bluuebunny/crossref_metadata_2025 huggingface dataset:
MUSCULAR MUSLIMS: SCOUTING IN LATE COLONIAL ALGERIA BETWEEN NATIONALISM AND RELIGION
Authors: Krais Jakob
Published: November 2019

The Islamic reformist movement in Algeria is often seen as a precursor to the independence movement, in which religion was supposedly integrated into nationalist identity politics. Focusing on the Muslim scout movements between the 1930s and 1950s, this article challenges this view by arguing that Islam continued to play a role beyond that of an identitarian marker. Influenced by Christian youth movements, the Muslim scouts developed ideas of a “muscular Islam” that remained central even after the movement split in two—one association close to the major nationalist party and another linked to the reformists.
Positive Externality of the American Jobs Creation Act of 2004
Authors: Hu Xiaoli , Li Oliver Zhen , Li Yuehua , Pei Sha
Published: November 2019

U.S. multinational enterprises repatriated over $300 billion under the 2004 tax holiday. The repatriated funds can improve debt financing environment of nonrepatriating firms, especially those that are financially constrained. We document that such an externality of the tax holiday increases debt financing and consequently investments for financially constrained nonrepatriating firms relative to less constrained nonrepatriating firms. Using private loan market data, we further confirm a link from repatriated funds to increased debt financing for financially constrained nonrepatriating firms. Overall, the 2004 tax holiday appears to have benefited the U.S. economy through its positive externality on the debt market.
Agreement syncretization and the loss of null subjects: quantificational models for Medieval French
Authors: Simonenko Alexandra , Crabbé Benoit , Prévost Sophie
Published: November 2019

This paper examines the nature of the dependency between the availability of null subjects and the “richness” of verbal subject agreement, known as Taraldsen's Generalisation (Adams, 1987; Rizzi, 1986; Roberts, 2014; Taraldsen, 1980). We present a corpus-based quantitative model of the syncretization of verbal subject agreement spanning the Medieval French period and evaluate two hypotheses relating agreement and null subjects: one relating the two as reflexes of the same grammatical property and a variational learning-based hypothesis whereby phonology-driven syncretization of agreement marking creates a learning bias against the null subject grammar. We show that only the latter approach has the potential to reconcile the intuition behind Taraldsen's Generalisation with the fact that it has proven nontrivial to formulate the notion of agreement richness in a way that would unequivocally predict whether a language has null subjects.
Toward fostering resilience on a large scale: Connecting communities of caregivers
Authors: Luthar Suniya S. , Kumar Nina L. , Benoit Renee
Published: November 2019

In interventions for at-risk children, Tom Dishion strongly exhorted programs that are short term, cost-effective, and delivered in families’ own communities, just as resilience researchers underscore the need for programs that provide ongoing support for children's primary caregivers, and are implementable on a large scale. Presented here are preliminary results on a short-term intervention for mothers, the Authentic Connections Virtual Groups. A previous randomized trial of the in-person version of this program, conducted with mothers at high risk for stress and burnout, showed significant benefits. There had been zero dropouts across the 3-month program, and participants showed significant improvements on psychological indices as well as cortisol, even 3 months after the program ended. In the present study, virtual groups were conducted with five sets of women, all white-collar professionals with highly stressful, exacting careers, and most also primary caregivers of their children. Again, there were zero dropouts. Mean satisfaction ratings were 9.6 of 10, and the Net Promoter Score (promoters vs. detractors) fell in the “world class” range. To illuminate mechanisms of change, participants’ responses to open-ended questions on the groups’ value are presented verbatim. Recurrently mentioned were the development of new, authentic connections and invaluable ongoing support. These results, with the low costs and ease of women's attendance, attest to the value of expanding offerings such as these, toward benefiting even more highly stressed mothers themselves as well as the children for whose care they are responsible.
Radiotherapy in desmoid fibromatosis: a 10-year experience from a tertiary care centre
Authors: Varghese Sunitha S. , Sidhique Sharief , Prabhu Anne J. , Pavamani Simon P. , Antonysamy B. , Titus Vijay T. K. , Nayak Sukriya , Backianathan Selvamani
Published: November 2019

Aim of the study:

To assess the relapse-free survival (RFS) and the factors influencing local recurrence in patients with desmoid fibromatosis (DF) treated at our centre and to determine the role of post-operative radiotherapy (RT) in improving local control.

Methods:

A retrospective analysis of 51 patients treated for DF from January 2004 to December 2013 was undertaken. The RFS was calculated using the Kaplan–Meier curve. Univariate analysis was done to assess correlation with tumour size, site, the extent of surgery, margin status and adjuvant RT with RFS.

Results:

The median age was 28 years with a male:female ratio of 1:3. The most common location of the tumour was anterior abdominal wall (47%). The median tumour size was 10 cm. Wide local excision was done in most patients. Complete resection with negative margin was achieved in eight patients. Post-operative RT was indicated for 43 patients of whom 19 received RT. At a median follow-up of 37 months, RFS in the complete resection with margin negative group was 100%. RFS for the patients with positive or close margins who received RT was 79% and for those who did not receive RT, it was 87%.

