bluuebunny/crossref_metadata_2025 huggingface dataset:
Spatial Distributions and Seasonal Changes of Current‐Use Pesticides from the North Pacific to the Arctic Oceans
Authors: Gao Yuan , Zheng Hongyuan , Xia Yinyue , Chen Min , Meng Xiang‐Zhou , Cai Minghong
Published: August 2019

Distributions of eight targeted current‐use pesticides (CUPs) chloroneb, simazine, atrazine, alachlor, dacthal, chlorobenzilate, methoxychlor, and permethrin were investigated in seawater and the atmosphere in a region covering the North Pacific to the Arctic Oceans during the 7th and 8th Chinese National Arctic Research Expedition (2016 and 2017) voyages of the research vessel R/V Xuelong (Snow Dragon in English). Total CUP concentrations in seawater have prominent seasonal and latitudinal trends, with higher concentrations occurring at lower latitudes in early summer. The major contributors of the CUPs (∑8CUP) did not alter over different seasons with dominant chloroneb, alachlor, and atrazine accounting for more than 90%, but their concentrations did have marked seasonal changes. However, the compositions of the eight analyzed CUPs varied indistinctly between seasons indicating a possible combined environmental impact on these compounds rather than the effects of individual chemical properties. Three‐day backward air mass trajectories indicate that atmospheric masses from northeastern China are responsible for the high concentrations of CUPs in East China and Japan Seas, whereas those from the North Atlantic Ocean contribute to the low levels in local area. Fugacity ratios indicate potential volatilization and equilibrium of chloroneb in the Canada Basin of the Arctic Ocean and Japan Sea, respectively, and deposition of other CUPs in both regions. However, atmospheric concentrations are decoupled from those in seawater, which indicates a low exchange rate.
The Permafrost Listeners
Authors: Joel Lucas
Published: August 2019

Geophysicists have discovered a way to monitor permafrost melt by measuring seismic waves so gentle they don’t shake a thing.
Does Involving Parents in Soil Sampling Identify Causes of Child Exposure to Lead? A Case Study of Community Engagement in Mining‐Impacted Towns in Peru
Authors: Landes Franziska C. , Inauen Jennifer , Ponce‐Canchihuamán Johny , Markowski Kathie , Ellis Tyler K. , van Geen Alexander
Published: August 2019

Over a million people in Peru may be exposed to lead (Pb) due to past or present mining‐related activities; however, neither soil Pb nor blood Pb are routinely monitored throughout the country. Because little is known about Pb contamination in smaller mining‐impacted towns, soil Pb was mapped in four such towns with a portable X‐ray fluorescence analyzer in 2015. The roadside mapping delineated hotspots of highly contaminated soil (1,000–6,000 mg/kg Pb) in two of the towns. The local health department, provided with a LeadCare II analyzer, then measured blood‐Pb levels >5 in 65% and >10 μg/dL in 15% of children (n = 200) up to 6 years of age in these same four communities. There were no clear relations between child blood‐Pb levels and Pb levels in soil samples collected inside (n = 50) or outside the home (n = 50). Increased child blood Pb was associated with decreased level of cleanliness of parent clothing (n = 136) and shoes (n = 138), linking a possible behavioral factor for transferring contaminated soil and dust to children. In order to explore individual exposure and variations in soil Pb, 10 parents of children with blood Pb >10 μg/dL and 10 parents of children with blood Pb <5 μg/dL were invited to collect soil samples in areas where their children play and screen it for Pb using a color‐based field procedure. Importantly, parents identified a new hotspot of Pb contamination that had been missed by the previous portable X‐ray fluorescence soil mapping. The findings highlight the feasibility and value of involving families impacted by environmental contamination to identify and reduce environmental health risk.
Deposition of Organic and Black Carbon: Direct Measurements at Three Remote Stations in the Himalayas and Tibetan Plateau
Authors: Yan Fangping , He Cenlin , Kang Shichang , Chen Pengfei , Hu Zhaofu , Han Xiaowen , Gautam Sangita , Yan Caiqing , Zheng Mei , Sillanpää Mika , Raymond Peter A. , Li Chaoliu
Published: August 2019

Carbonaceous matter in the atmosphere has an important influence on climate change. Currently, the deposition of carbonaceous matter is one of the largest uncertainties in the climate system. This phenomenon is common in remote regions, such as the Himalayas and Tibetan Plateau. In this study, for the first time, we reported in situ measurements of wet and dry deposition rates of carbonaceous matter at three remote stations: Nam Co, Lulang, and Everest. The results showed that the annual wet deposition rates of water‐insoluble organic carbon (WIOC) and black carbon (BC) were 60.2 and 5.8 mg·m−2·year−1, 330 and 34.6 mg·m−2·year−1, and 47.0 and 2.6 mg·m−2·year−1 at the Nam Co, Lulang, and Everest stations, respectively. Seasonal variations in the wet deposition rates of WIOC and BC were controlled by precipitation amount and their atmospheric concentrations. In addition, the wet scavenging ratios of WIOC and BC at Nam Co Station were close to those observed in other remote areas. The total BC deposition at Nam Co Station (15.3 mg·m−2·year−1) was higher than that from chemical transport models, implying a dominant role of dry deposition of BC in the total deposition at this station and an urgent need to improve the aerosol deposition in models for the Himalayas and Tibetan Plateau. It was found that the deposition rates of carbonaceous matter in the Himalayas and Tibetan Plateau had large spatial variation; thus, high‐resolution models need to be applied in the future.
Impact of energy turnover on the regulation of glucose homeostasis in healthy subjects
Authors: Büsing Franziska , Hägele Franziska Anna , Nas Alessa , Hasler Mario , Müller Manfred James , Bosy-Westphal Anja
Published: August 2019

Objective

Sedentary lifestyle increases the risk of type 2 diabetes. The aim of this study was to investigate the impact of different levels of energy turnover (ET; low, medium, and high level of physical activity and the corresponding energy intake) on glucose metabolism at zero energy balance, caloric restriction, and overfeeding.

