bluuebunny/crossref_metadata_2025 huggingface dataset:
In vitrolipolysis and lymphatic absorption ofn-3 long-chain PUFA in the rat: influence of the molecular lipid species as carrier
Authors: Sehl Anthony , Couëdelo Leslie , Chamekh-Coelho Ikram , Vaysse Carole , Cansell Maud
Published: June 2019

The aim of this work was to study the bioavailability of fatty acids (FA), focusing onn-3 long-chain (LC) PUFA, carried by different molecular lipid species, that is, phospholipids (PL) or TAG, with three formulations based on fish oils or marine PL, providing a similarn-3 LC PUFA amount. The digestive lipolysis was first assessed using anin vitroenzymatic model. Then, intestinal absorption and enterocyte metabolism were investigatedin vivo, on male Wistar rats through lymph lipid analysis. Thein vitroresults showed that the release ofn-3 LC PUFA from lipolysis was increased by 48 % when FA were provided as PL rather than TAG. Thein vivoresults demonstrated that EPA and DHA from both TAG and PL were similarly absorbed and incorporated into lymph lipids. However, DHA was mainly distributed at thesn-1/3 positions of lymph TAG when provided as marine PL, whereas it was equally distributed at the three positions with marine TAG. On the whole, even if the molecular lipid species ofn-3 LC PUFA did not greatly modify thein vivodigestion and absorption steps, it modulated the rearrangement of DHA on the glyceride positions of the lymph TAG, which may further impact the DHA metabolic fate and tissue accretion. Consequently, the present study has provided data which may be used to formulate lipid diets rich in DHA in the context of an insufficient consumption ofn-3 PUFA in Western countries.
Piperine as a new natural supplement with beneficial effects on the life-span and defence system of honeybees
Authors: Schulz M. , Łoś A. , Grzybek M. , Ścibior R. , Strachecka A.
Published: June 2019

Many factors, including pathogens, environmental change and breeding techniques, affect honeybee immunity/resistance, so substances and natural supplements that enhance it are desired. To eliminate the impact of unknown external factors, in 2016 a cage experiment was conducted under constant laboratory conditions (35 °C, 65% relative humidity). Bees in the control group were fed with sugar dissolved in water at ratio 1:1 ad libitum with no additives, while the other group was fed with sugar syrup (1:1) supplemented with piperine (3 µg/ml) ad libitum. The piperine-treated workers lived 9 days longer compared to the control group. In the piperine-consuming group, protein concentration and the activities of antioxidative enzymes, such as superoxide dismutase (SOD), glutathione peroxidase (GPx), catalase (CAT) and glutathione S-transferase (GST), were higher than in the control group. The activities of aspartate aminotransferase (AST), alanine aminotransferase (ALT) and alkaline phosphatase (ALP) were also higher in the piperine-treated group. Neutral and acidic proteases inhibitors, as well as neutral protease activities, were higher in the haemolymph of the piperine-treated workers than in untreated bees. Acidic protease activities in the haemolymph were higher in untreated workers only on days 18 and 32. Alkaline protease activities in the control bees were higher from day 10. From 10 days old, the total antioxidant capacity level was significantly higher in the haemolymph of piperine-treated workers. Piperine decreased DNA methylation levels significantly in the older bees. The compound could have the potential to be a natural diet supplement increasing apian resistance to stress factors.
Negotiating in Good Faith: Overcoming Legitimacy Problems in the Japan-South Korea Reconciliation Process
Authors: Le Tom Phuong
Published: June 2019

This article examines why the “history issue” continues to hinder Japanese-Korean relations after nominally successful negotiations such as the 1965 Treaty on Basic Relations between Japan and the Republic of Korea and the 2015 comfort women agreement. It contends that leaders put off and quite possibly sacrificed reconciliation in order to achieve treaties and agreements that addressed more immediate security, economic, and political needs. However, because agreements were not transparently negotiated, partly due to the lack of a neutral third-party mediator, Koreans believe the treaties were not fair nor final settlements. Additionally, the reconciliation process has been flawed because it haphazardly tackles disagreements and does not consider time. A third-party such as the United States should mediate a settlement between Japan and South Korea to ensure adequate confidence building measures. Such measures will lower the costs of giving and accepting an apology, increasing the chances of an enduring and legitimate treaty.
Diffraction of radio frequency waves by spatially modulated interfaces in the plasma edge in tokamaks
Authors: Papadopoulos A. D. , Glytsis E. N. , Ram A. K. , Valvis S. I. , Papagiannis P. , Hizanidis K. , Zisis A.
Published: June 2019

The use of radio frequency (RF) waves in fusion plasmas for heating, for non-inductive current generation, for profile control and for diagnostics has been well established. The RF waves, excited by antenna structures placed near the wall of a fusion device, have to propagate through density fluctuations at the plasma edge. These fluctuations can modify the properties of the RF waves that propagate towards the core of the plasma. A full-wave electromagnetic computational code ScaRF based on the finite difference frequency domain (FDFD) method has been developed to study the effect of density turbulence on RF waves. The anisotropic plasma permittivity used in the scattering studies is that for a magnetized, cold plasma. The code is used to study the propagation of an RF plane wave through a modulated, spatially periodic density interface. Such an interface could arise in the edge region due to magnetohydrodynamic instability or drift waves. The frequency of the plane wave is taken to be in the range of the electron cyclotron frequency. The scattering analysis is applicable to ITER-like plasmas, as well as to plasmas in medium sized tokamaks such as TCV, ASDEX-U and DIII-D. The effect of different density contrasts across the interface and of different spatial modulations are discussed. While ScaRF is used to study a periodic density fluctuation, the code is general enough to include different varieties of density fluctuations in the edge region – such as blobs and filaments, and spatially random fluctuations.
Similarity in benthic habitat and fish assemblages in the upper mesophotic and shallow water reefs in the West Philippine Sea
Authors: Quimpo Timothy Joseph R. , Cabaitan Patrick C. , Go Kevin Thomas B. , Dumalagan Edwin E. , Villanoy Cesar L. , Siringan Fernando P.
Published: June 2019