Conclusions:

Complete excision with negative margins gives the best local control in DF. The benefit of post-operative RT could not be ascertained.
Social bonding in diplomacy
Authors: Holmes Marcus , Wheeler Nicholas J.
Published: November 2019

It is widely recognized among state leaders and diplomats that personal relations play an important role in international politics. Recent work at the intersection of psychology, neuroscience, and sociology has highlighted the critical importance of face-to-face interactions in generating intention understanding and building trust. Yet, a key question remains as to why some leaders are able to ‘hit it off,’ generating a positive social bond, while other interactions ‘fall flat,’ or worse, are mired in negativity. To answer, we turn to micro-sociology – the study of everyday human interactions at the smallest scales – an approach that has theorized this question in other domains. Drawing directly from US sociologist Randall Collins, and related empirical studies on the determinants of social bonding, we develop a model of diplomatic social bonding that privileges interaction elements rather than the dispositional characteristics of the actors involved or the material environment in which the interaction takes place. We conclude with a discussion of how the study of interpersonal dyadic bonding interaction may move forward.
Fate of Weed Seeds after Impact Mill Processing in Midwestern and Mid-Atlantic United States
Authors: Shergill Lovreet S. , Bejleri Kreshnik , Davis Adam , Mirsky Steven B.
Published: November 2019

Harvest weed seed control (HWSC) technology such as impact mills that destroy weed seeds in seed-bearing chaff material during grain crop harvest, has been highly effective in Australian cropping systems. However, the impact mill has never been tested in soybeans and weeds common to soybean production systems in the Midwest and Mid-Atlantic US. We conducted stationary testing of Harrington Seed Destructor (HSD) impact mill and winter burial studies during 2015-2016 and 2017-2018 to determine (i) the efficacy of the impact mill to target weed seeds of seven common weeds in Midwestern and five in Mid-Atlantic US, and (ii) the fate of impact mill processed weed seeds after winter burial. The impact mill was highly effective in destroying seeds of all the species tested, with 93.5-99.8% weed seed destruction in 2015 and 85.6-100% in 2017. The weak relationships (positive or negative) between seed size and seed destruction by impact mill, and high percentage of weed seed destruction by impact mill across all seed sizes indicate that the biological or practical effect of seed size is limited. The impact mill-processed weed seeds that retained at least 50% of their original size, labeled as potentially viable seed (PVS), were buried for 90 d over winter to determine the fate of weed seeds after winter burial. At 90 d after burial (DAB), the impact mill processed PVS were significantly less viable than unprocessed control seeds, indicating that impact mill processing physically damaged the PVS and promoted seed mortality over winter. A very small fraction (< 0.4%) of the total weed seed processed by the impact mill remained viable after winter burial. The results presented here demonstrate that the impact mill is highly effective in increasing seed mortality and could potentially be used as a HWSC tactic for weed management in this region.
Watching Earth’s Interconnected Systems at Work
Authors: Schneider Fabian , Ferraz Ant�nio , Schimel David
Published: November 2019

Surface Biology and Geology, a new NASA Earth observation effort, is developing a path forward for monitoring the Earth system from space.
Special Election to Fill AGU Board Vacancy Begins 4 November
Authors: Davidson Eric
Published: November 2019

Two highly qualified candidates are on the ballot. AGU members should vote by 18 November.
We Have Broken Nature into More Than 990,000 Little Pieces
Authors: Duncombe Jenessa
Published: November 2019

Habitat fragmentation is splintering undeveloped areas on Earth.
Modeling of Diffuse Aurora due to Precipitation of H+‐H and SEP Electrons in the Nighttime Atmosphere of Mars: Monte Carlo Simulation and MAVEN Observation
Authors: Haider S. A. , Masoom J.
Published: November 2019

The nighttime limb intensity of diffuse auroral emission of CO2+ (B2Σu+ ‐ X2πg) Ultraviolet Doublet (UVD) is observed in the northern hemisphere of Mars during 17–21 December 2014 from Imaging Ultraviolet Spectrograph instrument onboard Mars Atmosphere and Volatile Evolution. We have used hybrid model and four‐dimensional yield spectrum approach based on Monte Carlo simulation to calculate the ionization rate, limb intensity, and ion and electron densities of diffuse aurora due to precipitation of solar energetic particle and proton‐hydrogen (H+‐H) fluxes in the nighttime ionosphere of Mars. It is found that the production rates of atmospheric ions (CO2+, N2+, and O+) are dominant in the upper ionosphere at about 100–150 km due to impact of H+‐H. The solar energetic particle formed auroral ionosphere (CO2+, NO+, and O+) in the middle ionosphere between 50 and 100 km due to precipitation of monoenergetic electrons of energies 25 to 100 keV. The simulated limb intensities of CO2+UVD due to impact of H+‐H and auroral electrons are compared with Imaging Ultraviolet Spectrograph observations. Our model results are overestimating the observations, but 100 keV electrons deposited maximum energy around 75 km, closer to the observed altitude of the maximum emission. The densities of upper ionosphere (O2+, NO+, and CO2+) due to impact of H+‐H are smaller by one to two orders of magnitude than that produced by auroral electrons in the middle ionosphere.
Effects of Anticyclonic Eddies on the Multicore Structure of the North Pacific Subtropical Mode Water Based on Argo Observations
Authors: Liu Cong , Xu Lixiao , Xie Shang‐Ping , Li Peiliang
Published: November 2019

