bluuebunny/crossref_metadata_2025 huggingface dataset:
An evaluation of the mourning tradition, the “First Feast,” in the context of palliative care: The possibility of incorporating cultural rituals into palliative care
Authors: Okan İsmail , Suren Mustafa , Onder Yalcin , Citil Riza , Akay Secil , Demir Tugce
Published: January 2019

Objective

Grief is intertwined with cultural and religious rituals that are highly appreciated in the quality standards of palliative care. Here, we aimed to investigate whether a cultural mourning ritual, the “First Feast,” can be used by palliative care teams to ease the grief response of the deceased patient's relatives.

Method

A questionnaire with 23 questions about the prevalence of the First Feast tradition, the content, the pros and cons, and whether it would be useful for the grieving relatives of deceased patients was prepared and given to the palliative care patients’ relatives. The data were evaluated using the chi-square test.

Result

A total of 427 participants were enrolled in the study; 60.7% were female and the mean age was 36 (±13.4). A total of 76.8% of the participants were from the Tokat region and 77.8% (n = 332) performed the First Feast tradition. A significant difference was observed among participants with Tokat origins and non-Tokat origins in terms of awareness of the tradition (84.8% and 69.7%, respectively; p = 0.001). Ninety-one percent of the participants acknowledged that the tradition helped to ease the grief response of the relatives.

Significance of results

The First Feast, a mourning tradition performed in Tokat and other parts of Turkey, might be a useful auxiliary method for palliative care teams to help grieving families.
Bringing the Church Back In: Ecclesiastical Influences on the Rise of Europe
Authors: Møller Jørgen
Published: January 2019

Recently, political scientists and economists have redoubled their attempts to understand the “Rise of Europe.” However, the role of the Catholic Church has been curiously ignored in most of this new research. The medieval West was shot through with Catholic values and institutions, and only by factoring in the Church can we understand the peculiar European development from the high Middle Ages onward. More particularly, the 11th century “crisis of church and state” set in train a series of developments that were crucial for the Rise of Europe. The Church was the main locale in which the development of representation, consent, and early bureaucratic institutions took place, and it contributed to creating, integrating, and maintaining the European multistate system. This note demonstrates that current scholarship has failed to factor in ecclesiastical influences and it shows how these gaps can be filled by a more careful reading of prior historical scholarship.
High maternal milk intake in the postnatal life reduces the incidence of breast cancer during adulthood in rats
Authors: Santiano F. E. , Zyla L. E. , Verde-Arboccó F. Campo , Sasso C. V. , Bruna F. A. , Pistone-Creydt V. , López-Fontana C. M. , Carón R. W.
Published: January 2019

Environmental factors during perinatal life can lead to changes in the mammary gland, making it susceptible to cancer in adulthood. Breastfeeding has a special importance since it takes place at a critical period of growth and development of the newborn. We aimed to analyze if an appropriate lactation protects the offspring against mammary carcinogenesis during adult life and explore the mechanisms involved in the protective effect. One-day-old Sprague-Dawley female rats were randomly distributed in litters of three (L3), eight (L8) or 12 (L12) pups per dam, to induce a differential consumption of breast milk. At 55 days of age, the animals were treated with a single dose of dimethylbenzanthracene to study tumor latency, incidence and progression. Histological, immunohistochemical and Western blot studies were performed. We observed lower incidence and higher latency in L3 compared to the other groups. The mitotic index and expression of proliferating cell nuclear antigen (PCNA) was significantly augmented in tumors of L12 rats compared to L3 and L8, while the apoptotic index was augmented in tumors of L3 v. L12. Cleaved caspase 8 was significantly higher in tumors from L3 compared to L12. Tumors developed in L3 have a greater number of apoptotic bodies and a greater expression of caspase 8. These results demonstrate that the animals that maintained a higher intake of maternal milk (L3) presented lower incidence and greater tumor latency. Lower consumption of breast milk (L12) would increase tumor mitosis and the expression of PCNA, explaining the higher tumor incidence observed in this group.
The role of offspring’s birthweight on the association between pre-pregnancy obesity and offspring’s childhood anthropometrics: a mediation analysis
Authors: Adane A. A. , Tooth L. R. , Mishra G. D.
Published: January 2019

While birthweight of offspring is associated with pre-pregnancy body mass index (BMI) and later risk of obesity, its mediating effect between the association of maternal pre-pregnancy BMI and offspring’s childhood anthropometrics has rarely been investigated. This study aimed to examine whether offspring birthweight is a mediator in the association between pre-pregnancy BMI and offspring’s childhood anthropometrics. The study included 1,618 mother–child pairs from the Australian Longitudinal Study on Women’s Health and Mothers and their Children’s Health Study. Children’s anthropometrics [mean age 8.6 (s.d. =3.0) years] were calculated from the mothers’ self-reported child weight and height measures. G-computation was used to estimate the natural direct and indirect (via birthweight) effects of pre-pregnancy BMI. In the fully adjusted model for maternal sociodemographic and lifestyle factors, the natural direct effects of pre-pregnancy obesity on child BMI-for-age, height-for-age, weight-for-age and weight-for-height outcomes were, β (95% confidence interval, CI), 0.75 (0.55, 0.95), 0.13 (−0.07, 0.32), 0.62 (0.44, 0.80) and 0.57 (0.24, 0.90), respectively. The corresponding natural indirect effects were 0.04 (−0.04, 0.12), −0.01 (−0.09, 0.07), −0.01 (−0.08, 0.07) and 0.09 (−0.05, 0.23). Similar results were observed for pre-pregnancy overweight and pre-pregnancy BMI as a continuous scale. Most of the effect of pre-pregnancy obesity on childhood weight-related anthropometric outcomes appears to be via a direct effect, not mediated through offspring’s birthweight.
Networks of Resilience: Legal Precarity and Transborder Citizenship among the Karen from Myanmar in Thailand
Authors: Balčaitė Indrė
Published: January 2019