Methods

Sixteen healthy individuals (13 men, 3 women, 25.1 ± 3.9 years, BMI 24.0 ± 3.2 kg/m2) participated in a randomized crossover intervention under metabolic ward conditions. Subjects passed 3 × 3 intervention days. Three levels of physical activity (PAL: low 1.3, medium 1.6, and high 1.8 achieved by walking at 4 km/h for 0, 3 × 55, or 3 × 110 min) were compared under three levels of energy balance (zero energy balance (EB): 100% of energy requirement (Ereq); caloric restriction (CR): 75% Ereq, and overfeeding (OF): 125% Ereq). Continuous interstitial glucose monitoring, C-peptide excretion, and HOMA–IR, as well as postprandial glucose and insulin were measured.

Results

Daylong glycemia and insulin secretion did not increase with higher ET at all conditions of energy balance (EB, CR, and OF), despite a correspondingly higher CHO intake (Δ low vs. high ET: +86 to 135 g of CHO/d). At CR, daylong glycemia (p = 0.02) and insulin secretion (p = 0.04) were even reduced with high compared with low ET. HOMA–IR was impaired with OF and improved with CR, whereas ET had no effect on fasting insulin sensitivity. A higher ET led to lower postprandial glucose and insulin levels under conditions of CR and OF.

Conclusion

Low-intensity physical activity can significantly improve postprandial glycemic response of healthy individuals, independent of energy balance.
Potent delivery of an MMP inhibitor to the tumor microenvironment with thermosensitive liposomes for the suppression of metastasis and angiogenesis
Authors: Lyu Yaqi , Xiao Qingqing , Yin Lifang , Yang Lei , He Wei
Published: August 2019

Metastasis is a major cause of chemotherapeutic failure and death. Degradation of a specific component of the extracellular matrix (ECM) by matrix metalloproteinases (MMPs) affects the physical barrier of the tumor microenvironment (TME) and induces metastasis. Here, lysolipid-containing thermosensitive liposomes (LTSLs) were prepared to deliver an MMP inhibitor, marimastat (MATT), to the TME to inhibit MMP activity and expression. LTSLs rapidly released their payloads at 42 °C. Compared with the saline control, MATT-LTSLs exhibited enhanced accumulation in the tumor and a 20-fold decrease in tumor growth in 4T1 tumor-bearing mice; moreover, MATT-LTSLs reduced MMP-2 and MMP-9 activity by 50% and 43%, respectively, and downregulated MMP-2 and MMP-9 expression in vivo by 30% and 43%, respectively. Most importantly, MATT-LTSL treatment caused a 7-fold decrease in metastatic lung nodules and a 6-fold reduction in microvessels inside the tumor. We believe this study provides an effective approach for the suppression of metastasis, and the use of a cytotoxic agent in combination with MATT is a potential strategy for metastatic cancer treatment.
Horizontally transmitted symbiont populations in deep-sea mussels are genetically isolated
Authors: Romero Picazo Devani , Dagan Tal , Ansorge Rebecca , Petersen Jillian M , Dubilier Nicole , Kupczok Anne
Published: August 2019

Eukaryotes are habitats for bacterial organisms where the host colonization and dispersal among individual hosts have consequences for the bacterial ecology and evolution. Vertical symbiont transmission leads to geographic isolation of the microbial population and consequently to genetic isolation of microbiotas from individual hosts. In contrast, the extent of geographic and genetic isolation of horizontally transmitted microbiota is poorly characterized. Here we show that chemosynthetic symbionts of individual Bathymodiolus brooksi mussels constitute genetically isolated subpopulations. The reconstruction of core genome-wide strains from high-resolution metagenomes revealed distinct phylogenetic clades. Nucleotide diversity and strain composition vary along the mussel life span and individual hosts show a high degree of genetic isolation. Our results suggest that the uptake of environmental bacteria is a restricted process in B. brooksi, where self-infection of the gill tissue results in serial founder effects during symbiont evolution. We conclude that bacterial colonization dynamics over the host life cycle is thus an important determinant of population structure and genome evolution of horizontally transmitted symbionts.
Chemosymbiotic bivalves contribute to the nitrogen budget of seagrass ecosystems
Authors: Cardini Ulisse , Bartoli Marco , Lücker Sebastian , Mooshammer Maria , Polzin Julia , Lee Raymond W , Micić Vesna , Hofmann Thilo , Weber Miriam , Petersen Jillian M
Published: August 2019

