bluuebunny/crossref_metadata_2025 huggingface dataset:
The SAMPL6 challenge on predicting octanol–water partition coefficients from EC-RISM theory
Authors: Tielker Nicolas , Tomazic Daniel , Eberlein Lukas , Güssregen Stefan , Kast Stefan M.
Published: January 2020

Results are reported for octanol–water partition coefficients (log P) of the neutral states of drug-like molecules provided during the SAMPL6 (Statistical Assessment of Modeling of Proteins and Ligands) blind prediction challenge from applying the “embedded cluster reference interaction site model” (EC-RISM) as a solvation model for quantum-chemical calculations. Following the strategy outlined during earlier SAMPL challenges we first train 1- and 2-parameter water-free (“dry”) and water-saturated (“wet”) models for n-octanol solvation Gibbs energies with respect to experimental values from the “Minnesota Solvation Database” (MNSOL), yielding a root mean square error (RMSE) of 1.5 kcal mol−1 for the best-performing 2-parameter wet model, while the optimal water model developed for the pKa part of the SAMPL6 challenge is kept unchanged (RMSE 1.6 kcal mol−1 for neutral compounds from a model trained on both neutral and ionic species). Applying these models to the blind prediction set yields a log P RMSE of less than 0.5 for our best model (2-parameters, wet). Further analysis of our results reveals that a single compound is responsible for most of the error, SM15, without which the RMSE drops to 0.2. Since this is the only compound in the challenge dataset with a hydroxyl group we investigate other alcohols for which Gibbs energy of solvation data for both water and n-octanol are available in the MNSOL database to demonstrate a systematic cause of error and to discuss strategies for improvement.
People with Positive Time Perspective are More Grateful and Happier: Gratitude Mediates the Relationship Between Time Perspective and Life Satisfaction
Authors: Przepiorka Aneta , Sobol-Kwapinska Malgorzata
Published: January 2020

The current study examined the associations between time perspective, dispositional gratitude, and life satisfaction. The aim of the study was to check if gratitude mediates the relationship between time perspectives and life satisfaction. The participants were 591 Polish people aged 18–73 (M = 30, SD 5.45). We used several measures: the Satisfaction with Life Scale, the Gratitude Questionnaire, the Zimbardo Time Perspective Inventory, the Carpe Diem Scale, and the Present-Eudaimonic Time Perspective Scale. We found that gratitude played a mediating role between the dimensions of time perspective and life satisfaction. The presented results were interpreted in the context of the Pollyanna effect.
Noise Measurements of a Low-Noise Amplifier in the FDM Readout System for SAFARI
Authors: Wang Qian , Audley Michael D. , Khosropanah Pourya , van der Kuur Jan , de Lange Gert , Aminaei Amin , Boersma Dick , van der Tak Floris , Gao Jian-Rong
Published: January 2020

The SPICA-SAFARI instrument requires extremely sensitive transition edge sensor (TES) arrays with a noise equivalent power of $$2 \times 10^{ - 19} \;{\text{W/}}\sqrt {\text{Hz}}$$2×10-19W/Hz and a readout system with an output noise that is dominated by the detector noise. It is essential to ensure the frequency domain multiplexing (FDM) readout system in SAFARI meets the noise requirement. The FDM system in SAFARI consists essentially of LC filters, a superconducting quantum interference device, a room-temperature low-noise amplifier (LNA), and a demultiplexer. Here we present a noise study of the LNA from a laboratory amplifier chain. We found the equivalent current and voltage noise of the LNA to be $$5.4\;{\text{pA/}}\sqrt {\text{Hz}}$$5.4pA/Hz and $$315\;{\text{pV/}}\sqrt {\text{Hz}}$$315pV/Hz, respectively, which are low enough to read out SAFARI’s TES arrays.
Convergence in the p-Contest
Authors: Kennerberg Philip , Volkov Stanislav
Published: January 2020

We study asymptotic properties of the following Markov system of $$N \ge 3$$N≥3 points in [0, 1]. At each time step, the point farthest from the current centre of mass, multiplied by a constant $$p>0$$p>0, is removed and replaced by an independent $$\zeta $$ζ-distributed point; the problem, inspired by variants of the Bak–Sneppen model of evolution and called a p-contest, was posed in Grinfeld et al. (J Stat Phys 146, 378–407, 2012). We obtain various criteria for the convergences of the system, both for $$p<1$$p<1 and $$p>1$$p>1. In particular, when $$p<1$$p<1 and $$\zeta \sim U[0,1]$$ζ∼U[0,1], we show that the limiting configuration converges to zero. When $$p>1$$p>1, we show that the configuration must converge to either zero or one, and we present an example where both outcomes are possible. Finally, when $$p>1$$p>1, $$N=3$$N=3 and $$\zeta $$ζ satisfies certain mild conditions (e.g. $$\zeta \sim U[0,1]$$ζ∼U[0,1]), we prove that the configuration converges to one a.s. Our paper substantially extends the results of Grinfeld et al. (Adv Appl Probab 47:57–82, 2015) and Kennerberg and Volkov (Adv Appl Probab 50:414–439, 2018) where it was assumed that $$p=1$$p=1. Unlike the previous models, one can no longer use the Lyapunov function based just on the radius of gyration; when $$0<p<1$$0<p<1 one has to find a more finely tuned function which turns out to be a supermartingale; the proof of this fact constitutes an unwieldy, albeit necessary, part of the paper.
Engaging Expectant and Parenting Adolescents: Lessons from the Massachusetts Pregnant and Parenting Teen Initiative
Authors: Egan Justine , Bhuiya Nazmim , Gil-Sanchez Lissette , Campbell Stephanie , Clark Jill
Published: January 2020

Introduction

Programs supporting adolescent parents have been shown to increase socio-economic opportunities and promote healthy child development for young families, but retaining young parents is challenging. The Massachusetts Pregnant and Parenting Teen Initiative (MPPTI) offers case management and linkages to community and clinical services to young families. We examine engagement strategies identified by MPPTI participants and staff members in relation to participant retention by program site to identify potential strategies for increasing program engagement.

