bluuebunny/crossref_metadata_2025 huggingface dataset:
Simultaneous Episodes of Heavy Rainfall in Morocco and Southern Alps: 1. Mesoscale Simulations and Episode Climatology (1979–2016)
Authors: Gangoiti G. , Sáez de Cámara E. , Alonso L. , Iza J. , García J. A. , Valdenebro V. , Gómez M. C. , Navazo M. , García E.
Published: January 2020

The torrential rain and southerly föhn episode on 14–16 November 2002 in the Alpine southside, which affected the Piedmont region, was concurrent with heavy rains in the northwest flanks of the Middle and High Atlas in Morocco. Both simultaneous rainfalls are analyzed, as well as the recent climatology of similar episodes. A mesoscale modelling system is used first to simulate the relevant atmospheric processes and then to map the evaporative sources of both targets. Moderate Resolution Imaging Spectroradiometer water vapor products, National Centers for Environmental Prediction reanalysis data sets, radiosondes, wind profilers, and surface rain gauges are used to substantiate the simulations. The evaporative source estimation is discussed in a companion article. The simultaneous episodes originated after the development of a narrow meridionally elongated upper level trough extending southward from the British Islands into Iberia, associated with a semi‐stationary large amplitude wave. A total of 43 similar episodes have been identified during the 38‐year period 1979–2016, averaging one episode per year. However, there is a large interannual variability, with several years with no episodes and, others, which can accumulate up to four episodes. The episode length shows also a high variability, from 2 to 7–8 days. The longest episodes usually include an enlarged “Mediterranean phase” for the rainfalls in the Alps. With respect to their seasonal variability, the largest fraction concentrates in autumn (60%), and no episodes are found from June to August. November accumulates the highest case occurrence (37%) and the observed variability cannot be explained by changes in the phase of the North Atlantic Oscillation.
Fast Transport Pathways Into the Northern Hemisphere Upper Troposphere and Lower Stratosphere During Northern Summer
Authors: Wu Yutian , Orbe Clara , Tilmes Simone , Abalos Marta , Wang Xinyue
Published: January 2020

This study identifies the fast (i.e.,
days–weeks) transport pathways that connect the Northern Hemisphere surface to the upper troposphere and lower stratosphere (UTLS) during northern summer by integrating a large (90 member) ensemble of Boundary Impulse Response tracers in the Whole Atmosphere Community Climate Model version 5. We show that there is a fast transport pathway that occurs over the southern slope of the Tibetan Plateau, northern India, the Arabian Sea, and Saudi Arabia; furthermore, we show that during July this pathway connects the Northern Hemisphere surface to the UTLS on a modal time scale of 5–10 days. A less efficient transport pathway is also identified over the western Pacific. A detailed budget analysis reveals that, while convective processes are responsible for transport to 200–300 hPa, the resolved dynamics, specifically the vertical eddy flux, dominate at 100–150 hPa. Transport variations are analyzed on weekly, monthly, and interannual time scales and are largely related to differences in the resolved dynamics in the UTLS.
Morphometric Characterization of Longitudinal Striae on Martian Landslides and Impact Ejecta Blankets and Implications for the Formation Mechanism
Authors: Pietrek Alexa , Hergarten Stefan , Kenkmann Thomas
Published: January 2020

Longitudinal striae are a shared characteristic of long run‐out landslides and layered ejecta crater deposits. They appear to be a fundamental feature of disintegrated mass flows, but their formation and the required conditions are poorly understood. We evaluated their similarity using spectral analysis and assessed the possibility of a common formation mechanism. The topography of striae is scale‐invariant in the form of a power law relationship of the power spectrum and the derived spectral exponent and amplitude factor, which are a measure for roughness, show similar correlations on both types of deposit. There is no correlation to geologic substrate units, latitude, or age. Parameter values are isotropic in horizontal direction for ejecta deposits and show a weak anisotropy for landslide deposits. Spectral parameter values of substrate topography match well with the values of the superposed deposit, which indicates that roughness is transferred from substrate to deposit surface during emplacement. Testing different geometric models, we find that a simple superposition of topography with a semideterministic, anisotropic pattern does not reproduce the patterns of our data. We find that phase locking of a surface with scale‐invariant properties creates striae with fractal properties close to our natural data sets as well as recreating other morphological features that can form alongside striae. Although the transferal of substrate roughness cannot be fully conciliated with conventional flow models, we find that a model that combines advection with lateral diffusion accounts for the unidirectional preservation of phase information and is also consistent with the scale‐invariance of striae.
Winter CO2 Efflux From Sagebrush Shrublands Distributed Across the Rain‐to‐Snow Transition Zone
Authors: Fellows Aaron W. , Flerchinger Gerald N. , Seyfried Mark S. , Biederman Joel A. , Lohse Kathleen A.
Published: January 2020

