bluuebunny/crossref_metadata_2025 huggingface dataset:
Local Candidate Effects in Canadian Elections
Authors: Allen Stevens Benjamin , Islam Md Mujahedul , de Geus Roosmarijn , Goldberg Jonah , McAndrews John R. , Mierke-Zatwarnicki Alex , Loewen Peter John , Rubenson Daniel
Published: August 2018

What impact do local candidates have on elections in single member district plurality electoral systems? We provide new evidence using data from a large election study carried out during the 2015 Canadian federal election. We improve on the measurement of local candidate effects by asking over 20,000 survey respondents to rate the candidates in their constituencydirectly. We present three estimates. We find that when all voters are considered together, local candidate evaluations are decisive for approximately 4 per cent of voters. Second, these evaluations are decisive for the outcome of 10 per cent of constituency contests. Third, when models are estimated for each constituency, we find significant evaluation effects for 14 per cent of candidates.
On a Criterion of Local Invertibility and Conformality for Slice Regular Quaternionic Functions
Authors: Gori Anna , Vlacci Fabio
Published: August 2018

A new criterion for local invertibility of slice regular quaternionic functions is obtained. This paper is motivated by the need to find a geometrical interpretation for analytic conditions on the real Jacobian associated with a slice regular function f. The criterion involves spherical and Cullen derivatives of f and gives rise to several geometric implications, including an application to related conformality properties.
Quantitation of viableCoxiella burnetiiin milk products using a liquid medium-based MPN-PCR assay
Authors: Shi Manman , Zhang Cheng , Stewart Diana
Published: August 2018

This Technical Research Communication describes a new method by which thermally treatedCoxiellain milk products may be grown in a liquid growth medium and quantitated using an MPN-PCR assay.Coxiellais generally not used in studies on thermal and non-thermal processing of milk due to the need for specialized and highly laborious techniques such as animal assays and tissue culture for determining viability. Recently, a liquid growth medium (ACCM-2) and modified atmosphere were used to growCoxiellafrom pure cultures, infected mouse tissues, and clinical samples, however, the ability to growCoxiellafrom a food such as milk has not been shown. The potential ability to enrichCoxielladirectly from contaminated milk presents a new avenue for conducting pasteurization research in which the viability of heat-treated or injured cultures could be more easily determined through direct enrichment ofCoxiellain ACCM-2. ACCM-2 medium allowed enrichment ofCoxiellafrom bovine whole milk and cream, whole goat, and whole camel milks but not whole water buffalo milk. Enrichment was possible from whole bovine milk containing as few as 6Coxiellage/ml of milk. The applicability of this ACCM-2 enrichment method was shown when using an MPN-PCR assay to quantitate the number of viableCoxiellaremaining in whole bovine milk after 64 °C thermal treatment for up to 10 min.
Co-occurrence of swine cysticercosis due toTaenia soliumandTaenia hydatigenain ethnic minority villages at the Thai–Myanmar border
Authors: Chaisiri K. , Kusolsuk T. , Homsuwan N. , Sanguankiat S. , Dekumyoy P. , Peunpipoom G. , Khiriphattharaphon S. , Sako Y. , Yanagida T. , Okamoto M. , Ito A.
Published: August 2018

As part of the international joint projects working towards the control of taeniosis/cysticercosis in Asia Pacific, epidemiological studies onTaenia soliumcysticercosis have been carried out in high-incidence populations, such as minority groups in Thailand. To assess the epidemiology of cysticercotic infections in pigs in the hill-tribe minority villages (Karen) in Tak province, Thailand, we conducted serological screening and necropsies. The patterns of antibody response toT. soliumantigens were then investigated using immunoblot assays. Of the 188 pig serum samples tested for antibody responses to partially purified low-molecular-weight antigens ofT. soliumcyst fluid, positive responses were detected in 37 samples (19.7%). Based on these results, 16 pigs (10 seropositive and 6 seronegative) were necropsied for investigation of cysticerci and intestinal parasites. All seropositive pigs were coinfected with bothT. soliumandTaenia hydatigenacysticerci, except one, which was infected withT. hydatigenaalone. Three of the six seronegative pigs were confirmed to be infected withT. hydatigena.Pigs infected withT. soliumshowed much stronger antibody responses than those infected withT. hydatigena. Our results demonstrate the co-occurrence of two swine cysticercoses due toT. soliumandT. hydatigenain the studied areas. This study also reveals the importance of direct confirmation of the presence of cysticerci by necropsy after serological screening. In addition to the prevalence of swine cysticercosis in these endemic areas, our findings also reveal potential implications for the development of serological diagnostic assays for swine cysticercosis.
Taking War Seriously
Authors: Blattberg Charles
Published: August 2018

Just war theory − as advanced by Michael Walzer, among others − fails to take war seriously enough. This is because it proposes that we regulate war with systematic rules that are comparable to those of a game. Three types of claims are advanced. The first is phenomenological: that the theory's abstract nature interferes with our judgment of what is, and should be, going on. The second is meta-ethical: that the theory's rules are not, in fact, systematic after all, there being inherent contradictions between them. And the third is practical: that by getting people to view war as like a game, the theory promotes its ‘aestheticization’ (play being a central mode of the aesthetic) such that those who fight are encouraged to act in dangerous ways. And war, it goes without saying, is already dangerous enough.
Depression across pregnancy and the postpartum, antidepressant use and the association with female sexual function
Authors: Galbally Megan , Watson Stuart J. , Permezel Michael , Lewis Andrew J.
Published: August 2018

Background

There is an established relationship between depression and sexual functioning in women. However, there is limited research examining the relationship between perinatal depression and sexual functioning.

