bluuebunny/crossref_metadata_2025 huggingface dataset:
An examination of Job's rule: protection and repair of the proteins of the translational apparatus in seeds
Authors: Dirk Lynnette M.A. , Downie A. Bruce
Published: October 2018

The proteins produced just prior to maturation desiccation in the developing, orthodox seed, are stored in the desiccated state and recruited as the functional proteome upon imbibition. For the resumption of protein function, these stored proteins must be protected from permanent denaturation while dehydrating, throughout desiccation, and during rehydration. For some forms of damage there is the possibility of repair following imbibition potentially coordinated with de-aggregation into monodispersed polypeptides capable of refolding into a functional configuration. While studying aspects of the natural protection and repair mechanism in seeds, evidence has accrued that those proteins directly involved in translation are particular targets of both protection and protein repair. Such a phenomenon was first described by Rajjouet al. (2008) examining the frequency with which proteins involved in translation were identified as differentially abundant between aged and un-aged Arabidopsis seeds and the translational competence of agedversusun-aged seeds. The inference drawn from these observations was that, of all the stored proteins, it is imperative that those involved in translation endure desiccation, quiescence and rehydration in a functional state if the seed is to survive. Proteins involved in any other process other than translation can be replaced from the stored transcriptome or byde novotranscription but no mRNA is of value without the translational machinery. This has become known as ‘Job's rule’ in honour of the laboratory from which this hypothesis was first put forward (Rajjouet al., 2008). We review in this manuscript the evidence accrued to date on which Job's rule is based.
Attitudes of health professionals concerning bedside rationing criteria: a survey from Portugal
Authors: Pinho Micaela , Veiga Pedro
Published: October 2018

This paper tests the factorial structure of a questionnaire comprising seven health care rationing criteria (waiting time, ‘rule of rescue’, parenthood of minors, health maximization, youngest first, positive and negative version of social merit) and explores the adherence to them of 254 Portuguese health care professionals, when considered individually and when confronted with two-in-two combinations. Data were collected through a self-administered questionnaire where respondents faced hypothetical rationing dilemmas comprising one rationing criterion and dichotomous options pairs with two rationing criteria. Confirmatory factor analysis and multinomial logistic regressions were used to validate the structure of the questionnaire and the data. The findings suggest that: (i) the hepta-factorial structure of the questionnaire presented a good fit of the data; and (ii) support for rationing criterion depends on whether they are individually considered or confronted in dichotomous options pairs. When only one criterion distinguishes the patients, healthcare professionals support six criteria (by descending order): waiting time, rule of rescue, health maximization, penalization of patients’ risky behaviors, youngest first and being parent of a young child. When two criteria were confronted, immediate threat of life/health and large expected benefits were the most preferred. Conversely, the positive version of social merit was an unappreciated rationing criterion.
The evolution of the tetrapod humerus: morphometrics, disparity, and evolutionary rates
Authors: RUTA Marcello , KRIEGER Jonathan , ANGIELCZYK Kenneth D. , WILLS Matthew A.
Published: October 2018

The present study explores the macroevolutionary dynamics of shape changes in the humeri of all major grades and clades of early tetrapods and their fish-like forerunners. Coordinate point eigenshape analysis applied to humeral outlines in extensor view reveals that fish humeri are more disparate than those of most early tetrapod groups and significantly separate from the latter. Our findings indicate sustained changes in humeral shape in the deepest portions of the tetrapod stem group and certain portions of the crown. In the first half of sampled tetrapod history, subclades show larger than expected humeral disparity, suggesting rapid diffusion into morphospace. Later in tetrapod evolution, subclades occupy smaller and non-overlapping morphospace regions. This pattern may reflect in part increasing specialisations in later tetrapod lineages. Bayesian shifts in rates of evolutionary change are distributed discontinuously across the phylogeny, and most of them occur within rather than between major groups. Most shifts with the highest Bayesian posterior probabilities are observed in lepospondyls. Similarly, maximum likelihood analyses of shifts support marked rate accelerations in lepospondyls and in various subclades within that group. In other tetrapod groups, rates either tend to slow down or experience only small increases. Somewhat surprisingly, no shifts are concurrent with structural, functional, or ecological innovations in tetrapod evolution, including the origin of digits, the water–land transition and increasing terrestrialisation. Although counterintuitive, these results are consistent with a model of continual phenotypic innovation that, although decoupled from key evolutionary changes, is possibly triggered by niche segregation in divergent clades and grades of early tetrapods.
Nursing professionals’ attitudes toward use of physical restraints in Styrian nursing homes Austria
Authors: Mayerl Hannes , Trummer Tanja , Stolz Erwin , Rásky Éva , Freidl Wolfgang
Published: October 2018