The South China Sea (SCS) is a biodiversity hotspot, however, most biodiversity surveys in the region are confined to shallow water reefs. Here, we studied the benthic habitat and fish assemblages in the upper mesophotic coral ecosystems (MCEs; 30–40 m) and SWRs (8–22 m) at three geographic locations (Luzon Strait; Palawan; and the Kalayaan Group of Islands) in the eastern SCS (also called the West Philippine Sea) using diver-based survey methods. Mean coral genera and fish species richness ranged from 17–25 (per 25 m2) and 11–17 (per 250 m2) in MCEs, respectively; although none of these were novel genera/species. Coral and fish assemblages were structured more strongly by location than by depth. Location differences were associated with the variability in benthic composition, wherein locations with higher hard coral cover had higher coral genera richness and abundance. Locations with higher algae and sand cover had higher diversity and density of fish herbivores and benthic invertivores. Fishing efforts may also have contributed to among-location differences as the highly exploited location had the lowest fish biomass. The low variation between depths may be attributed to the similar benthic composition at each location, the interconnectivity between depths due to hydrological conditions, fish motility, and the common fishing gears used in the Philippines that can likely extend beyond SWRs. Results imply that local-scale factors and anthropogenic disturbances probably dampen across-depth structuring in coral genera and fish species assemblages.
Marpa's commands in the Milarepa Life Story
Authors: Pickens John
Published: June 2019

In the Milarepa Life Story the Buddhist teacher Marpa issues many commands to his student, Milarepa, his wife, Dakmema, and his co-religionist, Lama Ngokpa. In these commands the co-occurrence of the imperative stem (skul tshig) and a given pronoun or vocative (khyod, bu, rang re, etc.) indicates a varying level of distance between himself and the addressee. Marpa's speech is also nuanced by the use of pronouns, vocatives, and nicknames across a variety of registers. Marpa's interlocutors, however, invariably use honorific titles and the deferential verb zhu ba to make their requests. The contrast highlights Marpa's authority, as his speech alone determines how close he is with an interlocutor at a given time.
The Roman Military Presence at Dalswinton, Dumfriesshire: a Reassessment of the Evidence from Aerial, Geophysical and LiDAR Survey
Authors: Hanson W.S. , Jones R.E. , Jones R.H.
Published: June 2019

The Roman military presence at Dalswinton is reassessed using a range of remote sensing techniques (geophysical survey, LiDAR and aerial photography). At Bankfoot the absence of internal buildings suggests the postulated vexillation fortress was a more temporary structure; while numerous pits/ovens were identified across the interior of the large Stracathro-type camp. The primary fort at Bankhead was provided with in-turned entrances and two small annexes attached to the north-west and south-east quadrants of the fort. A third much larger annexe extended southwards down to the river. Only pits and furnaces were recorded within the annexes, two of which were expanded in Phase 2. Various buildings, including legionary and auxiliary barracks, were identified in the expanded fort of Phase 2, whose orientation remained unchanged. A mixed garrison of legionaries and auxiliary cavalry is indicated for both periods of occupation. Finally, the fort was deliberately demolished. The Roman attribution of the three nearby enclosures at Butterhole Brae can no longer be supported.
Recurrence of quadratic differentials for harmonic measure
Authors: GADRE VAIBHAV , MAHER JOSEPH
Published: June 2019

We consider random walks on the mapping class group that have finite first moment with respect to the word metric, whose support generates a non-elementary subgroup and contains a pseudo-Anosov map whose invariant Teichmüller geodesic is in the principal stratum of quadratic differentials. We show that a Teichmüller geodesic typical with respect to the harmonic measure for such random walks, is recurrent to the thick part of the principal stratum. As a consequence, the vertical foliation of such a random Teichmüller geodesic has no saddle connections.
Patients’ experiences and preferences for primary care delivery: a focus group analysis
Authors: Norwood Patrícia , Correia Isabel , Veiga Paula , Watson Verity
Published: June 2019

Background:

In 2005, the Portuguese government launched a primary care (PC) reform. After a promising start, the reform is still incomplete and has been compromised by low investment. The incomplete nature of the reforms has resulted in the coexistence of different models of care delivery and heterogeneity in resource allocation and performance. PC has been extensively evaluated, but little is known about the patients’ views and preferences regarding PC and the ongoing reform.

Aim:

This study aims to examine patients’ experiences of and preferences for PC in Portugal and to explore their experience of the recent reforms.

Methods:

A qualitative study was undertaken which collected data from eight focus groups in the city of Braga, Portugal. Participants were recruited with the collaboration of eight local institutions. Focus groups’ discussions focused on patients’ experiences of and preferences for PC as well as their views on the reforms. Audio recordings were transcribed and analysed using an inductive thematic content analysis.