Methods

This study draws on the Mercy Pregnancy and Emotional Wellbeing Study and reports on 211 women recruited in early pregnancy and followed to 12 months postpartum. Women were assessed for depression using the Structured Clinical Interview for the DSM-IV, repeated measurement of depressive symptoms using the Edinburgh Postnatal Depression Scale and sexual functioning using the Female Sexual Functioning Inventory. Data were also collected on antidepressant use, mode of delivery, history of childhood trauma, breastfeeding and partner support.

Results

Women showed a decline in sexual functioning over pregnancy and the first 6 months postpartum, which recovered by 12 months. For women with depression, sexual functioning was lower throughout pregnancy and continued to be lower at 6 months postpartum than those without depression. Ongoing depressive symptoms at 12 months were also associated with lower sexual functioning. Sexual functioning was not predicted by mode of delivery, antidepressant use or childhood trauma. Breastfeeding predicted lower sexual functioning only at 6 months. Higher partner support predicted higher female sexual functioning.

Conclusions

Pregnancy and the postpartum are a time of reduced sexual functioning for women; however, women with depression are more likely to have lower levels of sexual functioning and this was not predicted by antidepressant use. In women with perinatal depression, consideration of the impact on sexual functioning should be an integral part of care.
Human, social and cultural predictors of productive activities in later life
Authors: Kim Seoyoun
Published: August 2018

While considerable scholarly attention has been given to factors influencing productive activity, less is known about how multiple forms of resources predict the maintenance or initiation of such activity over time. Using two-wave panel data of older adults from the National Social Life, Health, and Aging Project (NSHAP), the study investigated the relationship between measures of capital and changes in multiple types of productive activity. Findings showed that all three types of capital were associated with volunteering in cross-sectional analyses, but only education, neighbourhood socialisation and religious service attendance remain significant predictors of continued volunteerism. Human capital strongly influenced employment both cross-sectionally and over time. Aspects of social capital – marital status and network size – were linked to participation and initiation of care-giving activities. The findings demonstrate that different patterns emerge in cross-sectional and two-wave panel data of multiple productive activities, adjusting for baseline activity level and selective attrition. The project also suggests factors that promote or hinder continued engagement in productive activity.
Larger Chinese text spacing and size: effects on older users’ experience
Authors: Hou Guanhua , Dong Hua , Ning Weining , Han Lianghao
Published: August 2018

With declining vision ability, character spacing and size on smartphones designed for the general population are not accessible for older adults. This study aimed to explore how larger Chinese character spacing and size affect older adults’ user experience (UX). An orthogonal experiment was conducted. The optimal range of font size (FS), word spacing (WS) and line spacing (LS) were proposed utilising subjective evaluations to investigate the correlation of eye movement data with participants perceived UX. The results showed that improvement in different aspects of UX varied when FS, WS and LS increased. Overall, participants preferred larger FS, WS and LS, however, the larger FS, WS and LS values are more likely to cause errors and slower reading speed. These results suggest that the distinct combination of size and spacing depends on the motivation, needs and situation of older people when reading on a smartphone. These findings will help designers to provide better design for the older people.
Promises and pitfalls of integrating home-based health services into Shanghai's elder-care system
Authors: Chen Yan-Yan , Chen Honglin , Song Priscilla
Published: August 2018

Faced with the dramatic pace of population ageing, the Shanghai municipal government launched a pilot programme in 2013 designed to address this and to strengthen ageing-in-place arrangements by providing basic in-home medical services for residents above the age of 80. Yet after a two-year trial run, the ‘Home-Based Medical Care Scheme for the Oldest-Old’ (HBMCSOO) policy remained significantly under-utilised despite the increasing demand for medical services. Our multi-disciplinary research team of social workers and anthropologists identified two key factors impeding the implementation of home-based medical care services: (a) the distortion of policy implementation and (b) the inadequate professionalisation of community-based elder-care workers. Based on our evaluation of the pilot programme, the Shanghai municipal government made several practical adjustments to improve the subsequent city-wide policy implemented in 2016. While these changes mostly focused on minor adjustments to improve in-home medical services for the oldest-old, they represent an encouraging first step towards our call for a holistic integrated care system whose design and delivery takes into account local political and social contexts, including existing institutional infrastructure and cultural expectations about care-giving responsibilities. The challenges of implementing Shanghai's HBMCSOO policy ultimately provide instructive lessons on best practices for integrating medical and social services in order to improve ageing-in-place measures in diverse local settings around the world.
Rietveld refinement of X-ray powder diffraction data of Ca0.925Ce0.075Mn0.9Fe0.1O3 polycrystalline material
Authors: Murugesan G. , Nandan K. R. , Kalainathan S.
Published: August 2018

Polycrystalline Ca0.925Ce0.075Mn0.9Fe0.1O3 were prepared by sol-gel reaction at 1073 K. The compound was analyzed by a powder X-ray diffraction technique and found to be in single phase. The unit-cell parameters and atomic positions were refined using General Structure Analysis to an orthorhombic structure with space group Pnma (#62) a = 5.281 90 (33) Å, b = 7.4968 (45) Å, and c = 5.302 90 (32) Å.
A methodology for part classification with supervised machine learning
Authors: Rucco Matteo , Giannini Franca , Lupinetti Katia , Monti Marina
Published: August 2018