Abstract. Background: Given that nursing staff play a critical role in the decision regarding use of physical restraints, research has examined nursing professionals’ attitudes toward this practice. Aim: Since nursing professionals’ views on physical restraint use have not yet been examined in Austria to date, we aimed to explore nursing professionals’ attitudes concerning use of physical restraints in nursing homes of Styria (Austria). Method: Data were collected from a convenience sample of nursing professionals (N = 355) within 19 Styrian nursing homes, based on a cross-sectional study design. Attitudes toward the practice of restraint use were assessed by means of the Maastricht Attitude Questionnaire in the German version. Results: The overall results showed rather positive attitudes toward the use of physical restraints, yet the findings regarding the sub-dimensions of the questionnaire were mixed. Although nursing professionals tended to deny “good reasons” for using physical restraints, they evaluated the consequences of physical restraint use rather positive and considered restraint use as an appropriate health care practice. Nursing professionals’ views regarding the consequences of using specific physical restraints further showed that belts were considered as the most restricting and discomforting devices. Conclusions: Overall, Austrian nursing professionals seemed to hold more positive attitudes toward the use of physical restraints than counterparts in other Western European countries. Future nationwide large-scale surveys will be needed to confirm our findings.
Evaluating the Potential Impacts of the Diurnal Vertical Migration by Marine Organisms on Marine Biogeochemistry
Authors: Aumont Olivier , Maury Olivier , Lefort Stelly , Bopp Laurent
Published: October 2018

Diurnal vertical migration (DVM) of marine organisms is an ubiquitous phenomenon in the ocean that generates an active vertical transport of organic matter. However, the magnitude and consequences of this flux are largely unknown and are currently overlooked in ocean biogeochemical models. Here we present a global model of pelagic ecosystems based on the ocean biogeochemical model NEMO‐PISCES that is fully coupled to the upper trophic levels model Apex Predators ECOSystem Model, which includes an explicit description of migrating organisms. Evaluation of the model behavior proved to be challenging due to the scarcity of suitable observations. Nevertheless, the model appears to be able to simulate approximately both the migration depth and the relative biomass of migrating organisms. About one third of the epipelagic biomass is predicted to perform DVM. The flux of carbon driven by DVM is estimated to be 1.05 ± 0.15 PgC/year, about 18% of the passive flux of carbon due to sinking particles at 150 m. Comparison with local studies suggests that the model captures the correct magnitude of this flux. Oxygen is decreased in the mesopelagic domain by about 5 mmol m−3 relative to simulations of an ocean without DVM. Our study concludes that DVM drives a significant and very efficient flux of carbon to the mesopelagic domain, similar in magnitude to the transport of DOC. Relative to a model run without DVM, the consequences of this flux seem to be quite modest on oxygen, due to compensating effects between DVM and passive fluxes.
Northward Expansion and Intensification of Phytoplankton Growth During the Early Ice‐Free Season in Arctic
Authors: Renaut S. , Devred E. , Babin M.
Published: October 2018

In the last decades, reduction of the ice cover has been documented to affect the structure and the functioning of Arctic marine ecosystems. One direct consequence is earlier phytoplankton spring blooms and larger annual primary production compared with previous decades. However, the impact of changes in the dynamics of sea ice specifically on phytoplankton spring blooms, a major contributor of the annual primary production in the Arctic Ocean, remains poorly known. Here we report on their temporal and spatial variabilities in open waters between 2003 and 2013 using satellite ocean color data. We observed a significant increase in primary productivity of phytoplankton spring blooms in different sectors of the Arctic Ocean, especially in the Barents and Kara Seas. Satellite observations also revealed a northward expansion of these blooms at a rate of 1° per decade driven by the Barents and the Kara regions.
Mysterious Linear Features Across Saturn's Moon Dione
Authors: Martin Emily S. , Patthoff D. Alex
Published: October 2018

Our mapping of the wispy terrains on Saturn's moons Dione has revealed unique linear features that are generally long (tens to hundreds of kilometers), narrow (<5 km), and brighter than the surrounding terrains. We refer to these features as linear virgae. Similar features, with a limited distribution, have been observed on Rhea. Wherever linear virgae are observed, they appear to crosscut all other structures suggesting that they are among the youngest features on these satellites. Here we seek to constrain whether the linear virgae are endogenic, suggesting that the surface of Dione has been geologically active recently or if they are exogenic, suggesting a recent, or even ongoing, process in the Saturn system. We favor an exogenic mechanism for the formation of linear virgae on Dione by the emplacement of material across the surface by low‐velocity impacts of material sourced from Saturn's rings, co‐orbital moons, or encountering planetocentric debris.
Three‐Dimensional and Trans‐Hemispheric Changes in Ionospheric Electron Density Caused by the Great Solar Eclipse in North America on 21 August 2017
Authors: He Liming , Heki Kosuke , Wu Lixin
Published: October 2018

We report the three‐dimensional (3‐D) structure of the electron depletion caused by the great solar eclipse on 21 August 2017 derived from dense Global Navigation Satellite Systems (GNSS) total electron content observations. A linear least squares inversion was performed with a continuity constraint to stabilize the solution. The reconstructed 3‐D ionospheric electron density depletion showed a peak height at ~200 km. The depletion reached 42%, 60%, and 72%, below 250, 350, and 450 km, respectively, and the vertically integrated (150–450 km) decrease was 54%. We validated the accuracy of the electron density depletion at 200 km above the Millstone Hill observatory with the incoherent scatter radar observation and at 400 km using the in situ measurement by the Swarm satellite. The coincidence suggests that 3‐D tomography is useful for investigating the vertical structure of eclipse‐induced ionospheric changes. We further detected the electron depletion and enhancement with maximum values of 1.4–1.9 TECU and 0.7–1.0 TECU, respectively, in the geomagnetic conjugate region in the southern hemisphere.
Bacterial Carbon Cycling in the River Plume in the Northern South China Sea During Summer
Authors: Xu Jie , Li Xiangfu , Shi Zhen , Li Ruihuan , Li Qian
Published: October 2018