Findings:

The majority of participants perceived that the reform was positive. However, the improvements achieved by the reform were insufficient to lead to most participants having a positive experience of PC delivery in Portugal. Participants’ satisfaction/dissatisfaction with primary care was strongly associated with interpersonal relations and communication with doctors. Participants valued continuity of care, but felt the levels of responsiveness, flexibility and coordination in the current system were still unsatisfactory. Access and waiting times were seen as challenging and led participants to seek PC from emergency departments and private doctors.

Policy Implications:

The perception of increased inequity and the lack of effective choice undermined the social acceptability of the reform. Policies aimed at improving doctor–patient communication and continuity of care, as well as choice, may therefore lead to better satisfaction and more efficient use of health care settings.
Intrauterine growth restriction affects z-scores of anthropometric parameters during the first 6 years in very low-birth-weight-children born at less than 30 weeks of gestation
Authors: Shoji Hiromichi , Watanabe Akiko , Awaji Atsuko , Ikeda Naho , Hosozawa Mariko , Ohkawa Natsuki , Nishizaki Naoto , Hisata Ken , Kantake Masato , Obinata Kaoru , Shimizu Toshiaki
Published: June 2019

Objective:

Little is known about physical constitution outcomes for very preterm infants. Here, we compare z-scores of anthropometric parameters up to 6 years of age in children born with very low birth weight (VLBW) at less than 30 weeks of gestation, with or without intrauterine growth restriction (IUGR).

Design:

Participants were divided into four subgroups: male (M), small for gestational age (SGA) (n = 30); M, appropriate for gestational age (AGA) (n = 59); female (F), SGA (n = 24); and F, AGA (n = 61). z-Scores of body weight (BW), body length (BL), and body mass index (BMI) were assessed at birth, 1 year corrected age, 3 years of age, and 6 years of age.

Results:

For boys, BW and BMI were significantly lower among SGA children than among AGA children at all assessments, but there was no difference in BL at 3 or 6 years. For girls, BW and BL were significantly lower among SGA children than among AGA children at all assessments, but no difference was detected in BMI after 1.5 years. No significant variation in the z-score of BW or BMI in either SGA group was observed after 1 year. BL z-score in all groups gradually increased until 6 years of age.

Conclusion:

IUGR affects BW and BMI in boys and BW and BL in girls during the first 6 years in VLBW children born at less than 30 weeks of gestation. SGA children did not catch up in BW or BMI from 1 to 6 years of age.
Cotton tolerance to halauxifen-methyl applied preplant
Authors: Askew M. Carter , Cahoon Charles W. , York Alan C. , Flessner Michael L. , Langston David B. , Ferebee J. Harrison
Published: June 2019

Auxin herbicides are used in combinations to control glyphosate-resistant horseweed preplant burndown. Herbicide labels for 2,4-D–containing products require a 30-d rotation interval for planting cotton cultivars not resistant to 2,4-D. Dicamba labels require an accumulation of 2.5 cm of rain plus 21 d per 280 g ae ha–1 rotation interval for planting cotton cultivars not resistant to dicamba. Previous research has shown that cotton injury caused by dicamba applied 14 d before planting was transient with little effect on cotton yield, whereas 2,4-D has little effect on cotton when applied 7 d prior to planting. Injury caused by dicamba and 2,4-D is inversely related to rainfall received between herbicide application and cotton planting. Experiments were conducted to evaluate cotton tolerance to halauxifen-methyl, a new Group 4 herbicide, applied at intervals shorter than labeled requirements. Experiments were established near Painter and Suffolk, VA, and Belvidere, Clayton, Eure, Lewiston, and Rocky Mount, NC, during the 2017 and 2018 growing seasons. Herbicide treatments included halauxifen, dicamba, and 2,4-D applied 4, 3, 2, 1, and 0 wk before planting (WBP). Visible estimates of cotton growth reduction and total injury were collected 1, 2, and 4 wk after cotton emergence (WAE). Cotton stand and percentage of plants with distorted leaves were recorded 2 and 4 WAE. Cotton plant heights were recorded 4 and 8 WAE. Halauxifen was less injurious (9%) than dicamba (26%) or 2,4-D (21%) 2 WAE when herbicides were applied 0 WBP. Cotton stand reduction 2 WAE by halauxifen was less than 2,4-D and dicamba when applied 0 WBP. Injury observed from herbicides applied 1, 2, 3, and 4 WBP was minor, and no significant differences in cotton stand were observed. Early-season cotton injury was transient, and seed cotton yield was unaffected by any treatment.
Standards der histopathologischen und molekularen Diagnostik des kolorektalen Karzinoms
Authors: Dawson Heather , Lugli Alessandro
Published: June 2019

Zusammenfassung. Die pathologische Aufarbeitung von Biopsie- und Operationspräparaten spielt beim kolorektalen Karzinom für das Patientenmanagement eine wichtige Rolle. Aus diesem Grund ist eine sorgfältige Erhebung gewisser prognostisch und prädiktiv relevanter Faktoren unerlässlich für eine optimierte, individualisierte Patientenbehandlung. Zusätzlich haben Fortschritte von Behandlungsmöglichkeiten, deren Einsatz eine molekulare Diagnostik erfordert, zur Etablierung molekularer Tests in der Routine geführt. Diese Übersichtsarbeit soll der Leserschaft einen pragmatischen Überblick über die aktuell in der täglichen Praxis durchgeführten prognostischen und prädiktiven Biomarker des kolorektalen Karzinoms liefern.
The Effects of Anthropogenic Land Use Changes on Climate in China Driven by Global Socioeconomic and Emission Scenarios
Authors: Dong Na , Liu Zhen , Luo Ming , Fang Chaoyang , Lin Hui
Published: June 2019