In this paper, we report on a data analysis process for the automated classification of mechanical components. In particular, here, we describe, how to implement a machine learning system for the automated classification of parts belonging to several sub-categories. We collect models that are typically used in the mechanical industry, and then we represent each object by a collection of features. We illustrate how to set-up a supervised multi-layer artificial neural network with an ad-hoc classification schema. We test our solution on a dataset formed by 2354 elements described by 875 features and spanned among 15 sub-categories. We state the accuracy of classification in terms of average area under ROC curves and the ability to classify 606 unknown 3D objects by similarity coefficients. Our parts’ classification system outperforms a classifier based on the Light Field Descriptor, which, as far as we know, actually represents the gold standard for the identification of most types of 3D mechanical objects.
Excess mortality in Guadeloupe and Martinique, islands of the French West Indies, during the chikungunya epidemic of 2014
Authors: Freitas A. R. R. , Alarcón-Elbal P. M. , Donalisio M. R.
Published: August 2018

In some chikungunya epidemics, deaths are not completely captured by traditional surveillance systems, which record case and death reports. We evaluated excess deaths associated with the 2014 chikungunya virus (CHIKV) epidemic in Guadeloupe and Martinique, Antilles. Population (784 097 inhabitants) and mortality data, estimated by sex and age, were accessed from the Institut National de la Statistique et des Études Économiques in France. Epidemiological data, cases, hospitalisations and deaths on CHIKV were obtained from the official epidemiological reports of the Cellule de Institut de Veille Sanitaire in France. Excess deaths were calculated as the difference between the expected and observed deaths for all age groups for each month in 2014 and 2015, considering the upper limit of 99% confidence interval. The Pearson correlation coefficient showed a strong correlation between monthly excess deaths and reported cases of chikungunya (R= 0.81,p< 0.005) and with a 1-month lag (R= 0.87,p< 0.001); and a strong correlation was also observed between monthly rates of hospitalisation for CHIKV and excess deaths with a delay of 1 month (R= 0.87,p< 0.0005). The peak of the epidemic occurred in the month with the highest mortality, returning to normal soon after the end of the CHIKV epidemic. There were excess deaths in almost all age groups, and excess mortality rate was higher among the elderly but was similar between male and female individuals. The overall mortality estimated in the current study (639 deaths) was about four times greater than that obtained through death declarations (160 deaths). Although the aetiological diagnosis of all deaths associated with CHIKV infection is not always possible, already well-known statistical tools can contribute to the evaluation of the impact of CHIKV on mortality and morbidity in the different age groups.
How Landslides Become Disasters
Authors: Lehmann Peter , von Ruette Jonas , Or Dani
Published: August 2018

A new modeling platform, tested on two recent natural disasters, simulates conditions that dump landslide debris into rain-swollen rivers, often causing more damage than the landslides themselves.
A Detailed View on the Seasonality of Stable Carbon Isotopes Across the North Atlantic
Authors: Becker Meike , Steinhoff Tobias , Körtzinger Arne
Published: August 2018

The North Atlantic Ocean plays a major role in climate change not the least due to its importance in CO2 uptake and thus natural carbon sequestration. The CO2 concentration in its surface waters, which determines the ocean's CO2 sink/source function, varies on seasonal and interannual time scales and is mainly driven by air‐sea gas exchange, temperature variability, and biological production/respiration. The variability in stable carbon isotope signatures can provide further insight and help to improve the understanding of the controls of the surface ocean carbon system. In this work, a cavity ringdown spectrometer was coupled to a classical, equilibrator‐based pCO2 system on a voluntary observing ship line that regularly sails across the subpolar North Atlantic between North America and Europe. From 2012 to 2014, a 3‐year time series of underway surface δ13C(CO2) data was obtained along with continuous measurements of temperature, salinity, and fCO2. We perform a decomposition of thermal and nonthermal drivers of fCO2 and δ13C(CO2). The direct measurement of the surface ocean δ13C(CO2) allows us to estimate the mass flux and also the stable carbon isotope fractionation during air‐sea gas exchange. While the CO2 mass flow was in the range of 1–2 mol CO2·m−2·year−1 on the shelves and 2.5–3.5 mol CO2·m−2·year−1 in the open ocean, the isotope signature of this CO2 flux with respect to the sea surface ranged from −2.6 ± 1.4‰ on the shelves to −6.6 ± 0.9‰ in the western and −4.5 ± 0.9‰ in the eastern part of the open ocean section.
Characteristics of Water‐Heat Exchanges and Inconsistent Surface Temperature Changes at an Elevational Permafrost Site on the Qinghai‐Tibet Plateau
Authors: Luo D. L. , Jin H. J. , He R. X. , Wang X. F. , Muskett R. R. , Marchenko S. S. , Romanovsky V. E.
Published: August 2018