Methods

We employed a mixed-methods approach incorporating quantitative data on program participant characteristics and program retention by site with qualitative data from staff and participant interviews and focus groups.

Results

Key program engagement strategies identified by both MPPTI staff and youth participants were social-emotional supports, staffing model, and concrete supports. We found significant differences in program retention by site; the two sites with the highest levels of program retention offered all engagement strategies identified.

Discussion

Quantitative data on program retention coupled with qualitative data from staff and youth interviews suggests that in our program, there may be an association between the engagement strategies identified and levels of program retention.
Molecular investigation on the anomalous phenomenon at liquid desiccant surfaces for air conditioning
Authors: Luo Yimo , Akkurt Nevzat , Zhang Kai , Peng Hao , Zhang Xiaosong , She Xiaohui
Published: January 2020

It is necessary to disclose the two-phase interphase behavior in the liquid desiccant dehumidifier/regenerator applicable for air conditioning, but the present investigation is far from enough. In this paper, the surface structure of liquid desiccant solution is analyzed by molecular dynamics simulations. LiBr-H2O is chosen as the working solution with a concentration of 1 M and the system model is built with Gromacs. System temperatures vary from 300 to 350 K covering the temperature range of liquid desiccant dehumidification and regeneration. Density profiles of ions and water molecules are plotted along the vertical directions, and their distribution preferences on the solution surface are discussed. With the molecular simulation, it is found there is an ions-vapor layer with a thickness of 6–9 Å between the saturated vapor and bulk solution, which is not shown in the traditional macroscopic models. The results show that the density of water remains stable in the bulk while decreases sharply on the solution surface. However, the salt ions, i.e. Li+ and Br-, have a peak density on the surface. This ions-vapor layer behaves like a buffer to transfer water molecules from/to the bulk solution. More research will be required to investigate how to control the ions-vapor layer, so that air dehumidification and solution regeneration can be easily operated, which provides significant energy savings for the liquid desiccant air conditioning.
After Cahokia: Indigenous Repopulation and Depopulation of the Horseshoe Lake Watershed AD 1400–1900
Authors: White A.J. , Munoz Samuel E. , Schroeder Sissel , Stevens Lora R.
Published: January 2020

The occupation history of the Cahokia archaeological complex (ca. AD 1050–1400) has received significant academic attention for decades, but the subsequent repopulation of the region by indigenous peoples is poorly understood. This study presents demographic trends from a fecal stanol population reconstruction of Horseshoe Lake, Illinois, along with information from archaeological, historical, and environmental sources to provide an interpretation of post-Mississippian population change in the Cahokia region. Fecal stanol data indicate that the Cahokia region reached a population minimum by approximately AD 1400, regional population had rebounded by AD 1500, a population maximum was reached by AD 1650, and population declined again by AD 1700. The indigenous repopulation of the area coincides with environmental changes conducive to maize-based agriculture and bison-hunting subsistence practices of the Illinois Confederation. The subsequent regional depopulation corresponds to a complicated period of warfare, epidemic disease, Christianization, population movement, and environmental change in the eighteenth century. The recognition of a post-Mississippian indigenous population helps shape a narrative of Native American persistence over Native American disappearance.
An evaluation of the skills group component of DBT-A for parent/guardians: a mixed methods study
Authors: Flynn Daniel , Gillespie Conall , Joyce Mary , Spillane Ailbhe
Published: January 2020

Objectives:

Previous research indicates that dialectical behaviour therapy for adolescents (DBT-A) is effective in treating emotionally dysregulated adolescents with self-harm and/or suicidal ideation. As part of the DBT-A programme, parents attend the weekly skills group with their child. However, few studies have evaluated parental outcomes in DBT-A. This multi-site study aims to explore the outcomes and experiences of parents who participated in a 16-week DBT-A programme in Ireland.

Methods:

This study was conducted in community-based child and adolescent mental health services (CAMHS) in the national public health system in Ireland. Participants were parent/guardians of adolescents attending a DBT-A programme in their local CAMHS. Participants attended the group skills component of the DBT-A programme. This study utilised a mixed methods approach where both quantitative and qualitative data were collected from participants. Self-report measures of burden, grief and parental stress were completed at pre-intervention, post-intervention and 16-week follow-up. Qualitative written feedback was obtained at post-intervention. The data were analysed using multi-level linear mixed-effects models and content analysis.

Results:

One hundred participants (76% female) took part in this study. Significant decreases were reported for objective burden, subjective burden, grief and parental stress from pre- to post-intervention (p< 0.01). Participants reported that the skills component of DBT-A was useful in meeting their own needs and the needs of their child.