The land surface, which interacts with lower atmosphere, is subject to substantial amounts of human activities. It results in regional climate fluctuations and must be assessed with a combination of future socioeconomic and emission policies to improve regional resilience and responsive efficiency on global mitigation and adaptation. Spatial heterogeneity in regional climate induced by land use changes of future global socioeconomic and emission scenarios is explored. Comparisons are carried out among both historical and future land use‐induced regional meteorological changes to investigate various climatic roles of land use conversions in China. The underlying changes in the surface albedo, leaf area index, energy exchange, and water balances are also examined. It is found that the increase of the summer temperature and the diurnal temperature range are the largest under the fifth Shared Socioeconomic Pathway characterized by more intensive urbanization. While temperature increase from urbanization and deforestation can be offset by cooling from vegetation evaporation increase under the extreme Representative Concentration Pathway (RCP) 8.5, which has no climate mitigation policies and high greenhouse gas concentration. In addition, RCP4.5 scenario would cause an average temperature increase of 1.41°C by 2050 at an annual rate of 0.028°C in China. The global climatic forcing warms the entire region and enhances precipitation intensity, and these effects are more substantial than those by regional land use changes, showing a strong background influence. Our research reveals the future climatic responses to regional anthropogenic land use changes under various scenarios and policies and provides ways to downscale global mitigation impacts into regional insights.
Imaging the Deep Subsurface Plumbing of Old Faithful Geyser From Low‐Frequency Hydrothermal Tremor Migration
Authors: Wu Sin‐Mei , Lin Fan‐Chi , Farrell Jamie , Allam Amir
Published: June 2019

Old Faithful Geyser in Yellowstone is one of the most well‐known hydrothermal features in the world. Despite abundant geophysical studies, the structure of Old Faithful's plumbing system beneath ~20‐m depth remained largely elusive. By deploying a temporary dense three‐component geophone array, we observe 1–5 Hz low‐frequency hydrothermal tremor originating from Old Faithful's deeper conduit. By applying seismic interferometry and polarization analyses, we track seismic tremor source migration throughout the eruption/recharge cycle. The tremor source drops rapidly to ~80‐m depth right after the eruption and gradually ascends vertically back to ~20‐m depth, coinciding with the previously inferred bubble trap location. Likely excited by the liquid/steam phase transition, the observed tremor source migration can provide new constraints on the recharge process and deeper conduit geometry. Combined with the shallow conduit structure from previous studies, these results provide constraints on the major fluid pathway down to 80‐m depth.
Copula‐Based Convection‐Permitting Projections of Future Changes in Multivariate Drought Characteristics
Authors: Zhang B. , Wang S. , Wang Y.
Published: June 2019

Probabilistic projections of future drought characteristics play a crucial role in climate change adaptation and disaster risk reduction. This study presents a copula‐based probabilistic framework for projecting future changes in multivariable drought characteristics through convection‐permitting Weather Research and Forecasting simulations with 4‐km horizontal grid spacing. A probabilistic multivariate drought index is introduced to examine the joint effects of drought indicators with uncertainty intervals for four major river basins located in South Central Texas of the United States. Markov chain Monte Carlo is used to address uncertainties in assessing copula parameters and in predicting climate‐induced changes in hydrological regimes. Our findings reveal that the severity and intensity of drought episodes can be amplified when considering the compound effects of soil moisture and runoff regimes by using the probabilistic multivariate drought index. The South Central Texas region is projected to experience more drought events with shorter duration and higher intensity in a changing climate. The drought severity will not necessarily increase due to the decreasing drought duration. In addition, our findings indicate that the intensity of future droughts is expected to increase as a result of the deficiency of soil moisture even though precipitation extremes are projected to become more frequent. Moreover, climate change impacts on multivariate drought characteristics will intensify with the increasing temporal scales (i.e., short‐, medium‐, and long‐term droughts) although the number of future drought events may decrease by the end of this century.
Heterogeneity among traumatic spinal cord injuries at the thoracolumbar junction: helping select patients for clinical trials
Authors: Liu Shu-Jia , Wang Qiang , Tang He-Hu , Bai Jin-Zhu , Wang Fang-Yong , Lv Zhen , Chen Shi-Zheng , Liu Jie-Sheng , Hong Yi , Zhang Jun-Wei
Published: June 2019

Study design

Retrospective analysis.

Setting

China Rehabilitation Research Center, Beijing, China.

Objective

A retrospective study that documents the modalities and clarifies the heterogeneity among spinal cord injuries (SCIs) caused by trauma to the thoracolumbar vertebral junction.

Methods

X-ray and MRI imaging, neurological records, and the urodynamics results of 190 patients were reviewed and used to categorize different SCI modalities. First, injuries were divided into complete and incomplete injuries using the International Standard for Neurological Classification of Spinal Cord Injury. Next, the complete injuries were further grouped using the neurological level of injury and Long T2 signal from mid-sagittal MRI images, whereas the bulboconvernosus reflexes were also used as a reference to detect injury to the sacral cord.

Results

The SCI modalities were classified into five categories: pure complete epiconus lesion with caudal cord intact (G1), complete epiconus injury with conus medullaris (CM) totally involved in the lesion (G2), CM syndrome, cauda equine syndrome without sacral sparing (G3 and G4), and incomplete injury (G5).