Increase of surface temperatures has long been recognized as an unequivocal response to radiative forcing and one of the most important implications for global warming. However, it remains unclear whether the variation of ground surface temperature (GST) and soil temperatures is consistent with simultaneous changes of the near‐surface air and land (or skin) surface temperatures (Ta and LST). In this study, a seven‐year continuous observation of GST, Ta, and surface water and heat exchange was carried out at an elevational permafrost site at Chalaping, northeastern Qinghai‐Tibet Plateau. Results showed a distinct retarding of warming on the ground surface and subsurface under the presence of dense vegetation and moist peat substrates. Mean annual Ta and LST increased at noteworthy rates of 0.22 and 0.32 °C/a, respectively, while mean annual GST increased only at a rate of 0.057 °C/a. No obvious trends were detected for the four radiation budgets except the soil heat flux (G), which significantly increased at a rate of 0.29 W · m−2 · a−1, presumably inducing the melting of ground ice and resulted in much higher moisture content through the summers of 2015 and 2016 than preceding years and subsequent 2017 at the depths between 80 and 120 cm. However, no noticeable immediate variations of soil temperatures occurred owing to the large latent heat effect (thermal inertia) and the extending zero‐curtain period. We suggest that a better protected eco‐environment, particularly the surface vegetation, helps preserving the underlying permafrost, and thus to mitigates the potential degradation of elevational permafrost on the Qinghai‐Tibet Plateau.
Large‐Scale Traveling Ionospheric Disturbances Origin and Propagation: Case Study of the December 2015 Geomagnetic Storm
Authors: Cherniak Iurii , Zakharenkova Irina
Published: August 2018

We investigate the origin, occurrence, and propagation of large‐scale traveling ionospheric disturbances (LSTIDs) over the European region during the 19–21 December 2015 geomagnetic storm. Analysis of the total electron content (TEC) perturbation component is supported by the ground‐based Global Positioning System (GPS) and GLONASS (In Russian: GLObalnaya NAvigazionnaya Sputnikovaya Sistema) observations. The high spatial‐temporal resolution mapping approach provides a very detailed specification of the ionospheric small‐ to large‐scale disturbances associated with two major sources of the LSTIDs generation: the solar terminator passage during the quiet time and auroral activity caused by auroral particle precipitation and field‐aligned currents (FACs) intensification during geomagnetic disturbances. For the first time, the joint analysis of the ionospheric plasma irregularities, FACs, and LSTIDs reveals that a zone with the intense FACs and ionospheric irregularities occurred at the same region that represent the most probable source of LSTIDs excitation. During the main phase of the storm, the LSTIDs propagated equatorward from European high latitudes to middle latitudes (35–40°N) with the horizontal velocities of ~700–800 m/s. The LSTIDs as deduced from the TEC‐disturbed component had a much larger magnitude and propagate much longer distances during the daytime (sunlit part) than in the night. We found that an equatorward expansion of the strong ionospheric irregularities zone and an increase of the FACs magnitude led to a simultaneous intensification of the LSTIDs occurrence at high latitudes. The GPS ROTI (rate of TEC index) technique, a sensitive one for detection of the rapid ionospheric gradients and irregularities, could not recognize any signatures of the TIDs structures.
Examining the Potential of the Super Dual Auroral Radar Network for Monitoring the Space Weather Impact of Solar X‐Ray Flares
Authors: Fiori R. A. D. , Koustov A. V. , Chakraborty S. , Ruohoniemi J. M. , Danskin D. W. , Boteler D. H. , Shepherd S. G.
Published: August 2018

Increased electron density in the ionosphere due to photoionization by radiation emitted during a solar X‐ray flare impacts high‐frequency (HF) radio wave propagation. Shortwave fadeout (SWF) due to the enhanced D region absorption that results is characterized by the level of cosmic radio noise attenuation derived from riometer measurements. SWF impacts HF radio propagation and has been identified in the Super Dual Auroral Radar Network (SuperDARN) data. An X2.1 solar X‐ray flare that erupted on 11 March 2015 is examined to determine its effects on HF radio propagation. Riometer data indicate a sharp enhancement in absorption, which falls off with increasing solar zenith angle. SuperDARN radars observed a suppression of both ground scatter and ionospheric echoes. Ground scatter data indicated a rapid weakening of signal from far to near ranges followed by a ~20‐min interval of complete signal loss. Recovery lasted ~30 min and proceeded from near to far ranges. Prior to the complete signal loss, an apparent sharp velocity impulse (Doppler flash) lasting 1–2 min was observed in the ground scatter data. The peak of this flash preceded the onset of enhanced absorption. The onset of signal loss by SuperDARN preceded the onset of enhanced absorption observed by riometers. Both data sets observed a positive correlation between increasing delay in onset and increasing solar zenith angle with onset progressing at an average rate of 16.7°/min (0.060 min/°). Agreement between riometer and SuperDARN indicates the possibility of using a joint data set for improved monitoring of the space weather impact of solar X‐ray flares.
Seismic Tomography of Eastern Tibet: Implications for the Tibetan Plateau Growth
Authors: Zhang Fengxue , Wu Qingju , Li Yonghua , Zhang Ruiqing , Sun Lian , Pan Jiatie , Ding Zhifeng
Published: August 2018

The eastern region of the Tibetan Plateau and surrounding regions have gentle to moderate topographic gradients, contrasting the steep margins in northern and southern Tibet. The mechanisms for plateau growth in eastern Tibet are uncertain so far. Here we present a new shear wave tomography model of the Tibetan Plateau derived from S wave traveltimes from teleseismic waveforms recorded by the dense ChinArray seismic network. The model reveals the deep structures beneath the eastern region of the Tibetan Plateau and its adjacent regions, showing clear velocity contrast boundaries roughly along the eastern margins of the Tibetan Plateau. We interpret the slow velocity anomalies beneath the Tibetan Plateau as soft lithosphere, which absorbed most of the northeastward push of the Indian Plate, while the fast velocity anomalies beneath the region surrounding the plateau represent craton‐like rigid block roots. The deformation of the soft/weak lithospheric mantle beneath the Tibetan Plateau is constrained by the convergence between the Indian and Eurasian plates, and the framework of the surrounding rigid blocks. We suggest that weak lithosphere deformation (horizontal shortening and vertical stretching) accounts for the plateau growth in eastern Tibet.
PRMT1 mediates RANKL-induced osteoclastogenesis and contributes to bone loss in ovariectomized mice
Authors: Choi Joo-Hee , Jang Ah-Ra , Kim Dong-il , Park Min-Jung , Lim Seul-Ki , Kim Myung-Sun , Park Jong-Hwan
Published: August 2018