Heterotrophic bacterioplankton play a significant role in carbon cycle in oceans. It is crucial to identify regulators of bacterial carbon processing across marine environments. In summer 2016, a cruise was conducted to examine the links between bacterial metabolic rates and community composition, and potential mechanisms regulating bacterial growth efficiency in the plume‐impacted coastal area. Our results showed that the two aspects of bacterial metabolism responded differently. Bacterial production (3.69 to 57.1 μg C·L−1·day−1) at the surface increased by 40% to 21‐fold in response to the freshwater input. The enhanced bacterial production was attributed to an increase in bacterial abundance and cell‐specific bacterial production, which was linked to shifts in bacterial community composition and changing partition between anabolic and catabolic pathways. Bacterial groups that grew fast and preferred high molecular weight dissolved organic carbon were responsible for the increase in bacterial production. However, bacterial respiration increased (less than fourfold) to lesser extent than bacterial production. Consequently, bacterial growth efficiency increased dramatically (up to sevenfold) in response to the plume input. Bacterial respiration was primarily dependent on environmental conditions rather than bacterial community composition. The increased phytoplankton biomass modulated bacterial respiration in two contrasting ways likely by providing phytoplankton‐derived dissolved organic carbon, which not only improved bacterial abundance but also lowered cell‐specific bacterial respiration because of mitigating energy limitation. Our findings elucidated bacterial carbon processing in the plume‐impacted coastal waters and highlighted the potential role of bacterial community composition in regulating carbon cycling in oceans.
Dispersal of Hydrothermal Vent Larvae at East Pacific Rise 9–10°N Segment
Authors: Xu Guangyu , McGillicuddy D. J. , Mills S. W. , Mullineaux L. S.
Published: October 2018

A three‐dimensional, primitive‐equation, ocean circulation model coupled with a Lagrangian particle‐tracking algorithm is used to investigate the dispersal and settlement of planktonic larvae released from discrete hydrothermal habitats on the East Pacific Rise segment at 9–10°N. Model outputs show that mean circulation is anticyclonic around the ridge segment, which consists of a northward flow along the western flank and a southward flow along the eastern flank. Those flank jets are dispersal expressways for the along‐ridge larval transport and strongly affect its overall direction and spatial‐temporal variations. It is evident from model results that the transform faults bounding the ridge segment and off axis topography (the Lamont Seamount Chain) act as topographic barriers to larval dispersal in the along‐ridge direction. Furthermore, the presence of an overlapping spreading center and an adjacent local topographic high impedes the southward along‐ridge larval transport. The model results suggest that larval recolonization within ridge‐crest habitats is enhanced by the anticyclonic circulation around the ridge segment, and the overall recolonization rate is higher for larvae having a short precompetency period and an altitude above the bottom sufficient to avoid influence by the near‐bottom currents Surprisingly, for larvae having a long precompetency period (>10 days), the prolonged travel time allowed some of those larvae to return to their natal vent clusters, which results in an unexpected increase in connectivity among natal and neighboring sites. Overall, model‐based predictions of connectivity are highly sensitive to the larval precompetency period and vertical position in the water column.
Distribution and Diagenesis of Phosphorus in the Deep‐Sea Sediments of the Central Indian Basin
Authors: Linsy P. , Nagender Nath B. , Mascarenhas‐Pereira M. B. L. , Chauhan Teena , Sebastian Tyson , Babu C. P. , Kurian Siby , Miriyala Pavan , Kazip Armoury , Borole D. V. , Khadge N. H.
Published: October 2018

A regional solid‐phase phosphorus (P) speciation study in the Central Indian Basin (CIB) was carried out to elucidate the spatial distribution of sedimentary P species and P diagenesis in an oligotrophic setting. The results show that P enrichment is in the order of biogenic (Pbio) > authigenic (Pauth) > iron bound (PFe) > detrital (Pdet) > organic (Porg) P. The higher concentrations of Pbio are found in siliceous oozes, which are attributed to high biological productivity in the overlying waters compared to pelagic clay region. High Pauth and Pdet contents with low molar Corg/Preact ratios in the pelagic/red clays indicate the deposition of calcium fluorapatite and refractory material from the atmospheric input. The oxygenated bottom water promotes adsorption of P onto iron oxyhydroxides making the PFe an important sink. Remobilization of P within the sediments is limited because of well‐oxygenated conditions and an efficient adsorption by iron oxyhydroxides and clay‐sized sediments. A twofold increase in Ptotal and P‐species is observed in hydrothermally altered, ferruginous sediments from a seamount flank suggesting an important role of hydrothermal processes in P cycling. The calculated P accumulation rate in the present study ranges between 0.6 and 11.7 μmol·cm−2·kyr−1. The burial flux of P for the entire CIB (5.7 × 106 km2) is 0.01 × 1010 mol P per year which accounts for 0.05% of the global flux. The benthic P fluxes from the seawater to the sediments in the area range between 0.0093 and 0.133 μmol·cm−2·kyr−1 indicating that the CIB sediments are an important sink for P.
Variability of Martian Turbopause Altitudes
Authors: Slipski M. , Jakosky B. M. , Benna M. , Elrod M. , Mahaffy P. , Kass D. , Stone S. , Yelle R.
Published: October 2018