Conclusions

The heterogeneity of SCIs at the thoracolumbar junction was documented, a criterion we propose to be of great significance when selecting patients for clinical trials. In particular, the G2 group, which comprises nearly one third of the patients with epiconus lesions, is sometimes mistaken as G1, an observation that has thus far received insufficient attention.
Author Correction: Identification of TC2N as a novel promising suppressor of PI3K-AKT signaling in breast cancer
Authors: Hao Xiang-lin , Gao Li-yun , Deng Xiao-juan , Han Fei , Chen Hong-qiang , Jiang Xiao , Liu Wen-bin , Wang Dan-dan , Chen Jian-ping , Cui Zhi-hong , Ao Lin , Cao Jia , Liu Jin-yi
Published: June 2019

After publication of this article, it came to the attention of the authors that their names had been reordered. Professor. Jia Cao and Prof. Jin-yi Liu are the co-corresponding authors, and Prof. Jin-yi Liu should be the last author.
Platelet factor 4-containing immune complexes induce platelet activation followed by calpain-dependent platelet death
Authors: Nevzorova Tatiana A. , Mordakhanova Elmira R. , Daminova Amina G. , Ponomareva Anastasia A. , Andrianova Izabella A. , Le Minh Giang , Rauova Lubica , Litvinov Rustem I. , Weisel John W.
Published: June 2019

Heparin-induced thrombocytopenia (HIT) is a complication of heparin therapy sometimes associated with thrombosis. The hallmark of HIT is antibodies to the heparin/platelet factor 4 (PF4) complex that cause thrombocytopenia and thrombosis through platelet activation. Despite the clinical importance, the molecular mechanisms and late consequences of immune platelet activation are not fully understood. Here, we studied immediate and delayed effects of the complexes formed by human PF4 and HIT-like monoclonal mouse anti-human-PF4/heparin IgG antibodies (named KKO) on isolated human platelets in vitro. Direct platelet-activating effect of the KKO/PF4 complexes was corroborated by the overexpression of phosphatidylserine (PS) and P-selectin on the platelet surface. The immune platelet activation was accompanied by a decrease of the mitochondrial transmembrane potential (ΔΨm), concurrent with a significant gradual reduction of the ATP content in platelets, indicating disruption of energy metabolism. A combination of PS expression and mitochondrial depolarization induced by the PF4-containing immune complexes observed in a substantial fraction of platelets was considered as a sign of ongoing platelet death, as opposed to a subpopulation of activated live platelets with PS on the plasma membrane but normal ΔΨm. Both activated and dying platelets treated with KKO/PF4 formed procoagulant extracellular microvesicles bearing PS on their surface. Scanning and transmission electron microscopy revealed dramatic morphological changes of KKO/PF4-treated platelets, including their fragmentation, another indicator of cell death. Most of the effects of KKO/PF4 were prevented by an anti-FcγRII monoclonal antibody IV.3. The adverse functional and structural changes in platelets induced by the KKO/PF4 complexes were associated with strong time-dependent activation of calpain, but only trace cleavage of caspase 3. The results indicate that the pathogenic PF4-containing HIT-like immune complexes induce direct prothrombotic platelet activation via FcγRIIA receptors followed by non-apoptotic calpain-dependent death of platelets, which can be an important mechanism of thrombocytopenia during HIT development.
A girl with CLOVES syndrome with a recurrent PIK3CA somatic mutation and pancreatic steatosis
Authors: Hanafusa Hiroaki , Morisada Naoya , Nomura Tadashi , Kobayashi Daisuke , Akasaka Yoshinobu , Ye Ming Juan , Nozu Kandai , Nishimura Noriyuki , Iijima Kazumoto , Nakao Hideto
Published: June 2019

CLOVES syndrome is characterized by congenital lipomatous overgrowth, vascular malformation, epidermal nevi, and scoliosis/spinal malformation. It is caused by somatic mosaicism of gain-of-function variants of PIK3CA. Here, we describe a novel case of a 5-year-old Japanese girl with CLOVES and concurrent pancreatic steatosis. She had a recurrent somatic mutation in PIK3CA (NM_006218.3: c.1357G>A, p.Glu453Lys), elevated HbA1c levels, and pancreatic steatosis. This case indicates that pancreatic screening is critical for PIK3CA-related disorders.
Amplification of future energy demand growth due to climate change
Authors: van Ruijven Bas J. , De Cian Enrica , Sue Wing Ian
Published: June 2019

Future energy demand is likely to increase due to climate change, but the magnitude depends on many interacting sources of uncertainty. We combine econometrically estimated responses of energy use to income, hot and cold days with future projections of spatial population and national income under five socioeconomic scenarios and temperature increases around 2050 for two emission scenarios simulated by 21 Earth System Models (ESMs). Here we show that, across 210 realizations of socioeconomic and climate scenarios, vigorous (moderate) warming increases global climate-exposed energy demand before adaptation around 2050 by 25–58% (11–27%), on top of a factor 1.7–2.8 increase above present-day due to socioeconomic developments. We find broad agreement among ESMs that energy demand rises by more than 25% in the tropics and southern regions of the USA, Europe and China. Socioeconomic scenarios vary widely in the number of people in low-income countries exposed to increases in energy demand.
Chromosome dynamics near the sol-gel phase transition dictate the timing of remote genomic interactions
Authors: Khanna Nimish , Zhang Yaojun , Lucas Joseph S. , Dudko Olga K. , Murre Cornelis
Published: June 2019