Discussion:

DBT-A shows promise for parents as well as their adolescent child. Future studies should evaluate changes to family relationships following completion of the programme and also include controlled comparison groups.
Comparison of calculated and measured basic dosimetric parameters for total body irradiation with 6- and 18-MV photon beams
Authors: Hoseinnezhad Elham , Geraily Ghazale , Esfahani Mahbod , Farzin Mostafa , Gholami Somayeh
Published: January 2020

Purpose:

Total body irradiation (TBI) is an external beam radiation therapy in which large field size and extended source skin distances (SSDs) are applied to deliver a therapeutic dose to the whole body. As measurements in such situations are not common and have more uncertainties in comparison to standard dosimetry situations, it is more precise if calculated beam data can be used instead of measurements taken under TBI situations. The purpose of this study is to compare calculated beam data [percentage depth dose (PDD) and dose rate] with those obtained from simulated treatment measurements.

Materials and methods:

PDD and dose rates were measured for the 6- and 18-MV photon beams under TBI and standard conditions using 9,000 cm3water phantom and ion chambers (Markus and Farmer). The results were then compared with the calculated PDD and dose rate data. The beam flatness was also measured under TBI and standard conditions for both 6- and 18-MV photon beams, and the results were then compared.

Results:

A comparison of the measurement and calculated beam data shows that the difference between calculated and measured PDD values is −6·97 and −4·14% for the 6- and 18-MV photon beams, respectively. The ratio of calculated to measured dose rate was 1·09 and 1·02 for the 6- and 18-MV photon beams, respectively. The beam flatness under TBI conditions was 4·59% for 6-MV and 5·37% for 18-MV photon beam, whereas under standard conditions, these values were 1·50 and 1·98% for 6- and 18-MV radiation beams, respectively.

Findings:

According to the results, due to a high error level in dose rate and PDD calculations, these parameters must be directly measured under TBI conditions; however, regarding the obtained results, direct measurement is not necessary for the 18-MV photon beam.
Variations in the Magnetic Properties of Meteoritic Cloudy Zone
Authors: Nichols Claire I. O. , Bryson James F. J. , Blukis Roberts , Herrero‐Albillos Julia , Kronast Florian , Rüffer Rudolf , Chumakov Aleksandr I. , Harrison Richard J.
Published: January 2020

Iron and stony‐iron meteorites form the Widmanstätten pattern during slow cooling. This pattern is composed of several microstructures whose length‐scale, composition and magnetic properties are dependent upon cooling rate. Here we focus on the cloudy zone: a region containing nanoscale tetrataenite islands with exceptional paleomagnetic recording properties. We present a systematic review of how cloudy zone properties vary with cooling rate and proximity to the adjacent tetrataenite rim. X‐ray photoemission electron microscopy is used to compare compositional and magnetization maps of the cloudy zone in the mesosiderites (slow cooling rates), the IAB iron meteorites and the pallasites (intermediate cooling rates), and the IVA iron meteorites (fast cooling rates). The proportions of magnetic phases within the cloudy zone are also characterized using Mössbauer spectroscopy. We present the first observations of the magnetic state of the cloudy zone in the mesosiderites, showing that, for such slow cooling rates, tetrataenite islands grow larger than the multidomain threshold, creating large‐scale regions of uniform magnetization across the cloudy zone that render it unsuitable for paleomagnetic analysis. For the most rapidly cooled IVA meteorites, the time available for Fe‐Ni ordering is insufficient to allow tetrataenite formation, again leading to behavior that is unsuitable for paleomagnetic analysis. The most reliable paleomagnetic remanence is recorded by meteorites with intermediate cooling rates (
 2–500 °C Myr
) which produces islands that are “just right” in both size and degree of Fe‐Ni order.
The Impact of Barrier Layers on Arabian Sea Surface Temperature Variability
Authors: Echols Rosalind , Riser Stephen C.
Published: January 2020

Barrier layers (BLs) in the Arabian Sea may lead to increased mixed layer (ML) warming or cooling relative to non‐BL conditions, depending on differences in ML properties and atmospheric forcing. We use 13 years of profiling float data from the Arabian Sea to identify when and where each impact is likely based on analysis of the ML temperature tendency. We use a novel method based on the vertical spice profile to identify BLs and their characteristics. BLs are most likely to increase warming during the northeast monsoon, owing to temperature inversions, preceding the development of the miniwarm pool and onset of the southwest monsoon. This effect is nonuniform and is counteracted in some regions by increased penetration of solar radiation below the shallower ML associated with BL. Relative rates of cooling increase in the presence of BL during the southwest monsoon; intermonsoon periods show little net effect from BL.
Water Tracks Enhance Water Flow Above Permafrost in Upland Arctic Alaska Hillslopes
Authors: Evans Sarah G. , Godsey Sarah E. , Rushlow Caitlin R. , Voss Clifford
Published: January 2020