This study probes the relationship between legal precarity and transborder citizenship through the case of the Karen from Myanmar in Thailand. Collected through ethnographic multi-sited fieldwork between 2012 and 2016, interconnected individual life stories evolving across the Myanmar-Thailand border allow the critical interrogation of the political and legal categories of ‘migrancy’, ‘refugeeness’, and ‘citizenship’, teasing out their blurry boundaries in migrants’ experience. Following the recent critical research in legal ethnography, this study demonstrates that legal precarity is not simply an antithesis to citizenship. The social and legal dimensions of citizenship may diverge, creating in-between areas of not-yet-full-citizenship with varying levels of heft (Macklin 2007). The article consists of three parts. First, it offers a theoretical framework to reconcile the Karen legal precarity (even de facto statelessness) and citizenship, even on both sides of the border (legally impossible). Second, it presents the three groups of Karen in Thailand, produced by the interaction of three major waves of Karen eastward migration and tightening Thai citizenship and migration regulations: Thai Karen, refugees, and migrant workers. All three face varying levels of legal precarity of temporary status without full citizenship. However, the last part demonstrates the intertwined nature of those groups. A grassroots transborder perspective reveals the resilience of the Karen networks when pooling together resources of the hubs established on Thai soil by the three waves. Even the most recent arrivals in Thailand use those resources to move from one precarious legal status to another and even to clandestinely obtain citizenship.
Seed Germination Ecology of Soldier Thistle (Picnomon acarna): An Invasive Weed of Rainfed Crops in Iran
Authors: Nosratti Iraj , Almaleki Sajad , Chauhan Bhagirath S.
Published: January 2019

Soldier thistle [Picnomon acarna(L.) Cass.] is widely distributed throughout rainfed fields across western Iran, where it decreases crop yields and interferes with harvest operations. This study was conducted to determine the influence of different factors on seed germination and seedling emergence ofP. acarna. Freshly harvested seeds were dormant and required an after-ripening period for breaking dormancy. Seed germination was greatly promoted by light. Germination occurred over a wide spectrum of constant and fluctuating temperature regimes, ranging from 5 to 35 C, with highest germination at constant (74%) and fluctuating (94%) temperatures of 20 and 20/10 C. Seed germination ofP. acarnawas tolerant to osmotic potential, while salt stress significantly inhibited its germination percentage. pH was not an inhibiting factor for germination ofP. acarnaseeds. Seedling emergence decreased exponentially with an increase in seed burial depth in the soil; at soil burial depths of 4 cm or greater, no seedlings were able to reach the soil surface. The results suggest that significant seed germination ofP. acarnain rainfed fields is possible, and the weed has great potential to spread throughout rainfed systems in western Iran. Based on these results, effective control ofP. acarnacan be achieved by applying interrow cultivation in row crops and deep tillage at seedbed preparation.
One Best Way? Leader Behavior and Different Aspects of Team Performance
Authors: Herre Christiane , Klumb Petra , Schaffner Jana
Published: January 2019

Abstract. In two experiments, we tested differential effects of transformational, empowering, and task-oriented leader behavior on various aspects of team performance (quantity, quality, independence, subjective group performance) using three different tasks. In Experiment 1, 60 three-person teams completed a rank-order task and in Experiment 2, 54 three-person teams completed a construction and an information-search task. In both experiments, a videotaped team leader displayed transformational, empowering, or task-oriented leadership. Results suggested that leadership effectiveness may be a function of group outcome. Only for the tasks of Experiment 2 did transformational leadership result in superior outcomes, specifically regarding productivity and originality. Empowering leadership, in turn, yielded superior outcomes in terms of leader-independent thinking, while task-oriented leadership resulted in the highest subjective group performance ratings – except for the ranking task in which satisfaction ratings were highest for transformational leadership. Implications for research and practice are discussed.
Probing Jovian Broadband Kilometric Radio Sources Tied to the Ultraviolet Main Auroral Oval With Juno
Authors: Imai Masafumi , Greathouse Thomas K. , Kurth William S. , Gladstone G. Randall , Louis Corentin K. , Zarka Philippe , Bolton Scott J. , Connerney John E. P.
Published: January 2019

Observations of Jovian broadband kilometric (bKOM) radiation and ultraviolet (UV) auroras were acquired with the Waves and Juno‐UVS instruments for ∼2 hr over the northern and southern polar regions during Juno's perijoves 4, 5, and 6 passes (PJ4, PJ5, and PJ6). During all six time periods, Juno traversed auroral magnetic field lines connecting to the UV main auroral ovals, matching the estimates of bKOM radio source footprints. The localized bKOM radio sources for the PJ4 north pass map to magnetic field lines having distances of 10 to 12 Jovian radii (RJ) at the magnetic equator, whereas the extended bKOM radio sources for the other events map to field lines extending to 20–61 RJ. We found the peak bKOM intensities during Juno's potential radio source crossings show positive, negative, and no correlations with the UV main oval brightness and color ratio. Only the positive correlations suggest wave‐particle energy transport.
Magnetodisk Coordinates for Saturn
Authors: Carbary J. F.
Published: January 2019