The projected shifts in winter weather and snowpack conditions are expected to impact carbon storage in western U.S. rangelands. Sagebrush shrublands comprise much of the western United States, yet contribution of winter CO2 efflux to the overall carbon budget of these ecosystems remains uncertain. We explored factors controlling winter CO2 efflux measured using eddy covariance at five sagebrush‐dominated sites along an elevation/climate transect extending from 1,425 to 2,111 m. Results showed that winter CO2 efflux was modest but had important impacts on annual carbon budgets, and its impact increased in high‐elevation, snow‐dominated ecosystems compared to low, rain‐dominated ones. Observed cumulative winter CO2 efflux accounted for 8–30% of annual gross ecosystem production (GEP) and roughly approximated annual net carbon uptake. Omission of winter periods would have increased net uptake by 1.5 to 2.2 times. Within‐site variability in observed 30‐min winter CO2 efflux was related to soil temperature and moisture. Between‐site variability was attributed to available carbon stocks, including soil organic carbon and the previous year's GEP. At low elevations, lack of snow cover to insulate soil from freezing, coupled with lower carbon stocks, limited CO2 efflux. Conversely, large carbon stocks and deep snowpack that prevented soil freezing at high elevation led to increased CO2 efflux. These results show how climate and biota exert strong controls on winter ecosystem respiration and extend our understanding of how state factors influence winter CO2 efflux. Collectively, our findings suggest that an upward climatic shift in the rain‐to‐snow transition elevation may alter the carbon budget of sagebrush shrublands.
On the Occurrence of GPS Signal Amplitude Degradation for Receivers on Board LEO Satellites
Authors: Xiong Chao , Xu Ji‐Sheng , Stolle Claudia , van den Ijssel Jose , Yin Fan , Kervalishvili Guram N. , Zangerl Franz
Published: January 2020

Transient signal loss of the global positioning system (GPS) has been frequently observed by receivers on board the European Space Agency's Swarm mission when the satellites encounter ionospheric plasma irregularities. In this study we provided the first comparison of the GPS signal amplitude degradations from receivers on board low Earth orbiting satellites at different altitudes. Intense carrier phase variations but almost no amplitude fades (less than 2 dB Hz) are observed when the spaceborne receiver lies right inside the ionospheric plasma irregularities, like the case for the Swarm and CHAMP satellites flying at about 400–500 km. This indicates that the strong phase variation, but not the amplitude fades, causes the receivers to stop tracking the GPS signals. When the receiver is located 100–200 km below the slab of plasma irregularities, like the case for the GOCE satellite flying at about 250 km, signal amplitude fades exceeding 10 dB Hz are observed, in addition to strong phase variation. Our results suggest that a considerable distance of the receiver to the plasma irregularity slab is needed to affect the Fresnel diffractive process and further causes GPS signal amplitude fades.
CRISPR/Cas9-generated models uncover therapeutic vulnerabilities of del(11q) CLL cells to dual BCR and PARP inhibition
Authors: Quijada-Álamo Miguel , Hernández-Sánchez María , Alonso-Pérez Verónica , Rodríguez-Vicente Ana E. , García-Tuñón Ignacio , Martín-Izquierdo Marta , Hernández-Sánchez Jesús María , Herrero Ana B. , Bastida José María , San Segundo Laura , Gruber Michaela , García Juan Luis , Yin Shanye , ten Hacken Elisa , Benito Rocío , Ordóñez José Luis , Wu Catherine J. , Hernández-Rivas Jesús María
Published: January 2020

The deletion of 11q (del(11q)) invariably comprises ATM gene in chronic lymphocytic leukemia (CLL). Concomitant mutations in this gene in the remaining allele have been identified in 1/3 of CLL cases harboring del(11q), being the biallelic loss of ATM associated with adverse prognosis. Although the introduction of targeted BCR inhibition has significantly favored the outcomes of del(11q) patients, responses of patients harboring ATM functional loss through biallelic inactivation are unexplored, and the development of resistances to targeted therapies have been increasingly reported, urging the need to explore novel therapeutic approaches. Here, we generated isogenic CLL cell lines harboring del(11q) and ATM mutations through CRISPR/Cas9-based gene-editing. With these models, we uncovered a novel therapeutic vulnerability of del(11q)/ATM-mutated cells to dual BCR and PARP inhibition. Ex vivo studies in the presence of stromal stimulation on 38 CLL primary samples confirmed a synergistic action of the combination of olaparib and ibrutinib in del(11q)/ATM-mutated CLL patients. In addition, we showed that ibrutinib produced a homologous recombination repair impairment through RAD51 dysregulation, finding a synergistic link of both drugs in the DNA damage repair pathway. Our data provide a preclinical rationale for the use of this combination in CLL patients with this high-risk cytogenetic abnormality.
p53 controls genomic stability and temporal differentiation of human neural stem cells and affects neural organization in human brain organoids
Authors: Marin Navarro Ana , Pronk Robin Johan , van der Geest Astrid Tjitske , Oliynyk Ganna , Nordgren Ann , Arsenian-Henriksson Marie , Falk Anna , Wilhelm Margareta
Published: January 2020

In this study, we take advantage of human induced pluripotent stem (iPS) cell-derived neural stem cells and brain organoids to study the role of p53 during human brain development. We knocked down (KD) p53 in human neuroepithelial stem (NES) cells derived from iPS cells. Upon p53KD, NES cells rapidly show centrosome amplification and genomic instability. Furthermore, a reduced proliferation rate, downregulation of genes involved in oxidative phosphorylation (OXPHOS), and an upregulation of glycolytic capacity was apparent upon loss of p53. In addition, p53KD neural stem cells display an increased pace of differentiating into neurons and exhibit a phenotype corresponding to more mature neurons compared to control neurons. Using brain organoids, we modeled more specifically cortical neurogenesis. Here we found that p53 loss resulted in brain organoids with disorganized stem cell layer and reduced cortical progenitor cells and neurons. Similar to NES cells, neural progenitors isolated from brain organoids also show a downregulation in several OXPHOS genes. Taken together, this demonstrates an important role for p53 in controlling genomic stability of neural stem cells and regulation of neuronal differentiation, as well as maintaining structural organization and proper metabolic gene profile of neural progenitors in human brain organoids.
Correction: TNFR2 induced priming of the inflammasome leads to a RIPK1-dependent cell death in the absence of XIAP
Authors: Knop Janin , Spilgies Lisanne M. , Rufli Stefanie , Reinhart Ramona , Vasilikos Lazaros , Yabal Monica , Owsley Erika , Jost Philipp J. , Marsh Rebecca A. , Wajant Harald , Robinson Mark D. , Kaufmann Thomas , Wong W. Wei-Lynn
Published: January 2020