Upland permafrost regions occupy approximately one third of the Arctic landscape. In upland regions, hydrologic fluxes are influenced by water tracks, curvilinear features on hillslopes that preferentially fill with and route water in response to snowmelt and rainfall when the soil above continuous permafrost thaws in the summer. As continued warming of the Arctic may alter hydrologic cycling leading to increased frequency of extreme hydrologic events like drought and flooding as well as modification of biogeochemical cycling, it is imperative to untangle the interplay between precipitation, runoff, and subsurface flow as water is routed from upland Arctic regions to the Arctic Ocean. This study quantifies how ground surface temperatures affect groundwater discharge from hillslopes with water tracks in the upland Arctic by employing a three‐dimensional, physically based subsurface flow model with variable saturation and freeze and thaw capabilities that is calibrated to field measurements from the Upper Kuparuk River watershed on the North Slope of Alaska, USA. Model analysis indicates that higher ground surface temperatures along water track hillslopes promote increases in groundwater discharge where water tracks act as conduits for large‐recharge events and continue to discharge groundwater into the autumn after the adjacent hillslope has frozen. Simulating the conditions that distinguish water tracks from their hillslope watersheds changes subsurface water storage and ground thermal responses but does not alter the total magnitude of groundwater discharge outside of parameter uncertainty. These findings suggest that water tracks play a complex and critical role in hydrologic cycles of the upland Arctic.
Catchment‐Scale Characterization of Intermittent Stream Infiltration; a Geophysics Approach
Authors: Shanafield Margaret , Gutiérrrez‐Jurado Karina , White Nicholas , Hatch Michael , Keane Robert
Published: January 2020

In arid basins, infiltration through streambeds is considered the primary contributor to groundwater recharge; however, estimating streambed recharge at catchment scale remains a challenge. Moreover, a spatial understanding of streambed infiltration is crucial for estimating where and how much aquifer recharge occurs and where recharge could be enhanced. This study explored the use of continuously sampling shallow geophysical measurements over many kilometers of dry streambed in an intermittent stream basin. In total, approximately 30 km of streambed was traversed, capturing representative portions of first through fifth order stream reaches across the six major soil groups in the study area. The results show a general trend from lower to higher apparent conductivity with change in soil type along the catchment gradient, suggesting a general progression from sandy to clayey soils. The presence of a low permeability layer in the shallowest soils across most soil types and all orders of stream gradient suggests streambed clogging would impair recharge, and that cracking of clays and lateral infiltration is very likely to play an important role in aquifer recharge. This method provided a rapid and relatively simple way to gather information on potential areas for streambed infiltration at a larger scale than is possible with other methods.
The Vaasa Migmatitic Complex (Svecofennian Orogen, Finland): Buildup of a LP‐HT Dome During Nuna Assembly
Authors: Chopin Francis , Korja Annakaisa , Nikkilä Kaisa , Hölttä Pentti , Korja Toivo , Abdel Zaher Mohamed , Kurhila Matti , Eklund Olav , Rämö O. Tapani
Published: January 2020

Tectonic evolution of the Paleoproterozoic Vaasa migmatitic complex (VMC) in the central part of the Svecofennian accretionary orogen is deciphered using aeromagnetic and gravity maps, deep seismic and magnetotelluric profiles, and structural and metamorphic data. The VMC is a semicircular structure with migmatitic rim and granitic core composed of several subdomes. It evolved in three main tectonic events (D1–D3). The D1 event (ca. 1.89–1.88 Ga) corresponds to the stacking of supracrustal rocks and the formation of an inverted metamorphic gradient. Anatexis at LP‐HT metamorphic conditions enabled the material to flow. The D2 event (ca. 1.88–1.87 Ga) corresponds to large‐scale folding of the partially molten crust within an orocline. It is marked by folds with an E‐W vertical axial planar foliation. The late D3 event resulted from mass redistribution owing to mechanical instabilities within the hinge of the orocline. It is marked by vertical shearing (ca. 1.87–1.85 Ga) in the marginal parts of the complex and along the granitoid subdomes. The seismic reflection profile (FIRE 3a) and magnetotelluric profiles (MT‐PE and MT‐B2) image large‐scale D1 stacking structures within an accretionary prism. Near vertical breaks in crustal‐scale reflectivity and conductivity models are interpreted as D3 shear zones. The VMC is an example of early mass and heat transfer within a collage of hot supracrustal rocks in an accretionary belt. Partial melting enhanced the flow of material, the production, and rise of magma as well as exhumation, marked by magmatic domes in the hinge of the orocline.
CMIP5 Climate Models Overestimate Cooling by Volcanic Aerosols
Authors: Chylek Petr , Folland Chris , Klett James D. , Dubey Manvendra K.
Published: January 2020

We compare projections of the observed hemispherical mean surface temperature (HadCRUT4.6.0.0) and the ensemble mean of CMIP5 climate models' simulations on a set of standard regression model forcing variables. We find that the volcanic aerosol regression coefficients of the CMIP5 simulations are consistently significantly larger (by 40–49%) than the volcanic aerosol coefficients of the observed temperature. The probability that the observed differences are caused just by chance is much less than 0.01. The overestimate is due to the climate models' response to volcanic aerosol radiative forcing. The largest overestimate occurs in the winter season of each hemisphere. We hypothesize that the models' parameterization of aerosol‐cloud interactions within ice and mixed phase clouds is a likely source of this discrepancy. Furthermore, the models significantly underestimate the effect of solar variability on temperature for both hemispheres.
NT157 has antineoplastic effects and inhibits IRS1/2 and STAT3/5 in JAK2V617F-positive myeloproliferative neoplasm cells
Authors: Fenerich Bruna Alves , Fernandes Jaqueline Cristina , Rodrigues Alves Ana Paula Nunes , Coelho-Silva Juan Luiz , Scopim-Ribeiro Renata , Scheucher Priscila Santos , Eide Christopher A. , Tognon Cristina E. , Druker Brian J. , Rego Eduardo Magalhães , Machado-Neto João Agostinho , Traina Fabiola
Published: January 2020