In many seagrass sediments, lucinid bivalves and their sulfur-oxidizing symbionts are thought to underpin key ecosystem functions, but little is known about their role in nutrient cycles, particularly nitrogen. We used natural stable isotopes, elemental analyses, and stable isotope probing to study the ecological stoichiometry of a lucinid symbiosis in spring and fall. Chemoautotrophy appeared to dominate in fall, when chemoautotrophic carbon fixation rates were up to one order of magnitude higher as compared with the spring, suggesting a flexible nutritional mutualism. In fall, an isotope pool dilution experiment revealed carbon limitation of the symbiosis and ammonium excretion rates up to tenfold higher compared with fluxes reported for nonsymbiotic marine bivalves. These results provide evidence that lucinid bivalves can contribute substantial amounts of ammonium to the ecosystem. Given the preference of seagrasses for this nitrogen source, lucinid bivalves’ contribution may boost productivity of these important blue carbon ecosystems.
The transcriptional landscape of lncRNAs reveals the oncogenic function of LINC00511 in ER-negative breast cancer
Authors: Zhang Jian , Sui Shiyao , Wu Hao , Zhang Jinfeng , Zhang Xingda , Xu Shouping , Pang Da
Published: August 2019

Advances in the molecular characteristics of cancers have facilitated the classification system from morphology to molecular characteristic-based subtypes. Cancer profiling has expanded in its focus from protein-coding genes to noncoding RNAs, with advances in the depth and quality of transcriptome sequencing. Here, we examined the profiles of long noncoding RNAs (lncRNAs) according to breast cancer subtype categories in The Cancer Genome Atlas (TCGA) database to identify a cohort of breast cancer- and oestrogen receptor (ER)-negative-associated lncRNAs. According to the prioritization of variation in ER-negative-associated lncRNAs, we identified and investigated the role of LINC00511 in breast cancer. We determined that high LINC00511 expression was an unfavourable prognostic factor for patients with breast cancer. Furthermore, LINC00511 promoted tumour growth by accelerating the G1/S transition and inhibiting apoptosis. At the transcriptional level, ER deficiency directly affected the expression of LINC00511 activated by transcription factor AP-2 (TFAP-2) in breast cancer cells. Moreover, mechanistic investigations demonstrated that ER-negative-associated LINC00511 interacted with enhancer of zeste homologue 2 (EZH2, the catalytic subunit of polycomb repressive complex 2, PRC2) and recruited PRC2 to mediate histone methylation, contributing to the repression of CDKN1B in the nucleus. This process resulted in altered ER-negative breast cancer cell biology. By highlighting the oncogenic function of LINC00511, we revealed the role of lncRNAs in regulating the network of cell cycle control in ER-negative breast cancer and suggested the exploitation of LINC00511 as an anticancer therapy in the future.
Diamond-Blackfan anemia caused by chromosome 1p22 deletion encompassing RPL5
Authors: Tominaga Makiko , Hamanoue Satoshi , Goto Hiroaki , Saito Toshiyuki , Nagai Jun-ichi , Masuno Mitsuo , Umeda You , Kurosawa Kenji
Published: August 2019

Diamond-Blackfan anemia (DBA) is an inherited anemia with multiple congenital malformations, and mutations in ribosomal protein genes have been identified as the underlying cause. We describe a female patient with mild DBA due to 1p22 deletion, encompassing the gene encoding 60S ribosomal protein L5 (RPL5). Considering previously reported cases together with our patient, we suggest that RPL5 haploinsufficiency might cause a less severe form of DBA than loss-of-function mutations.
Computer simulations of food oral processing to engineer teeth cleaning
Authors: Skamniotis C. G. , Elliott M. , Charalambides M. N.
Published: August 2019

Oral biofilm accumulation in pets is a growing concern. It is desirable to address this problem via non-invasive teeth cleaning techniques, such as through friction between teeth and food during chewing. Therefore, pet food design tools are needed towards optimising cleaning efficacy. Developing such tools is challenging, as several parameters affecting teeth cleaning should be considered: the food’s complex mechanical response, the contacting surfaces topology as well as the wide range of masticatory and anatomical characteristics amongst breeds. We show that Finite Element (FE) models can efficiently account for all these parameters, through the simulation of food deformation and fracture during the first bite. This reduces the need for time consuming and costly in-vivo or in-vitro trials. Our in-silico model is validated through in-vitro tests, demonstrating that the initial oral processing stage can be engineered through computers with high fidelity.
Identification of drug-specific public TCR driving severe cutaneous adverse reactions
Authors: Pan Ren-You , Chu Mu-Tzu , Wang Chuang-Wei , Lee Yun-Shien , Lemonnier Francois , Michels Aaron W. , Schutte Ryan , Ostrov David A. , Chen Chun-Bing , Phillips Elizabeth Jane , Mallal Simon Alexander , Mockenhaupt Maja , Bellón Teresa , Tassaneeyakul Wichittra , White Katie D. , Roujeau Jean-Claude , Chung Wen-Hung , Hung Shuen-Iu
Published: August 2019

Drug hypersensitivity such as severe cutaneous adverse reactions (SCAR), including Stevens–Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN), could be life-threatening. Here, we enroll SCAR patients to investigate the T cell receptor (TCR) repertoire by next-generation sequencing. A public αβTCR is identified from the cytotoxic T lymphocytes of patients with carbamazepine-SJS/TEN, with its expression showing drug/phenotype-specificity and an bias for HLA-B*15:02. This public αβTCR has binding affinity for carbamazepine and its structural analogs, thereby mediating the immune response. Adoptive transfer of T cell expressing this public αβTCR toHLA-B*15:02transgenic mice receiving oral administration of carbamazepine induces multi-organ injuries and symptoms mimicking SCAR, including hair loss, erythema, increase of inflammatory lymphocytes in the skin and blood, and liver and kidney dysfunction. Our results not only demonstrate an essential role of TCR in the immune synapse mediating SCAR, but also implicate potential clinical applications and development of therapeutics.
Quantifying the impact of uncertainty on threat management for biodiversity
Authors: Nicol Sam , Brazill-Boast James , Gorrod Emma , McSorley Adam , Peyrard Nathalie , Chadès Iadine
Published: August 2019