The original version of this article contained an error in the name of one of the co-authors (Erika Owsley). This has been corrected in the PDF and HTML versions.
The systemic and governmental agendas in presidential attention to climate change in Mexico 1994–2018
Authors: Balderas Torres Arturo , Lazaro Vargas Priscila , Paavola Jouni
Published: January 2020

Ambitious climate action requires sustained long-term attention from political leaders. To understand how climate change entered the political agenda in a developing country, we examine from an agenda-setting perspective the attention paid by Mexican presidents to this issue from 1994 to 2018. We perform a longitudinal analysis of 968 documents referring to climate change published by four presidencies to describe changes in attention levels over time and to determine how changes in international agreements and public policies (i.e. systemic agenda) and National Development Plans (NDPs)(i.e. governmental agenda) influence them. Our results indicate international agreements and national legislation establish a baseline for inclusion of climate change into governmental actions. Agenda changes driven by international agreements result in reactive changes in attention, while ambitious approaches are aligned with proactive NDPs. Our results also indicate public awareness and electoral periods can open windows of opportunity for reframing agendas and promoting ambitious climate action.
Genetic deletion of mast cell serotonin synthesis prevents the development of obesity and insulin resistance
Authors: Yabut Julian M. , Desjardins Eric M. , Chan Eric J. , Day Emily A. , Leroux Julie M. , Wang Bo , Crane Elizabeth D. , Wong Wesley , Morrison Katherine M. , Crane Justin D. , Khan Waliul I. , Steinberg Gregory R.
Published: January 2020

Obesity is linked with insulin resistance and is characterized by excessive accumulation of adipose tissue due to chronic energy imbalance. Increasing thermogenic brown and beige adipose tissue futile cycling may be an important strategy to increase energy expenditure in obesity, however, brown adipose tissue metabolic activity is lower with obesity. Herein, we report that the exposure of mice to thermoneutrality promotes the infiltration of white adipose tissue with mast cells that are highly enriched with tryptophan hydroxylase 1 (Tph1), the rate limiting enzyme regulating peripheral serotonin synthesis. Engraftment of mast cell-deficient mice with Tph1−/− mast cells or selective mast cell deletion of Tph1 enhances uncoupling protein 1 (Ucp1) expression in white adipose tissue and protects mice from developing obesity and insulin resistance. These data suggest that therapies aimed at inhibiting mast cell Tph1 may represent a therapeutic approach for the treatment of obesity and type 2 diabetes.
Chromosome arm aneuploidies shape tumour evolution and drug response
Authors: Shukla Ankit , Nguyen Thu H. M. , Moka Sarat B. , Ellis Jonathan J. , Grady John P. , Oey Harald , Cristino Alexandre S. , Khanna Kum Kum , Kroese Dirk P. , Krause Lutz , Dray Eloise , Fink J. Lynn , Duijf Pascal H. G.
Published: January 2020

Chromosome arm aneuploidies (CAAs) are pervasive in cancers. However, how they affect cancer development, prognosis and treatment remains largely unknown. Here, we analyse CAA profiles of 23,427 tumours, identifying aspects of tumour evolution including probable orders in which CAAs occur and CAAs predicting tissue-specific metastasis. Both haematological and solid cancers initially gain chromosome arms, while only solid cancers subsequently preferentially lose multiple arms. 72 CAAs and 88 synergistically co-occurring CAA pairs multivariately predict good or poor survival for 58% of 6977 patients, with negligible impact of whole-genome doubling. Additionally, machine learning identifies 31 CAAs that robustly alter response to 56 chemotherapeutic drugs across cell lines representing 17 cancer types. We also uncover 1024 potential synthetic lethal pharmacogenomic interactions. Notably, in predicting drug response, CAAs substantially outperform  mutations and focal deletions/amplifications combined. Thus, CAAs predict cancer prognosis, shape tumour evolution, metastasis and drug response, and may advance precision oncology.
Wireless battery-free body sensor networks using near-field-enabled clothing
Authors: Lin Rongzhou , Kim Han-Joon , Achavananthadith Sippanat , Kurt Selman A. , Tan Shawn C. C. , Yao Haicheng , Tee Benjamin C. K. , Lee Jason K. W. , Ho John S.
Published: January 2020

Networks of sensors placed on the skin can provide continuous measurement of human physiological signals for applications in clinical diagnostics, athletics and human-machine interfaces. Wireless and battery-free sensors are particularly desirable for reliable long-term monitoring, but current approaches for achieving this mode of operation rely on near-field technologies that require close proximity (at most a few centimetres) between each sensor and a wireless readout device. Here, we report near-field-enabled clothing capable of establishing wireless power and data connectivity between multiple distant points around the body to create a network of battery-free sensors interconnected by proximity to functional textile patterns. Using computer-controlled embroidery of conductive threads, we integrate clothing with near-field-responsive patterns that are completely fabric-based and free of fragile silicon components. We demonstrate the utility of the networked system for real-time, multi-node measurement of spinal posture as well as continuous sensing of temperature and gait during exercise.
Context-sensitive adjustment of pointing in great apes
Authors: Tauzin Tibor , Bohn Manuel , Gergely György , Call Josep
Published: January 2020