The turbopause and homopause represent the transition from strong turbulence and mixing in the middle atmosphere to a molecular‐diffusion‐dominated region in the upper atmosphere. We use neutral densities measured by the Neutral Gas and Ion Mass Spectrometer on the Mars Atmospheric and Volatile EvolutioN spacecraft from February 2015 to October 2016 to investigate the temperature structure and fluctuations of the Martian upper atmosphere. We compare those with temperature measurements of the lower atmosphere from the Mars Reconnaissance Orbiter's Mars Climate Sounder. At the lowest Mars Atmospheric and Volatile EvolutioN altitudes we often observe a statically stable region where waves propagate freely. In contrast, regions from about 20 km up to at least 70 km are reduced in stability where waves are expected to dissipate readily due to breaking/saturation. We derive homopause altitudes from Neutral Gas and Ion Mass Spectrometer N2 and Ar densities and find that it varies between 60 and 140 km. From the standard deviations in monthly averaged temperature profiles, we determine the wave turbopause altitude where applicable and find that these altitudes agree with the homopause altitudes. We show that the homopause variability is driven by order of magnitude changes in CO2 densities, which drastically affect the altitude at which the eddy diffusion is equal to the molecular diffusion. These variations are observed as a function of local time, latitude, and season. That the turbopause/homopause does not track a fixed density level means that the eddy diffusion coefficient at the turbopause can vary significantly, suggesting differences in the dominant breaking waves and tidal modes.
High‐Resolution Land Surface Modeling of Hydrological Changes Over the Sanjiangyuan Region in the Eastern Tibetan Plateau: 1. Model Development and Evaluation
Authors: Yuan Xing , Ji Peng , Wang Linying , Liang Xin‐Zhong , Yang Kun , Ye Aizhong , Su Zhongbo , Wen Jun
Published: October 2018

High‐resolution modeling became popular in recent years due to the availability of multisource observations, advances in understanding fine‐scale processes, and improvements in computing facilities. However, modeling of hydrological changes over mountainous regions is still a great challenge due to the sensitivity of highland water cycle to global warming, tightly coupled hydrothermal processes, and limited observations. Here we show a successful high‐resolution (3 km) land surface modeling over the Sanjiangyuan region located in the eastern Tibetan plateau, which is the headwater of three major Asian rivers. By developing a new version of a Conjunctive Surface‐Subsurface Process model named as CSSPv2, we increased Nash‐Sutcliffe efficiency by 62–130% for streamflow simulations due to the introduction of a storage‐based runoff generation scheme, reduced errors by up to 31% for soil moisture modeling after considering the effect of soil organic matter on porosity and hydraulic conductivity. Compared with ERA‐Interim and Global Land Data Assimilation System version 1.0 reanalysis products, CSSPv2 reduced errors by up to 30%, 69%, 92%, and 40% for soil moisture, soil temperature, evapotranspiration, and terrestrial water storage change, respectively, as evaluated against in situ and satellite observations. Moreover, CSSPv2 well captured the elevation‐dependent ground temperature warming trends and the decreased frozen dates during 1979–2014, and significant increasing trends (p < 0.05) in evapotranspiration and terrestrial water storage during 1982–2011 and 2003–2014 respectively, while ERA‐Interim and Global Land Data Assimilation System version 1.0 showed no trends or even negative trends. This study implies the necessity of developing high‐resolution land surface models in realistically representing hydrological changes over highland areas that are sentinels to climate change.
Do borderline personality disorder and attention-deficit/hyperactivity disorder co-aggregate in families? A population-based study of 2 million Swedes
Authors: Kuja-Halkola Ralf , Lind Juto Kristina , Skoglund Charlotte , Rück Christian , Mataix-Cols David , Pérez-Vigil Ana , Larsson Johan , Hellner Clara , Långström Niklas , Petrovic Predrag , Lichtenstein Paul , Larsson Henrik
Published: October 2018

Large-scale family studies on the co-occurrence of attention-deficit/hyperactivity disorder (ADHD) and borderline personality disorder (BPD) are lacking. Thus, we aimed to estimate the co-occurrence and familial co-aggregation of clinically ascertained ADHD and BPD diagnoses using the entire Swedish population. In a register-based cohort design we included individuals born in Sweden 1979–2001, and identified their diagnoses during 1997–2013; in total, 2,113,902 individuals were included in the analyses. We obtained clinical diagnoses of ADHD and BPD from inpatient and outpatient care. Individuals with an ADHD diagnosis had an adjusted (for birth year, sex, and birth order) odds ratio (aOR) of 19.4 (95% confidence interval [95% CI] = 18.6–20.4) of also having a BPD diagnosis, compared to individuals not diagnosed with ADHD. Having a sibling with ADHD also increased the risk for BPD (monozygotic twins, aOR = 11.2, 95% CI = 3.0–42.2; full siblings, aOR = 2.8, 95% CI = 2.6–3.1; maternal half-siblings, aOR = 1.4, 95% CI = 1.2–1.7; paternal half-siblings, aOR = 1.5, 95% CI = 1.3–1.7). Cousins also had an increased risk. The strength of the association between ADHD and BPD was similar in females and males, and full siblings showed similar increased risks regardless of sex. Among both males and females, ADHD and BPD co-occur within individuals and co-aggregate in relatives; the pattern suggests shared genetic factors and no robust evidence for etiologic sex differences was found. Clinicians should be aware of increased risks for BPD in individuals with ADHD and their relatives, and vice versa.
Revisiting Montreal: New Insights into Symptoms and Their Causes, and Implications for the Future of GERD
Authors: Hungin A. Pali S. , Molloy-Bland Michael , Scarpignato Carmelo
Published: October 2018