The magnetosphere of Saturn is known to be warped into a bowl shape, and the severity of the warping varies with the seasonal tilt of Saturn's spin axis in its orbital plane. This peculiar geometry complicates the analysis of many magnetospheric phenomena, because they are symmetric about the warped magnetodisk equator rather than the spin equator. To reorganize the Cassini data, a new coordinate system is proposed wherein a zA coordinate represents the perpendicular distance above or below the warped surface, and a ρA coordinate represents the arc length along the surface from the origin to where the perpendicular intersects the surface. Using the Cassini spacecraft trajectory, examples show how these disk coordinates (ρA, zA) significantly deviate from the standard spin‐equatorial coordinates (ρ, z), especially outside the orbit of Titan. Another example indicates that fluxes of energetic electrons are well organized in this new system. Supporting information tabulates the disk coordinates as a function of time during the Cassini mission.
New Diagnosis for Energy Flow From Solar Wind to Ionosphere During Substorm: Global MHD Simulation
Authors: Ebihara Y. , Tanaka T. , Kamiyoshikawa N.
Published: January 2019

To investigate the energy involved by a substorm, we performed global magnetohydrodynamics simulation for different solar wind conditions. The intensity of the auroral electrojet increases with the southward component of interplanetary magnetic field (IMF) and the solar wind velocity, which is consistent with observations. To evaluate the energy that enters the magnetosphere, we first defined a solar wind effective cross‐sectional area in which all the Poynting fluxes entering the magnetosphere pass through. We found that the solar wind magnetic energy is insufficient to provide the magnetic energy entering the magnetosphere (intake magnetic energy) for southward IMF. About 33–88% of the intake magnetic energy is converted from the solar wind kinetic energy. About 2–7% of the solar wind kinetic energy (passing through the effective area) is converted to the magnetic energy that enters the magnetosphere. Significant contribution from the solar wind kinetic energy makes the energy coupling function complicated. The effective area also depends on the solar wind parameters, also making it complicated. An interesting point is that the rates of energy stored and released in the lobe also depend on the solar wind parameters. The ionospheric Joule heating rate is well correlated with the intake magnetic energy at onset, and during the substorm expansion. The correlation coefficients between them are better than that of the ε parameter. These results imply that both the directly driven process (manifested by intake magnetic energy) and loading‐unloading process (manifested by stored/released energy in the lobe) are largely regulated by the solar wind condition.
Green Icebergs Revisited
Authors: Warren Stephen G. , Roesler Collin S. , Brandt Richard E. , Curran Mark
Published: January 2019

Ice crystals form in supercooled seawater beneath several Antarctic ice shelves; as they rise to the ice‐shelf base they scavenge particles from the water and incorporate them into the growing basal ice. The resulting marine ice can be ~100 m thick; it differs from sea ice in that it is clear, desalinated, and bubble‐free. Icebergs of marine ice vary in color from blue to green, depending on the nature and abundance of foreign constituents in the seawater that became trapped in the ice as it grew. A red or yellow material (i.e., one that absorbs blue light), in combination with the blue of ice, can shift the wavelength of minimum absorption to green. Previously, dissolved organic carbon (DOC) had been proposed to be responsible for the green color. Subsequent measurements of low DOC values in green icebergs, together with the recent finding of large concentrations of iron in marine ice from the Amery Ice Shelf, suggest that the color of green icebergs is caused more by iron‐oxide minerals than by DOC. These icebergs travel great distances from their origin; when they melt they can deliver iron as a nutrient to the Southern Ocean.
Significant Biologically Mediated CO2 Uptake in the Pacific Arctic During the Late Open Water Season
Authors: Juranek L. , Takahashi T. , Mathis J. , Pickart R.
Published: January 2019

Shifting baselines in the Arctic atmosphere‐sea ice‐ocean system have significant potential to alter biogeochemical cycling and ecosystem dynamics. In particular, the impact of increased open water duration on lower trophic level productivity and biological CO2 sequestration is poorly understood. Using high‐resolution observations of surface seawater dissolved O2/Ar and pCO2 collected in the Pacific Arctic in October 2011 and 2012, we evaluate spatial variability in biological metabolic status (autotrophy vs heterotrophy) as constrained by O2/Ar saturation (∆O2/Ar) as well as the relationship between net biological production and the sea‐air gradient of pCO2 (∆pCO2). We find a robust relationship between ∆pCO2 and ∆O2/Ar (correlation coefficient of −0.74 and −0.61 for 2011 and 2012, respectively), which suggests that biological production in the late open water season is an important determinant of the air‐sea CO2 gradient at a timeframe of maximal ocean uptake for CO2 in this region. Patchiness in biological production as indicated by ∆O2/Ar suggests spatially variable nutrient supply mechanisms supporting late season growth amidst a generally strongly stratified and nutrient‐limited condition.
Montanari Receives 2018 William Kaula Award
Authors:   AGU
Published: January 2019

Alberto Montanari received the William Kaula Award at the 2018 AGU Fall Meeting Honors Ceremony, held 12 December 2018 in Washington, D. C. The award honors an individual “for unselfish service to the scientific community through extraordinary dedication to, and exceptional efforts on behalf of, the Union’s publications program.”
Keeping a Watch on Seaweeds: The Forests of the World’s Coasts
Authors: Miloslavich Patricia , Johnson Craig , Benedetti-Cecchi Lisandro
Published: January 2019