Great apes are able to request objects from humans by pointing. It is unclear, however, whether this is an associated response to a certain set of cues (e.g. the presence and attention of a human addressee) or a communicative signal which can be adjusted to relevant aspects of the spatial and social context. In three experiments, we tested captive great apes’ flexible use of pointing gestures. We manipulated the communicative context so that the default pointing response of apes would have indicated an undesired object, either due to 1) the spatial arrangements of the target objects, 2) the perspective of the addressee or 3) the knowledge of the addressee about the target objects’ location. The results of the three experiments indicate that great apes can successfully adjust their pointing to the spatial configuration of the referent environment such as distance and location of food. However, we found no evidence that they take the perspective or the knowledge of the addressee into account when doing so. This implies that pointing in great apes is a context-sensitive, but maybe less versatile, communicative signal compared to human pointing.
A comparison of methods for the isolation and separation of extracellular vesicles from protein and lipid particles in human serum
Authors: Brennan K. , Martin K. , FitzGerald S. P. , O’Sullivan J. , Wu Y. , Blanco A. , Richardson C. , Mc Gee M. M.
Published: January 2020

Extracellular vesicles (EVs) are nano-sized vesicles containing nucleic acid and protein cargo that are released from a multitude of cell types and have gained significant interest as potential diagnostic biomarkers. Human serum is a rich source of readily accessible EVs; however, the separation of EVs from serum proteins and non-EV lipid particles represents a considerable challenge. In this study, we compared the most commonly used isolation techniques, either alone or in combination, for the isolation of EVs from 200 µl of human serum and their separation from non-EV protein and lipid particles present in serum. The size and yield of particles isolated by each method was determined by nanoparticle tracking analysis, with the variation in particle size distribution being used to determine the relative impact of lipoproteins and protein aggregates on the isolated EV population. Purification of EVs from soluble protein was determined by calculating the ratio of EV particle count to protein concentration. Finally, lipoprotein particles co-isolated with EVs was determined by Western blot analysis of lipoprotein markers APOB and APOE. Overall, this study reveals that the choice of EV isolation procedure significantly impacts EV yield from human serum, together with the presence of lipoprotein and protein contaminants.
Diversity, compositional and functional differences between gut microbiota of children and adults
Authors: Radjabzadeh Djawad , Boer Cindy G. , Beth Sanne A. , van der Wal Pelle , Kiefte-De Jong Jessica C. , Jansen Michelle A. E. , Konstantinov Sergey R. , Peppelenbosch Maikel P. , Hays John P. , Jaddoe Vincent W. V. , Ikram M. Arfan , Rivadeneira Fernando , van Meurs Joyce B. J. , Uitterlinden André G. , Medina-Gomez Carolina , Moll Henriette A. , Kraaij Robert
Published: January 2020

The gut microbiota has been shown to play diverse roles in human health and disease although the underlying mechanisms have not yet been fully elucidated. Large cohort studies can provide further understanding into inter-individual differences, with more precise characterization of the pathways by which the gut microbiota influences human physiology and disease processes. Here, we aimed to profile the stool microbiome of children and adults from two population-based cohort studies, comprising 2,111 children in the age-range of 9 to 12 years (the Generation R Study) and 1,427 adult individuals in the range of 46 to 88 years of age (the Rotterdam Study). For the two cohorts, 16S rRNA gene profile datasets derived from the Dutch population were generated. The comparison of the two cohorts showed that children had significantly lower gut microbiome diversity. Furthermore, we observed higher relative abundances of genus Bacteroides in children and higher relative abundances of genus Blautia in adults. Predicted functional metagenome analysis showed an overrepresentation of the glycan degradation pathways, riboflavin (vitamin B2), pyridoxine (vitamin B6) and folate (vitamin B9) biosynthesis pathways in children. In contrast, the gut microbiome of adults showed higher abundances of carbohydrate metabolism pathways, beta-lactam resistance, thiamine (vitamin B1) and pantothenic (vitamin B5) biosynthesis pathways. A predominance of catabolic pathways in children (valine, leucine and isoleucine degradation) as compared to biosynthetic pathways in adults (valine, leucine and isoleucine biosynthesis) suggests a functional microbiome switch to the latter in adult individuals. Overall, we identified compositional and functional differences in gut microbiome between children and adults in a population-based setting. These microbiome profiles can serve as reference for future studies on specific human disease susceptibility in childhood, adulthood and specific diseased populations.
A Nondestructive Eggshell Thickness Measurement Technique Using Terahertz Waves
Authors: Khaliduzzaman Alin , Konagaya Keiji , Suzuki Tetsuhito , Kashimori Ayuko , Kondo Naoshi , Ogawa Yuichi
Published: January 2020

Eggshells play a number of important roles in the avian and reptile kingdom: protection of internal contents and as a major source of minerals for developing embryos. However, when researching these respective roles, eggshell thickness measurement remains a bottleneck due to the lack of a non-destructive measurement techniques. As a result, many avian and reptile research protocols omit consideration of eggshell thickness bias on egg or embryo growth and development. Here, we validate a non-destructive method to estimate eggshell thickness based on terahertz (THz) reflectance spectroscopy using chicken white coloured eggs. Since terahertz waves are reflected from outer air-eggshell interface, as well as the inner eggshell-membrane boundary, the resulting interference signals depend on eggshell thickness. Thus, it is possible to estimate shell thickness from the oscillation distance in frequency-domain. A linear regression-based prediction model for non-destructive eggshell thickness measurement was developed, which had a coefficient of determination (R2) of 0.93, RMSEP of 0.009, RPD of 3.45 and RER 13.67. This model can estimate eggshell thickness to a resolution of less than 10 μm. This method has the potential to expand the protocols in the field of avian and reptile research, as well as be applied to industrial grading of eggs.
Unique IL-13Rα2/STAT3 mediated IL-13 regulation detected in lung conventional dendritic cells, 24 h post viral vector vaccination
Authors: Roy Sreeja , Liu Ho-Ying , Jaeson Muhammad Irwan , Deimel Lachlan Paul , Ranasinghe Charani
Published: January 2020