Protein arginine methylation is a novel form of posttranslational modification mediated by protein arginine methyltransferase (PRMTs). PRMT1, a major isoform of the PRMT family, is responsible for various biological functions, including cellular differentiation. Although the important function that PRMT1 plays in various tissues is being increasingly recognized, its role in receptor activation of NF-κB ligand (RANKL)-induced osteoclastogenesis or osteoporosis has not yet been described. Here, we show that PRMT1 is essential for RANKL-induced osteoclastogenesis in vitro and for bone loss in vivo. RANKL treatment increased the expression of PRMT1 and its nuclear localization in bone marrow-derived macrophages (BMDMs) in a c-Jun N-terminal kinase (JNK)-dependent manner. Silencing PRMT1 attenuated RANKL-induced osteoclastogenesis by decreasing tartrate-resistant acid phosphatase (TRAP)-positive cells and inhibiting F-actin ring formation and bone resorption, which was confirmed in a separate experiment using haploinsufficient cells fromPRMT1+/-mice. Our results also revealed that PRMT1 regulates the transcription activity of NF-κB by directly interacting with it in RANKL-treated BMDMs. An in vivo study showed that the haploinsufficiency of PRMT1 reduced the enzyme activity of TRAP and increased the bone mineral density in the metaphysis of ovariectomized (OVX) mice. Finally, treatment with estrogen (E2) downregulated the RANKL-induced expression of PRMT1, suggesting that estrogen may exert an inhibitory effect on osteoclastogenesis by suppressing PRMT1 expression. Our results suggest that PRMT1 plays an important role in the progression of osteoporosis and that it might be a good therapeutic target for postmenopausal osteoporosis.
Structured illumination microscopy imaging reveals localization of replication protein A between chromosome lateral elements during mammalian meiosis
Authors: Yoon Seobin , Choi Eui-Hwan , Kim Jung-Woong , Kim Keun P.
Published: August 2018

An important event enabling meiotic prophase I to proceed is the close juxtaposition of conjoined chromosome axes of homologs and their assembly via an array of transverse filaments and meiosis-specific axial elements into the synaptonemal complex (SC). During meiosis, recombination requires the establishment of a platform for recombinational interactions between the chromosome axes and their subsequent stabilization. This is essential for ensuring crossover recombination and proper segregation of homologous chromosomes. Thus, well-established SCs are essential for supporting these processes. The regulation of recombination intermediates on the chromosome axis/SC and dynamic positioning of double-strand breaks are not well understood. Here, using super-resolution microscopy (structured illumination microscopy), we determined the localization of the replication protein A (RPA) complex on the chromosome axes in the early phase of leptonema/zygonema and within the CEs of SC in the pachynema during meiotic prophase in mouse spermatocytes. RPA, which marks the intermediate steps of pairing and recombination, appears in large numbers and is positioned on the chromosome axes at the zygonema. In the pachynema, RPA foci are reduced but do not completely disappear; instead, they are placed between lateral elements. Our results reveal the precise structure of SC and localization dynamics of recombination intermediates on meiocyte chromosomes undergoing homolog pairing and meiotic recombination.
Metabolic reprogramming of acute lymphoblastic leukemia cells in response to glucocorticoid treatment
Authors: Dyczynski Matheus , Vesterlund Mattias , Björklund Ann-Charlotte , Zachariadis Vasilios , Janssen Jerry , Gallart-Ayala Hector , Daskalaki Evangelia , Wheelock Craig E. , Lehtiö Janne , Grandér Dan , Tamm Katja Pokrovskaja , Nilsson Roland
Published: August 2018

Glucocorticoids (GCs) are metabolic hormones with immunosuppressive effects that have proven effective drugs against childhood acute lymphoblastic leukemia (ALL). Yet, the role of metabolic reprogramming in GC-induced ALL cell death is poorly understood. GCs efficiently block glucose uptake and metabolism in ALL cells, but this does not fully explain the observed induction of autophagy and cell death. Here, we have performed parallel time-course proteomics, metabolomics, and isotope-tracing studies to examine in detail the metabolic effects of GCs on ALL cells. We observed metabolic events associated with growth arrest, autophagy, and catabolism prior to onset of apoptosis: nucleotide de novo synthesis was reduced, while certain nucleobases accumulated; polyamine synthesis was inhibited; and phosphatidylcholine synthesis was induced. GCs suppressed not only glycolysis but also entry of both glucose and glutamine into the TCA cycle. In contrast, expression of glutamine-ammonia ligase (GLUL) and cellular glutamine content was robustly increased by GC treatment, suggesting induction of glutamine synthesis, similar to nutrient-starved muscle. Modulating medium glutamine and dimethyl-α-ketoglutarate (dm-αkg) to favor glutamine synthesis reduced autophagosome content of ALL cells, and dm-αkg also rescued cell viability. These data suggest that glutamine synthesis affects autophagy and possibly onset of cell death in response to GCs, which should be further explored to understand mechanism of action and possible sources of resistance.
Overexpression of homeodomain-interacting protein kinase 2 (HIPK2) attenuates sepsis-mediated liver injury by restoring autophagy
Authors: Jiang Zhengyu , Bo Lulong , Meng Yan , Wang Chen , Chen Tianxing , Wang Changli , Yu Xiya , Deng Xiaoming
Published: August 2018