The Montreal definition of gastroesophageal reflux disease (GERD) provided a rationale for acid suppression medication without investigation, thus enhancing the management of the substantial symptom burden in these patients. Increased proton-pump inhibitor use has also highlighted their limitations, with one third of “typical” symptoms known to be refractory. Most refractory symptoms are ascribed to reflux hypersensitivity (RH) and functional heartburn (FH). RH may be caused by impaired esophageal mucosal barrier function and sensitization of peripheral esophageal receptors. Central sensitization may also contribute to the perception of non-pathologic reflux in RH, and the perception of physiological stimuli in FH. Importantly, mechanisms underlying GERD, RH, and FH are (in theory) not mutually exclusive, further complicating patient management. Methods used to distinguish GERD from RH and FH are impractical for use in epidemiological studies and pragmatic care and may have limited diagnostic accuracy. This is impeding accurate prevalence estimates and risk factor determination and the identification of new therapies. Direct assessment of mucosal barrier function by measuring impedance is a promising candidate for improved diagnosis. Ultimately though the concept of GERD as a composite, symptom-based entity needs re-evaluation, so that new understandings of upper GI symptoms can direct more precise management.
A phylogenomic and ecological analysis of the globally abundant Marine Group II archaea (Ca. Poseidoniales ord. nov.)
Authors: Rinke Christian , Rubino Francesco , Messer Lauren F , Youssef Noha , Parks Donovan H , Chuvochina Maria , Brown Mark , Jeffries Thomas , Tyson Gene W , Seymour Justin R , Hugenholtz Philip
Published: October 2018

Marine Group II (MGII) archaea represent the most abundant planktonic archaeal group in ocean surface waters, but our understanding of the group has been limited by a lack of cultured representatives and few sequenced genomes. Here, we conducted a comparative phylogenomic analysis of 270 recently available MGII metagenome-assembled genomes (MAGs) to investigate their evolution and ecology. Based on a rank-normalised genome phylogeny, we propose that MGII is an order-level lineage for which we propose the name Candidatus Poseidoniales (after Gr. n. Poseidon, God of the sea), comprising the families Candidatus Poseidonaceae fam. nov. (formerly subgroup MGIIa) and Candidatus Thalassarchaeaceae fam. nov. (formerly subgroup MGIIb). Within these families, 21 genera could be resolved, many of which had distinct biogeographic ranges and inferred nutrient preferences. Phylogenetic analyses of key metabolic functions suggest that the ancestor of Ca. Poseidoniales was a surface water-dwelling photoheterotroph that evolved to occupy multiple related ecological niches based primarily on spectral tuning of proteorhodopsin genes. Interestingly, this adaptation appears to involve an overwrite mechanism whereby an existing single copy of the proteorhodopsin gene is replaced by a horizontally transferred copy, which in many instances should allow an abrupt change in light absorption capacity. Phototrophy was lost entirely from five Ca. Poseidoniales genera coinciding with their adaptation to deeper aphotic waters. We also report the first instances of nitrate reductase in two genera acquired via horizontal gene transfer (HGT), which was a potential adaptation to oxygen limitation. Additional metabolic traits differentiating families and genera include flagellar-based adhesion, transporters, and sugar, amino acid, and peptide degradation. Our results suggest that HGT has shaped the evolution of Ca. Poseidoniales to occupy a variety of ecological niches and to become the most successful archaeal lineage in ocean surface waters.
Novel dihydroartemisinin derivative DHA-37 induces autophagic cell death through upregulation of HMGB1 in A549 cells
Authors: Liu Xiufeng , Wu Juanjuan , Fan Menglin , Shen Chen , Dai Wenling , Bao Yini , Liu Ji-Hua , Yu Bo-Yang
Published: October 2018

Dihydroartemisinin (DHA) and its analogs are reported to possess selective anticancer activity. Here, we reported a novel DHA derivative DHA-37 that exhibited more potent anticancer activity on the cells tested. Distinct from DHA-induced apoptosis, DHA-37 triggered excessive autophagic cell death, and became the main contributor to DHA-37-induced A549 cell death. Incubation of the cells with DHA-37 but not DHA produced increased dots distribution of GFP-LC3 and expression ratio of LC3-II/LC3-I, and enhanced the formation of autophagic vacuoles as revealed by TEM. Treatment with the autophagy inhibitor 3-MA, LY294002, or chloroquine could reverse DHA-37-induced cell death. In addition, DHA-37-induced cell death was associated significantly with the increased expression of HMGB1, and knockdown of HMGB1 could reverse DHA-37-induced cell death. More importantly, the elevated HMGB1 expression induced autophagy through the activation of the MAPK signal but not PI3K-AKT–mTOR pathway. In addition, DHA-37 also showed a wonderful performance in A549 xenograft mice model. These findings suggest that HMGB1 as a target candidate for apoptosis-resistant cancer treatment and artemisinin-based drugs could be used in inducing autophagic cell death.
Plasminogen activation is required for the development of radiation-induced dermatitis
Authors: Fallah Mahsa , Shen Yue , Brodén Jessica , Bäckman Assar , Lundskog Bertil , Johansson Michael , Blomquist Michael , Liu Kui , Wilczynska Malgorzata , Ny Tor
Published: October 2018

