weitenberg J. , Esser D. , Schulte J. , Russbueldt P. , Limpert J. , Kling M. F. , Kleineberg U. , Pupeza I.
Published: January 2019

Laser-dressed photoelectron spectroscopy, employing extreme-ultraviolet attosecond pulses obtained by femtosecond-laser-driven high-order harmonic generation, grants access to atomic-scale electron dynamics. Limited by space charge effects determining the admissible number of photoelectrons ejected during each laser pulse, multidimensional (i.e. spatially or angle-resolved) attosecond photoelectron spectroscopy of solids and nanostructures requires high-photon-energy, broadband high harmonic sources operating at high repetition rates. Here, we present a high-conversion-efficiency, 18.4-MHz-repetition-rate cavity-enhanced high harmonic source emitting 5 × 105 photons per pulse in the 25-to-60-eV range, releasing 1 × 1010 photoelectrons per second from a 10-µm-diameter spot on tungsten, at space charge distortions of only a few tens of meV. Broadband, time-of-flight photoelectron detection with nearly 100% temporal duty cycle evidences a count rate improvement between two and three orders of magnitude over state-of-the-art attosecond photoelectron spectroscopy experiments under identical space charge conditions. The measurement time reduction and the photon energy scalability render this technology viable for next-generation, high-repetition-rate, multidimensional attosecond metrology.
A Rho-actin signaling pathway shapes cell wall boundaries in Arabidopsis xylem vessels
Authors: Sugiyama Yuki , Nagashima Yoshinobu , Wakazaki Mayumi , Sato Mayuko , Toyooka Kiminori , Fukuda Hiroo , Oda Yoshihisa
Published: January 2019

Patterned cell wall deposition is crucial for cell shapes and functions. In Arabidopsis xylem vessels, ROP11 GTPase locally inhibits cell wall deposition through microtubule disassembly, inducing pits in cell walls. Here, we show that an additional ROP signaling pathway promotes cell wall growth at pit boundaries. Two proteins, Boundary of ROP domain1 (BDR1) and Wallin (WAL), localize to pit boundaries and regulate cell wall growth. WAL interacts with F-actin and promotes actin assembly at pit boundaries while BDR1 is a ROP effector. BDR1 interacts with WAL, suggesting that WAL could be recruited to the plasma membrane by a ROP-dependent mechanism. These results demonstrate that BDR1 and WAL mediate a ROP-actin pathway that shapes pit boundaries. The study reveals a distinct machinery in which two closely associated ROP pathways oppositely regulate cell wall deposition patterns for the establishment of tiny but highly specialized cell wall domains.
Forecasting dryland vegetation condition months in advance through satellite data assimilation
Authors: Tian Siyuan , Van Dijk Albert I. J. M. , Tregoning Paul , Renzullo Luigi J.
Published: January 2019

Dryland ecosystems are characterised by rainfall variability and strong vegetation response to changes in water availability over a range of timescales. Forecasting dryland vegetation condition can be of great value in planning agricultural decisions, drought relief, land management and fire preparedness. At monthly to seasonal time scales, knowledge of water stored in the system contributes more to predictability than knowledge of the climate system state. However, realising forecast skill requires knowledge of the vertical distribution of moisture below the surface and the capacity of the vegetation to access this moisture. Here, we demonstrate that contrasting satellite observations of water presence over different vertical domains can be assimilated into an eco-hydrological model and combined with vegetation observations to infer an apparent vegetation-accessible water storage (hereafter called accessible storage). Provided this variable is considered explicitly, skilful forecasts of vegetation condition are achievable several months in advance for most of the world’s drylands.
River channel connectivity shifts metabolite composition and dissolved organic matter chemistry
Authors: Lynch Laurel M. , Sutfin Nicholas A. , Fegel Timothy S. , Boot Claudia M. , Covino Timothy P. , Wallenstein Matthew D.
Published: January 2019