With inadequate resources to manage the threats facing biodiversity worldwide, achieving projected management outcomes is critical for efficient resource allocation and species recovery. Despite this, conservation plans to mitigate threats rarely articulate the likelihood of management success. Here we develop a general value of information approach to quantify the impact of uncertainty on 20 threatening processes affecting 976 listed species and communities. To our knowledge, this is the most comprehensive quantification of the impacts of uncertainty on threat management. We discover that, on average, removing uncertainty about management effectiveness could triple the gain in persistence achieved by managing under current uncertainty. Management of fire, invasive animals and a plant pathogen are most impeded by uncertainty; management of invasive plants is least impacted. Our results emphasise the tremendous importance of reducing uncertainty about species responses to management, and show that failure to consider management effectiveness wastes resources and impedes species recovery.
Past–future information bottleneck for sampling molecular reaction coordinate simultaneously with thermodynamics and kinetics
Authors: Wang Yihang , Ribeiro João Marcelo Lamim , Tiwary Pratyush
Published: August 2019

The ability to rapidly learn from high-dimensional data to make reliable bets about the future is crucial in many contexts. This could be a fly avoiding predators, or the retina processing gigabytes of data to guide human actions. In this work we draw parallels between these and the efficient sampling of biomolecules with hundreds of thousands of atoms. For this we use the Predictive Information Bottleneck framework used for the first two problems, and re-formulate it for the sampling of biomolecules, especially when plagued with rare events. Our method uses a deep neural network to learn the minimally complex yet most predictive aspects of a given biomolecular trajectory. This information is used to perform iteratively biased simulations that enhance the sampling and directly obtain associated thermodynamic and kinetic information. We demonstrate the method on two test-pieces, studying processes slower than milliseconds, calculating free energies, kinetics and critical mutations.
Comprehensive transcriptomic analysis of cell lines as models of primary tumors across 22 tumor types
Authors: Yu K. , Chen B. , Aran D. , Charalel J. , Yau C. , Wolf D. M. , van ‘t Veer L. J. , Butte A. J. , Goldstein T. , Sirota M.
Published: August 2019

Cancer cell lines are a cornerstone of cancer research but previous studies have shown that not all cell lines are equal in their ability to model primary tumors. Here we present a comprehensive pan-cancer analysis utilizing transcriptomic profiles from The Cancer Genome Atlas and the Cancer Cell Line Encyclopedia to evaluate cell lines as models of primary tumors across 22 tumor types. We perform correlation analysis and gene set enrichment analysis to understand the differences between cell lines and primary tumors. Additionally, we classify cell lines into tumor subtypes in 9 tumor types. We present our pancreatic cancer results as a case study and find that the commonly used cell line MIA PaCa-2 is transcriptionally unrepresentative of primary pancreatic adenocarcinomas. Lastly, we propose a new cell line panel, the TCGA-110-CL, for pan-cancer studies. This study provides a resource to help researchers select more representative cell line models.
Blood stem cell-forming haemogenic endothelium in zebrafish derives from arterial endothelium
Authors: Bonkhofer Florian , Rispoli Rossella , Pinheiro Philip , Krecsmarik Monika , Schneider-Swales Janina , Tsang Ingrid Ho Ching , de Bruijn Marella , Monteiro Rui , Peterkin Tessa , Patient Roger
Published: August 2019

Haematopoietic stem cells are generated from the haemogenic endothelium (HE) located in the floor of the dorsal aorta (DA). Despite being integral to arteries, it is controversial whether HE and arterial endothelium share a common lineage. Here, we present a transgenic zebrafish runx1 reporter line to isolate HE and aortic roof endothelium (ARE)s, excluding non-aortic endothelium. Transcriptomic analysis of these populations identifies Runx1-regulated genes and shows that HE initially expresses arterial markers at similar levels to ARE. Furthermore, runx1 expression depends on prior arterial programming by the Notch ligand dll4. Runx1−/− mutants fail to downregulate arterial genes in the HE, which remains integrated within the DA, suggesting that Runx1 represses the pre-existing arterial programme in HE to allow progression towards the haematopoietic fate. These findings strongly suggest that, in zebrafish, aortic endothelium is a precursor to HE, with potential implications for pluripotent stem cell differentiation protocols for the generation of transplantable HSCs.
Manganese and iron deficiency in Southern Ocean Phaeocystis antarctica populations revealed through taxon-specific protein indicators
Authors: Wu Miao , McCain J. Scott P. , Rowland Elden , Middag Rob , Sandgren Mats , Allen Andrew E. , Bertrand Erin M.
Published: August 2019

Iron and light are recognized as limiting factors controlling Southern Ocean phytoplankton growth. Recent field-based evidence suggests, however, that manganese availability may also play a role. Here we examine the influence of iron and manganese on protein expression and physiology in Phaeocystis antarctica, a key Antarctic primary producer. We provide taxon-specific proteomic evidence to show that in-situ Southern Ocean Phaeocystis populations regularly experience stress due to combined low manganese and iron availability. In culture, combined low iron and manganese induce large-scale changes in the Phaeocystis proteome and result in reorganization of the photosynthetic apparatus. Natural Phaeocystis populations produce protein signatures indicating late-season manganese and iron stress, consistent with concurrently observed stimulation of chlorophyll production upon additions of manganese or iron. These results implicate manganese as an important driver of Southern Ocean productivity and demonstrate the utility of peptide mass spectrometry for identifying drivers of incomplete macronutrient consumption.
Microbial carbon use efficiency predicted from genome-scale metabolic models
Authors: Saifuddin Mustafa , Bhatnagar Jennifer M. , Segrè Daniel , Finzi Adrien C.
Published: August 2019