This study demonstrates that 24 h following viral vector-based vaccination IL-13Rα2 functions as a master sensor on conventional dendritic cells (cDCs), abetted by high protein stability coupled with minimal mRNA expression, to rapidly regulate DC mediated IL-13 responses at the lung mucosae, unlike IL-13Rα1. Under low IL-13, IL-13Rα2 performs as a primary signalling receptor, whilst under high IL-13, acts to sequester IL-13 to maintain homeostasis, both in a STAT3-dependent manner. Likewise, we show that viral vector-derived IL-13 levels at the vaccination site can induce differential STAT3/STAT6 paradigms in lung cDC, that can get regulated collaboratively or independently by TGF-β1 and IFN-γ. Specifically, low IL-13 responses associated with recombinant Fowlpox virus (rFPV) is regulated by early IL-13Rα2, correlated with STAT3/TGF-β1 expression. Whilst, high IL-13 responses, associated with recombinant Modified Vaccinia Ankara (rMVA) is regulated in an IL-13Rα1/STAT6 dependent manner associated with IFN-γR expression bias. Different viral vaccine vectors have previously been shown to induce unique adaptive immune outcomes. Taken together current observations suggest that IL-13Rα2-driven STAT3/STAT6 equilibrium at the cDC level may play an important role in governing the efficacy of vector-based vaccines. These new insights have high potential to be exploited to improve recombinant viral vector-based vaccine design, according to the pathogen of interest and/or therapies against IL-13 associated disease conditions.
Sodium-induced population shift drives activation of thrombin
Authors: Kahler Ursula , Kamenik Anna S. , Kraml Johannes , Liedl Klaus R.
Published: January 2020

The equilibrium between active E and inactive E* forms of thrombin is assumed to be governed by the allosteric binding of a Na+ ion. Here we use molecular dynamics simulations and Markov state models to sample transitions between active and inactive states. With these calculations we are able to compare thermodynamic and kinetic properties depending on the presence of Na+. For the first time, we directly observe sodium-induced conformational changes in long-timescale computer simulations. Thereby, we are able to explain the resulting change in activity. We observe a stabilization of the active form in presence of Na+ and a shift towards the inactive form in Na+-free simulations. We identify key structural features to quantify and monitor this conformational shift. These include the accessibility of the S1 pocket and the reorientation of W215, of R221a and of the Na+ loop. The structural characteristics exhibit dynamics at various timescales: Conformational changes in the Na+ binding loop constitute the slowest observed movement. Depending on its orientation, it induces conformational shifts in the nearby substrate binding site. Only after this shift, residue W215 is able to move freely, allowing thrombin to adopt a binding-competent conformation.
Silencing E3 Ubiqutin ligase ITCH as a potential therapy to enhance chemotherapy efficacy in p53 mutant neuroblastoma cells
Authors: Meng Jinhong , Tagalakis Aristides D. , Hart Stephen L.
Published: January 2020

P53 mutations are responsible for drug-resistance of tumour cells which impacts on the efficacy of treatment. Alternative tumour suppressor pathways need to be explored to treat p53- deficient tumours. The E3 ubiquitin ligase, ITCH, negatively regulates the tumour suppressor protein TP73, providing a therapeutic target to enhance the sensitivity of the tumour cells to the treatment. In the present study, two p53-mutant neuroblastoma cell lines were used as in vitro models. Using immunostaining, western blot and qPCR methods, we firstly identified that ITCH was expressed on p53-mutant neuroblastoma cell lines. Transfection of these cell lines with ITCH siRNA could effectively silence the ITCH expression, and result in the stabilization of TP73 protein, which mediated the apoptosis of the neuroblastoma cells upon irradiation treatment. Finally, in vivo delivery of the ITCH siRNA using nanoparticles to the neuroblastoma xenograft mouse model showed around 15–20% ITCH silencing 48 hours after transfection. Our data suggest that ITCH could be silenced both in vitro and in vivo using nanoparticles, and silencing of ITCH sensitizes the tumour cells to irradiation treatment. This strategy could be further explored to combine the chemotherapy/radiotherapy treatment to enhance the therapeutic effects on p53-deficient neuroblastoma.
Teratological cases of the antennae in the family Aradidae (Hemiptera: Heteroptera)
Authors: Taszakowski Artur , Kaszyca-Taszakowska Natalia
Published: January 2020

Teratological cases of the antennae in the family Aradidae (Hemiptera: Heteroptera) are widely described for the first time. Four hundred seventy-six specimens of flat bugs were studied, and antennal malformations were found in 14 of them (2.94%) (belonging to eight species and three subfamilies: Aradinae, Aneurinae and Mezirinae). All of the teratologies were observed using optical microscopy; moreover, in order to determine any compensatory regeneration, selected cases were also studied using a scanning electron microscope. In almost all of the specimens, the successful regeneration of the sensory organs to various degrees was observed. Additional results were the discovery of a previously unrecognized type of sensillum in flat bugs – a campaniform sensillum as well as significant differences in the distribution of the sensilla depending on the systematic affiliation.
Variation in chemokines plasma concentrations in primary care depressed patients associated with Internet-based cognitive-behavioral therapy
Authors: Romero-Sanchiz Pablo , Nogueira-Arjona Raquel , Araos Pedro , Serrano Antonia , Barrios Vicente , Argente Jesús , Garcia-Marchena Nuria , Lopez-Tellez Antonio , Rodriguez-Moreno Silvia , Mayoral Fermin , Pavón Francisco J. , Fonseca Fernando Rodríguez de
Published: January 2020