Diverse antibody repertoires are generated through remote genomic interactions involving immunoglobulin variable (VH), diversity (DH) and joining (JH) gene segments. How such interactions are orchestrated remains unknown. Here we develop a strategy to track VH-DHJH motion in B-lymphocytes. We find that VH and DHJH segments are trapped in configurations that allow only local motion, such that spatially proximal segments remain in proximity, while spatially remote segments remain remote. Within a subset of cells, however, abrupt changes in VH-DHJH motion are observed, plausibly caused by temporal alterations in chromatin configurations. Comparison of experimental and simulated data suggests that constrained motion is imposed by a network of cross-linked chromatin chains characteristic of a gel phase, yet poised near the sol phase, a solution of independent chromatin chains. These results suggest that chromosome organization near the sol-gel phase transition dictates the timing of genomic interactions to orchestrate gene expression and somatic recombination.
Enzymatic biosynthesis and immobilization of polyprotein verified at the single-molecule level
Authors: Deng Yibing , Wu Tao , Wang Mengdi , Shi Shengchao , Yuan Guodong , Li Xi , Chong Hanchung , Wu Bin , Zheng Peng
Published: June 2019

The recent development of chemical and bio-conjugation techniques allows for the engineering of various protein polymers. However, most of the polymerization process is difficult to control. To meet this challenge, we develop an enzymatic procedure to build polyprotein using the combination of a strict protein ligase OaAEP1 (Oldenlandia affinis asparaginyl endopeptidases 1) and a protease TEV (tobacco etch virus). We firstly demonstrate the use of OaAEP1-alone to build a sequence-uncontrolled ubiquitin polyprotein and covalently immobilize the coupled protein on the surface. Then, we construct a poly-metalloprotein, rubredoxin, from the purified monomer. Lastly, we show the feasibility of synthesizing protein polymers with rationally-controlled sequences by the synergy of the ligase and protease, which are verified by protein unfolding using atomic force microscopy-based single-molecule force spectroscopy (AFM-SMFS). Thus, this study provides a strategy for polyprotein engineering and immobilization.
Endothelial cell clonal expansion in the development of cerebral cavernous malformations
Authors: Malinverno Matteo , Maderna Claudio , Abu Taha Abdallah , Corada Monica , Orsenigo Fabrizio , Valentino Mariaelena , Pisati Federica , Fusco Carmela , Graziano Paolo , Giannotta Monica , Yu Qing Cissy , Zeng Yi Arial , Lampugnani Maria Grazia , Magnusson Peetra U. , Dejana Elisabetta
Published: June 2019

Cerebral cavernous malformation (CCM) is a neurovascular familial or sporadic disease that is characterised by capillary-venous cavernomas, and is due to loss-of-function mutations to any one of three CCM genes. Familial CCM follows a two-hit mechanism similar to that of tumour suppressor genes, while in sporadic cavernomas only a small fraction of endothelial cells shows mutated CCM genes. We reported that in mouse models and in human patients, endothelial cells lining the lesions have different features from the surrounding endothelium, as they express mesenchymal/stem-cell markers. Here we show that cavernomas originate from clonal expansion of few Ccm3-null endothelial cells that express mesenchymal/stem-cell markers. These cells then attract surrounding wild-type endothelial cells, inducing them to express mesenchymal/stem-cell markers and to contribute to cavernoma growth. These characteristics of Ccm3-null cells are reminiscent of the tumour-initiating cells that are responsible for tumour growth. Our data support the concept that CCM has benign tumour characteristics.
Variation in trends of consumption based carbon accounts
Authors: Wood Richard , Moran Daniel D. , Rodrigues João F. D. , Stadler Konstantin
Published: June 2019

The UNFCCC requires the annual reporting of greenhouse gas emissions. These inventories focus on emissions within a territory, and do not capture the effect of emissions embodied in imports. Consumption based carbon accounting (CBCA) has been proposed as a complementary method to capture these emissions, and a number of global models have been developed to operationalise CBCA. However, discrepancies in country-level CBCA results occur, which can cause concern for the practical use of CBCA. Despite these quantitative difference in results, do they provide robust results when changes over time are investigated? Here we present results of all the major global models and normalise the model results by looking at changes over time relative to a common base year value. We give an analysis of the variability across the models, both before and after normalisation in order to give insights into variance at national and regional level. A dataset of harmonised results (based on means) and measures of dispersion is presented, providing a baseline dataset for CBCA validation and analysis.
Controlling for Artifacts in Widefield Optical Coherence Tomography Angiography Measurements of Non-Perfusion Area
Authors: De Pretto Lucas R. , Moult Eric M. , Alibhai A. Yasin , Carrasco-Zevallos Oscar M. , Chen Siyu , Lee ByungKun , Witkin Andre J. , Baumal Caroline R. , Reichel Elias , de Freitas Anderson Zanardi , Duker Jay S. , Waheed Nadia K. , Fujimoto James G.
Published: June 2019

The recent clinical adoption of optical coherence tomography (OCT) angiography (OCTA) has enabled non-invasive, volumetric visualization of ocular vasculature at micron-scale resolutions. Initially limited to 3 mm × 3 mm and 6 mm × 6 mm fields-of-view (FOV), commercial OCTA systems now offer 12 mm × 12 mm, or larger, imaging fields. While larger FOVs promise a more complete visualization of retinal disease, they also introduce new challenges to the accurate and reliable interpretation of OCTA data. In particular, because of vignetting, wide-field imaging increases occurrence of low-OCT-signal artifacts, which leads to thresholding and/or segmentation artifacts, complicating OCTA analysis. This study presents theoretical and case-based descriptions of the causes and effects of low-OCT-signal artifacts. Through these descriptions, we demonstrate that OCTA data interpretation can be ambiguous if performed without consulting corresponding OCT data. Furthermore, using wide-field non-perfusion analysis in diabetic retinopathy as a model widefield OCTA usage-case, we show how qualitative and quantitative analysis can be confounded by low-OCT-signal artifacts. Based on these results, we suggest methods and best-practices for preventing and managing low-OCT-signal artifacts, thereby reducing errors in OCTA quantitative analysis of non-perfusion and improving reproducibility. These methods promise to be especially important for longitudinal studies detecting progression and response to therapy.
The logic behind neural control of breathing pattern
Authors: Ben-Tal Alona , Wang Yunjiao , Leite Maria C. A.
Published: June 2019