Recent data indicate that IGF1R/IRS signaling is a potential therapeutic target in BCR-ABL1-negative myeloproliferative neoplasms (MPN); in this pathway, IRS2 is involved in the malignant transformation induced by JAK2V617F, and upregulation of IGF1R signaling induces the MPN phenotype. NT157, a synthetic compound designed as an IGF1R-IRS1/2 inhibitor, has been shown to induce antineoplastic effects in solid tumors. Herein, we aimed to characterize the molecular and cellular effects of NT157 in JAK2V617F-positive MPN cell lines (HEL and SET2) and primary patient hematopoietic cells. In JAK2V617F cell lines, NT157 decreased cell viability, clonogenicity, and cell proliferation, resulting in increases in apoptosis and cell cycle arrest in the G2/M phase (p < 0.05). NT157 treatment inhibited IRS1/2, JAK2/STAT, and NFκB signaling, and it activated the AP-1 complex, downregulated four oncogenes (CCND1, MYB, WT1, and NFKB1), and upregulated three apoptotic-related genes (CDKN1A, FOS, and JUN) (p < 0.05). NT157 induced genotoxic stress in a JAK2/STAT-independent manner. NT157 inhibited erythropoietin-independent colony formation in cells from polycythemia vera patients (p < 0.05). These findings further elucidate the mechanism of NT157 action in a MPN context and suggest that targeting IRS1/2 proteins may represent a promising therapeutic strategy for MPN.
Transcriptomic profiling of skeletal muscle adaptations to exercise and inactivity
Authors: Pillon Nicolas J. , Gabriel Brendan M. , Dollet Lucile , Smith Jonathon A. B. , Sardón Puig Laura , Botella Javier , Bishop David J. , Krook Anna , Zierath Juleen R.
Published: January 2020

The molecular mechanisms underlying the response to exercise and inactivity are not fully understood. We propose an innovative approach to profile the skeletal muscle transcriptome to exercise and inactivity using 66 published datasets. Data collected from human studies of aerobic and resistance exercise, including acute and chronic exercise training, were integrated using meta-analysis methods (www.metamex.eu). Here we use gene ontology and pathway analyses to reveal selective pathways activated by inactivity, aerobic versus resistance and acute versus chronic exercise training. We identify NR4A3 as one of the most exercise- and inactivity-responsive genes, and establish a role for this nuclear receptor in mediating the metabolic responses to exercise-like stimuli in vitro. The meta-analysis (MetaMEx) also highlights the differential response to exercise in individuals with metabolic impairments. MetaMEx provides the most extensive dataset of skeletal muscle transcriptional responses to different modes of exercise and an online interface to readily interrogate the database.
The proteasome 19S cap and its ubiquitin receptors provide a versatile recognition platform for substrates
Authors: Martinez-Fonts Kirby , Davis Caroline , Tomita Takuya , Elsasser Suzanne , Nager Andrew R. , Shi Yuan , Finley Daniel , Matouschek Andreas
Published: January 2020

Proteins are targeted to the proteasome by the attachment of ubiquitin chains, which are markedly varied in structure. Three proteasome subunits–Rpn10, Rpn13, and Rpn1–can recognize ubiquitin chains. Here we report that proteins with single chains of K48-linked ubiquitin are targeted for degradation almost exclusively through binding to Rpn10. Rpn1 can act as a co-receptor with Rpn10 for K63 chains and for certain other chain types. Differences in targeting do not correlate with chain affinity to receptors. Surprisingly, in steady-state assays Rpn13 retarded degradation of various single-chain substrates. Substrates with multiple short ubiquitin chains can be presented for degradation by any of the known receptors, whereas those targeted to the proteasome through a ubiquitin-like domain are degraded most efficiently when bound by Rpn13 or Rpn1. Thus, the proteasome provides an unexpectedly versatile binding platform that can recognize substrates targeted for degradation by ubiquitin chains differing greatly in length and topology.
Extensive rewiring of the EGFR network in colorectal cancer cells expressing transforming levels of KRASG13D
Authors: Kennedy Susan A. , Jarboui Mohamed-Ali , Srihari Sriganesh , Raso Cinzia , Bryan Kenneth , Dernayka Layal , Charitou Theodosia , Bernal-Llinares Manuel , Herrera-Montavez Carlos , Krstic Aleksandar , Matallanas David , Kotlyar Max , Jurisica Igor , Curak Jasna , Wong Victoria , Stagljar Igor , LeBihan Thierry , Imrie Lisa , Pillai Priyanka , Lynn Miriam A. , Fasterius Erik , Al-Khalili Szigyarto Cristina , Breen James , Kiel Christina , Serrano Luis , Rauch Nora , Rukhlenko Oleksii , Kholodenko Boris N. , Iglesias-Martinez Luis F. , Ryan Colm J. , Pilkington Ruth , Cammareri Patrizia , Sansom Owen , Shave Steven , Auer Manfred , Horn Nicola , Klose Franziska , Ueffing Marius , Boldt Karsten , Lynn David J. , Kolch Walter
Published: January 2020