Sepsis is the leading cause of death in intensive care units worldwide. Autophagy has recently been shown to protect against sepsis-induced liver injury. Here, we investigated the roles of homeodomain-interacting protein kinase 2 (HIPK2) in the molecular mechanism of sepsis-induced liver injury. HIPK2 expression was reduced in sepsis-induced liver injury, and HIPK2 overexpression increased the survival rate and improved caecal ligation and puncture (CLP)-induced liver injury by reducing serum and liver aspartate transaminase (AST), alanine transaminase (ALT), and alkaline phosphatase (ALP) levels in mice with sepsis. HIPK2 overexpression significantly decreased CLP-induced release of inflammatory cytokines into the serum and attenuated oxidative stress-associated indicators in mice with CLP-induced liver injury, whereas HIPK2 knockdown produced the opposite results, suggesting that HIPK2 is a negative regulator of sepsis. Furthermore, HIPK2 overexpression inhibited lipopolysaccharide (LPS)-induced apoptosis of primary hepatocytes, increased the autophagic flux, and restored both autophagosome and autolysosome formation in the livers of CLP-induced mice by suppressing calpain signalling. Importantly, HIPK2 overexpression reduced the elevated cytosolic Ca2+ concentration in LPS-treated primary hepatocytes by interacting with calpain 1 and calmodulin. Finally, several anti-inflammatory drugs, including resveratrol, aspirin, vitamin E and ursolic acid, significantly increased the levels of the HIPK2 mRNA and protein by modulating promoter activity and the 3′-UTR stability of the HIPK2 gene. In conclusion, HIPK2 overexpression may improve sepsis-induced liver injury by restoring autophagy and thus might be a promising target for the clinical treatment of sepsis.
PARP12 (ARTD12) suppresses hepatocellular carcinoma metastasis through interacting with FHL2 and regulating its stability
Authors: Shao Changjuan , Qiu Yangyang , Liu Juan , Feng Huan , Shen Suqin , Saiyin Hexige , Yu Wenbo , Wei Youheng , Yu Long , Su Wei , Wu Jiaxue
Published: August 2018

PARP12 is a mono-ADP-ribosyltransferase, but its function remains largely unknown. Here, we identified four-and-a-half LIM-only protein 2 (FHL2) as a functional partner of PARP12 through protein affinity purification. Although PARP12 did not mono-ADP-ribosylate FHL2 in vitro and in vivo, PARP12 deficiency decreased the protein level of FHL2 by promoting its ubiquitination and increased the expression level of transforming growth factor beta1 (TGF-β1), which is independent of PARP12 enzymatic activity. We also provided evidence that PARP12 deficiency increased the migration and invasion of hepatocellular carcinoma (HCC) cells and promoted HCC metastasis in vivo by regulating the epithelial–mesenchymal transition process. These results indicated that PARP12 is a tumor suppressor that plays an important role in HCC metastasis through the regulation of FHL2 stability and TGF-β1 expression.
Recombinant milk fat globule-EGF factor-8 reduces apoptosis via integrin β3/FAK/PI3K/AKT signaling pathway in rats after traumatic brain injury
Authors: Gao Yong-Yue , Zhang Zi-Huan , Zhuang Zong , Lu Yue , Wu Ling-Yun , Ye Zhen-nan , Zhang Xiang-Sheng , Chen Chun-Lei , Li Wei , Hang Chun-Hua
Published: August 2018

Accumulating evidence suggests neuronal apoptosis has the potential to lead to more harmful effects in the pathological processes following traumatic brain injury (TBI). Previous studies have established that milk fat globule-EGF factor-8 (MFG-E8) provides neuroprotection through modulation of inflammation, oxidative stress, and especially apoptosis in cerebral ischemia and neurodegenerative disease. However, the effects of MFG-E8 on neuronal apoptosis in TBI have not yet been investigated. Therefore, we explored the role of MFG-E8 on anti-apoptosis and its potential mechanism following TBI. In the first set of experiments, adult male Sprague–Dawley (SD) rats were randomly divided into Sham and TBI groups that were each further divided into five groups representing different time points (6 h, 24 h, 72 h, and 7 days) (n = 9 each). Western blotting, quantitative real-time PCR, and immunofluorescence staining were performed to identify the expression and cellular localization of MFG-E8. In the second set of experiments, four groups were randomly assigned: Sham group, TBI + Vehicle group, and TBI + rhMFG-E8 (1 and 3 µg) (n = 15). Recombinant human MFGE8 (rhMFG-E8) was administrated as two concentrations through intracerebroventricular (i.c.v.) injection at 1 h after TBI induction. Brain water content, neurological severity score, western blotting, and immunofluorescence staining were measured at 24 and 72 h following TBI. In the final set of experiments, MFG-E8 siRNA (500 pmol/3 µl), integrin β3 siRNA (500 pmol/3 µl), and PI3K inhibitor LY294002 (5 and 20 µM) were injected i.c.v. and thereafter rats exposed to TBI. Western blotting, immunofluorescence staining, brain water content, neurological severity score, and Fluoro-Jade C (FJC) staining were used to investigate the effect of the integrin-β3/FAK/PI3K/AKT signaling pathway on MFG-E8-mediated anti-apoptosis after TBI. The expression of MFG-E8 was mainly located in microglial cells and increased to peak at 24 h after TBI. Treatment with rhMFG-E8 (3 µg) markedly decreased brain water content, improved neurological deficits, and reduced neuronal apoptosis at 24 and 72 h after TBI. rhMFG-E8 significantly enhanced the expression of integrin-β3/FAK/PI3K/AKT pathway-related components. Administration of integrin-β3 siRNA and LY294002 (5 and 20 µM) abolished the effect of rhMFG-E8 on anti-apoptosis and neuroprotection after TBI. This study demonstrated for the first time that rhMFG-E8 inhibits neuronal apoptosis and offers neuroprotection. This is suggested to occur through the modulation of the integrin-β3/FAK/PI3K/AKT signaling pathway, highlighting rhMFG-E8 as a potentially promising therapeutic strategy for TBI patients.
Correction: Novel variants in COL4A4 and COL4A5 are rare causes of FSGS in two unrelated families
Authors: Hines Stephanie L. , Agarwal Anjali , Ghandour Mohamedanwar , Aslam Nabeel , Mohammad Ahmed N. , Atwal Paldeep S.
Published: August 2018