The North Pacific subtropical mode water (STMW) often displays a “multicore structure” with more than one minimum in the vertical potential vorticity profile. Anticyclonic eddies (AEs) play an important role in STMW formation and transport, but their effect on the multicore structure of the STMW has not been fully studied. Here, we investigated the formation and evolution of STMW multicore structures in AEs using Argo profiles, which followed two AEs in the STMW formation region for approximately 1.5 years from 2013 to 2015. We found that after the two AEs formed east of 150°E, they trapped the local cold and dense STMW and migrated westward. Since sea surface temperatures increased toward the west, warmer and lighter STMWs were formed during the winter ventilation process as the two AEs moved westward. The newly formed STMW rode on the preexisting cold and dense STMW inside the eddy core, forming a multicore structure in the STMW. Given that water mass properties within AEs are much more conservative, the multicore structure of STMW is much more easily formed inside AEs than outside of eddies. There was a larger (smaller) proportion of profiles containing multiple STMW cores inside (outside) the AE cores, indicating that the AEs were “hot spots” for developing the multicore structure of STMW. The occurrence of the multicore structure of STMW in AEs was highest in spring (March–May) but decreased quickly as the season progressed.
Irrigation Impact on Water and Energy Cycle During Dry Years Over the United States Using Convection‐Permitting WRF and a Dynamical Recycling Model
Authors: Yang Zhao , Qian Yun , Liu Ying , Berg Larry K. , Hu Huancui , Dominguez Francina , Yang Ben , Feng Zhe , Gustafson William I. , Huang Maoyi , Tang Qi
Published: November 2019

An irrigation scheme is implemented in the Weather Research and Forecasting (WRF) model to investigate irrigation impacts over the Continental U.S. (CONUS). Four major irrigated regions and two downwind regions were chosen to understand irrigation impacts over different climate regimes with a focus on irrigation‐induced changes on the water and energy cycles. The Dynamic Recycling Model (DRM) is employed to quantify precipitation induced by irrigation and the precipitation recycling ratios over each irrigated region. With the irrigation scheme, WRF improves the simulated precipitation, surface skin temperature, and energy fluxes compared to reference datasets. For the energy cycle, irrigation increases latent heat flux over the irrigated regions along with reduced sensible heat flux. The evaporative cooling effect induced by irrigation leads to a cooler surface and less outgoing longwave radiation at the surface. Irrigation also intensifies the hydrological cycle over the irrigated regions, reflected by the increased precipitation, evapotranspiration, recycling ratio, and moisture export. Downwind regions exhibit increased precipitation and evaporation, decreased moisture flux divergence, and less consistent variations in recycling ratio. The precipitation increases over the irrigated regions can be partly explained by the more unstable low‐level conditions, while reduced net moisture export is coincident with the precipitation increases over the downwind regions.
Reply to Comment on “Comparing Paleomagnetic Study Means with Apparent Wander Paths: A Case Study and Paleomagnetic Test of the Greater India versus Greater Indian Basin Hypotheses”
Authors: Rowley David B.
Published: November 2019

Key Points

van Hinsbergen has mischaracterized the analysis presented
Motor cortex facilitation: a marker of attention deficit hyperactivity disorder co-occurrence in autism spectrum disorder
Authors: Pedapati Ernest V. , Mooney Lindsey N. , Wu Steve W. , Erickson Craig A. , Sweeney John A. , Shaffer Rebecca C. , Horn Paul S. , Wink Logan K. , Gilbert Donald L.
Published: November 2019

The neural correlates distinguishing youth with Autism Spectrum Disorder (ASD-) and ASD with co-occurring Attention Deficit Hyperactivity Disorder (ASD+) are poorly understood despite significant phenotypic and prognostic differences. Paired-pulse transcranial magnetic stimulation (TMS) measures, including intracortical facilitation (ICF), short interval cortical inhibition (SICI), and cortical silent period (CSP) were measured in an age matched cohort of youth with ASD- (n = 20), ASD + (n = 29), and controls (TDC) (n = 24). ASD− and ASD+ groups did not differ by IQ or social functioning; however, ASD+ had significantly higher inattention and hyperactivity ratings. ICF (higher ratio indicates greater facilitation) in ASD+ (Mean 1.0, SD 0.19) was less than ASD− (Mean 1.3, SD 0.36) or TDC (Mean 1.2, SD 0.24) (F2,68 = 6.5,p = 0.003; post-hoc tests, ASD+ vs either TDC or ASD−,p ≤ 0.05). No differences were found between groups for SICI or age corrected active/resting motor threshold (AMT/RMT). Across all ASD youth (ASD− and ASD+), ICF was inversely correlated with worse inattention (Conners-3 Inattention (r = −0.41;p < 0.01) and ADHDRS-IV Inattention percentile (r = −0.422,p < 0.01) scores. ICF remains intact in ASD− but is impaired in ASD+. Lack of ICF is associated with inattention and executive function across ASD. Taken with the present findings, ADHD may have a distinct electrophysiological “signature” in ASD youth. ICF may constitute an emerging biomarker to study the physiology of ADHD in ASD, which may align with disease prognosis or treatment response.
Overall and progression-free survival with cabazitaxel in metastatic castration-resistant prostate cancer in routine clinical practice: the FUJI cohort
Authors:   on behalf of the FUJI Investigators, Rouyer Magali , Oudard Stéphane , Joly Florence , Fizazi Karim , Tubach Florence , Jove Jérémy , Lacueille Clémentine , Lamarque Stéphanie , Guiard Estelle , Balestra Aurélie , Droz-Perroteau Cécile , Fourrier-Reglat Annie , Moore Nicholas
Published: November 2019

Background

Cabazitaxel is a treatment of metastatic castration-resistant prostate cancer (mCRPC) after docetaxel failure. The FUJI cohort aimed to confirm the real-life overall and progression-free survival (OS, PFS) and safety of cabazitaxel.