How the presence of inflammation has repercussions for brain function is a topic of active research into depression. Signals released from immune system-related cells, including chemokines, might be indicative of active depression and can, hypothetically, serve as biomarkers of response to interventions, both pharmacological and psychological. The objective of this study is to analyze the peripheral plasma concentrations of CXCL12, CCL11, CX3CL1 and CCL2 in a cohort of depressed primary-care patients, as well as their evolution after an internet-based cognitive-behavioral intervention. The concentrations of those chemokines were measured in 66 primary-care patients with mild and moderate depression, before and after the intervention, as well as 60 controls, using multiplex immunoassays. Concentrations of CXCL12 and CCL2 were significantly higher in the clinical sample in comparison with controls. A stable multivariate discriminative model between both groups was found. Concentrations of all chemokines decreased after the internet-based psychological intervention. These findings support the implication of chemokines in depression, even in a sample of patients with mild and moderate severity. Furthermore, they demonstrate the need for further multidisciplinary research that confirms how biomarkers such as plasma chemokines can serve as a marker for depression and are sensitive to non-pharmacological interventions.
Altered dorsal CA1 neuronal population coding in the APP/PS1 mouse model of Alzheimer’s disease
Authors: Chockanathan Udaysankar , Warner Emily J. , Turpin Loel , O’Banion M. Kerry , Padmanabhan Krishnan
Published: January 2020

While the link between amyloid β (Aβ) accumulation and synaptic degradation in Alzheimer’s disease (AD) is known, the consequences of this pathology on population coding remain unknown. We found that the entropy, a measure of the diversity of network firing patterns, was lower in the dorsal CA1 region in the APP/PS1 mouse model of Aβ pathology, relative to controls, thereby reducing the population’s coding capacity. Our results reveal a network level signature of the deficits Aβ accumulation causes to the computations performed by neural circuits.
Embryo survival in the oviduct not significantly influenced by major histocompatibility complex social signaling in the horse
Authors: Jeannerat E. , Marti E. , Thomas S. , Herrera C. , Sieme H. , Wedekind C. , Burger D.
Published: January 2020

The major histocompatibility complex (MHC) influences sexual selection in various vertebrates. Recently, MHC-linked social signaling was also shown to influence female fertility in horses (Equus caballus) diagnosed 17 days after fertilization. However, it remained unclear at which stage the pregnancy was terminated. Here we test if MHC-linked cryptic female choice in horses happens during the first days of pregnancy, i.e., until shortly after embryonic entrance into the uterus and before fixation in the endometrium. We exposed estrous mares to one of several unrelated stallions, instrumentally inseminated them with semen of another stallion, and flushed the uterus 8 days later to test for the presence of embryos. In total 68 embryos could be collected from 97 experimental trials. This success rate of 70.1% was significantly different from the mean pregnancy rate of 45.7% observed 17 days after fertilization using the same experimental protocol but without embryo flushing. Embryo recovery rate was not significantly dependent on whether the mares had been socially exposed to an MHC-dissimilar or an MHC-similar stallion. These observations suggest that MHC-linked maternal strategies affect embryo survival mainly (or only) during the time of fixation in the uterus.
An intra-bacterial activity for a T3SS effector
Authors: El Qaidi Samir , Scott Nichollas E. , Hays Michael P. , Geisbrecht Brian V. , Watkins Shelby , Hardwidge Philip R.
Published: January 2020

Many Gram-negative bacterial pathogens interact with mammalian cells by using type III secretion systems (T3SS) to inject virulence proteins into host cells. A subset of these injected protein ‘effectors’ are enzymes that inhibit the function of host proteins by catalyzing the addition of unusual post-translational modifications. The E. coli and Citrobacter rodentium NleB effectors, as well as the Salmonella enterica SseK effectors are glycosyltransferases that modify host protein substrates with N-acetyl glucosamine (GlcNAc) on arginine residues. This post-translational modification disrupts the normal functioning of host immune response proteins. T3SS effectors are thought to be inactive within the bacterium and fold into their active conformations after they are injected, due to the activity of chaperones that keep the effectors in a structural state permissive for secretion. While performing mass spectrometry experiments to identify glycosylation substrates of NleB orthologs, we unexpectedly observed that the bacterial glutathione synthetase (GshB) is glycosylated by NleB on arginine residue R256. NleB-mediated glycosylation of GshB resulted in enhanced GshB activity, leading to an increase in glutathione production, and promoted C. rodentium survival in oxidative stress conditions. These data represent, to our knowledge, the first intra-bacterial activity for a T3SS effector and show that arginine-GlcNAcylation, once thought to be restricted to host cell compartments, also plays an important role in regulating bacterial physiology.
A normalized drug response metric improves accuracy and consistency of anticancer drug sensitivity quantification in cell-based screening
Authors: Gupta Abhishekh , Gautam Prson , Wennerberg Krister , Aittokallio Tero
Published: January 2020

