bluuebunny/crossref_metadata_2025 huggingface dataset:
Primary Health Care Pediatricians’ Self-Perception of Theoretical Knowledge and Practical Skills in Life-Threatening Emergencies: A Cross-Sectional Study
Authors: Cernuda Martínez José Antonio , Castro Delgado Rafael , Arcos González Pedro
Published: February 2020

Introduction:

Within out-of-hospital emergencies, Primary Health Care (PHC) pediatricians will likely be the first to provide health care at the scene of a life-threatening emergency (LTE) in children. Pediatricians should be trained to initially intervene, safely and effectively the LTEs, including the activation of Emergency Medical Systems (EMS), an adequate stabilization of patients and transport to the hospital.

Study Objectives:

The aims of this study are to know the training received for out-of-hospital LTEs by PHC pediatricians of the Principality of Asturias (Spain) and the perception they have about their own theoretical knowledge and practical skills in a series of emergency procedures used in LTEs; also, to analyze the differences according to the geographical context of their work.

Methods:

This was a cross-sectional, descriptive, and observational study of a sample of 27 PHC pediatricians from PHC Service of Asturias, Spain, from among the total of 88 pediatricians who make up the staff of pediatricians, conducted from April through May 2019. The survey was designed ad hoc using the Curriculum in Primary Care Pediatrics (CPCP) proposed by the European Confederation of Primary Care Pediatricians (ECPCP; Europe), which indicates the theoretical and practical procedures that must be acquired by the PHC pediatricians. It is composed of 30 procedures or techniques employed in LTEs using a 11-point Likert scale rating to detect their self-perception about theoretical knowledge and practical skills from zero (“Minimum”) to 10 (“Maximum”).

Results:

There are significant differences in the mean of theoretical knowledge and practical skills in many procedures or techniques studied, depending on the different areas of work.

Conclusion:

Asturian pediatricians are generally well-prepared to solve LTEs with a few exceptions. The degree of self-perception and acquisition of general theoretical knowledge and general practical skills in LTEs is heterogeneous, with differences according to the scope of work.
Kant on Feelings, Sensations and the Gap Between Rationality and Morality
Authors: Rueger Alexander
Published: February 2020

In §3 of the Critique of Judgement Kant argues that if the feeling of pleasure were a sensation distinct from whatever representation gives rise to the feeling, then we would be – in the terminology of the Metaphysics of Morals – rational beings (vernünftige Wesen) but not moral beings (Vernunftwesen); we would inescapably (and blamelessly) be hedonists. I reconstruct this at first glance strange argument and suggest, first, that Kant’s actual view of pleasure is an attitudinal theory that avoids the problem of hedonism. Second, the argument of §3 is to be understood in the context of Kant’s emphasis on moral feeling and its cultivation in his writings since the Critique of Practical Reason.
A screening method for sleep disturbances at the end-of-life
Authors: Ibáñez del Prado Celia , Cruzado Juan Antonio
Published: February 2020

Objective

To evaluate sleep disturbances and to verify the accuracy of three screening tests to detect them in patients at the end-of-life admitted in a hospital palliative care unit.

Method

The level of sleep disturbances was evaluated through the Pittsburgh Sleep Quality Index (PSQI) in 150 palliative patients. This questionnaire was the criterion variable for testing the three screening tests used: Edmonton Symptom Assessment System (ESAS-Sleep subscale); the single question “How much do you worry about your sleep problems?” which is answered on a scale of 0–10 (Sleep-Worry-Q) and another single question: “Do you think you have sleep problems?” with two response categories, Yes/No (Sleep-Problem-Q).

Results

According to the PSQI (cut-off point: 8), 87% of patients presented sleep disturbances. The ESAS-Sleep (cut-off point: 3) showed a sensitivity of 0.87, a specificity of 0.58, and an AUC of 0.729; the Sleep-Worry-Q (cut-off point: 4) showed a sensitivity of 0.95, a specificity of 0.68, and an AUC of 0.854; the Sleep-Problem-Q obtained a sensitivity of 0.92 and a specificity of 0.65.