Planning the Implementation of a Global Long-Term Observing and Data Sharing Strategy for Macroalgal Communities; Hobart, Tasmania, Australia, 24–26 September 2018
One-Pixel Views of Earth Reveal Seasonal Changes
Authors: Kornei Katherine
Published: January 2019

By averaging satellite images of the Earth down to a single pixel, researchers trace how the planet’s mean color varies over time, results that inform observations of distant exoplanets.
Rooftop Gardens Make Use of the Air We Breathe Below
Authors: Bates Sofie
Published: January 2019

Growing plants near building air vents may help them grow better, while reducing the carbon emissions from the people exhaling inside.
Gene expression, proteome and calcium signaling alterations in immortalized hippocampal astrocytes from an Alzheimer’s disease mouse model
Authors: Rocchio Francesca , Tapella Laura , Manfredi Marcello , Chisari Mariangela , Ronco Francesca , Ruffinatti Federico Alessandro , Conte Eleonora , Canonico Pier Luigi , Sortino Maria Angela , Grilli Mariagrazia , Marengo Emilio , Genazzani Armando A. , Lim Dmitry
Published: January 2019

Evidence is rapidly growing regarding a role of astroglial cells in the pathogenesis of Alzheimer’s disease (AD), and the hippocampus is one of the important brain regions affected in AD. While primary astroglial cultures, both from wild-type mice and from rodent models of AD, have been useful for studying astrocyte-specific alterations, the limited cell number and short primary culture lifetime have limited the use of primary hippocampal astrocytes. To overcome these limitations, we have now established immortalized astroglial cell lines from the hippocampus of 3xTg-AD and wild-type control mice (3Tg-iAstro and WT-iAstro, respectively). Both 3Tg-iAstro and WT-iAstro maintain an astroglial phenotype and markers (glutamine synthetase, aldehyde dehydrogenase 1 family member L1 and aquaporin-4) but display proliferative potential until at least passage 25. Furthermore, these cell lines maintain the potassium inward rectifying (Kir) current and present transcriptional and proteomic profiles compatible with primary astrocytes. Importantly, differences between the 3Tg-iAstro and WT-iAstro cell lines in terms of calcium signaling and in terms of transcriptional changes can be re-conducted to the changes previously reported in primary astroglial cells. To illustrate the versatility of this model we performed shotgun mass spectrometry proteomic analysis and found that proteins related to RNA binding and ribosome are differentially expressed in 3Tg-iAstro vs WT-iAstro. In summary, we present here immortalized hippocampal astrocytes from WT and 3xTg-AD mice that might be a useful model to speed up research on the role of astrocytes in AD.
Differential roles of TNFα-TNFR1 and TNFα-TNFR2 in the differentiation and function of CD4+Foxp3+ induced Treg cells in vitro and in vivo periphery in autoimmune diseases
Authors: Yang Sujuan , Xie Chichu , Chen Ye , Wang Julie , Chen Xiaoqing , Lu Zhengqi , June Rayford R. , Zheng Song Guo
Published: January 2019

Tumor Necrosis Factor (TNF) α is a multifunctional cytokine with pro-inflammatory and anti-inflammatory characteristics. Increasing evidence suggests that thymus-derived, natural regulatory T cells (nTreg) express a remarkably high level of TNF Receptor 2 (TNFR2) and TNFα modulates the number or function of nTreg via TNFR2 in autoimmune diseases. Nonetheless, Treg cells consist of at least nTreg and iTreg that are induced in the periphery or in vitro and two subsets may have different biological characteristics. However, the role of TNF-TNFR signaling in development and function of these iTreg cells is less clear. In this study, we systemically studied the effect of TNFα and its receptor signals on iTreg differentiation, proliferation, and function in vitro and in vivo. We further investigated the expression and requirement of TNFR1 or TNFR2 expression on iTreg by utilizing TNFR1−/− and TNFR2−/− mice. We found that exogenous TNFα facilitated iTreg differentiation and function in vitro. TNFR2 deficiency hampered iTreg differentiation, proliferation, and function, while TNFR1 deficiency decreased the differentiation of inflammatory T cells such as Th1 and Th17 cells but maintained the regulatory capabilities of iTreg both in vitro and in vivo. Using colitis model, we also revealed TNFR2 but not TNFR1 deficiency compromised the iTreg functionality. Interestingly, inflammation affects TNFR expression on nTreg but not iTreg subset. Our results demonstrate that exogenous TNFα may enhance the differentiation and function of iTreg via TNFR2 signaling. The expression of TNFR2 on Treg might be downregulated in some autoimmune diseases, accompanied by an increased level of TNFR1. Thus, TNFR2 agonists or TNFR1-specific antagonists hold a potential promise for clinical application in treating patients with autoimmune diseases.
MCPIP1 regulates the sensitivity of pancreatic beta-cells to cytokine toxicity
Authors: Tyka Karolina , Jörns Anne , Turatsinze Jean-Valery , Eizirik Decio L. , Lenzen Sigurd , Gurgul-Convey Ewa
Published: January 2019