The originally published version of this Article contained an error in the name of the author Nabeel Aslam, which was incorrectly given as Aslam Nabeel. This has now been corrected in both the PDF and HTML versions of the Article.
Social environment mediates cancer progression in Drosophila
Authors: Dawson Erika H. , Bailly Tiphaine P. M. , Dos Santos Julie , Moreno Céline , Devilliers Maëlle , Maroni Brigitte , Sueur Cédric , Casali Andreu , Ujvari Beata , Thomas Frederic , Montagne Jacques , Mery Frederic
Published: August 2018

The influence of oncogenic phenomena on the ecology and evolution of animal species is becoming an important research topic. Similar to host–pathogen interactions, cancer negatively affects host fitness, which should lead to the selection of host control mechanisms, including behavioral traits that best minimize the proliferation of malignant cells. Social behavior is suggested to influence tumor progression. While the ecological benefits of sociality in gregarious species are widely acknowledged, only limited data are available on the role of the social environment on cancer progression. Here, we exposed adult Drosophila, with colorectal-like tumors, to different social environments. We show how subtle variations in social structure have dramatic effects on the progression of tumor growth. Finally, we reveal that flies can discriminate between individuals at different stages of tumor development and selectively choose their social environment accordingly. Our study demonstrates the reciprocal links between cancer and social interactions and how sociality may impact health and fitness in animals and its potential implications for disease ecology.
A systems-level framework for drug discovery identifies Csf1R as an anti-epileptic drug target
Authors: Srivastava Prashant K. , van Eyll Jonathan , Godard Patrice , Mazzuferi Manuela , Delahaye-Duriez Andree , Van Steenwinckel Juliette , Gressens Pierre , Danis Benedicte , Vandenplas Catherine , Foerch Patrik , Leclercq Karine , Mairet-Coello Georges , Cardenas Alvaro , Vanclef Frederic , Laaniste Liisi , Niespodziany Isabelle , Keaney James , Gasser Julien , Gillet Gaelle , Shkura Kirill , Chong Seon-Ah , Behmoaras Jacques , Kadiu Irena , Petretto Enrico , Kaminski Rafal M. , Johnson Michael R.
Published: August 2018

The identification of drug targets is highly challenging, particularly for diseases of the brain. To address this problem, we developed and experimentally validated a general computational framework for drug target discovery that combines gene regulatory information with causal reasoning (“Causal Reasoning Analytical Framework for Target discovery”—CRAFT). Using a systems genetics approach and starting from gene expression data from the target tissue, CRAFT provides a predictive framework for identifying cell membrane receptors with a direction-specified influence over disease-related gene expression profiles. As proof of concept, we applied CRAFT to epilepsy and predicted the tyrosine kinase receptor Csf1R as a potential therapeutic target. The predicted effect of Csf1R blockade in attenuating epilepsy seizures was validated in three pre-clinical models of epilepsy. These results highlight CRAFT as a systems-level framework for target discovery and suggest Csf1R blockade as a novel therapeutic strategy in epilepsy. CRAFT is applicable to disease settings other than epilepsy.
Imaging soliton dynamics in optical microcavities
Authors: Yi Xu , Yang Qi-Fan , Yang Ki Youl , Vahala Kerry
Published: August 2018

Solitons are self-sustained wavepackets that occur in many physical systems. Their recent demonstration in optical microresonators has provided a new platform for the study of nonlinear optical physics with practical implications for miniaturization of time standards, spectroscopy tools, and frequency metrology systems. However, despite its importance to the understanding of soliton physics, as well as development of new applications, imaging the rich dynamical behavior of solitons in microcavities has not been possible. These phenomena require a difficult combination of high-temporal-resolution and long-record-length in order to capture the evolving trajectories of closely spaced microcavity solitons. Here, an imaging method is demonstrated that visualizes soliton motion with sub-picosecond resolution over arbitrary time spans. A wide range of complex soliton transient behavior are characterized in the temporal or spectral domain, including soliton formation, collisions, spectral breathing, and soliton decay. This method can serve as a visualization tool for developing new soliton applications and understanding complex soliton physics in microcavities.
GePMI: A statistical model for personal intestinal microbiome identification
Authors: Wang Zicheng , Lou Huazhe , Wang Ying , Shamir Ron , Jiang Rui , Chen Ting
Published: August 2018