Methods

Multicentre, non-interventional cohort of French mCRPC patients initiating cabazitaxel between 2013 and 2015, followed 18 months.

Results

Four hundred one patients were recruited in 42 centres. At inclusion, median age was 70, main metastatic sites were bones (87%), lymph nodes (42%) and visceral (20%). 18% had cabazitaxel in 2nd-line treatment, 39% in 3rd-line and 43% in 4th-line or beyond. All had prior docetaxel, and 82% prior abiraterone, enzalutamide or both. Median duration of cabazitaxel treatment was 3.4 months. Median OS from cabazitaxel initiation was 11.9 months [95% CI: 10.1–12.9]. In multivariate analyses, grade ≥ 3 adverse events, visceral metastases, polymedication, and >5 bone metastases were associated with a shorter OS. Main grade ≥ 3 adverse events were haematological with 8% febrile neutropenia.

Conclusion

Real-life survival with cabazitaxel in FUJI was shorter than in TROPIC (pivotal trial, median OS 15.1 months) or PROSELICA (clinical trial 20 vs 25 mg/m2, median OS, respectively, 13.4 and 14.5 months). There was no effect of treatment-line on survival. No unexpected adverse concerns were identified.

Study registration

It was registered with the European Medicines Agency EUPASS registry, available at www.encepp.eu, as EUPAS10391. It has been approved as an ENCEPP SEAL study.
Survival after cancer in children, adolescents and young adults in the Nordic countries from 1980 to 2013
Authors: Rostgaard Klaus , Hjalgrim Henrik , Madanat-Harjuoja Laura , Johannesen Tom B. , Collin Sofia , Hjalgrim Lisa L.
Published: November 2019

Background

The present study aimed to assess whether the widespread concern of inferior cancer survival in adolescents and young adults (AYAs) compared with children and adults holds true in a Nordic setting with important differences in healthcare organisation compared with the United States (e.g. free access to healthcare) and the United Kingdom (e.g. young teenagers are treated in paediatric departments).

Methods

Five-year relative survival was calculated for 17 diagnostic groups in patients diagnosed in 2000–2013 in three diagnostic age categories: children (0–14 years), AYAs (15–24 years) and adults (25–34 years).

Results

For 13 out of 17 diagnostic groups examined, there was no difference in survival between AYAs and neighbouring age categories. For acute lymphoblastic leukaemias, astrocytomas, rhabdomyosarcomas and non-rhabdomyosarcoma soft tissue sarcomas we found survival in children to be superior to that in AYAs. For these four diagnostic groups, the rate of survival improvement over three calendar periods (1980–1989, 1990–1999 and 2000–2013) was not particularly low in AYAs compared with neighbouring age categories.

Conclusions

The present study suggests that in an affluent setting with free access to healthcare, meaningful differences in survival between AYA patients and either childhood or adult patients are a phenomenon of the past for most AYA cancer diagnostic groups.
Natural and non-natural antioxidative compounds: potential candidates for treatment of vascular calcification
Authors: Chao Chia-Ter , Yeh Hsiang-Yuan , Tsai You-Tien , Chuang Pei-Huan , Yuan Tzu-Hang , Huang Jenq-Wen , Chen Huei-Wen
Published: November 2019

Vascular calcification (VC) is highly prevalent in patients with advanced age, or those with chronic kidney disease and diabetes, accounting for substantial global cardiovascular burden. The pathophysiology of VC involves active mineral deposition by transdifferentiated vascular smooth muscle cells exhibiting osteoblast-like behavior, building upon cores with or without apoptotic bodies. Oxidative stress drives the progression of the cellular phenotypic switch and calcium deposition in the vascular wall. In this review, we discuss potential compounds that shield these cells from the detrimental influences of reactive oxygen species as promising treatment options for VC. A comprehensive summary of the current literature regarding antioxidants for VC is important, as no effective therapy is currently available for this disease. We systematically searched through the existing literature to identify original articles investigating traditional antioxidants and novel compounds with antioxidant properties with regard to their effectiveness against VC in experimental or clinical settings. We uncovered 36 compounds with antioxidant properties against VC pathology, involving mechanisms such as suppression of NADPH oxidase, BMP-2, and Wnt/β-catenin; anti-inflammation; and activation of Nrf2 pathways. Only two compounds have been tested clinically. These findings suggest that a considerable opportunity exists to harness these antioxidants for therapeutic use for VC. In order to achieve this goal, more translational studies are needed.
Multisite phosphorylation drives phenotypic variation in (p)ppGpp synthetase-dependent antibiotic tolerance
Authors: Libby Elizabeth A. , Reuveni Shlomi , Dworkin Jonathan
Published: November 2019

Isogenic populations of cells exhibit phenotypic variability that has specific physiological consequences. Individual bacteria within a population can differ in antibiotic tolerance, but whether this variability can be regulated or is generally an unavoidable consequence of stochastic fluctuations is unclear. Here we report that a gene encoding a bacterial (p)ppGpp synthetase in Bacillus subtilis, sasA, exhibits high levels of extrinsic noise in expression. We find that sasA is regulated by multisite phosphorylation of the transcription factor WalR, mediated by a Ser/Thr kinase-phosphatase pair PrkC/PrpC, and a Histidine kinase WalK of a two-component system. This regulatory intersection is crucial for controlling the appearance of outliers; rare cells with unusually high levels of sasA expression, having increased antibiotic tolerance. We create a predictive model demonstrating that the probability of a given cell surviving antibiotic treatment increases with sasA expression. Therefore, multisite phosphorylation can be used to strongly regulate variability in antibiotic tolerance.
A meta-analysis of global fungal distribution reveals climate-driven patterns
Authors: Větrovský Tomáš , Kohout Petr , Kopecký Martin , Machac Antonin , Man Matěj , Bahnmann Barbara Doreen , Brabcová Vendula , Choi Jinlyung , Meszárošová Lenka , Human Zander Rainier , Lepinay Clémentine , Lladó Salvador , López-Mondéjar Rubén , Martinović Tijana , Mašínová Tereza , Morais Daniel , Navrátilová Diana , Odriozola Iñaki , Štursová Martina , Švec Karel , Tláskal Vojtěch , Urbanová Michaela , Wan Joe , Žifčáková Lucia , Howe Adina , Ladau Joshua , Peay Kabir Gabriel , Storch David , Wild Jan , Baldrian Petr
Published: November 2019