Biogeochemical processing of dissolved organic matter (DOM) in headwater rivers regulates aquatic food web dynamics, water quality, and carbon storage. Although headwater rivers are critical sources of energy to downstream ecosystems, underlying mechanisms structuring DOM composition and reactivity are not well quantified. By pairing mass spectrometry and fluorescence spectroscopy, here we show that hydrology and river geomorphology interactively shape molecular patterns in DOM composition. River segments with a single channel flowing across the valley bottom export DOM with a similar chemical profile through time. In contrast, segments with multiple channels of flow store large volumes of water during peak flows, which they release downstream throughout the summer. As flows subside, losses of lateral floodplain connectivity significantly increase the heterogeneity of DOM exported downstream. By linking geomorphologic landscape-scale processes with microbial metabolism, we show DOM heterogeneity increases as a function of fluvial complexity, with implications for ecosystem function and watershed management.
Nuclear lipid droplets derive from a lipoprotein precursor and regulate phosphatidylcholine synthesis
Authors: Sołtysik Kamil , Ohsaki Yuki , Tatematsu Tsuyako , Cheng Jinglei , Fujimoto Toyoshi
Published: January 2019

The origin and physiological significance of lipid droplets (LDs) in the nucleus is not clear. Here we show that nuclear LDs in hepatocytes are derived from apolipoprotein B (ApoB)-free lumenal LDs, a precursor to very low-density lipoproprotein (VLDL) generated in the ER lumen by microsomal triglyceride transfer protein. ApoB-free lumenal LDs accumulate under ER stress, grow within the lumen of the type I nucleoplasmic reticulum, and turn into nucleoplasmic LDs by disintegration of the surrounding inner nuclear membrane. Oleic acid with or without tunicamycin significantly increases the formation of nucleoplasmic LDs, to which CTP:phosphocholine cytidylyltransferase α (CCTα) is recruited, resulting in activation of phosphatidylcholine (PC) synthesis. Perilipin-3 competes with CCTα in binding to nucleoplasmic LDs, and thus, knockdown and overexpression of perilipin-3 increases and decreases PC synthesis, respectively. The results indicate that nucleoplasmic LDs in hepatocytes constitute a feedback mechanism to regulate PC synthesis in accordance with ER stress.
Visible light-induced direct α C–H functionalization of alcohols
Authors: Niu Linbin , Liu Jiamei , Liang Xing-An , Wang Shengchun , Lei Aiwen
Published: January 2019

Considering the synthetic value of introducing active alcoholic hydroxyl group, developing C–H functionalization of alcohols is of significance. Herein, we present a photochemical method that under visible light irradiation, selectfluor can effectively promote the oxidative cross-coupling between alcohols and heteroarenes without the external photocatalysis, achieving the selective α sp3 C–H arylation of alcohol, even in the presence of ether. The N-F activation of selectfluor under blue LEDs irradiation is evidenced by electron paramagnetic resonance (EPR) study, which is the key process for the oxidative activation of α sp3 C–H alcohols. The observed reactivity may have significant implications for chemical transformations.
Publisher Correction: Long-term functional and structural preservation of precision-cut human myocardium under continuous electromechanical stimulation in vitro
Authors: Fischer Carola , Milting Hendrik , Fein Evelyn , Reiser Elisabeth , Lu Kun , Seidel Thomas , Schinner Camilla , Schwarzmayr Thomas , Schramm Rene , Tomasi Roland , Husse Britta , Cao-Ehlker Xiaochun , Pohl Ulrich , Dendorfer Andreas
Published: January 2019

The original version of this Article incorrectly acknowledged Elisabeth Reiser and Rene Schramm as a corresponding author. This has now been corrected in both the PDF and HTML versions of the Article.
Genome structure and evolution of Antirrhinum majus L
Authors: Li Miaomiao , Zhang Dongfen , Gao Qiang , Luo Yingfeng , Zhang Hui , Ma Bin , Chen Chunhai , Whibley Annabel , Zhang Yu’e , Cao Yinghao , Li Qun , Guo Han , Li Junhui , Song Yanzhai , Zhang Yue , Copsey Lucy , Li Yan , Li Xiuxiu , Qi Ming , Wang Jiawei , Chen Yan , Wang Dan , Zhao Jinyang , Liu Guocheng , Wu Bin , Yu Lili , Xu Chunyan , Li Jiang , Zhao Shancen , Zhang Yijing , Hu Songnian , Liang Chengzhi , Yin Ye , Coen Enrico , Xue Yongbiao
Published: January 2019