The respiratory rhythm generator is spectacular in its ability to support a wide range of activities and adapt to changing environmental conditions, yet its operating mechanisms remain elusive. We show how selective control of inspiration and expiration times can be achieved in a new representation of the neural system (called a Boolean network). The new framework enables us to predict the behavior of neural networks based on properties of neurons, not their values. Hence, it reveals the logic behind the neural mechanisms that control the breathing pattern. Our network mimics many features seen in the respiratory network such as the transition from a 3-phase to 2-phase to 1-phase rhythm, providing novel insights and new testable predictions.
An Effective Meta-analysis of Magnetic Stimulation Therapy for Urinary Incontinence
Authors: He Qing , Xiao Kaiwen , Peng Liao , Lai Junyu , Li Hong , Luo Deyi , Wang Kunjie
Published: June 2019

Magnetic stimulation (MS) is a novel approach for treating urinary incontinence (UI), but its applicability remains unclear. This systematic review and meta-analysis were conducted to evaluate the effects of MS treatment on UI. A literature search was performed in EMBASE, PubMed and Cochrane Library (from May 2018 to August 2018), and all randomized control trials (RCTs) published in English were screened to determine whether they met the inclusion criteria. A manual search of the reference lists of the retrieved studies was also performed. Eleven studies involving 612 patients were included in this review. According to the results of the meta-analysis, MS therapy relieved UI symptoms evaluated using the International Consultation on Incontinence Questionnaire-Short Form (ICIQ-SF) score (mean difference [MD] −3.03, 95% CI −3.27 to −2.79). In addition, the frequency of UI in the MS treatment group was also alleviated compared with sham group (MD −1.42, 95% CI −2.15 to −0.69). Finally, MS treatment improved the quality of life of patients with UI (standardized mean difference [SMD] −1.00, 95% CI −1.24 to −0.76). Our meta-analysis preliminarily indicates that MS treatment is an effective therapeutic modality for patients with UI. Nevertheless, additional large, high quality RCTs with a longer follow-up period that use consistent stimulation methods and analyse comparable outcomes are required to validate the efficacy.
Protective effects of the Francisella tularensis ΔpdpC mutant against its virulent parental strain SCHU P9 in Cynomolgus macaques
Authors: Tian Deyu , Uda Akihiko , Ami Yasushi , Hotta Akitoyo , Park Eun-sil , Nagata Noriyo , Iwata-Yoshikawa Naoko , Yamada Akio , Hirayama Kazuhiro , Miura Kozue , Koyama Yuki , Azaki Mika , Morikawa Shigeru
Published: June 2019

Tularemia is a severe infectious zoonotic disease caused byFrancisella tularensis. AlthoughF. tularensisis considered to be a potential biological weapon due to its high infectivity and mortality rate, no vaccine has been currently licensed. Recently, we reported thatF. tularensisSCHU P9 derived ΔpdpCstrain lacking the pathogenicity determinant protein C gene conferred stable and good protection in a mouse lethal model. In this study, the protective effect of ΔpdpCwas evaluated using a monkey lethal model. Two cynomolgus macaques (Macaca fascicularis) intratracheally challenged with the virulent strain SCHU P9 were euthanized on 7 and 11 days post-challenge after the development of severe clinical signs. The bacterial replication in alveolar macrophages and type II epithelial cells in the lungs would cause severe pneumonia accompanied by necrosis. Conversely, two animals subcutaneously immunized with ΔpdpCsurvived 3 weeks after SCHU P9 challenge. Though one of the two animals developed mild symptoms of tularemia, bacterial replication was limited in the respiratory organs, which may be due to a high level of humoral and cellular immune responses againstF. tularensis. These results suggest that the ΔpdpCmutant would be a safe and promising candidate as a live attenuated tularemia vaccine.
Field trial of a probiotic bacteria to protect bats from white-nose syndrome
Authors: Hoyt Joseph R. , Langwig Kate E. , White J. Paul , Kaarakka Heather M. , Redell Jennifer A. , Parise Katy L. , Frick Winifred F. , Foster Jeffrey T. , Kilpatrick A. Marm
Published: June 2019

Tools for reducing wildlife disease impacts are needed to conserve biodiversity. White-nose syndrome (WNS), caused by the fungus Pseudogymnoascus destructans, has caused widespread declines in North American bat populations and threatens several species with extinction. Few tools exist for managers to reduce WNS impacts. We tested the efficacy of a probiotic bacterium, Pseudomonas fluorescens, to reduce impacts of WNS in two simultaneous experiments with caged and free-flying Myotis lucifugus bats at a mine in Wisconsin, USA. In the cage experiment there was no difference in survival between control and P. fluorescens-treated bats. However, body mass, not infection intensity, predicted mortality, suggesting that within-cage disturbance influenced the cage experiment. In the free-flying experiment, where bats were able to avoid conspecific disturbance, infection intensity predicted the date of emergence from the mine. In this experiment treatment with P. fluorescens increased apparent overwinter survival five-fold compared to the control group (from 8.4% to 46.2%) by delaying emergence of bats from the site by approximately 32 days. These results suggest that treatment of bats with P. fluorescens may substantially reduce WNS mortality, and, if used in combination with other interventions, could stop population declines.
Genome-wide analyses of long non-coding RNA expression profiles and functional network analysis in esophageal squamous cell carcinoma
Authors: Ma Junliang , Xiao Yuhang , Tian Bo , Chen Shaolin , Zhang Baihua , Wu Jie , Wu Zhining , Li Xu , Tang Jinming , Yang Desong , Zhou Yong , Wang Hui , Su Min , Wang Wenxiang
Published: June 2019