The evolutionary and environmental factors that shape fungal biogeography are incompletely understood. Here, we assemble a large dataset consisting of previously generated mycobiome data linked to specific geographical locations across the world. We use this dataset to describe the distribution of fungal taxa and to look for correlations with different environmental factors such as climate, soil and vegetation variables. Our meta-study identifies climate as an important driver of different aspects of fungal biogeography, including the global distribution of common fungi as well as the composition and diversity of fungal communities. In our analysis, fungal diversity is concentrated at high latitudes, in contrast with the opposite pattern previously shown for plants and other organisms. Mycorrhizal fungi appear to have narrower climatic tolerances than pathogenic fungi. We speculate that climate change could affect ecosystem functioning because of the narrow climatic tolerances of key fungal taxa.
Landscape determinants of density of blacklegged ticks, vectors of Lyme disease, at the northern edge of their distribution in Canada
Authors: Talbot Benoit , Slatculescu Andreea , Thickstun Charles R. , Koffi Jules K. , Leighton Patrick A. , McKay Roman , Kulkarni Manisha A.
Published: November 2019

In eastern North America, including Canada, Lyme disease is caused by Borrelia burgdorferi sensu stricto and transmitted to humans by the blacklegged tick, Ixodes scapularis. The last decade has seen a growing incidence of Lyme disease in Canada, following the northward range expansion of I. scapularis tick populations from endemic areas in eastern United States. This may be attributable to movement of the many hosts that they parasitize, including songbirds, deer and small mammals. In this study, we wanted to test the effect of spatial, temporal and ecological variables, on blacklegged tick density and infection rates, near the northern limit of their distribution in Ontario and Quebec, Canada. We found an effect of both proportion of forested areas and distance to roads, on density of I. scapularis ticks and prevalence of infection by B. burgdorferi. We also found an effect of both sampling year and ordinal sampling data on prevalence of infection by B. burgdorferi. In six adjacent sites showing evidence of reproducing I. scapularis populations, we found that forest composition and structure influenced density of I. scapularis ticks. Our results suggest that blacklegged tick density and infection rate in Canada may be influenced by a variety of factors.
Genome Wide Meta-Analysis identifies common genetic signatures shared by heart function and Alzheimer’s disease
Authors: Sáez M. E. , González-Pérez A. , Hernández-Olasagarre B. , Beà A. , Moreno-Grau S. , de Rojas I. , Monté-Rubio G. , Orellana A. , Valero S. , Comella J. X. , Sanchís D. , Ruiz A.
Published: November 2019

Echocardiography has become an indispensable tool for the study of heart performance, improving the monitoring of individuals with cardiac diseases. Diverse genetic factors associated with echocardiographic measures have been previously reported. The impact of several apoptotic genes in heart development identified in experimental models prompted us to assess their potential association with human cardiac function. This study aimed at investigating the possible association of variants of apoptotic genes with echocardiographic traits and to identify new genetic markers associated with cardiac function. Genome wide data from different studies were obtained from public repositories. After quality control and imputation, a meta-analysis of individual association study results was performed. Our results confirmed the role of caspases and other apoptosis related genes with cardiac phenotypes. Moreover, enrichment analysis showed an over-representation of genes, including some apoptotic regulators, associated with Alzheimer’s disease. We further explored this unexpected observation which was confirmed by genetic correlation analyses. Our findings show the association of apoptotic gene variants with echocardiographic indicators of heart function and reveal a novel potential genetic link between echocardiographic measures in healthy populations and cognitive decline later on in life. These findings may have important implications for preventative strategies combating Alzheimer’s disease.
Quantification of intracellular N-terminal β-actin arginylation
Authors: Chen Li , Kashina Anna
Published: November 2019

Actin is a ubiquitous, essential, and highly abundant protein in all eukaryotic cells that performs key roles in contractility, adhesion, migration, and leading edge dynamics. The two non-muscle actins, β- and γ-, are ubiquitously present in every cell type and are nearly identical to each other at the amino acid level, but play distinct intracellular roles. The mechanisms regulating this distinction have been the focus of recent interest in the field. Work from our lab has previously shown that β-, but not γ-, actin undergoes N-terminal arginylation on Asp3. While functional evidence suggest that this arginylation may be important to actin’s function, progress in these studies so far has been hindered by difficulties in arginylated actin detection, precluding estimations of the abundance of arginylated actin in cells, and its occurrence in different tissues and cell types. The present study represents the first antibody-based quantification of the percentage of arginylated actin in migratory non-muscle cells under different physiological conditions, as well as in different cells and tissues. We find that while the steady-state level of arginylated actin is relatively low, it is consistently present in vivo, and is somewhat more prominent in migratory cells. Inhibition of N-terminal actin acetylation dramatically increases the intracellular actin arginylation level, suggesting that these two modifications may directly compete in vivo. These findings constitute an essential step in our understanding of actin regulation by arginylation, and in uncovering the dynamic interplay of actin’s N-terminal modifications in vivo.
Using a Single Daytime Performance Test to Identify Most Individuals at High-Risk for Performance Impairment during Extended Wake
Authors: St. Hilaire Melissa A. , Kristal Bruce S. , Rahman Shadab A. , Sullivan Jason P. , Quackenbush John , Duffy Jeanne F. , Barger Laura K. , Gooley Joshua J. , Czeisler Charles A. , Lockley Steven W.
Published: November 2019