Protein-protein-interaction networks (PPINs) organize fundamental biological processes, but how oncogenic mutations impact these interactions and their functions at a network-level scale is poorly understood. Here, we analyze how a common oncogenic KRAS mutation (KRASG13D) affects PPIN structure and function of the Epidermal Growth Factor Receptor (EGFR) network in colorectal cancer (CRC) cells. Mapping >6000 PPIs shows that this network is extensively rewired in cells expressing transforming levels of KRASG13D(mtKRAS). The factors driving PPIN rewiring are multifactorial including changes in protein expression and phosphorylation. Mathematical modelling also suggests that the binding dynamics of low and high affinity KRAS interactors contribute to rewiring. PPIN rewiring substantially alters the composition of protein complexes, signal flow, transcriptional regulation, and cellular phenotype. These changes are validated by targeted and global experimental analysis. Importantly, genetic alterations in the most extensively rewired PPIN nodes occur frequently in CRC and are prognostic of poor patient outcomes.
FICD activity and AMPylation remodelling modulate human neurogenesis
Authors: Kielkowski Pavel , Buchsbaum Isabel Y. , Kirsch Volker C. , Bach Nina C. , Drukker Micha , Cappello Silvia , Sieber Stephan A.
Published: January 2020

Posttranslational modification (PTM) of proteins represents an important cellular mechanism for controlling diverse functions such as signalling, localisation or protein–protein interactions. AMPylation (also termed adenylylation) has recently been discovered as a prevalent PTM for regulating protein activity. In human cells AMPylation has been exclusively studied with the FICD protein. Here we investigate the role of AMPylation in human neurogenesis by introducing a cell-permeable propargyl adenosine pronucleotide probe to infiltrate cellular AMPylation pathways and report distinct modifications in intact cancer cell lines, human-derived stem cells, neural progenitor cells (NPCs), neurons and cerebral organoids (COs) via LC–MS/MS as well as imaging methods. A total of 162 AMP modified proteins were identified. FICD-dependent AMPylation remodelling accelerates differentiation of neural progenitor cells into mature neurons in COs, demonstrating a so far unknown trigger of human neurogenesis.
Author Correction: Metal-coordinated sub-10 nm membranes for water purification
Authors: You Xinda , Wu Hong , Zhang Runnan , Su Yanlei , Cao Li , Yu Qianqian , Yuan Jinqiu , Xiao Ke , He Mingrui , Jiang Zhongyi
Published: January 2020

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
Biobased chiral semi-crystalline or amorphous high-performance polyamides and their scalable stereoselective synthesis
Authors: Stockmann Paul N. , Van Opdenbosch Daniel , Poethig Alexander , Pastoetter Dominik L. , Hoehenberger Moritz , Lessig Sebastian , Raab Johannes , Woelbing Marion , Falcke Claudia , Winnacker Malte , Zollfrank Cordt , Strittmatter Harald , Sieber Volker
Published: January 2020

The use of renewable feedstock is one of the twelve key principles of sustainable chemistry. Unfortunately, bio-based compounds often suffer from high production cost and low performance. To fully tap the potential of natural compounds it is important to utilize their functionalities that could make them superior compared to fossil-based resources. Here we show the conversion of (+)-3-carene, a by-product of the cellulose industry into ε-lactams from which polyamides. The lactams are selectively prepared in two diastereomeric configurations, leading to semi-crystalline or amorphous, transparent polymers that can compete with the thermal properties of commercial high-performance polyamides. Copolyamides with caprolactam and laurolactam exhibit an increased glass transition and amorphicity compared to the homopolyamides, potentially broadening the scope of standard polyamides. A four-step one-vessel monomer synthesis, applying chemo-enzymatic catalysis for the initial oxidation step, is established. The great potential of the polyamides is outlined.
Insights into the regulation of molecular mechanisms involved in energy shortage in detached citrus fruit
Authors: Romero Paco , Alférez Fernando , Establés-Ortiz Beatriz , Lafuente María T.
Published: January 2020

Harvested fruit undergo carbon and energy deprivation. However, the events underlying this energy-related stress in detached fruit and their involvement in cell damage have not yet been elucidated. We showed that supplementing detached sweet oranges with additional carbon or energy sources reduced peel damage, while inhibitors of energy metabolism increased it. We investigated the effect of an exogenous source of carbon (glycerol), energy (ATP), and an inhibitor of energy metabolism 2-deoxy-D-glucose (DeOGlc) + sodium iodoacetate (IAc), on the transcriptome of harvested fruit flavedo (outer peel part). ATP and Gly induced common, but also specific, alternative modes of energy metabolism by reducing the stress caused by energy shortage. They also induced shifts in energy metabolism that led to the production of the intermediates required for plant defense secondary metabolites to form. ATP and Gly triggered changes in the expression of the genes involved in cell lesion containment through a defined pathway involving hormones and redox-mediated signaling. DeOGlc + IAc had a contrasting effect on some of these mechanisms. These chemicals altered the biological processes related to membrane integrity and molecular mechanisms involving reactive oxygen species (ROS) production, and lipid and protein degradation.
A Small Compound Targeting Prohibitin with Potential Interest for Cognitive Deficit Rescue in Aging mice and Tau Pathology Treatment
Authors: Guyot Anne-Cécile , Leuxe Charlotte , Disdier Clémence , Oumata Nassima , Costa Narciso , Roux Gwenaëlle Le , Varela Paloma F. , Duchon Arnaud , Charbonnier Jean Baptiste , Herault Yann , Pavoni Serena , Galons Hervé , Andriambeloson Emile , Wagner Stéphanie , Meijer Laurent , Lund Amie K. , Mabondzo Aloïse
Published: January 2020