Skin damage caused by radiation therapy (radiodermatitis) is a severe side effect of radiotherapy in cancer patients, and there is currently a lack of effective strategies to prevent or treat such skin damage. In this work, we show with several lines of evidence that plasminogen, a pro-inflammatory factor, is key for the development of radiodermatitis. After skin irradiation in wild-type (plg+/+) mice, the plasminogen level increased in the irradiated area, leading to severe skin damage such as ulcer formation. However, plasminogen-deficient (plg−/−) mice and mice lacking plasminogen activators were mostly resistant to radiodermatitis. Moreover, treatment with a plasminogen inhibitor, tranexamic acid, decreased radiodermatitis in plg+/+ mice and prevented radiodermatitis in plg+/− mice. Together with studies at the molecular level, we report that plasmin is required for the induction of inflammation after irradiation that leads to radiodermatitis, and we propose that inhibition of plasminogen activation can be a novel treatment strategy to reduce and prevent the occurrence of radiodermatitis in patients.
Oleanolic acid enhances neural stem cell migration, proliferation, and differentiation in vitro by inhibiting GSK3β activity
Authors: Zhang Shi Qing , Lin Kai Li , Law Cheuk Yu , Liu Bin , Fu Xiu Qiong , Tse Wing Sze , Wong Samantha Sze Man , Sze Stephen Cho Wing , Yung Ken Kin Lam
Published: October 2018

Oleanolic acid (OA), one of the bioactive ingredients in ginseng, has been reported to have neuroprotective activities. However, the effects and its mechanism on neural stem cell (NSC) induction are not entirely clear. In the present study, we investigated the effects of OA on promoting the migration, proliferation, and differentiation of neural stem cells (NSCs). Migration and proliferation were investigated by using neural-specific markers, neurosphere assay, and Cell Counting Kit-8, respectively. We found OA remarkably promoted neural migration and proliferation of NSCs in a time- and dose-dependent manner. Differentiation was analyzed by western blotting and immunofluorescence staining, which found MAP2 expression was remarkably increased, whereas Nestin was dramatically decreased. In addition, OA increased phosphorylation of GSK3β at Ser9 and expression of active forms of β-catenin. Furthermore, NSCs with constitutively active GSK3β (S9A) significantly suppressed the OA-induced proliferation and neural differentiation. These results showed that OA could stimulate NSC proliferation and neural differentiation in vitro via suppressing the activity of GSK3β. Our findings may have significant implications for the treatment of neurodegenerative diseases.
Mycobacterial DnaB helicase intein as oxidative stress sensor
Authors: Kelley Danielle S. , Lennon Christopher W. , Li Zhong , Miller Michael R. , Banavali Nilesh K. , Li Hongmin , Belfort Marlene
Published: October 2018

Inteins are widespread self-splicing protein elements emerging as potential post-translational environmental sensors. Here, we describe two inteins within one protein, the Mycobacterium smegmatis replicative helicase DnaB. These inteins, DnaBi1 and DnaBi2, have homology to inteins in pathogens, splice with vastly varied rates, and are differentially responsive to environmental stressors. Whereas DnaBi1 splicing is reversibly inhibited by oxidative and nitrosative insults, DnaBi2 is not. Using a reporter that measures splicing in a native intein-containing organism and western blotting, we show that H2O2 inhibits DnaBi1 splicing in M. smegmatis. Intriguingly, upon oxidation, the catalytic cysteine of DnaBi1 forms an intramolecular disulfide bond. We report a crystal structure of the class 3 DnaBi1 intein at 1.95 Å, supporting our findings and providing insight into this splicing mechanism. We propose that this cysteine toggle allows DnaBi1 to sense stress, pausing replication to maintain genome integrity, and then allowing splicing immediately when permissive conditions return.
Master clinical medical knowledge at certificated-doctor-level with deep learning model
Authors: Wu Ji , Liu Xien , Zhang Xiao , He Zhiyang , Lv Ping
Published: October 2018

Mastering of medical knowledge to human is a lengthy process that typically involves several years of school study and residency training. Recently, deep learning algorithms have shown potential in solving medical problems. Here we demonstrate mastering clinical medical knowledge at certificated-doctor-level via a deep learning framework Med3R, which utilizes a human-like learning and reasoning process. Med3R becomes the first AI system that has successfully passed the written test of National Medical Licensing Examination in China 2017 with 456 scores, surpassing 96.3% human examinees. Med3R is further applied for providing aided clinical diagnosis service based on real electronic medical records. Compared to human experts and competitive baselines, our system can provide more accurate and consistent clinical diagnosis results. Med3R provides a potential possibility to alleviate the severe shortage of qualified doctors in countries and small cities of China by providing computer-aided medical care and health services for patients.
Large-scale genome-wide enrichment analyses identify new trait-associated genes and pathways across 31 human phenotypes
Authors: Zhu Xiang , Stephens Matthew
Published: October 2018