Esophageal cancer (EC) is a serious malignancy and that is the fifth leading cause of cancer-related death worldwide. Esophageal squamous cell carcinoma (ESCC) is the main subtype of EC in China. In recent years, long non-coding RNAs (lncRNAs) have demonstrated to be novel tumor-associated regulatory factors. However, the functions and mechanisms of lncRNAs in ESCC have not been fully understood. In this study, we attempted to construct Genome-wide expression profiles of lncRNAs and their potential functions in ESCC. By using microarray, we found a total of 2,366 lncRNAs (1,032 upregulated and 1,334 downregulated) and 3,052 mRNAs (1,477 upregulated and 1,575 downregulated) were differentially expressed between the paired five ESCC tumor tissues and adjacent normal esophageal tissues (fold change, FC ≥2.0 or ≤0.5, p ≤ 0.05). Eight lncRNAs were detected by qRT-PCR to verify the results of the microarray, and the clinicopathological parameters were analyzed in 53 patients with ESCC. GO analysis and KEGG pathway analysis showed that the main biological functions of these abnormal lncRNAs were related to immune response, extracellular vesicular exosome, and protein binding. At the same time, the cis and trans models were used to analyze the potential synergistic regulatory relationship between lncRNAs and their potential target genes. Related genes were the processes that affect cell growth, differentiation, and migration. Then we mapped the lncRNAs-mRNAs co-expression pattern by calculating the PCCs of each lncRNA and mRNA expression value. Furthermore, we investigated the function and potential mechanism of a novel highly expressed lncRNA, lnc-KIAA1244-2, and found that its expression is associated with tumor size, N classification and clinical stage. Knockdown of lnc-KIAA1244-2 inhibited the cell proliferation and inhibited the TNFAIP3 expression in Eca-109 cells. Taken together, the expression patterns of lncRNAs and mRNAs in ESCC tumor tissues are different from those in normal adjacent tissues, and some abnormal expressed lncRNAs may play important roles in the development and progression of ESCC. Lnc-KIAA1244-2 could promote the cell proliferation of ESCC cells and might be a potent therapeutic target for ESCC.
The contribution of gut bacteria to insecticide resistance and the life histories of the major malaria vector Anopheles arabiensis (Diptera: Culicidae)
Authors: Barnard Kirsten , Jeanrenaud Alexander C. S. N. , Brooke Basil D. , Oliver Shüné V.
Published: June 2019

The gut microbiota of mosquitoes is a crucial determinant of their fitness. As such, the biology of the gut microbiota of Anopheles arabiensis, a major malaria vector of Southern Africa, was investigated. Two laboratory strains of An. arabiensis were used; SENN, an insecticide susceptible strain, and SENN-DDT, a resistant strain. The strains were supplemented with either non-commensal bacteria or antibiotics via a sucrose source to sterilize the gut. The strains were fed the broad-spectrum bactericidal antibiotic gentamicin, or a preferentially gram-positive bactericidal (vancomycin), gram-negative bactericidal (streptomycin) or broad-spectrum bacteriostatic (erythromycin), either by sugar supplementation or by artificially-spiked blood-meal. The effects on adult mosquito longevity and insecticide resistance phenotype were assessed. Bacteria from the midgut of both strains were characterised by MALDI-TOF mass spectroscopy. Bactericidal antibiotics increased longevity in SENN-DDT. Bacterial supplementation increased insecticide tolerance. Antibiotic supplementation via sugar decreased tolerance to the insecticides deltamethrin and malathion. Blood-supplemented vancomycin decreased insecticide resistance, while gentamicin and streptomycin increased resistance. SENN showed a greater gut bacterial diversity than SENN-DDT, with both strains dominated by Gram-negative bacteria. This study suggests a crucial role for bacteria in An. arabiensis life history, and that gut microflora play variable roles in insecticide resistant and susceptible mosquitoes.
Patterning of High-Viscosity Silver Paste by an Electrohydrodynamic-Jet Printer for Use in TFT Applications
Authors: Can Thi Thu Thuy , Nguyen Tuan Canh , Choi Woon-Seop
Published: June 2019

Electrohydrodynamic (EHD) jet printing has a variety of benefits compared to conventional inkjet techniques, such as high resolution and the ability to work with high-viscosity pastes. In this work, Ag nanoparticles with 4000 cPs were chosen because they are printable on various substrates for electronic devices. The effects of additive on the high-viscosity Ag paste formulation were investigated, and pattern lines narrower than 100 μm were achieved by EHD-jet printing with an average sheet resistance of 0.027 Ω □−1. Furthermore, solution-processed oxide TFTs were fabricated with EHD jet-printed Ag electrodes for the first time. The electrical properties obtained were a current ratio of 1.5 × 106, a mobility of approximately 1 cm2 V−1s−1, a threshold voltage of 21.5 V, and a subthreshold slope of 3.05 V dec−1.