Snapdragon (Antirrhinum majus L.), a member of the Plantaginaceae family, is an important model for plant genetics and molecular studies on plant growth and development, transposon biology and self-incompatibility. Here we report a near-complete genome assembly of A. majus cultivar JI7 (A. majus cv.JI7) comprising 510 Megabases (Mb) of genomic sequence and containing 37,714 annotated protein-coding genes. Scaffolds covering 97.12% of the assembled genome were anchored on eight chromosomes. Comparative and evolutionary analyses revealed that a whole-genome duplication event occurred in the Plantaginaceae around 46–49 million years ago (Ma). We also uncovered the genetic architectures associated with complex traits such as flower asymmetry and self-incompatibility, identifying a unique duplication of TCP family genes dated to around 46–49 Ma and reconstructing a near-complete ψS-locus of roughly 2 Mb. The genome sequence obtained in this study not only provides a representative genome sequenced from the Plantaginaceae but also brings the popular plant model system of Antirrhinum into the genomic age.
Adiposity in relation to risks of fatty liver, cirrhosis and liver cancer: a prospective study of 0.5 million Chinese adults
Authors: Pang Yuanjie , Kartsonaki Christiana , Turnbull Iain , Guo Yu , Chen Yiping , Clarke Robert , Bian Zheng , Bragg Fiona , Millwood Iona Y. , Yang Ling , Huang Ying , Yang Yan , Zhang Xukui , Chen Junshi , Li Liming , Holmes Michael V. , Chen Zhengming
Published: January 2019

Adiposity is an increasing public health problem in China. We aimed to examine the associations of adiposity with non-alcoholic fatty liver disease (NAFLD) and other chronic liver diseases in Chinese adults. The prospective China Kadoorie Biobank recruited 512,891 adults aged 30–79 years from 10 areas. During 10 years of follow-up, 7,386 incident liver disease cases were recorded among 503,991 participants without prior cancer or chronic liver disease at baseline. The mean body mass index (BMI) (SD) was 23.7 (3.3) kg/m2 and mean waist circumference (WC) 80.3 (9.8) cm, with 33% having BMI ≥25 kg/m2. Throughout the range examined (BMI 15–50) BMI showed a log-linear positive association with NAFLD (n = 1,298), with adjusted HR per 5 kg/m2 of 2.81 (95% CI 2.63–3.01), adjusting for regression dilution. There were also positive associations of percent body fat, WC, and waist-to-hip ratio with NAFLD, with HRs per 1-SD of 2.27 (2.14–2.41), 2.60 (2.44–2.76), and 1.84 (1.76–1.92). BMI was unrelated to viral hepatitis (n = 1,477), and had a U-shaped association with cirrhosis (n = 2,082) and an inverse association with liver cancer (n = 2,568), which disappeared after excluding the first 5 years of follow-up. Among Chinese adults, adiposity was a major risk factor for NAFLD but not other chronic liver diseases.
Genomic regions of speciation and adaptation among three species of grouse
Authors: Kozma Radoslav , Rödin-Mörch Patrik , Höglund Jacob
Published: January 2019

Understanding the molecular basis of adaption is one of the central goals in evolutionary biology and when investigated across sister species it can provide detailed insight into the mechanisms of speciation. Here, we sequence the genomes of 34 individuals from three closely related grouse species in order to uncover the genomic architecture of speciation and the genes involved in adaptation. We identify 6 regions, containing 7 genes that show lineage specific signs of differential selection across the species. These genes are involved in a variety of cell processes ranging from stress response to neural, gut, olfactory and limb development. Genome wide neutrality test statistics reveal a strong signal of population expansion acting across the genomes. Additionally, we uncover a 3.5 Mb region on chromosome 20 that shows considerably lower levels of differentiation across the three grouse lineages, indicating possible action of uniform selection in this region.
Urotensin-related gene transcripts mark developmental emergence of the male forebrain vocal control system in songbirds
Authors: Bell Zachary W. , Lovell Peter , Mello Claudio V. , Yip Ping K. , George Julia M. , Clayton David F.
Published: January 2019