Significance of results

Patients at the end-of-life, near the time of death, have high levels of sleep disturbances that can be detected early, with better diagnostic accuracy, with the Sleep-Worry-Q. Although from a clinical point of view, the application of the Sleep-Problem-Q may be more advantageous, as it presents good diagnostic accuracy, greater simplicity, and brevity.
Bringing The “Ring” Back In: The Politics Of Booty Capitalism
Authors: Broxmeyer Jeffrey D.
Published: February 2020

One striking parallel between the Gilded Age and today is the return of the “ring” as a volatile form of governance. Rings are small bands of entrepreneurs who, through capture of key political institutions, exploit the coalition-building imperatives of party politics to rapidly accumulate large personal fortunes. The vernacular hails from the 1860s and 1870s, when the Tweed Ring, Gold Ring, Whiskey Ring, and Bank Ring, among others, scandalized the public with smash and grab practices. In the Trump era, Paul Manafort's career and the president's family business share many similarities to these classic episodes, both in the contested origin of private wealth and the circulation of profits throughout the political system. Rings thus have a tendency to recur in American political development. When electoral politics becomes financialized, speculators may seize opportunities to extract a hefty surplus from the public domain. In premodern contexts, Max Weber called this plundering phenomenon “booty capitalism.” The variant specific to American electoral institutions highlights a periodic conflict in democratic capitalism that arises over the legitimacy of political wealth accumulation.
A Cross‐System Comparison of Dark Carbon Fixation in Coastal Sediments
Authors: Vasquez‐Cardenas Diana , Meysman Filip J. R. , Boschker Henricus T. S.
Published: February 2020

Dark carbon fixation (DCF) by chemoautotrophic microorganisms can sustain food webs in the seafloor by local production of organic matter independent of photosynthesis. The process has received considerable attention in deep sea systems, such as hydrothermal vents, but the regulation, depth distribution, and global importance of coastal sedimentary DCF have not been systematically investigated. Here we surveyed eight coastal sediments by means of stable isotope probing (13C‐DIC) combined with bacterial biomarkers (phospholipid‐derived fatty acids) and compiled additional rates from literature into a global database. DCF rates in coastal sediments range from 0.07 to 36.30 mmol C m−2 day−1, and there is a linear relation between DCF and water depth. The CO2 fixation ratio (DCF/CO2 respired) also shows a trend with water depth, decreasing from 0.09 in nearshore environments to 0.04 in continental shelf sediments. Five types of depth distributions of chemoautotrophic activity are identified based on the mode of pore water transport (advective, bioturbated, and diffusive) and the dominant pathway of microbial sulfur oxidation. Extrapolated to the global coastal ocean, we estimate a DCF rate of 0.04 to 0.06 Pg C year−1, which is less than previous estimates based on indirect measurements (0.15 Pg C year−1), but remains substantially higher than the global DCF rate at deep sea hydrothermal vents (0.001–0.002 Pg C year−1).
Updated Neutron‐Monitor Yield Function: Bridging Between In Situ and Ground‐Based Cosmic Ray Measurements
Authors: Mishev Alexander L. , Koldobskiy Sergey A. , Kovaltsov Gennady A. , Gil Agnieszka , Usoskin Ilya G.
Published: February 2020

An updated yield function for a standard NM64 neutron monitor (NM) is computed and extended to different atmospheric depths from sea level to 500 g/cm
(
5.7 km altitude) and is presented as lookup tables and a full parametrization. The yield function was validated using the cosmic ray spectra directly measured in space by the AMS‐02 experiment during the period May 2011 through May 2017 and confronted with count rates of all NM64‐type NMs being in operation during this period. Using this approach, stability of all the selected NMs was analyzed for the period 2011–2017. Most of NMs appear very stable and suitable for studies of long‐term solar modulation of cosmic rays. However, some NMs suffer from instabilities like trends, apparent jumps, or strong seasonal waves in the count rates.
Investigating Spectral Distortion of Local Volcano Infrasound by Nonlinear Propagation at Sakurajima Volcano, Japan
Authors: Maher Sean P. , Matoza Robin S. , de Groot‐Hedlin Catherine D. , Gee Kent L. , Fee David , Yokoo Akihiko
Published: February 2020