Respiration by soil bacteria and fungi is one of the largest fluxes of carbon (C) from the land surface. Although this flux is a direct product of microbial metabolism, controls over metabolism and their responses to global change are a major uncertainty in the global C cycle. Here, we explore an in silico approach to predict bacterial C-use efficiency (CUE) for over 200 species using genome-specific constraint-based metabolic modeling. We find that potential CUE averages 0.62 ± 0.17 with a range of 0.22 to 0.98 across taxa and phylogenetic structuring at the subphylum levels. Potential CUE is negatively correlated with genome size, while taxa with larger genomes are able to access a wider variety of C substrates. Incorporating the range of CUE values reported here into a next-generation model of soil biogeochemistry suggests that these differences in physiology across microbial taxa can feed back on soil-C cycling.
Mild replication stress causes chromosome mis-segregation via premature centriole disengagement
Authors: Wilhelm Therese , Olziersky Anna-Maria , Harry Daniela , De Sousa Filipe , Vassal Helène , Eskat Anja , Meraldi Patrick
Published: August 2019

Replication stress, a hallmark of cancerous and pre-cancerous lesions, is linked to structural chromosomal aberrations. Recent studies demonstrated that it could also lead to numerical chromosomal instability (CIN). The mechanism, however, remains elusive. Here, we show that inducing replication stress in non-cancerous cells stabilizes spindle microtubules and favours premature centriole disengagement, causing transient multipolar spindles that lead to lagging chromosomes and micronuclei. Premature centriole disengagement depends on the G2 activity of the Cdk, Plk1 and ATR kinases, implying a DNA-damage induced deregulation of the centrosome cycle. Premature centriole disengagement also occurs spontaneously in some CIN+ cancer cell lines and can be suppressed by attenuating replication stress. Finally, we show that replication stress potentiates the effect of the chemotherapeutic agent taxol, by increasing the incidence of multipolar cell divisions. We postulate that replication stress in cancer cells induces numerical CIN via transient multipolar spindles caused by premature centriole disengagement.
Experimental test of error-tradeoff uncertainty relation using a continuous-variable entangled state
Authors: Liu Yang , Ma Zhihao , Kang Haijun , Han Dongmei , Wang Meihong , Qin Zhongzhong , Su Xiaolong , Peng Kunchi
Published: August 2019

Heisenberg’s original uncertainty relation is related to measurement effect, which is different from the preparation uncertainty relation. However, it has been shown that Heisenberg’s error disturbance uncertainty relation is not valid in some cases. We experimentally test the error-tradeoff uncertainty relation by using a continuous-variable Gaussian Einstein–Podolsky–Rosen (EPR)-entangled state. Based on the quantum correlation between the two entangled optical beams, the errors on amplitude and phase quadratures of one EPR optical beam coming from joint measurement are estimated, respectively, which are used to verify the error–tradeoff relation. Especially, the error–tradeoff relation for error-free measurement of one observable is verified in our experiment. We also verify the error–tradeoff relations for nonzero errors and mixed state by introducing loss on one EPR beam. Our experimental results demonstrate that Heisenberg’s error–tradeoff relation is violated in some cases for a continuous-variable system, while the Ozawa’s and Branciard’s relations are valid.
Magnetism and in-gap states of 3d transition metal atoms on superconducting Re
Authors: Schneider Lucas , Steinbrecher Manuel , Rózsa Levente , Bouaziz Juba , Palotás Krisztián , dos Santos Dias Manuel , Lounis Samir , Wiebe Jens , Wiesendanger Roland
Published: August 2019

Magnetic atoms on heavy-element superconducting substrates are potential building blocks for realizing topological superconductivity in one- and two-dimensional atomic arrays. Their localized magnetic moments induce so-called Yu-Shiba-Rusinov (YSR) states inside the energy gap of the substrate. In the dilute limit, where the electronic states of the array atoms are only weakly coupled, proximity of the YSR states to the Fermi energy is essential for the formation of topological superconductivity in the band of YSR states. Here, we reveal via scanning tunnel spectroscopy and ab initio calculations of a series of 3d transition metal atoms (Mn, Fe, Co) adsorbed on the heavy-element superconductor Re that the increase of the Kondo coupling and sign change in magnetic anisotropy with d-state filling is accompanied by a shift of the YSR states through the energy gap of the substrate and a crossing of the Fermi level. The uncovered systematic trends enable the identification of the most promising candidates for the realization of topological superconductivity in arrays of similar systems.
AqSolDB, a curated reference set of aqueous solubility and 2D descriptors for a diverse set of compounds
Authors: Sorkun Murat Cihan , Khetan Abhishek , Er Süleyman
Published: August 2019