Songbirds communicate through learned vocalizations, using a forebrain circuit with convergent similarity to vocal-control circuitry in humans. This circuit is incomplete in female zebra finches, hence only males sing. We show that the UTS2B gene, encoding Urotensin-Related Peptide (URP), is uniquely expressed in a key pre-motor vocal nucleus (HVC), and specifically marks the neurons that form a male-specific projection that encodes timing features of learned song. UTS2B-expressing cells appear early in males, prior to projection formation, but are not observed in the female nucleus. We find no expression evidence for canonical receptors within the vocal circuit, suggesting either signalling to other brain regions via diffusion or transduction through other receptor systems. Urotensins have not previously been implicated in vocal control, but we find an annotation in Allen Human Brain Atlas of increased UTS2B expression within portions of human inferior frontal cortex implicated in human speech and singing. Thus UTS2B (URP) is a novel neural marker that may have conserved functions for vocal communication.
DeepSeqPan, a novel deep convolutional neural network model for pan-specific class I HLA-peptide binding affinity prediction
Authors: Liu Zhonghao , Cui Yuxin , Xiong Zheng , Nasiri Alierza , Zhang Ansi , Hu Jianjun
Published: January 2019

Interactions between human leukocyte antigens (HLAs) and peptides play a critical role in the human immune system. Accurate computational prediction of HLA-binding peptides can be used for peptide drug discovery. Currently, the best prediction algorithms are neural network-based pan-specific models, which take advantage of the large amount of data across HLA alleles. However, current pan-specific models are all based on the pseudo sequence encoding for modeling the binding context, which is based on 34 positions identified from the HLA protein-peptide bound structures in early works. In this work, we proposed a novel deep convolutional neural network model (DCNN) for HLA-peptide binding prediction, in which the encoding of the HLA sequence and the binding context are both learned by the network itself without requiring the HLA-peptide bound structure information. Our DCNN model is also characterized by its binding context extraction layer and dual outputs with both binding affinity output and binding probability outputs. Evaluation on public benchmark datasets shows that our DeepSeqPan model without HLA structural information in training achieves state-of-the-art performance on a large number of HLA alleles with good generalization capability. Since our model only needs raw sequences from the HLA-peptide binding pairs, it can be applied to binding predictions of HLAs without structure information and can also be applied to other protein binding problems such as protein-DNA and protein-RNA bindings. The implementation code and trained models are freely available at https://github.com/pcpLiu/DeepSeqPan.
Fingerprint of silicic magma degassing visualised through chlorine microscopy
Authors: Yoshimura Shumpei , Kuritani Takeshi , Matsumoto Akiko , Nakagawa Mitsuhiro
Published: January 2019

Volatile-rich silicic magma erupts either explosively as a jet of a mixture of pyroclasts and high-temperature gas, or non-explosively to effuse lava. The bifurcation of the eruption style is widely recognised as being controlled by the efficiency of open-system gas loss from vesiculated magma during ascent. However, the fundamental question of how the gas escapes from highly viscous magma still remains unsolved because the pathways of gas flow are rarely preserved in dense lava. Here we show that such pathways are visualised in groundmass glass using high-resolution chlorine (Cl) mapping analysis on the rhyolitic lava of the Mukaiyama volcano, Japan. The results showed that the glass was highly heterogeneous in Cl content. A spatial distribution of the Cl content in the groundmass glass showed that volatiles diffused towards most bubbles, but the bubbles collapsed into the dense melt rather than growing. All observations, in combination with melt inclusion analysis, indicate that vesiculation, the formation of interconnected bubble channels, open-system gas loss via the channels, and channel collapse repeated within the period of a few days to two weeks during ascent. This cycle repeated individually in centimetre-sized portions of magma with different timing.
L-amino acid oxidase from Bothrops atrox snake venom triggers autophagy, apoptosis and necrosis in normal human keratinocytes
Authors: Costal-Oliveira Fernanda , Stransky Stephanie , Guerra-Duarte Clara , Naves de Souza Dayane L. , Vivas-Ruiz Dan E. , Yarlequé Armando , Sanchez Eladio Flores , Chávez-Olórtegui Carlos , Braga Vania M. M.
Published: January 2019