We explored the predictive value of a neurobehavioral performance assessment under rested baseline conditions (evaluated at 8 hours awake following 8 hours of sleep) on neurobehavioral response to moderate sleep loss (evaluated at 20 hours awake two days later) in 151 healthy young participants (18–30 years). We defined each participant’s response-to-sleep-loss phenotype based on the number of attentional failures on a 10-min visual psychomotor vigilance task taken at 20 hours awake (resilient: less than 6 attentional failures, n = 26 participants; non-resilient: 6 or more attentional failures, n = 125 participants). We observed that 97% of rested participants with 2 or more attentional failures (n = 73 of 151) and 100% of rested participants with 3 or more attentional failures (n = 57 of 151) were non-resilient after moderate sleep loss. Our approach can accurately identify a significant proportion of individuals who are at high risk for neurobehavioral performance impairment from staying up late with a single neurobehavioral performance assessment conducted during rested conditions. Additional methods are needed to predict the future performance of individuals who are not identified as high risk during baseline.
Structures of GapR reveal a central channel which could accommodate B-DNA
Authors: Tarry Michael J. , Harmel Christoph , Taylor James A. , Marczynski Gregory T. , Schmeing T. Martin
Published: November 2019

GapR is a nucleoid-associated protein required for the cell cycle of Caulobacter cresentus. We have determined new crystal structures of GapR to high resolution. As in a recently published structure, a GapR monomer folds into one long N-terminal α helix and two shorter α helices, and assembles into a tetrameric ring with a closed, positively charged, central channel. In contrast to the conclusions drawn from the published structures, we observe that the central channel of the tetramer presented here could freely accommodate B-DNA. Mutation of six conserved lysine residues lining the cavity and electrophoretic mobility gel shift experiments confirmed their role in DNA binding and the channel as the site of DNA binding. Although present in our crystals, DNA could not be observed in the electron density maps, suggesting that DNA binding is non-specific, which could be important for tetramer-ring translocation along the chromosome. In conjunction with previous GapR structures we propose a model for DNA binding and translocation that explains key published observations on GapR and its biological functions.
The β-oxidation pathway is downregulated during diapause termination in Calanus copepods
Authors: Skottene Elise , Tarrant Ann M. , Olsen Anders J. , Altin Dag , Østensen Mari-Ann , Hansen Bjørn Henrik , Choquet Marvin , Jenssen Bjørn M. , Olsen Rolf Erik
Published: November 2019

Calanuscopepods are keystone species in marine ecosystems, mainly due to their high lipid content, which is a nutritious food source for e.g. juvenile fish. Accumulated lipids are catabolized to meet energy requirements during dormancy (diapause), which occurs during the last copepodite stage (C5). The current knowledge of lipid degradation pathways during diapause termination is limited. We characterized changes in lipid fullness and generated transcriptional profiles in C5s during termination of diapause and progression towards adulthood. Lipid fullness of C5s declined linearly during developmental progression, but more β-oxidation genes were upregulated in early C5s compared to late C5s and adults. We identified four possible master regulators of energy metabolism, which all were generally upregulated in early C5s, compared to late C5s and adults. We discovered that one of two enzymes in the carnitine shuttle is absent from the calanoid copepod lineage. Based on the geographical location of the sampling site, the field-samples were initially presumed to consist ofC. finmarchicus. However, the identification ofC. glacialisin some samples underlines the need for performing molecular analyses to reliably identifyCalanusspecies. Our findings contributes to a better understanding of molecular events occurring during diapause and diapause termination in calanoid copepods.
Integrating multi-platform genomic datasets for kidney renal clear cell carcinoma subtyping using stacked denoising autoencoders
Authors: Gu Tongjun , Zhao Xiwu
Published: November 2019

Clear cell renal cell carcinoma (ccRCC) is highly heterogeneous and is the most lethal cancer of all urologic cancers. We developed an unsupervised deep learning method, stacked denoising autoencoders (SdA), by integrating multi-platform genomic data for subtyping ccRCC with the goal of assisting diagnosis, personalized treatments and prognosis. We successfully found two subtypes of ccRCC using five genomics datasets for Kidney Renal Clear Cell Carcinoma (KIRC) from The Cancer Genome Atlas (TCGA). Correlation analysis between the last reconstructed input and the original input data showed that all the five types of genomic data positively contribute to the identification of the subtypes. The first subtype of patients had significantly lower survival probability, higher grade on neoplasm histology and higher stage on pathology than the other subtype of patients. Furthermore, we identified a set of genes, proteins and miRNAs that were differential expressed (DE) between the two subtypes. The function annotation of the DE genes from pathway analysis matches the clinical features. Importantly, we applied the model learned from KIRC as a pre-trained model to two independent datasets from TCGA, Lung Adenocarcinoma (LUAD) dataset and Low Grade Glioma (LGG), and the model stratified the LUAD and LGG patients into clinical associated subtypes. The successful application of our method to independent groups of patients supports that the SdA method and the model learned from KIRC are effective on subtyping cancer patients and most likely can be used on other similar tasks. We supplied the source code and the models to assist similar studies at https://github.com/tjgu/cancer_subtyping.
Mechanisms of GABAB receptor enhancement of extrasynaptic GABAA receptor currents in cerebellar granule cells
Authors: Khatri Shailesh N. , Wu Wan-Chen , Yang Ying , Pugh Jason R.
Published: November 2019