Neurodegenerative diseases, including Alzheimer’s and Parkinson’s disease, are characterized by increased protein aggregation in the brain, progressive neuronal loss, increased inflammation, and neurogenesis impairment. We analyzed the effects of a new purine derivative drug, PDD005, in attenuating mechanisms involved in the pathogenesis of neurodegenerative diseases, using bothin vivoandin vitromodels. We show that PDD005 is distributed to the brain and can rescue cognitive deficits associated with aging in mice. Treatment with PDD005 prevents impairment of neurogenesis by increasing sex-determining region Y-box 2, nestin, and also enhances synaptic function through upregulation of synaptophysin and postsynaptic density protein 95. PDD005 treatment also reduced neuro-inflammation by decreasing interleukin-1β expression, activation of astrocytes, and microglia. We identified prohibitin as a potential target in mediating the therapeutic effects of PDD005 for the treatment of cognitive deficit in aging mice. Additionally, in the current study, glycogen synthase kinase appears to attenuate tau pathology.
Parkinson patients without tremor show changed patterns of mechanical muscle oscillations during a specific bilateral motor task compared to controls
Authors: Schaefer Laura V. , Bittmann Frank N.
Published: January 2020

The pathophysiology of Parkinson’s disease (PD) is still not understood. There are investigations which show a changed oscillatory behaviour of brain circuits or changes in variability of, e.g., gait parameters in PD. The aim of this study was to investigate whether or not the motor output differs between PD patients and healthy controls. Thereby, patients without tremor are investigated in the medication off state performing a special bilateral isometric motor task. The force and accelerations (ACC) were recorded as well as the Mechanomyography (MMG) of the biceps brachii, the brachioradialis and of the pectoralis major muscles using piezoelectric-sensors during the bilateral motor task at 60% of the maximal isometric contraction. The frequency, a specific power ratio, the amplitude variation and the slope of amplitudes were analysed. The results indicate that the oscillatory behaviour of motor output in PD patients without tremor deviates from controls: thereby, the 95%-confidence-intervals of power ratio and of amplitude variation of all signals are disjoint between PD and controls and show significant differences in group comparisons (power ratio: p = 0.000–0.004, r = 0.441–0.579; amplitude variation: p = 0.000–0.001, r = 0.37–0.67). The mean frequency shows a significant difference for ACC (p = 0.009, r = 0.43), but not for MMG. It remains open, whether this muscular output reflects changes of brain circuits and whether the results are reproducible and specific for PD.
Quality control of multiplex antibody detection in samples from large-scale surveys: the example of malaria in Haiti
Authors: van den Hoogen Lotus L. , Présumé Jacquelin , Romilus Ithamare , Mondélus Gina , Elismé Tamara , Sepúlveda Nuno , Stresman Gillian , Druetz Thomas , Ashton Ruth A. , Joseph Vena , Eisele Thomas P. , Hamre Karen E. S. , Chang Michelle A. , Lemoine Jean F. , Tetteh Kevin K. A. , Boncy Jacques , Existe Alexandre , Drakeley Chris , Rogier Eric
Published: January 2020

Measuring antimalarial antibodies can estimate transmission in a population. To compare outputs, standardized laboratory testing is required. Here we describe the in-country establishment and quality control (QC) of a multiplex bead assay (MBA) for three sero-surveys in Haiti. Total IgG data against 21 antigens were collected for 32,758 participants. Titration curves of hyperimmune sera were included on assay plates, assay signals underwent 5-parameter regression, and inspection of the median and interquartile range (IQR) for the y-inflection point was used to determine assay precision. The medians and IQRs were similar for Surveys 1 and 2 for most antigens, while the IQRs increased for some antigens in Survey 3. Levey-Jennings charts for selected antigens provided a pass/fail criterion for each assay plate and, of 387 assay plates, 13 (3.4%) were repeated. Individual samples failed if IgG binding to the generic glutathione-S-transferase protein was observed, with 659 (2.0%) samples failing. An additional 455 (1.4%) observations failed due to low bead numbers (<20/analyte). The final dataset included 609,438 anti-malaria IgG data points from 32,099 participants; 96.6% of all potential data points if no QC failures had occurred. The MBA can be deployed with high-throughput data collection and low inter-plate variability while ensuring data quality.
A Silicon Photonic Data Link with a Monolithic Erbium-Doped Laser
Authors: Li Nanxi , Xin Ming , Su Zhan , Magden Emir Salih , Singh Neetesh , Notaros Jelena , Timurdogan Erman , Purnawirman Purnawirman , Bradley Jonathan D. B. , Watts Michael R.
Published: January 2020

To meet the increasing demand for data communication bandwidth and overcome the limits of electrical interconnects, silicon photonic technology has been extensively studied, with various photonics devices and optical links being demonstrated. All of the optical data links previously demonstrated have used either heterogeneously integrated lasers or external laser sources. This work presents the first silicon photonic data link using a monolithic rare-earth-ion-doped laser, a silicon microdisk modulator, and a germanium photodetector integrated on a single chip. The fabrication is CMOS compatible, demonstrating data transmission as a proof-of-concept at kHz speed level, and potential data rate of more than 1 Gbps. This work provides a solution for the monolithic integration of laser sources on the silicon photonic platform, which is fully compatible with the CMOS fabrication line, and has potential applications such as free-space communication and integrated LIDAR.
Understanding the Lipid and Protein Corona Formation on Different Sized Polymeric Nanoparticles
Authors: Lima Tânia , Bernfur Katja , Vilanova Manuel , Cedervall Tommy
Published: January 2020