Human gut microbiomes consist of a large number of microbial genomes, which vary by diet and health conditions and from individual to individual. In the present work, we asked whether such variation or similarity could be measured and, if so, whether the results could be used for personal microbiome identification (PMI). To address this question, we herein propose a method to estimate the significance of similarity among human gut metagenomic samples based on reference-free, long k-mer features. Using these features, we find that pairwise similarities between the metagenomes of any two individuals obey a beta distribution and that a p value derived accordingly well characterizes whether two samples are from the same individual or not. We develop a computational framework called GePMI (Generating inter-individual similarity distribution for Personal Microbiome Identification) and apply it to several human gut metagenomic datasets (>300 individuals and >600 samples in total). From the results of GePMI, most of the human gut microbiomes can be identified (auROC = 0.9470, auPRC = 0.8702). Even after antibiotic treatment or fecal microbiota transplantation, the individual k-mer signature still maintains a certain specificity.
Glassy Dynamics in a heavy ion irradiated NbSe2 crystal
Authors: Eley S. , Khilstrom K. , Fotovat R. , Xiao Z. L. , Chen A. , Chen D. , Leroux M. , Welp U. , Kwok W. K. , Civale L.
Published: August 2018

Fascination with glassy states has persisted since Fisher introduced the vortex-glass as a new thermodynamic phase that is a true superconductor that lacks conventional long-range order. Though Fisher’s original model considered point disorder, it was later predicted that columnar defects (CDs) could also induce glassiness — specifically, a Bose-glass phase. In YBa2Cu3O7−x (YBCO), glassy states can cause distinct behavior in the temperature (T ) dependent rate of thermally activated vortex motion (S). The vortex-glass state produces a plateau in S(T ) whereas a Bose-glass can transition into a state hosting vortex excitations called double-kinks that can expand, creating a large peak in S(T ). Although glass phases have been well-studied in YBCO, few studies exist of other materials containing CDs that could contribute to distinguishing universal behavior. Here, we report on the effectiveness of CDs tilted ~30° from the c-axis in reducing S in a NbSe2 crystal. The magnetization is 5 times higher and S is minimized when the field is parallel to the defects versus aligned with the c-axis. We see signatures of glassiness in both field orientations, but do not observe a peak in S(T ) nor a plateau at values observed in YBCO. Finally, we discuss the possibility that competing disorder induces a field-orientation-driven transition from a Bose-glass to an anisotropic glass involving both point and columnar disorder.
A new meroterpenoid functions as an anti-tumor agent in hepatoma cells by downregulating mTOR activation and inhibiting EMT
Authors: Wan Haoqiang , Li Jiemei , Zhang Keda , Zou Xiaoting , Ge Lanlan , Zhu Fuqiang , Zhou Huirong , Gong Minna , Wang Tianwa , Chen Dongling , Peng Shusong , Zhou Boping , Zeng Xiaobin
Published: August 2018

Liver cancer, also known as primary liver cancer, is cancer that starts in the liver. JNU-144, a new meroterpenoid purified from Lithospermum erythrorhizon, has exhibited promising anticancer activity; however, the molecular mechanisms of action of JNU-144 on malignant cells remain unclear. Our studies revealed that JNU-144 suppressed cell viability and proliferation in hepatoma cells by downregulating mTOR activation. Meanwhile, JNU-144 activated the intrinsic apoptosis pathway and subsequently triggered apoptotic cell death in SMMC-7721 cells. We also found that JNU-144 inhibited the epithelial–mesenchymal transition in both SMMC-7721 and HepG2 cells through reprogramming of epithelial–mesenchymal transition (EMT)-related gene expression or regulating protein instability. These findings indicate that JNU-144 exerts potent anticancer activity in hepatoma cells and may be developed as a potential therapeutic drug.
Author Correction: Inhibitory effects of superoxide dismutase 3 on Propionibacterium acnes-induced skin inflammation
Authors: Nguyen Cuong Thach , Sah Shyam Kishor , Zouboulis Christos C. , Kim Tae-Yoon
Published: August 2018

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has been fixed in the paper.
Quantitative progression of retinitis pigmentosa by optical coherence tomography angiography
Authors: Jauregui Ruben , Park Karen Sophia , Duong Jimmy K. , Mahajan Vinit B. , Tsang Stephen H.
Published: August 2018

Optical coherence tomography angiography (OCT-A) is a non-invasive alternative to fluorescein angiography that allows for the study of the retinal and choroidal vasculatures. In this retrospective cohort study of 28 patients with retinitis pigmentosa (RP), we used OCT-A to quantify changes in perfusion density, foveal avascular zone (FAZ) area, and choriocapillaris blood flow over time and correlated these variables with ellipsoid zone (EZ) line width and best-corrected visual acuity (BCVA). Perfusion density decreased by 2.42 ± 0.62% per year at the superior capillary plexus (SCP) (P = 0.001) and 2.41 ± 0.76% per year at the deep capillary plexus (DCP) (P = 0.004). FAZ area increased by 0.078 ± 0.021 mm2 per year (P = 0.001) at the SCP and 0.152 ± 0.039 mm2 per year (P = 0.001) at the DCP. No changes were observed in the choriocapillaris blood flow. EZ line width had the strongest correlation to perfusion density at the SCP (r = 0.660 and 0.635, first and second visit, respectively, P = 0.001), while BCVA most strongly correlated with FAZ area at the SCP (r = 0.679 and 0.548, P = 0.001 and 0.003). Our results suggest that OCT-A is a useful tool for monitoring RP disease progression and may be used to measure retinal vascular parameters as outcomes in clinical trials.