Accurate quantification of drug effects is crucial for identifying pharmaceutically actionable cancer vulnerabilities. Current cell viability-based measurements often lead to biased response estimates due to varying growth rates and experimental artifacts that explain part of the inconsistency in high-throughput screening results. We developed an improved drug scoring model, normalized drug response (NDR), which makes use of both positive and negative control conditions to account for differences in cell growth rates, and experimental noise to better characterize drug-induced effects. We demonstrate an improved consistency and accuracy of NDR compared to existing metrics in assessing drug responses of cancer cells in various culture models and experimental setups. Notably, NDR reliably captures both toxicity and viability responses, and differentiates a wider spectrum of drug behavior, including lethal, growth-inhibitory and growth-stimulatory modes, based on a single viability readout. The method will therefore substantially reduce the time and resources required in cell-based drug sensitivity screening.
Characterization methods in porous materials for the rational design of multi-step processing in the context of a paper microfluidic phenylalanine test
Authors: Wentland Lael , Polaski Rachel , Fu Elain
Published: January 2020

We present an example of rational device design in the context of an improved paper microfluidic phenylalanine detection device using detailed characterization of fluid and reagent interactions within the device.
Nitro reduction-based fluorescent probes for carbon monoxide require reactivity involving a ruthenium carbonyl moiety
Authors: Yuan Zhengnan , Yang Xiaoxiao , De La Cruz Ladie Kimberly , Wang Binghe
Published: January 2020

Nitro reduction-based fluorescent CO probes only sense ruthenium-based CO donors, CORM-2 and CORM-3, not CO in general.
The binding mode of vilazodone in the human serotonin transporter elucidated by ligand docking and molecular dynamics simulations
Authors: Zhang Yang , Zheng Guoxun , Fu Tingting , Hong Jiajun , Li Fengcheng , Yao Xiaojun , Xue Weiwei , Zhu Feng
Published: January 2020

Vilazodone is a novel antidepressant for the treatment of major depressive disorder with the action mechanism of inhibiting the human serotonin reuptake transporter (hSERT), not only occupying the S1 binding site, but also extending to the S2 site.
Reassessing destructive quantum interference in azulene-based devices
Authors: Saraiva-Souza Aldilene , Smeu Manuel , Guo Hong
Published: January 2020

We show that the different anchoring moieties on azulene based devices are more relevant for the occurrence of destructive QI than the coupling position.
Proton dynamics in molecular solvent clusters as an indicator for hydrogen bond network strength in confined geometries
Authors: Saak Clara-Magdalena , Richter Clemens , Unger Isaak , Mucke Melanie , Nicolas Christophe , Hergenhahn Uwe , Caleman Carl , Huttula Marko , Patanen Minna , Björneholm Olle
Published: January 2020

The size-dependence of proton-dynamics occurring upon core-ionisation is linked to a weakening of the hydrogen-bond network in molecular clusters.
Supramolecular materials based on AIE luminogens (AIEgens): construction and applications
Authors: Li Jie , Wang Jianxing , Li Haoxuan , Song Nan , Wang Dong , Tang Ben Zhong
Published: January 2020

This review presents comprehensive discussions on the recent development in supramolecular materials based on luminogens with aggregation-induced emission (AIE) characteristics.
Regioselective C–H hydroxylation of n-alkanes using Shilov-type Pt catalysis in perfluorinated micro-emulsions
Authors: Janssen Michiel , De Vos Dirk E.
Published: January 2020

In this work, the potential of combining Shilov-type PtII and micellar catalysis to realize the challenging terminal C–H hydroxylation of saturated n-alkanes using water as the reaction medium is demonstrated.
Transition metal dichalcogenides for alkali metal ion batteries: engineering strategies at the atomic level
Authors: Chen Biao , Chao Dongliang , Liu Enzuo , Jaroniec Mietek , Zhao Naiqin , Qiao Shi-Zhang
Published: January 2020

This review provides enriched information for understanding the charge storage mechanisms of transition metal dichalcogenides (TMDs), as well as the importance of intrinsic structure engineering for enhancing the performance of TMDs in energy storage.
Core–shell graphene oxide–polymer hollow fibers as water filters with enhanced performance and selectivity
Authors: Kovtun Alessandro , Bianchi Antonio , Zambianchi Massimo , Bettini Cristian , Corticelli Franco , Ruani Giampiero , Bocchi Letizia , Stante Francesco , Gazzano Massimo , Marforio Tainah Dorina , Calvaresi Matteo , Minelli Matteo , Navacchia Maria Luisa , Palermo Vincenzo , Melucci Manuela
Published: January 2020

Graphene oxide (GO) coated hollow fiber filters could selectively capture three target water contaminants. The separation mechanism relies on synergic physical size exclusion and intercalation of solute 6 molecules between GO layers
Synthesis of metallic mixed 3R and 2H Nb1+xS2 nanoflakes by chemical vapor deposition
Authors: Mohmad Abdul Rahman , Hamzah Azrul Azlan , Yang Jieun , Wang Yan , Bozkurt Ibrahim , Shin Hyeon Suk , Jeong Hu Young , Chhowalla Manish
Published: January 2020

Systematic study of the effect of chemical vapor deposition conditions on the incorporation of Nb interstitials between NbS2 layers.
A flexible 3-dimensional microelectrode array for in vitro brain models
Authors: Soscia David A. , Lam Doris , Tooker Angela C. , Enright Heather A. , Triplett Michael , Karande Piyush , Peters Sandra K. G. , Sales Ana Paula , Wheeler Elizabeth K. , Fischer Nicholas O.
Published: January 2020

A flexible 3D microelectrode array (3DMEA) device was developed that non-invasively interrogates electrophysiology of 3D in vitro neuronal cultures.
Reporter system architecture affects measurements of noncanonical amino acid incorporation efficiency and fidelity
Authors: K. A. Potts , J. T. Stieglitz , M. Lei , J. A. Van Deventer
Published: January 2020