The autoimmune-mediated beta-cell death in type 1 diabetes (T1DM) is associated with local inflammation (insulitis). We examined the role of MCPIP1 (monocyte chemotactic protein–induced protein 1), a novel cytokine-induced antiinflammatory protein, in this process. Basal MCPIP1 expression was lower in rat vs. human islets and beta-cells. Proinflammatory cytokines stimulated MCPIP1 expression in rat and human islets and in insulin-secreting cells. Moderate overexpression of MCPIP1 protected insulin-secreting INS1E cells against cytokine toxicity by a mechanism dependent on the presence of the PIN/DUB domain in MCPIP1. It also reduced cytokine-induced Chop and C/ebpβ expression and maintained MCL-1 expression. The shRNA-mediated suppression of MCPIP1 led to the potentiation of cytokine-mediated NFκB activation and cytokine toxicity in human EndoC-βH1 beta-cells. MCPIP1 expression was very high in infiltrated beta-cells before and after diabetes manifestation in the LEW.1AR1-iddm rat model of human T1DM. The extremely high expression of MCPIP1 in clonal beta-cells was associated with a failure of the regulatory feedback-loop mechanism, ER stress induction and high cytokine toxicity. In conclusion, our data indicate that the expression level of MCPIP1 affects the susceptibility of insulin-secreting cells to cytokines and regulates the mechanism of beta-cell death in T1DM.
Indispensable role of the Ubiquitin-fold modifier 1-specific E3 ligase in maintaining intestinal homeostasis and controlling gut inflammation
Authors: Cai Yafei , Zhu Guangxun , Liu Siyang , Pan Zezheng , Quintero Michaela , Poole Candace J. , Lu Chunwan , Zhu Huabin , Islam Bianca , Riggelen Jan van , Browning Darren , Liu Kebin , Blumberg Richard , Singh Nagendra , Li Honglin
Published: January 2019

Intestinal exocrine secretory cells, including Paneth and goblet cells, have a pivotal role in intestinal barrier function and mucosal immunity. Dysfunction of these cells may lead to the pathogenesis of human diseases such as inflammatory bowel disease (IBD). Therefore, identification and elucidation of key molecular mechanisms that regulate the development and function of these exocrine cells would be crucial for understanding of disease pathogenesis and discovery of new therapeutic targets. The Ufm1 conjugation system is a novel ubiquitin-like modification system that consists of Ufm1 (Ubiquitin modifier 1), Uba5 (Ufm1-activating enzyme, E1), Ufc1 (Ufm1-conjugating enzyme, E2) and poorly characterized Ufm1 E3 ligase(s). Recent mouse genetic studies have demonstrated its indispensable role in embryonic development and hematopoiesis. Yet its role in other tissues and organs remains poorly defined. In this study, we found that both Ufl1 and Ufbp1, two key components of the Ufm1 E3 ligase, were highly expressed in the intestinal exocrine cells. Ablation of either Ufl1 and Ufbp1 led to significant loss of both Paneth and goblet cells, which in turn resulted in dysbiotic microbiota and increased susceptibility to experimentally induced colitis. At the cellular and molecular levels, Ufbp1 deficiency caused elevation of endoplasmic reticulum stress and activation of the Unfolded Protein Response (UPR) and cell death program. Administration of small molecular chaperone partially prevented loss of Paneth cells caused by acute Ufbp1 deletion. Taken together, our results have provided unambiguous evidence for the crucial role of the Ufm1 E3 ligase in maintenance of intestinal homeostasis and protection from inflammatory diseases.
The metacaspase Yca1 maintains proteostasis through multiple interactions with the ubiquitin system
Authors: Shrestha Amit , Brunette Steve , Stanford William Lloyd , Megeney Lynn Arthur
Published: January 2019

Metacaspase enzymes are critical regulatory factors that paradoxically engage apoptosis and also maintain cell viability. For example, the Saccharomyces cerevisiae metacaspase Yca1 has been shown to be important for maintaining cellular proteostasis during stress, and the loss of this enzyme results in increased retention of aggregated material within the insoluble proteome. However, the molecular mechanism(s) by which Yca1 maintains cellular proteostasis remains unknown. Here, using proteomic analysis coupled with protein interaction studies we identified a direct interplay between Yca1 and the ubiquitin-proteasome system. We noted multiple ubiquitination sites on Yca1 and established Rsp5 as the candidate E3 ligase involved in this process. Further characterization of the ubiquitination sites identified the K355 residue on Yca1 as a critical modification for proteostasis function, managing both insoluble protein content and vacuolar response. We also identified a Yca1 phosphorylation site at S346, which promoted interaction with Rsp5 and the aggregate dispersal function of the metacaspase. Interestingly, proteomic analysis also revealed that Yca1 interacts with the ubiquitin precursor protein Rps31, cleaving the protein to release free ubiquitin. In turn, loss of Yca1 or its catalytic activity reduced the levels of monomeric ubiquitin in vivo, concurrent to increased protein aggregation. The K355 and S346 residues were also observed to influence the abundance of low-molecular weight ubiquitin. Together, these observations suggest that Yca1 maintains proteostasis and limits protein aggregation by ensuring a free flow of monoubiquitin, an essential precursor for ligase-enhanced Yca1 enzymatic activity and general proteasome-mediated protein degradation.
Somatosensory alpha oscillations gate perceptual learning efficiency
Authors: Brickwedde Marion , Krüger Marie C. , Dinse Hubert R.
Published: January 2019