Many neurons, including cerebellar granule cells, exhibit a tonic GABA current mediated by extrasynaptic GABAA receptors. This current is a critical regulator of firing and the target of many clinically relevant compounds. Using a combination of patch clamp electrophysiology and photolytic uncaging of RuBi-GABA we show that GABAB receptors are tonically active and enhance extrasynaptic GABAA receptor currents in cerebellar granule cells. This enhancement is not associated with meaningful changes in GABAA receptor potency, mean channel open-time, open probability, or single-channel current. However, there was a significant (~40%) decrease in the number of channels participating in the GABA uncaging current and an increase in receptor desensitization. Furthermore, we find that adenylate cyclase, PKA, CaMKII, and release of Ca2+ from intracellular stores are necessary for modulation of GABAA receptors. Overall, this work reveals crosstalk between postsynaptic GABAA and GABAB receptors and identifies the signaling pathways and mechanisms involved.
MUC4-ErbB2 Oncogenic Complex: Binding studies using Microscale Thermophoresis
Authors: Liberelle Maxime , Magnez Romain , Thuru Xavier , Bencheikh Yamina , Ravez Severine , Quenon Camille , Drucbert Anne-Sophie , Foulon Catherine , Melnyk Patricia , Van Seuningen Isabelle , Lebègue Nicolas
Published: November 2019

The MUC4 membrane-bound mucin is a large O-glycoprotein involved in epithelial homeostasis. At the cancer cell surface MUC4 interacts with ErbB2 receptor via EGF domains to promote cell proliferation and migration. MUC4 is highly regarded as a therapeutic target in pancreatic cancer as it is not expressed in healthy pancreas, while it is neoexpressed in early preneoplastic stages (PanINs). However, the association/dissociation constant of MUC4-ErbB2 complex is unknown. Protein-protein interactions (PPIs) have become a major area of research in the past years and the characterization of their interactions, especially by biophysical methods, is intensively used in drug discovery. To characterize the MUC4-ErbB2 interaction, we used MicroScale Thermophoresis (MST), a powerful method for quantitative protein interaction analysis under challenging conditions. We worked with CHO cell lysates containing either the transmembrane β subunit of MUC4 (MUC4β) or a truncated mutant encompassing only the EGF domains (MUC4EGF3+1+2). MST studies have led to the characterization of equilibrium dissociation constants (Kd) for MUC4β-ErbB2 (7–25 nM) and MUC4EGF3+1+2/ErbB2 (65–79 nM) complexes. This work provides new information regarding the MUC4-ErbB2 interaction at the biophysical level and also confirms that the presence of the three EGF domains of MUC4 is sufficient to provide efficient interaction. This technological approach will be very useful in the future to validate small molecule binding affinities targeting MUC4-ErbB2 complex for drug discovery development in cancer. It will also be of high interest for the other known membrane mucins forming oncogenic complexes with ErbBs at the cancer cell surface.
Effects of non-solvents and electrolytes on the formation and properties of cellulose I filaments
Authors: Wang Ling , Lundahl Meri J. , Greca Luiz G. , Papageorgiou Anastassios C. , Borghei Maryam , Rojas Orlando J.
Published: November 2019

Coagulation is a critical process in the assembly of cellulose nanofibrils into filaments by wet spinning; however, so far, the role of the coagulation solvent has not been systematically elucidated in this context. This work considers organic non-solvents (ethanol, acetone) and aqueous electrolyte solutions (NaCl(aq), HCl(aq), CaCl2(aq)) for the coagulation of negatively charged cellulose nanofibrils via wet spinning. The associated mechanisms of coagulation with such non-solvents resulted in different spinnability, coagulation and drying time. The properties of the achieved filaments varied depending strongly on the coagulant used: filaments obtained from electrolytes (using Ca2+ and H+ as counterions) demonstrated better water/moisture stability and thermomechanical properties. In contrast, the filaments formed from organic non-solvents (with Na+ as counterions) showed high moisture sorption and low hornification when subjected to cycles of high and low humidity (dynamic vapor sorption experiments) and swelled extensively upon immersion in water. Our observations highlight the critical role of counter-ions and non-solvents in filament formation and performance. Some of the fundamental aspects are further revealed by using quartz crystal microgravimetry with model films of nanocelluloses subjected to the respective solvent exchange.
Tumor necrosis factor induces rapid down-regulation of TXNIP in human T cells
Authors: Levring Trine B. , Kongsbak-Wismann Martin , Rode Anna K. O. , Al-Jaberi Fatima A. H. , Lopez Daniel V. , Met Özcan , Woetmann Anders , Bonefeld Charlotte M. , Ødum Niels , Geisler Carsten
Published: November 2019