Snake venom L-amino acid oxidases (LAAOs) are flavoproteins, which perform diverse biological activities in the victim such as edema, myotoxicity and cytotoxicity, contributing to the development of clinical symptoms of envenomation. LAAO cytotoxicity has been described, but the temporal cascade of events leading to cell death has not been explored so far. This study evaluates the involvement of LAAO in dermonecrosis in mice and its cytotoxic effects in normal human keratinocytes, the major cell type in the epidermis, a tissue that undergoes extensive necrosis at the snakebite site. Pharmacological inhibition by the antioxidant NAC (N-acetyl cysteine) prevented B. atrox venom-induced necrosis. Consistent with the potential role of oxidative stress in wounding, treatment with purified LAAO decreased keratinocyte viability with an Effective Concentration (EC50) of 5.1 μg/mL. Cytotoxicity caused by LAAO was mediated by H2O2 and treated cells underwent autophagy, followed by apoptosis and necrosis. LAAO induced morphological alterations that precede cell death. Our results show the chronological events leading to cell death and the temporal resolution from autophagy, apoptosis and necrosis as distinct mechanisms triggered by LAAO. Fluorescently-labelled LAAO was efficiently and rapidly internalized by keratinocytes, suggesting that catalysis of intracellular substrates may contribute to LAAO toxicity. A better understanding of LAAO cytotoxicity and its mechanism of action will help to identify potential therapeutic strategies to ameliorate localized snake envenomation symptoms.
Comparative analysis of complete chloroplast genome sequences of four major Amorphophallus species
Authors: Liu Erxi , Yang Chaozhu , Liu Jiangdong , Jin Surong , Harijati Nunung , Hu Zhongli , Diao Ying , Zhao Lingling
Published: January 2019

Amorphophallus (Araceae) contains more than 170 species that are mainly distributed in Asia and Africa. Because the bulbs of Amorphophallus are rich in glucomannan, they have been widely used in food, medicine, the chemical industry and so on. To better understand the evolutionary relationships and mutation patterns in the chloroplast genome of Amorphophallus, the complete chloroplast genomes of four species were sequenced. The chloroplast genome sequences of A. albus, A. bulbifer, A. konjac and A. muelleri ranged from 162,853 bp to 167,424 bp. The A. albus chloroplast (cp) genome contains 113 genes, including 79 protein-coding genes, 30 tRNA genes and 4 rRNA genes. The A. bulbifer cp genome contains 111 genes, including 78 protein-coding genes, 29 tRNA genes and 4 rRNA genes. A. muelleri contains 111 and 113 genes, comprising 78 and 80 protein-coding genes, respectively, 29 tRNA genes and 4 rRNA genes. The IR (inverted repeat) region/LSC (long single copy) region and IR/SSC (short single copy) region borders of the four Amorphophallus cp genomes were compared. In addition to some genes being deleted, variations in the copy numbers and intron numbers existed in some genes in the four cp genomes. One hundred thirty-four to 164 SSRs (simple sequence repeats) were detected in the four cp genomes. In addition, the highest mononucleotide SSRs were composed of A and T repeat units, and the majority of dinucleotides were composed of AT and TA. SNPs (single nucleotide polymorphisms) and indels (insertion-deletions) were calculated from coding genes and noncoding genes, respectively. These divergences comprising SSRs, SNPs and indel markers will be useful in testing the maternal inheritance of the chloroplast genome, identifying species differentiation and even in breeding programs. Furthermore, the regression of ndhK was detected from four Amorphophallus cp genomes in our study. Complete cp genome sequences of four Amorphophallus species and other plants were used to perform phylogenetic analyses. The results showed that Amorphophallus was clustered in Araceae, and Amorphophallus was divided into two clades; A. albus and A. konjac were clustered in one clade, and A. bulbifer and A. muelleri were clustered in another clade. Phylogenetic analysis among the Amorphophallus genus was conducted based on matK and rbcL. The phylogenetic trees showed that the relationships among the Amorphophallus species were consistent with their geographical locations. The complete chloroplast genome sequence information for the four Amorphophallus species will be helpful for elucidating Amorphophallus phylogenetic relationships.