Sound waves generated by erupting volcanoes can be used to infer important source dynamics, yet acoustic source‐time functions may be distorted during propagation, even at local recording distances (
15 km). The resulting uncertainty in source estimates can be reduced by improving constraints on propagation effects. We aim to quantify potential distortions caused by wave steepening during nonlinear propagation, with the aim of improving the accuracy of volcano‐acoustic source predictions. We hypothesize that wave steepening causes spectral energy transfer away from the dominant source frequency. To test this, we apply a previously developed single‐point, frequency domain, quadspectral density‐based nonlinearity indicator to 30 acoustic signals from Vulcanian explosion events at Sakurajima Volcano, Japan, in an 8‐day data set collected by five infrasound stations in 2013 with 2.3‐ to 6.2‐km range. We model these results with a 2‐D axisymmetric finite‐difference method that includes rigid topography, wind, and nonlinear propagation. Simulation results with flat ground indicate that wave steepening causes up to
2 dB (1% of source level) of cumulative upward spectral energy transfer for Sakurajima amplitudes. Correction for nonlinear propagation may therefore provide a valuable second‐order improvement in accuracy for source parameter estimates. However, simulations with wind and topography introduce variations in the indicator spectra on order of a few decibels. Nonrandom phase relationships generated during propagation or at the source may be misinterpreted as nonlinear spectral energy transfer. The nonlinearity indicator is therefore best suited to small source‐receiver distances (e.g.,
2 km) and volcanoes with simple sources (e.g., gas‐rich strombolian explosions) and topography.
FARP1 boosts CDC42 activity from integrin αvβ5 signaling and correlates with poor prognosis of advanced gastric cancer
Authors: Hirano Takuro , Shinsato Yoshinari , Tanabe Kan , Higa Nayuta , Kamil Muhammad , Kawahara Kohichi , Yamamoto Masatatsu , Minami Kentaro , Shimokawa Michiko , Arigami Takaaki , Yanagita Shigehiro , Matushita Daisuke , Uenosono Yoshikazu , Ishigami Sumiya , Kijima Yuko , Maemura Kosei , Kitazono Ikumi , Tanimoto Akihide , Furukawa Tatsuhiko , Natsugoe Shoji
Published: February 2020

Considering the poor prognosis of most advanced cancers, prevention of invasion and metastasis is essential for disease control. Ras homologous (Rho) guanine exchange factors (GEFs) and their signaling cascade could be potential therapeutic targets in advanced cancers. We conducted in silico analyses of The Cancer Genome Atlas expression data to identify candidate Rho-GEF genes showing aberrant expression in advanced gastric cancer and found FERM, Rho/ArhGEF, and pleckstrin domain protein 1 (FARP1) expression is related to poor prognosis. Analyses in 91 clinical advanced gastric cancers of the relationship of prognosis and pathological factors with immunohistochemical expression of FARP1 indicated that high expression of FARP1 is significantly associated with lymphatic invasion, lymph metastasis, and poor prognosis of the patients (P = 0.025). In gastric cancer cells, FARP1 knockdown decreased cell motility, whereas FARP1 overexpression promoted cell motility and filopodium formation via CDC42 activation. FARP1 interacted with integrin β5, and a potent integrin αvβ5 inhibitor (SB273005) prevented cell motility in only high FARP1-expressing gastric cancer cells. These results suggest that the integrin αvβ5-FARP1-CDC42 axis plays a crucial role in gastric cancer cell migration and invasion. Thus, regulatory cascade upstream of Rho can be a specific and promising target of advanced cancer treatment.
p73 – NAV3 axis plays a critical role in suppression of colon cancer metastasis
Authors: Uboveja Apoorva , Satija Yatendra Kumar , Siraj Fouzia , Sharma Ira , Saluja Daman
Published: February 2020