Cognition and perception are closely coupled to alpha power, but whether there is a link between alpha power and perceptual learning efficacy is unknown. Here we show that somatosensory alpha power can be successfully up- and down-regulated with short-term neurofeedback training, which in turn controls subsequent tactile perceptual learning. We find that neurofeedback-induced increases in alpha power lead to enhanced learning, whereas reductions in alpha power impede learning. As a consequence, interindividual learning variability is substantially reduced. No comparable impact is observed for oscillatory power in theta, beta, and lower gamma frequency bands. Our results demonstrate that high pre-learning alpha levels are a requirement for reaching high learning efficiency. These data provide further evidence that alpha oscillations shape the functional architecture of the brain network by gating neural resources and thereby modulating levels of preparedness for upcoming processing.
In-situ formation of one-dimensional coordination polymers
in molecular junctions
Authors: Vladyka Anton , Perrin Mickael L. , Overbeck Jan , Ferradás Rubén R. , García-Suárez Víctor , Gantenbein Markus , Brunner Jan , Mayor Marcel , Ferrer Jaime , Calame Michel
Published: January 2019

We demonstrate the bottom-up in-situ formation of organometallic
oligomer chains at the single-molecule level. The chains are formed using the
mechanically controllable break junction technique operated in a liquid environment,
and consist of alternating isocyano-terminated benzene monomers coordinated to gold
atoms. We show that the chaining process is critically determined by the surface
density of molecules. In particular, we demonstrate that by reducing the local
supply of molecules within the junction, either by lowering the molecular
concentration or by adding side groups, the oligomerization process can be
suppressed. Our experimental results are supported by ab-initio simulations,
confirming that the isocyano terminating groups display a high tendency to form
molecular chains, as a result of their high affinity for gold. Our findings open the
road for the controlled formation of one-dimensional, single coordination-polymer
chains as promising model systems of organometallic frameworks.
Higher order effects in organic LEDs with sub-bandgap turn-on
Authors: Engmann Sebastian , Barito Adam J. , Bittle Emily G. , Giebink Noel C. , Richter Lee J. , Gundlach David J.
Published: January 2019

Spin-dependent nonlinear processes in organic materials such as singlet-fission and triplet-triplet annihilation could increase the performance for photovoltaics, detectors, and light emitting diodes. Rubrene/C60 light emitting diodes exhibit a distinct low voltage (half-bandgap) threshold for emission. Two origins for the low voltage turn-on have been proposed: (i) Auger assisted energy up-conversion, and (ii) triplet-triplet annihilation. We test these proposals by systematically altering the rubrene/C60 interface kinetics by introducing thin interlayers. Quantitative analysis of the unmodified rubrene/C60 device suggests that higher order processes can be ruled out as the origin of the sub-bandgap turn-on. Rather, band-to-band recombination is the most likely radiative recombination process. However, insertion of a bathocuproine layer yields a 3-fold increase in luminance compared to the unmodified device. This indicates that suppression of parasitic interface processes by judicious modification of the interface allows a triplet-triplet annihilation channel to be observed.
Approximate Bayesian computation with deep learning supports a third archaic introgression in Asia and Oceania
Authors: Mondal Mayukh , Bertranpetit Jaume , Lao Oscar
Published: January 2019

Since anatomically modern humans dispersed Out of Africa, the evolutionary history of Eurasian populations has been marked by introgressions from presently extinct hominins. Some of these introgressions have been identified using sequenced ancient genomes (Neanderthal and Denisova). Other introgressions have been proposed for still unidentified groups using the genetic diversity present in current human populations. We built a demographic model based on deep learning in an Approximate Bayesian Computation framework to infer the evolutionary history of Eurasian populations including past introgression events in Out of Africa populations fitting the current genetic evidence. In addition to the reported Neanderthal and Denisovan introgressions, our results support a third introgression in all Asian and Oceanian populations from an archaic population. This population is either related to the Neanderthal-Denisova clade or diverged early from the Denisova lineage. We propose the use of deep learning methods for clarifying situations with high complexity in evolutionary genomics.
Early preclinical detection of prions in the skin of prion-infected animals
Authors: Wang Zerui , Manca Matteo , Foutz Aaron , Camacho Manuel V. , Raymond Gregory J. , Race Brent , Orru Christina D. , Yuan Jue , Shen Pingping , Li Baiya , Lang Yue , Dang Johnny , Adornato Alise , Williams Katie , Maurer Nicholas R. , Gambetti Pierluigi , Xu Bin , Surewicz Witold , Petersen Robert B. , Dong Xiaoping , Appleby Brian S. , Caughey Byron , Cui Li , Kong Qingzhong , Zou Wen-Quan
Published: January 2019

A definitive pre-mortem diagnosis of prion disease depends on brain biopsy for prion detection currently and no validated alternative preclinical diagnostic tests have been reported to date. To determine the feasibility of using skin for preclinical diagnosis, here we report ultrasensitive serial protein misfolding cyclic amplification (sPMCA) and real-time quaking-induced conversion (RT-QuIC) assays of skin samples from hamsters and humanized transgenic mice (Tg40h) at different time points after intracerebral inoculation with 263K and sCJDMM1 prions, respectively. sPMCA detects skin PrPSc as early as 2 weeks post inoculation (wpi) in hamsters and 4 wpi in Tg40h mice; RT-QuIC assay reveals earliest skin prion-seeding activity at 3 wpi in hamsters and 20 wpi in Tg40h mice. Unlike 263K-inoculated animals, mock-inoculated animals show detectable skin/brain PrPSc only after long cohabitation periods with scrapie-infected animals. Our study provides the proof-of-concept evidence that skin prions could be a biomarker for preclinical diagnosis of prion disease.
Non defect-stabilized thermally stable single-atom catalyst
Authors: Lang Rui , Xi Wei , Liu Jin-Cheng , Cui Yi-Tao , Li Tianbo , Lee Adam Fraser , Chen Fang , Chen Yang , Li Lei , Li Lin , Lin Jian , Miao Shu , Liu Xiaoyan , Wang Ai-Qin , Wang Xiaodong , Luo Jun , Qiao Botao , Li Jun , Zhang Tao
Published: January 2019