Genome-wide association studies (GWAS) aim to identify genetic factors associated with phenotypes. Standard analyses test variants for associations individually. However, variant-level associations are hard to identify and can be difficult to interpret biologically. Enrichment analyses help address both problems by targeting sets of biologically related variants. Here we introduce a new model-based enrichment method that requires only GWAS summary statistics. Applying this method to interrogate 4,026 gene sets in 31 human phenotypes identifies many previously-unreported enrichments, including enrichments of endochondral ossification pathway for height, NFAT-dependent transcription pathway for rheumatoid arthritis, brain-related genes for coronary artery disease, and liver-related genes for Alzheimer’s disease. A key feature of our method is that inferred enrichments automatically help identify new trait-associated genes. For example, accounting for enrichment in lipid transport genes highlights association between MTTP and low-density lipoprotein levels, whereas conventional analyses of the same data found no significant variants near this gene.
Self-powered H2 production with bifunctional hydrazine as sole consumable
Authors: Liu Xijun , He Jia , Zhao Shunzheng , Liu Yunpeng , Zhao Zhe , Luo Jun , Hu Guangzhi , Sun Xiaoming , Ding Yi
Published: October 2018

Splitting hydrazine into H2 and N2 by electro-catalyzing hydrogen evolution and hydrazine oxidation reactions is promising for replacing fossil energy with H2. However, current hydrazine splitting is achieved using external powers to drive the two reactions, which is inapplicable to outdoor use. Here, Fe-doped CoS2 nanosheets are developed as a bifunctional electrocatalyst for the two reactions, by which direct hydrazine fuel cells and overall-hydrazine-splitting units are realized and integrated to form a self-powered H2 production system. Without external powers, this system employs hydrazine bifunctionally as the fuel of direct hydrazine fuel cell and the splitting target, namely a sole consumable, and exhibits an H2 evolution rate of 9.95 mmol h−1, a 98% Faradaic efficiency and a 20-h stability, all comparable to the best reported for self-powered water splitting. These performances are due to that Fe doping decreases the free-energy changes of H adsorption and adsorbed NH2NH2 dehydrogenation on CoS2.
Composite fermion liquid to Wigner solid transition in the lowest Landau level of zinc oxide
Authors: Maryenko D. , McCollam A. , Falson J. , Kozuka Y. , Bruin J. , Zeitler U. , Kawasaki M.
Published: October 2018

Interactions between the constituents of a condensed matter system can drive it through a plethora of different phases due to many-body effects. A prominent platform for it is a dilute two-dimensional electron system in a magnetic field, which evolves intricately through various gaseous, liquid and solid phases governed by Coulomb interaction. Here we report on the experimental observation of a phase transition between the composite fermion liquid and adjacent magnetic field induced phase with a character of Wigner solid. The experiments are performed in the lowest Landau level of a MgZnO/ZnO two-dimensional electron system with attributes of both a liquid and a solid. An in-plane magnetic field component applied on top of the perpendicular magnetic field extends the Wigner-like phase further into the composite fermion liquid phase region. Our observations indicate the direct competition between a composite fermion liquid and a Wigner solid formed either by electrons or composite fermions.
Closing the gender gap in competitiveness through priming
Authors: Balafoutas Loukas , Fornwagner Helena , Sutter Matthias
Published: October 2018

Men have been observed to have a greater willingness to compete compared to women, and it is possible that this contributes to gender differences in wages and career advancement. Policy interventions such as quotas are sometimes used to remedy this but these may cause unintended side-effects. Here, we present experimental evidence that a simple and practically costless tool—priming subjects with power—can close the gender gap in competitiveness. While in a neutral as well as in a low-power priming situation men are much more likely than women to choose competition, this gap vanishes when subjects are primed with a high-power situation. We show that priming with high power makes competition entry decisions more realistic and also that it reduces the level of risk tolerance among male participants, which can help explain why it leads to a closing down of the gender gap in competitiveness.
Monomerization of the photoconvertible fluorescent protein SAASoti by rational mutagenesis of single amino acids
Authors: Solovyev Ilya D. , Gavshina Alexandra V. , Katti Aditya S. , Chizhik Alexey I. , Vinokurov Leonid M. , Lapshin Grigory D. , Ivashina Tatiana V. , Khrenova Maria G. , Kireev Igor I. , Gregor Ingo , Enderlein Jörg , Savitsky Alexander P.
Published: October 2018

Photoconvertible fluorescent proteins (PCFPs) are widely used as markers for the visualization of intracellular processes and for sub-diffraction single-molecule localization microscopy. Although wild type of a new photoconvertible fluorescent protein SAASoti tends to aggregate, we succeeded, via rational mutagenesis, to obtain variants that formed either tetramers or monomers. We compare two approaches: one is based on the structural similarity between SAASoti and Kaede, which helped us to identify a single point mutation (V127T) at the protein’s hydrophobic interface that leads to monomerization. The other is based on a chemical modification of amino groups of SAASoti with succinic anhydride, which converts the protein aggregates into monomers. Mass-spectrometric analysis helped us to identify that the modification of a single ε-amino group of lysine K145 in the strongly charged interface AB was sufficient to convert the protein into its tetrameric form. Furthermore, site-directed mutagenesis was used to generate mutants that proved to be either monomeric or tetrameric, both capable of rapid green-to-red photoconversion. This allows SAASoti to be used as a photoconvertible fluorescent marker for in vivo cell studies.
Change points, memory and epidemic spreading in temporal networks
Authors: P. Peixoto Tiago , Gauvin Laetitia
Published: October 2018