When in contact with biological fluids, nanoparticles dynamically absorb biomolecules like proteins and lipids onto their surface, forming a “corona”. This biocorona is a dynamic and complex structure that determines how host cells respond to nanoparticles. Despite the common use of mouse models in pre-clinical and toxicological experiments, the impact of corona formed in mouse serum on the biophysical and biological properties of different size NP has not been thoroughly explored. Furthering the knowledge on the corona formed on NP exposed to mouse serum proteins can help in understanding what role it might have in in vivo studies at systemic, tissue, and cellular levels. To investigate biocorona formation, different sized polystyrene NP were exposed to mouse serum. Our data show a size- and time-dependent protein and lipid corona formation. Several proteins were identified and apolipoproteins were by far the most common group on the NPs surfaces. Moreover, we observed that cholesterol and triglycerides effectively bind to NP emphasizing that proteins are not the only biomolecules with high-affinity binding to nanomaterial surfaces. These results highlight that further knowledge on NP interactions with mouse serum is necessary regarding the common use of this model to predict the in vivo efficiency of NP.
Multi-omics characterization of a diet-induced obese model of non-alcoholic steatohepatitis
Authors: Ægidius Helene M. , Veidal Sanne S. , Feigh Michael , Hallenborg Philip , Puglia Michele , Pers Tune H. , Vrang Niels , Jelsing Jacob , Kornum Birgitte R. , Blagoev Blagoy , Rigbolt Kristoffer T. G.
Published: January 2020

To improve the understanding of the complex biological processes underlying the development of non-alcoholic steatohepatitis (NASH), a multi-omics approach combining bulk RNA-sequencing based transcriptomics, quantitative proteomics and single-cell RNA-sequencing was used to characterize tissue biopsies from histologically validated diet-induced obese (DIO) NASH mice compared to chow-fed controls. Bulk RNA-sequencing and proteomics showed a clear distinction between phenotypes and a good correspondence between mRNA and protein level regulations, apart from specific regulatory events discovered by each technology. Transcriptomics-based gene set enrichment analysis revealed changes associated with key clinical manifestations of NASH, including impaired lipid metabolism, increased extracellular matrix formation/remodeling and pro-inflammatory responses, whereas proteomics-based gene set enrichment analysis pinpointed metabolic pathway perturbations. Integration with single-cell RNA-sequencing data identified key regulated cell types involved in development of NASH demonstrating the cellular heterogeneity and complexity of NASH pathogenesis.
The Association Between Play Fighting and Information Gathering during Subsequent Contests
Authors: Weller Jennifer E. , Turner Simon P. , Farish Marianne , Camerlink Irene , Arnott Gareth
Published: January 2020

Many hypotheses regarding the evolution of social play have been suggested, including the development of later-life assessment skills. However, the link between play fighting experience and information gathering during contests has yet to be examined. This paper explores the association between play fighting and contest assessment strategy in the domestic pig (Sus scrofa). Using an established framework, we provide evidence suggesting play fighting frequency may affect the extent to which individuals incorporate information regarding their own and their competitors’ resource holding potential (RHP) in escalation decisions. Pigs were allocated as ‘high play’ or ‘low play’ based upon their relative play fighting frequency. To maximise variation in play, 12 litters underwent a socialisation treatment while the remaining 12 litters were kept isolated within their home pen (i.e. control treatment). At eight weeks of age contests were staged between pairs of unfamiliar pigs, using 19 ‘high play’ dyads and 19 ‘low play’ dyads. While ‘high play’ dyads were observed to rely on a pure self-assessment strategy, ‘low play dyads’ did not meet the predictions of either self- or mutual assessment, suggesting their contest behaviour may have been motivated by alternative factors. We suggest that early life play fighting may therefore allow individuals to develop an accurate estimate of their RHP.
Clonally selected primitive endothelial cells promote occlusive pulmonary arteriopathy and severe pulmonary hypertension in rats exposed to chronic hypoxia
Authors: Bhagwani Aneel R. , Farkas Daniela , Harmon Brennan , Authelet Kayla J. , Cool Carlyne D. , Kolb Martin , Goncharova Elena , Yoder Mervin C. , Clauss Matthias , Freishtat Robert , Farkas Laszlo
Published: January 2020

One current concept suggests that unchecked proliferation of clonally selected precursors of endothelial cells (ECs) contribute to severe pulmonary arterial hypertension (PAH). We hypothesized that clonally selected ECs expressing the progenitor marker CD117 promote severe occlusive pulmonary hypertension (PH). The remodelled pulmonary arteries of PAH patients harboured CD117+ ECs. Rat lung CD117+ ECs underwent four generations of clonal expansion to enrich hyperproliferative ECs. The resulting clonally enriched ECs behaved like ECs, as measured by in vitro and in vivo angiogenesis assays. The same primitive ECs showed a limited ability for mesenchymal lineage differentiation. Endothelial differentiation and function were enhanced by blocking TGF-β signalling, promoting bone morphogenic protein (BMP) signalling. The transplantation of the EC clones caused arterio-occlusive PH in rats exposed to chronic hypoxia. These EC clones engrafted in the pulmonary arteries. Yet cessation of chronic hypoxia promoted lung cell apoptosis and resolution of vascular lesions. In conclusion, this is to the best of our knowledge, the first report that clonally enriched primitive ECs promote occlusive pulmonary arteriopathy and severe PH. These primitive EC clones further give rise to cells of endothelial and mesenchymal lineage as directed by BMP and TGF-β signaling.