In addition to antigen-driven signals, T cells need co-stimulatory signals for robust activation. Several receptors, including members of the tumor necrosis factor receptor superfamily (TNFRSF), can deliver co-stimulatory signals to T cells. Thioredoxin interacting protein (TXNIP) is an important inhibitor of glucose uptake and cell proliferation, but it is unknown how TXNIP is regulated in T cells. The aim of this study was to determine expression levels and regulation of TXNIP in human T cells. We found that naïve T cells express high levels of TXNIP and that treatment of blood samples with TNF results in rapid down-regulation of TXNIP in the T cells. TNF-induced TXNIP down-regulation correlated with increased glucose uptake. Furthermore, we found that density gradient centrifugation (DGC) induced down-regulation of TXNIP. We demonstrate that DGC induced TNF production that paralleled the TXNIP down-regulation. Treatment of blood with toll-like receptor (TLR) ligands induced TNF production and TXNIP down-regulation, suggesting that damage-associated molecular patterns (DAMPs), such as endogenous TLR ligands, released during DGC play a role in DGC-induced TXNIP down-regulation. Finally, we demonstrate that TNF-induced TXNIP down-regulation is dependent on caspase activity and is caused by caspase-mediated cleavage of TXNIP.
Organo-mineral associations in chert of the 3.5 Ga Mount Ada Basalt raise questions about the origin of organic matter in Paleoarchean hydrothermally influenced sediments
Authors: Alleon Julien , Flannery David T. , Ferralis Nicola , Williford Kenneth H. , Zhang Yong , Schuessler Jan A. , Summons Roger E.
Published: November 2019

Hydrothermal and metamorphic processes could have abiotically produced organo-mineral associations displaying morphological and isotopic characteristics similar to those of fossilized microorganisms in ancient rocks, thereby leaving false-positive evidence for early life in the geological record. Recent studies revealed that geologically-induced alteration processes do not always completely obliterate all molecular information about the original organic precursors of ancient microfossils. Here, we report the molecular, geochemical, and mineralogical composition of organo-mineral associations in a chert sample from the ca. 3.47 billion-year-old (Ga) Mount Ada Basalt, in the Pilbara Craton, Western Australia. Our observations indicate that the molecular characteristics of carbonaceous matter are consistent with hydrothermally altered biological organics, although significantly distinct from that of organic microfossils discovered in a chert sample from the ca. 3.43 Ga Strelley Pool Formation in the same area. Alternatively, the presence of native metal alloys in the chert, previously believed to be unstable in such hydrothermally influenced environments, indicates strongly reducing conditions that were favorable for the abiotic formation of organic matter. Drawing definitive conclusions about the origin of most Paleoarchean organo-mineral associations therefore requires further characterization of a range of natural samples together with experimental simulations to constrain the molecular composition and geological fate of hydrothermally-generated condensed organics.
Author Correction: Lower Extremity Joint Contributions to Trunk Control During Walking in Persons with Transtibial Amputation
Authors: Yoder Adam J. , Silder Amy , Farrokhi Shawn , Dearth Christopher L. , Hendershot Brad D.
Published: November 2019

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
Author Correction: Synthesis of MgAC-Fe3O4/TiO2 hybrid nanocomposites via sol-gel chemistry for water treatment by photo-Fenton and photocatalytic reactions
Authors: Bui Vu Khac Hoang , Park Duckshin , Pham Tuyet Nhung , An Yejin , Choi Jin Seok , Lee Hyun Uk , Kwon Oh-Hyeok , Moon Ju-Young , Kim Ki-Tae , Lee Young-Chul
Published: November 2019

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
Rare-earth metal and actinide organoimide chemistry
Authors: Schädle Dorothea , Anwander Reiner
Published: November 2019

Elaborate synthesis schemes pave the way to f-element and group 3 complexes with multiply bonded imido ligands displaying intriguing reactivity.
Enhanced electrophoretic separation of proteins by tethered SiO2 nanoparticles in an SDS-polyacrylamide gel network
Authors: Sajjadi Sayyed Hashem , Ahmadzadeh Hossein , Goharshadi Elaheh K.
Published: November 2019

Tethered nanoparticles (NPs) are able to improve the separation efficiency of proteins in SDS-polyacrylamide gel electrophoresis (SDS-PAGE) due to their capability of enhancing heat dissipation during electrophoresis and restriction of electrophoretic movement of NPs.
Chemo-enzymatic three-step conversion of glucose to kojic acid
Authors: Lassfolk Robert , Suonpää Anu , Birikh Klara , Leino Reko
Published: November 2019

A method for producing kojic acid from glucose via glucosone using a chemo-enzymatic three-step approach was developed.
Bromine-bridged Dy2 single-molecule magnet: magnetic anisotropy driven by cis/trans stereoisomers
Authors: Li Min , Wu Haipeng , Xia Zhengqiang , Montigaud Vincent , Cador Olivier , Le Guennic Boris , Ke Hongshan , Wang Wenyuan , Xie Gang , Chen Sanping
Published: November 2019

The peculiar cis/trans stereoisomers in a bromine-bridged Dy2 single-molecule magnet drive the orthogonal magnetic moments and tune the magnetic interactions, leading to a large energy barrier of 684 K.
Planarity of terphenyl rings possessing o-carborane cages: turning on intramolecular-charge-transfer-based emission
Authors: So Hyunhee , Kim Jea Ho , Lee Ji Hye , Hwang Hyonseok , An Duk Keun , Lee Kang Mun
Published: November 2019

Two terphenyl-o-carboranyl compounds were fully characterised and a comparison of the photophysical characteristics verified that the planarity of aryl groups appended on o-carborane strongly influences intramolecular-charge-transfer-based emission.