Surface-supported isolated atoms in single-atom catalysts (SACs) are usually stabilized by diverse defects. The fabrication of high-metal-loading and thermally stable SACs remains a formidable challenge due to the difficulty of creating high densities of underpinning stable defects. Here we report that isolated Pt atoms can be stabilized through a strong covalent metal-support interaction (CMSI) that is not associated with support defects, yielding a high-loading and thermally stable SAC by trapping either the already deposited Pt atoms or the PtO2units vaporized from nanoparticles during high-temperature calcination. Experimental and computational modeling studies reveal that iron oxide reducibility is crucial to anchor isolated Pt atoms. The resulting high concentrations of single atoms enable specific activities far exceeding those of conventional nanoparticle catalysts. This non defect-stabilization strategy can be extended to non-reducible supports by simply doping with iron oxide, thus paving a new way for constructing high-loading SACs for diverse industrially important catalytic reactions.
Half-quantum vortices and walls bounded by strings in the polar-distorted phases of topological superfluid 3He
Authors: Mäkinen J. T. , Dmitriev V. V. , Nissinen J. , Rysti J. , Volovik G. E. , Yudin A. N. , Zhang K. , Eltsov V. B.
Published: January 2019

Symmetries of the physical world have guided formulation of fundamental laws, including relativistic quantum field theory and understanding of possible states of matter. Topological defects (TDs) often control the universal behavior of macroscopic quantum systems, while topology and broken symmetries determine allowed TDs. Taking advantage of the symmetry-breaking patterns in the phase diagram of nanoconfined superfluid 3He, we show that half-quantum vortices (HQVs)—linear topological defects carrying half quantum of circulation—survive transitions from the polar phase to other superfluid phases with polar distortion. In the polar-distorted A phase, HQV cores in 2D systems should harbor non-Abelian Majorana modes. In the polar-distorted B phase, HQVs form composite defects—walls bounded by strings hypothesized decades ago in cosmology. Our experiments establish the superfluid phases of 3He in nanostructured confinement as a promising topological media for further investigations ranging from topological quantum computing to cosmology and grand unification scenarios.
A diversity-oriented rhodamine library for wide-spectrum bactericidal agents with low inducible resistance against resistant pathogens
Authors: Luo Xiao , Qian Liujia , Xiao Yansheng , Tang Yao , Zhao Yang , Wang Xia , Gu Luyan , Lei Zuhai , Bao Jianming , Wu Jiahui , He Tingting , Hu Fupin , Zheng Jing , Li Honglin , Zhu Weiping , Shao Lei , Dong Xiaojing , Chen Daijie , Qian Xuhong , Yang Youjun
Published: January 2019

Antimicrobial resistance is a public health emergency and warrants coordinated global efforts. Challenge is that no alternative molecular platform has been identified for discovery of abundant antimicrobial hit compounds. Xanthene libraries have been screened for bioactive compounds. However, the potentially accessible chemistry space of xanthene dyes is limited by the existing xanthene synthesis. Herein we report a mild one-step synthesis, which permits late-stage introduction of a xanthene moiety onto i.e. natural products, pharmaceuticals, and bioactive compounds and construction of a focused library of rhodamine dyes exhibiting facile functional, topographical and stereochemical diversity. In vitro screening yields 37 analogs with mid-to-high bactericidal activity against WHO priority drug-resistant pathogens. These findings suggest that synthetic dye libraries exhibiting high structural diversity is a feasible chemical space combating antibacterial resistance, to complement the natural sources.
Clinical resistance to crenolanib in acute myeloid leukemia due to diverse molecular mechanisms
Authors: Zhang Haijiao , Savage Samantha , Schultz Anna Reister , Bottomly Daniel , White Libbey , Segerdell Erik , Wilmot Beth , McWeeney Shannon K. , Eide Christopher A. , Nechiporuk Tamilla , Carlos Amy , Henson Rachel , Lin Chenwei , Searles Robert , Ho Hoang , Lam Yee Ling , Sweat Richard , Follit Courtney , Jain Vinay , Lind Evan , Borthakur Gautam , Garcia-Manero Guillermo , Ravandi Farhad , Kantarjian Hagop M. , Cortes Jorge , Collins Robert , Buelow Daelynn R. , Baker Sharyn D. , Druker Brian J. , Tyner Jeffrey W.
Published: January 2019