Quantitative reporter systems are critical tools for engineering cells to synthesize proteins containing diverse chemical functionality.
Preference for low-coordination sites by adsorbed CO on small platinum nanoparticles
Authors: Hossain M. Jakir , Rahman M. M. , Jafar Sharif Md.
Published: January 2020

Successfully synthesized PVP stabilized Pt NPs from 1.4 to 4.8 nm. Two new bands at 2021 cm−1and 1994 cm−1were observed in the FTIR spectra of adsorbed12CO on Pt NPs which are assigned to the edge and corner sites at Pt surface respectively.
Femtosecond laser-induced non-thermal welding for a single Cu nanowire glucose sensor
Authors: Yu Yongchao , Deng Yangbao , Al Hasan Md Abdullah , Bai Yanfeng , Li Ruo-Zhou , Deng Shuguang , Joshi Pooran , Shin Seungha , Hu Anming
Published: January 2020

Experiments and simulations of FS laser induced nonthermal welding for single Cu nanowires on a flexible substrate.
Novel biobased high toughness PBAT/PEF blends: morphology, thermal properties, crystal structures and mechanical properties
Authors: Zhang Qiang , Jiang Min , Wang Guoqiang , Zhou Guangyuan
Published: January 2020

A novel series of PBAT/PEF blends with 1–50 wt% PEF content displayed typical sea-island morphology structure and had excellent toughness properties.
Changing stereoselectivity and regioselectivity in copper(i)-catalyzed 5-exo cyclization by chelation and rigidity in aminoalkyl radicals: synthesis towards diverse bioactive N-heterocycles
Authors: Sadanandan Sandhya , Gupta Dharmendra Kumar
Published: January 2020

Chelation, rigidity and carbon-radical positions in aminoalkyl precursors disturb the usual 2,4-trans diastereoselectivity and 5-exo mode in Cu(i)-catalyzed ATRC.
Pentasulfurated benzene-cored asterisks: relationship between crystal structure and luminescence properties
Authors: Villa Marco , D’Agostino Simone , Sabatino Piera , Noel Raymond , Busto José , Roy Myriam , Gingras Marc , Ceroni Paola
Published: January 2020

Pentasulfurated benzene chromophores are not luminescent in fluid solution and are phosphorescent in the solid state; in particular, the cyano-derivative which displays a bright orange luminescence.
New main-group ferrocenyldithiocarbamates and conversion to ferrocene oxazolidine-2-thione and -2-one
Authors: Yadav Reena , Singh Suryabhan , Trivedi Manoj , Kociok-Köhn Gabriele , Rath Nigam P. , Köhn Randolf D. , Muddassir Mohd. , Kumar Abhinav
Published: January 2020

Three new main-group ferrocenyl dithiocarbamates and a pure cyclised product, 3-ferrocenylmethyl-oxazolidine-2-thione, were isolated using copper powder.
Nanoparticle translocation across the lung surfactant film regulated by grafting polymers
Authors: Bai Xuan , Li Mujun , Hu Guoqing
Published: January 2020

Conditioning of grafting polymers, including their length, terminal charge, and grafting density, can result in different translocation processes of nanoparticles across the lung surfactant film.
Metal oxide heterojunctions using a printable nickel oxide ink
Authors: Ramachandran Hari , Jahanara Mohammad Mahaboob , Nair Nitheesh M. , Swaminathan P.
Published: January 2020

We present a printed p-NiO/n-AZO heterojunction exhibiting high rectification ratios using a NiO ink synthesized by a chemical route.
Efficient donor–acceptor emitter based nonsymmetrical connection for organic emitting diodes with improving exciton utilization
Authors: Jayabharathi Jayaraman , Anudeebhana Jagathratchagan , Thanikachalam Venugopal , Sivaraj Sekar , Prabhakaran Annadurai
Published: January 2020

New strategy is developed to construct efficient blue emissive materials using unsymmetrical connection with identical phenanthrimidazole groups leads to donor–acceptor (D–A) architecture.
Importance of device structure and interlayer design in storage stability of naphthalene diimide-based all-polymer solar cells
Authors: Lee Changyeon , Lee Junbok , Lee Seungjin , Lee Wonho , You Hoseon , Woo Han Young , Kim Bumjoon J.
Published: January 2020

Our work highlights the importance of device structure and interlayer design in the storage stability of NDI-based all-PSCs and suggests design guidelines for efficient and burn-in free all-PSCs.
Aptamer-based nanostructured interfaces for the detection and release of circulating tumor cells
Authors: Ding Pi , Wang Zhili , Wu Zeen , Zhu Weipei , Liu Lifen , Sun Na , Pei Renjun
Published: January 2020

This paper summarizes various aptamer-functionalized nanostructured interfaces for the detection and release of circulating tumor cells.
A wide linearity range and high sensitivity flexible pressure sensor with hierarchical microstructures via laser marking
Authors: Li Zhaoyang , Zhang Bo , Li Kun , Zhang Tong , Yang Xiaoniu
Published: January 2020

The performance of a hierarchical microstructure-based flexible pressure sensor with a wide linearity range and high sensitivity, and the applications of the flexible pressure sensor for human activities.
N-Heterocyclic carbene (NHC)-catalyzed tandem imine umpolung–aza-Michael addition–oxidation of β-carboline cyclic imines
Authors: Satyam Killari , Harish Battu , Nanubolu Jagadeesh Babu , Suresh Surisetti
Published: January 2020

N-Heterocyclic carbene (NHC)-catalyzed tandem imine umpolung–aza-Michael addition–oxidation of cyclic imines for the synthesis of a wide range of biologically relevant β-carboline-1-one derivatives has been disclosed.