Water is a ubiquitous solvent in chemistry and life. It is therefore no surprise that the aqueous solubility of compounds has a key role in various domains, including but not limited to drug discovery, paint, coating, and battery materials design. Measurement and prediction of aqueous solubility is a complex and prevailing challenge in chemistry. For the latter, different data-driven prediction models have recently been developed to augment the physics-based modeling approaches. To construct accurate data-driven estimation models, it is essential that the underlying experimental calibration data used by these models is of high fidelity and quality. Existing solubility datasets show variance in the chemical space of compounds covered, measurement methods, experimental conditions, but also in the non-standard representations, size, and accessibility of data. To address this problem, we generated a new database of compounds, AqSolDB, by merging a total of nine different aqueous solubility datasets, curating the merged data, standardizing and validating the compound representation formats, marking with reliability labels, and providing 2D descriptors of compounds as a Supplementary Resource.
Brain-behaviour modes of covariation in healthy and clinically depressed young people
Authors: Mihalik Agoston , Ferreira Fabio S. , Rosa Maria J. , Moutoussis Michael , Ziegler Gabriel , Monteiro Joao M. , Portugal Liana , Adams Rick A. , Romero-Garcia Rafael , Vértes Petra E. , Kitzbichler Manfred G. , Váša František , Vaghi Matilde M. , Bullmore Edward T. , Fonagy Peter , Goodyer Ian M. , Jones Peter B. ,   NSPN Consortium, Hauser Tobias , Neufeld Sharon , Clair Michelle St , Whitaker Kirstie , Inkster Becky , Prabhu Gita , Ooi Cinly , Toseeb Umar , Widmer Barry , Bhatti Junaid , Villis Laura , Alrumaithi Ayesha , Birt Sarah , Bowler Aislinn , Cleridou Kalia , Dadabhoy Hina , Davies Emma , Firkins Ashlyn , Granville Sian , Harding Elizabeth , Hopkins Alexandra , Isaacs Daniel , King Janchai , Kokorikou Danae , Maurice Christina , McIntosh Cleo , Memarzia Jessica , Mills Harriet , O’Donnell Ciara , Pantaleone Sara , Scott Jenny , Fearon Pasco , Suckling John , van Harmelen Anne-Laura , Kievit Rogier , Dolan Raymond , Mourão-Miranda Janaina
Published: August 2019

Understanding how variations in dimensions of psychometrics, IQ and demographics relate to changes in brain connectivity during the critical developmental period of adolescence and early adulthood is a major challenge. This has particular relevance for mental health disorders where a failure to understand these links might hinder the development of better diagnostic approaches and therapeutics. Here, we investigated this question in 306 adolescents and young adults (14–24 y, 25 clinically depressed) using a multivariate statistical framework, based on canonical correlation analysis (CCA). By linking individual functional brain connectivity profiles to self-report questionnaires, IQ and demographic data we identified two distinct modes of covariation. The first mode mapped onto an externalization/internalization axis and showed a strong association with sex. The second mode mapped onto a well-being/distress axis independent of sex. Interestingly, both modes showed an association with age. Crucially, the changes in functional brain connectivity associated with changes in these phenotypes showed marked developmental effects. The findings point to a role for the default mode, frontoparietal and limbic networks in psychopathology and depression.
Early Cellular Responses of Prostate Carcinoma Cells to Sepantronium Bromide (YM155) Involve Suppression of mTORC1 by AMPK
Authors: Danielpour David , Gao Zhaofeng , Zmina Patrick M. , Shankar Eswar , Shultes Benjamin C. , Jobava Raul , Welford Scott M. , Hatzoglou Maria
Published: August 2019

The imidazolium compound YM155, first discovered as a potent inhibitor of Survivin, effectively kills many carcinomas in preclinical models. However, the upstream signaling mechanism triggered by YM155 remains unclear. Here we studied early signaling responses in vitro in prostate and renal cancer cell lines in a dose-dependent manner. We found that YM155 rapidly activates the retinoblastoma protein, correlating with the loss of expression of all three Cyclin Ds. Using Western blot, various selective chemical inhibitors and q-PCR, we show that YM155-mediated decrease in protein levels of Cyclin Ds, Survivin and Mcl-1 is independent of transcription or proteasomal control mechanisms. Moreover, we provide the first evidence that YM155 changes the phosphorylation status of known mTOR-target proteins involved in translational control, namely ribosomal protein S6 (rS6) and 4E-BP1. Our data support that YM155 achieves this by blocking mTORC1 via the phosphorylation of Raptor at S792 through activated AMPKα (T172). Furthermore, we also used a polysome profile, supporting that YM155 markedly suppresses cap-dependent translation of mRNAs which include Survivin, Cyclin D1 and Mcl-1. We provide the first evidence that YM155 functions as a potent activator of AMPKα, a robust suppressor of mTORC1 and an attenuator of global protein synthesis.
Human pressures on two estuaries of the Iberian Peninsula are reflected in food web structure
Authors: Donázar-Aramendía I. , Sánchez-Moyano J. E. , García-Asencio I. , Miró J. M. , Megina C. , García-Gómez J. C.
Published: August 2019

As a result of the increased urban and agricultural development in coastal environments, estuaries are among the most modified and threatened aquatic ecosystems. This study used stable isotopes to examine the effects of human impacts by contrasting the food web structures of two Iberian estuaries exposed to different degrees of human pressure. More complex feeding pathways were found in the more altered estuary (Guadalquivir). Greater spread among species along the carbon axis suggests that the primary consumers exploit organic matter with various origins, whereas different nitrogen signals of the secondary consumers suggest that they feed on different suites of prey. In contrast, the similar isotopic signals of secondary consumers in the relatively little influenced estuary (Guadiana) suggests similarity in diet composition and feeding on the same organic matter sources. Understanding trophic interactions in estuaries is vital for defining proper management and conservation, and the preliminary data provided here are one step in this direction.
ANO5 mutations in the Polish limb girdle muscular dystrophy patients: Effects on the protein structure
Authors: Jarmula Adam , Łusakowska Anna , Fichna Jakub P. , Topolewska Malgorzata , Macias Anna , Johnson Katherine , Töpf Ana , Straub Volker , Rosiak Edyta , Szczepaniak Krzysztof , Dunin-Horkawicz Stanisław , Maruszak Aleksandra , Kaminska Anna M. , Redowicz Maria Jolanta
Published: August 2019