Dynamic networks exhibit temporal patterns that vary across different time scales, all of which can potentially affect processes that take place on the network. However, most data-driven approaches used to model time-varying networks attempt to capture only a single characteristic time scale in isolation — typically associated with the short-time memory of a Markov chain or with long-time abrupt changes caused by external or systemic events. Here we propose a unified approach to model both aspects simultaneously, detecting short and long-time behaviors of temporal networks. We do so by developing an arbitrary-order mixed Markov model with change points, and using a nonparametric Bayesian formulation that allows the Markov order and the position of change points to be determined from data without overfitting. In addition, we evaluate the quality of the multiscale model in its capacity to reproduce the spreading of epidemics on the temporal network, and we show that describing multiple time scales simultaneously has a synergistic effect, where statistically significant features are uncovered that otherwise would remain hidden by treating each time scale independently.
Relative positioning of Kv11.1 (hERG) K+ channel cytoplasmic domain-located fluorescent tags toward the plasma membrane
Authors: Barros Francisco , Domínguez Pedro , de la Peña Pilar
Published: October 2018

Recent cryo-EM data have provided a view of the KCNH potassium channels molecular structures. However, some details about the cytoplasmic domains organization and specially their rearrangements associated to channel functionality are still lacking. Here we used the voltage-dependent dipicrylamine (DPA)-induced quench of fluorescent proteins (FPS) linked to different positions at the cytoplasmic domains of KCNH2 (hERG) to gain some insights about the coarse structure of these channel parts. Fast voltage-clamp fluorometry with HEK293 cells expressing membrane-anchored FPs under conditions in which only the plasma membrane potential is modified, demonstrated DPA voltage-dependent translocation and subsequent FRET-triggered FP quenching. Our data demonstrate for the first time that the distance between an amino-terminal FP tag and the intracellular plasma membrane surface is shorter than that between the membrane and a C-terminally-located tag. The distances varied when the FPs were attached to other positions along the channel cytoplasmic domains. In some cases, we also detected slower fluorometric responses following the fast voltage-dependent dye translocation, indicating subsequent label movements orthogonal to the plasma membrane. This finding suggests the existence of additional conformational rearrangements in the hERG cytoplasmic domains, although their association with specific aspects of channel operation remains to be established.
Functionalisation of Polydimethylsiloxane (PDMS)- Microfluidic Devices coated with Rock Minerals
Authors: Alzahid Yara A. , Mostaghimi Peyman , Gerami Alireza , Singh Ankita , Privat Karen , Amirian Tammy , Armstrong Ryan T.
Published: October 2018

Fluid flow in porous rocks is commonly capillary driven and thus, dependent on the surface characteristics of rock grains and in particular the connectivity of corners and crevices in which fluids reside. Traditional microfluidic fabrication techniques do not provide a connected pathway of crevices that are essential to mimic multiphase flow in rocks. Here, geo-material microfluidic devices with connected pathways of corners and crevices were created by functionalising Polydimethylsiloxane (PDMS) with rock minerals. A novel fabrication process that provides attachment of rock minerals onto PDMS was demonstrated. The geo-material microfluidic devices were compared to carbonate and sandstone rocks by using energy dispersive X-ray spectroscopy, scanning electron microscopy (SEM), contact angle measurements, and a surface profilometer. Based on SEM coupled with energy-dispersive X-ray spectrometry (SEM-EDS) analyses, roughness measurements, contact angle, wettability, and roughness were comparable to real rocks. In addition, semivariograms showed that mineral deposition across the different geo-material devices was nearly isotropic. Lastly, important multiphase flow phenomena, such as snap-off and corner flow mechanisms, equivalent to those occurring in reservoir rocks have been visualised. The presented approach can be used to visualise rock-fluid interactions that are relevant to subsurface engineering applications, such as hydrocarbon recovery and CO2 sequestration.
Skyrmion Lattice Topological Hall Effect near Room Temperature
Authors: Leroux Maxime , Stolt Matthew J. , Jin Song , Pete Douglas V. , Reichhardt Charles , Maiorov Boris
Published: October 2018

Magnetic skyrmions are stable nanosized spin structures that can be displaced at low electrical current densities. Because of these properties, they have been proposed as building blocks of future electronic devices with unprecedentedly high information density and low energy consumption. The electrical detection of an ordered skyrmion lattice via the Topological Hall Effect (THE) in a bulk crystal, has so far been demonstrated only at cryogenic temperatures in the MnSi family of compounds. Here, we report the observation of a skyrmion lattice Topological Hall Effect near room temperature (276 K) in a mesoscopic lamella carved from a bulk crystal of FeGe. This region coincides with the skyrmion lattice location revealed by neutron scattering. We provide clear evidence of a re-entrant helicoid magnetic phase adjacent to the skyrmion phase, and discuss the large THE amplitude (5 nΩ.cm) in view of the ordinary Hall Effect.