FLT3 mutations are prevalent in AML patients and confer poor prognosis. Crenolanib, a potent type I pan-FLT3 inhibitor, is effective against both internal tandem duplications and resistance-conferring tyrosine kinase domain mutations. While crenolanib monotherapy has demonstrated clinical benefit in heavily pretreated relapsed/refractory AML patients, responses are transient and relapse eventually occurs. Here, to investigate the mechanisms of crenolanib resistance, we perform whole exome sequencing of AML patient samples before and after crenolanib treatment. Unlike other FLT3 inhibitors, crenolanib does not induce FLT3 secondary mutations, and mutations of the FLT3 gatekeeper residue are infrequent. Instead, mutations of NRAS and IDH2 arise, mostly as FLT3-independent subclones, while TET2 and IDH1 predominantly co-occur with FLT3-mutant clones and are enriched in crenolanib poor-responders. The remaining patients exhibit post-crenolanib expansion of mutations associated with epigenetic regulators, transcription factors, and cohesion factors, suggesting diverse genetic/epigenetic mechanisms of crenolanib resistance. Drug combinations in experimental models restore crenolanib sensitivity.
Improved TMC1 gene therapy restores hearing and balance in mice with genetic inner ear disorders
Authors: Nist-Lund Carl A. , Pan Bifeng , Patterson Amy , Asai Yukako , Chen Tianwen , Zhou Wu , Zhu Hong , Romero Sandra , Resnik Jennifer , Polley Daniel B. , Géléoc Gwenaelle S. , Holt Jeffrey R.
Published: January 2019

Fifty percent of inner ear disorders are caused by genetic mutations. To develop treatments for genetic inner ear disorders, we designed gene replacement therapies using synthetic adeno-associated viral vectors to deliver the coding sequence for Transmembrane Channel-Like (Tmc) 1 or 2 into sensory hair cells of mice with hearing and balance deficits due to mutations in Tmc1 and closely related Tmc2. Here we report restoration of function in inner and outer hair cells, enhanced hair cell survival, restoration of cochlear and vestibular function, restoration of neural responses in auditory cortex and recovery of behavioral responses to auditory and vestibular stimulation. Secondarily, we find that inner ear Tmc gene therapy restores breeding efficiency, litter survival and normal growth rates in mouse models of genetic inner ear dysfunction. Although challenges remain, the data suggest that Tmc gene therapy may be well suited for further development and perhaps translation to clinical application.
A conserved dimer interface connects ERH and YTH family proteins to promote gene silencing
Authors: Xie Guodong , Vo Tommy V. , Thillainadesan Gobi , Holla Sahana , Zhang Beibei , Jiang Yiyang , Lv Mengqi , Xu Zheng , Wang Chongyuan , Balachandran Vanivilasini , Shi Yunyu , Li Fudong , Grewal Shiv I. S.
Published: January 2019

Gene regulatory mechanisms rely on a complex network of RNA processing factors to prevent untimely gene expression. In fission yeast, the highly conserved ortholog of human ERH, called Erh1, interacts with the YTH family RNA binding protein Mmi1 to form the Erh1-Mmi1 complex (EMC) implicated in gametogenic gene silencing. However, the structural basis of EMC assembly and its functions are poorly understood. Here, we present the co-crystal structure of the EMC that consists of Erh1 homodimers interacting with Mmi1 in a 2:2 stoichiometry via a conserved molecular interface. Structure-guided mutation of the Mmi1Trp112 residue, which is required for Erh1 binding, causes defects in facultative heterochromatin assembly and gene silencing while leaving Mmi1-mediated transcription termination intact. Indeed, EMC targets masked in mmi1∆ due to termination defects are revealed in mmi1W112A. Our study delineates EMC requirements in gene silencing and identifies an ERH interface required for interaction with an RNA binding protein.
Electric-field control of spin accumulation direction for spin-orbit torques
Authors: Mishra Rahul , Mahfouzi Farzad , Kumar Dushyant , Cai Kaiming , Chen Mengji , Qiu Xuepeng , Kioussis Nicholas , Yang Hyunsoo
Published: January 2019

Electric field is an energy-efficient tool that can be leveraged to control spin–orbit torques (SOTs). Although the amount of current-induced spin accumulation in a heavy metal (HM)/ferromagnet (FM) heterostructure can be regulated to a certain degree using an electric field in various materials, the control of its direction has remained elusive so far. Here, we report that both the direction and amount of current-induced spin accumulation at the HM/FM interface can be dynamically controlled using an electric field in an oxide capped SOT device. The applied electric field transports oxygen ions and modulates the HM/FM interfacial chemistry resulting in an interplay between the spin Hall and the interfacial torques which in turn facilitates a non-volatile and reversible control over the direction and magnitude of SOTs. Our electric-field controlled spin-orbitronics device can be programmed to behave either like the SOT systems with a positive spin Hall angle or a negative spin Hall angle.
New drugs for pharmacological extension of replicative life span in normal and progeroid cells
Authors: Vatolin Sergei , Radivoyevitch Tomas , Maciejewski Jaroslaw P.
Published: January 2019

A high-throughput anti-aging drug screen was developed that simultaneously measures senescence-associated β-galactosidase activity and proliferation. Applied to replicatively pre-aged fibroblasts, this screen yielded violuric acid (VA) and 1-naphthoquinone-2-monoxime (N2N1) as its top two hits. These lead compounds extended the replicative life spans of normal and progeroid human cells in a dose-dependent manner and also extended the chronological life spans of mice and C. elegans. They are further shown here to function as redox catalysts in oxidations of NAD(P)H. They thus slow age-related declines in NAD(P)+/NAD(P)H ratios. VA participates in non-enzymatic electron transfers from NAD(P)H to oxidized glutathione or peroxides. N2N1 transfers electrons from NAD(P)H to cytochrome c or CoQ10 via NAD(P)H dehydrogenase (quinone) 1 (NQO1). Our results indicate that pharmacologic manipulation of NQO1 activity via redox catalysts may reveal mechanisms of senescence and aging.