LGMD2L is a subtype of limb-girdle muscular dystrophy (LGMD), caused by recessive mutations in ANO5, encoding anoctamin-5 (ANO5). We present the analysis of five patients with skeletal muscle weakness for whom heterozygous mutations within ANO5 were identified by whole exome sequencing (WES). Patients varied in the age of the disease onset (from 22 to 38 years) and severity of the morphological and clinical phenotypes. Out of the nine detected mutations one was novel (missense p.Lys132Met, accompanied by p.His841Asp) and one was not yet characterized in the literature (nonsense, p.Trp401Ter, accompanied by p.Asp81Gly). The p.Asp81Gly mutation was also identified in another patient carrying a p.Arg758Cys mutation as well. Also, a c.191dupA frameshift (p.Asn64LysfsTer15), the first described and common mutation was identified. Mutations were predicted by in silico tools to have damaging effects and are likely pathogenic according to criteria of the American College of Medical Genetics and Genomics (ACMG). Indeed, molecular modeling of mutations revealed substantial changes in ANO5 conformation that could affect the protein structure and function. In addition, variants in other genes associated with muscle pathology were identified, possibly affecting the disease progress. The presented data indicate that the identified ANO5 mutations contribute to the observed muscle pathology and broaden the genetic spectrum of LGMD myopathies.
Ex vivo assessment of bicuspidization repair in treating severe functional tricuspid regurgitation: a stereo-scopic PIV study
Authors: Nguyen Yen Ngoc , Kabinejadian Foad , Ismail Munirah , Kong William Kok-Fai , Tay Edgar Lik Wui , Leo Hwa Liang
Published: August 2019

There has been a resurgence of interest in the treatment of severe functional tricuspid regurgitation (FTR) due to the awareness of its poor outcomes and potential percutaneous therapies. Kay bicuspidization has been adapted in percutaneous therapies but its clinical outcome remains uncertain. The present study evaluates the efficacy of Kay repair in a novel ex vivo pulsatile system. Porcine tricuspid valve (TV) (n = 3) was extracted and incorporated into a patient-specific silicon right ventricle (RV) emulating severe FTR, on which Kay repair was subsequently performed. TV area metrics and RV hemodynamic assessment by means of stereo-scopic particle image velocimetry were quantified in both FTR and post-repair conditions. Bicuspidization led to significant increase in cardiac output although the overall increment due to this approach alone was generally small, possibly due to existence of residual TR and the large reduction in TV opening area. Kinetic energy and viscous loss levels were increased post-repair, especially during diastolic filling. Main vortex structures generally maintained post-procedural. However, there was enhanced swirling motion in larger RV domain. Although this might reduce mural-thrombus risk, the relatively more complex vortex phenomenon likely resulted in elevated viscous loss observed and may potentially impact long-term adaptation. The RV hemodynamic alteration after tricuspid repair could be used to predict the success of these future transcatheter solutions.
A promising form-stable phase change material prepared using cost effective pinecone biochar as the matrix of palmitic acid for thermal energy storage
Authors: Wan Ye-chao , Chen Yan , Cui Zhi-xing , Ding Han , Gao Shu-feng , Han Zhi , Gao Jun-kai
Published: August 2019

A promising new form-stable phase change material (PA/PB) was fabricated using pinecone biochar (PB) as the supporting material of palmitic acid (PA). The biochar of PB with large surface area was produced by forest residue of pinecone, and it was cheap, environment friendly and easy to prepare. The PB was firstly utilized as the supporter of PA and the characterizations of PA/PB were analyzed by the BET, SEM, XRD, DSC, TGA, FT-IR and thermal conductivity tester. The results demonstrated that the PA was physically absorbed by the PB and the crystal structure of the PA was not destroyed. The results of DSC showed that the fusing and crystallization points of the form-stable phase change material with the maximum content of PA (PA/PB-4) were 59.25 °C and 59.13 °C, and its fusing and freezing latent heat were 84.74 kJ/kg and 83.81 kJ/kg, respectively. The results of TGA suggested that the thermal stability of the PA/PB-4 composite was excellent, which could be used for the applications of thermal energy storage. Furthermore, the thermal conductivity of PA/PB-4 was 0.3926 W/(m∙K), which was increased by 43.76% compared with that of the pure PA. Thus, the study results indicated that the PA/PB-4 had great potential for thermal energy storage applications.
The droplet size of emulsion adjuvants has significant impact on their potency, due to differences in immune cell-recruitment and -activation
Authors: Shah Ruchi R. , Taccone Marianna , Monaci Elisabetta , Brito Luis A. , Bonci Alessandra , O’Hagan Derek T. , Amiji Mansoor M. , Seubert Anja
Published: August 2019

Self-emulsification is routinely used for oral delivery of lipophilic drugs in vivo, with the emulsion forming in vivo. We modified this technique to prepare novel oil-in-water emulsions of varying droplet size and composition on bench to enable adjuvanted vaccine delivery. We used these formulations to show that smaller droplets (20 nm) were much less effective as adjuvants for an influenza vaccine in mice than the emulsion droplet size of commercial influenza vaccine adjuvants (~160 nm). This was unexpected, given the many claims in the literature of the advantages of smaller particulates. We also undertook cell-recruitment mechanistic studies at site of injection and draining lymph nodes to directly address the question of why the smaller droplets were less effective. We discovered that emulsion droplet size and composition have a considerable impact on the ability to recruit immune cells to the injection site. We believe that further work is warranted to more extensively explore the question of whether, the smaller is not ‘better’, is a more common observation for particulate adjuvants.
Heart Rate Variability reveals the fight between racially biased and politically correct behaviour
Authors: Di Palma M. , Arcangeli E. , Lattanzi D. , Gabbiadini A. , Gallucci M. , Cuppini R. , Minelli A. , Berlingeri M.
Published: August 2019

In this study, we explored vagally-mediated heart rate variability (vmHRV) responses, a psychophysiological index of cognitive self-regulatory control, to map the dynamics associated with empathic responses for pain towards an out-group member. Accordingly, Caucasian participants were asked to judge the experience of African and Caucasian actors touched with either a neutral or a harmful stimulus. Results showed that (1) explicit judgment of pain intensity in African actors yielded higher rating score and (2) took longer time compared to Caucasian actors, (3) these behavioural outcomes were associated with a significant increment of RMSSD, Log-HF-HRV and HF-HRV n.u., (4) resting HF-HRV n.u. predicted the participants’ lag-time to judge painful stimulations delivered to African actors. Interestingly, these dynamics were associated with a measure of implicit racial attitudes and were, in part, abolished when participants performed a concurrent task during videos presentation. Taken together our results support the idea that a cognitive effort is needed to self-regulate our implicit attitude as predicted by the ‘Contrasting Forces Model’.
Polarization dependence of second harmonic generation from plasmonic nanoprism arrays
Authors: Raygoza-Sánchez K. Y. , Rocha-Mendoza I. , Segovia P. , Krasavin A. V. , Marino G. , Cesca T. , Michieli N. , Mattei G. , Zayats A. V. , Rangel-Rojo R.
Published: August 2019

The second order nonlinear optical response of gold nanoprisms arrays is investigated by means of second harmonic generation (SHG) experiments and simulations. The polarization dependence of the nonlinear response exhibits a 6-fold symmetry, attributed to the local field enhancement through the excitation of the surface plasmon resonances in bow-tie nanoantennas forming the arrays. Experiments show that for polarization of the input light producing excitation of the plasmonic resonances in the bow-tie nanoantennas, the SHG signal is enhanced; this despite the fact that the linear absorption spectrum is not dependent on polarization. The results are confirmed by electrodynamic simulations which demonstrate that SHG is also determined by the local field distribution in the nanoarrays. Moreover, the maximum of SHG intensity is observed at slightly off-resonance excitation, as implemented in the experiments, showing a close relation between the polarization dependence and the structure of the material, additionally revealing the importance of the presence of non-normal electric field components as under focused beam and oblique illumination.
Development of a viability digital PCR protocol for the selective detection and quantification of live Erwinia amylovora cells in cankers
Authors: Santander Ricardo D. , Meredith Christopher L. , Aćimović Srđan G.
Published: August 2019

Fire blight is a devastating disease of apple and pear caused by the bacterium Erwinia amylovora. One of its main symptoms is canker formation on perennial tissues which may lead to the death of limbs and/or the entire tree. E. amylovora overwinters in cankers which play an important role in initiating fire blight epidemics. However, knowledge of pathogen biology in cankers is scarce, in part due to limitations of classical microbiology methods and the inability of most molecular techniques to distinguish live from dead cells. In this work, a viability digital PCR (v-dPCR) protocol using propidium monoazide (PMA) was developed, allowing for the first time the selective detection and absolute quantification of E. amylovora live cells in apple and pear cankers collected in two time periods. Some key factors affecting the v-dPCR performance were the maceration buffer composition, the target DNA amplicon length, the thermal cycle number and the use of sodium dodecyl sulfate or PMA enhancer for Gram-negative bacteria to improve the effect of PMA. In the future, this methodology could shed light on E. amylovora population dynamics in cankers and provide clues on the effect of management practices, host cultivar, host water/nutritional status, etc., on bacterial survival.
Extended indirect calorimetry with isotopic CO2 sensors for prolonged and continuous quantification of exogenous vs. total substrate oxidation in mice
Authors: Fernández-Calleja José M. S. , Bouwman Lianne M. S. , Swarts Hans J. M. , Oosting Annemarie , Keijer Jaap , van Schothorst Evert M.
Published: August 2019

Indirect calorimetry (InCa) estimates whole-body energy expenditure and total substrate oxidation based on O2 consumption and CO2 production, but does not allow for the quantification of oxidation of exogenous substrates with time. To achieve this, we incorporated 13CO2 and 12CO2 gas sensors into a commercial InCa system and aimed to demonstrate their performance and added value. As a performance indicator, we showed the discriminative oscillations in 13CO2 enrichment associated with food intake in mice fed diets containing naturally low (wheat) vs high (maize) 13C enrichment. To demonstrate the physiological value, we quantified exogenous vs total carbohydrate and fat oxidation continuously, in real time in mice varying in fat mass. Diet-induced obese mice were fed a single liquid mixed meal containing 13C-isotopic tracers of glucose or palmitate. Over 13 h, ~70% glucose and ~48% palmitate ingested were oxidised. Exogenous palmitate oxidation depended on body fat mass, which was not the case for exogenous glucose oxidation. We conclude that extending an InCa system with 13CO2 and 12CO2 sensors provides an accessible and powerful technique for real-time continuous quantification of exogenous and whole-body substrate oxidation in mouse models of human metabolic physiology.