p73 is a member of the p53 tumor suppressor family, which transactivates p53-responsive genes and mediates DNA damage response. Recent evidences suggest that p73 exerts its tumor suppressor functions by suppressing metastasis, but the exact mechanism remains unknown. Here, we identify Navigator-3 (NAV3), a microtubule-binding protein, as a novel transcriptional target of p73, which gets upregulated by DNA damage in a p73-dependent manner and plays a vital role in p73-mediated inhibition of cancer cell invasion, migration, and metastasis. Induction of p73 in response to DNA damage leads to rapid increase in endogenous NAV3 mRNA and protein levels. Through bioinformatic analysis, we identified two p73-binding sites in NAV3 promoter. Consistent with this, p73 binding to NAV3 promoter was confirmed through luciferase, Chromatin Immunoprecipitation, and site-directed mutagenesis assays. Abrogation of NAV3 and p73 expression significantly increased the invasion and migration rate of colorectal cancer cells as confirmed by wound-healing, cell invasion, and cell migration assays. Also, knockdown of NAV3 decreased the expression of E-cadherin and increased the expression of other prominent mesenchymal markers such as N-cadherin, Snail, Vimentin, and Fibronectin. Immunohistochemistry analysis revealed the downregulation of both NAV3 and p73 expression in metastatic colon cancer tissues as compared to non-metastatic cancer tissues. Additionally, the expression pattern of NAV3 and p73 showed extensively significant correlation in both non-metastatic and metastatic human colon cancer tissue samples. Taken together, our study provide conclusive evidence that Navigator-3 is a direct transcriptional target of p73 and plays crucial role in response to genotoxic stress in p73-mediated inhibition of cancer cell invasion, migration, and metastasis.
Correction: Loss of PARP-1 attenuates diabetic arteriosclerotic calcification via Stat1/Runx2 axis
Authors: Li Peng , Wang Ying , Liu Xue , Liu Bin , Wang Zhao-yang , Xie Fei , Qiao Wen , Liang Er-shun , Lu Qing-hua , Zhang Ming-xiang
Published: February 2020

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
Breathing is coupled with voluntary action and the cortical readiness potential
Authors: Park Hyeong-Dong , Barnoud Coline , Trang Henri , Kannape Oliver A. , Schaller Karl , Blanke Olaf
Published: February 2020

Voluntary action is a fundamental element of self-consciousness. The readiness potential (RP), a slow drift of neural activity preceding self-initiated movement, has been suggested to reflect neural processes underlying the preparation of voluntary action; yet more than fifty years after its introduction, interpretation of the RP remains controversial. Based on previous research showing that internal bodily signals affect sensory processing and ongoing neural activity, we here investigated the potential role of interoceptive signals in voluntary action and the RP. We report that (1) participants initiate voluntary actions more frequently during expiration, (2) this respiration-action coupling is absent during externally triggered actions, and (3) the RP amplitude is modulated depending on the respiratory phase. Our findings demonstrate that voluntary action is coupled with the respiratory system and further suggest that the RP is associated with fluctuations of ongoing neural activity that are driven by the involuntary and cyclic motor act of breathing.
Complete structure of the chemosensory array core signalling unit in an E. coli minicell strain
Authors: Burt Alister , Cassidy C. Keith , Ames Peter , Bacia-Verloop Maria , Baulard Megghane , Huard Karine , Luthey-Schulten Zaida , Desfosses Ambroise , Stansfeld Phillip J. , Margolin William , Parkinson John S. , Gutsche Irina
Published: February 2020

Motile bacteria sense chemical gradients with transmembrane receptors organised in supramolecular signalling arrays. Understanding stimulus detection and transmission at the molecular level requires precise structural characterisation of the array building block known as a core signalling unit. Here we introduce an Escherichia coli strain that forms small minicells possessing extended and highly ordered chemosensory arrays. We use cryo-electron tomography and subtomogram averaging to provide a three-dimensional map of a complete core signalling unit, with visible densities corresponding to the HAMP and periplasmic domains. This map, combined with previously determined high resolution structures and molecular dynamics simulations, yields a molecular model of the transmembrane core signalling unit and enables spatial localisation of its individual domains. Our work thus offers a solid structural basis for the interpretation of a wide range of existing data and the design of further experiments to elucidate signalling mechanisms within the core signalling unit and larger array.
Discovering the genes mediating the interactions between chronic respiratory diseases in the human interactome
Authors: Maiorino Enrico , Baek Seung Han , Guo Feng , Zhou Xiaobo , Kothari Parul H. , Silverman Edwin K. , Barabási Albert-László , Weiss Scott T. , Raby Benjamin A. , Sharma Amitabh
Published: February 2020

The molecular and clinical features of a complex disease can be influenced by other diseases affecting the same individual. Understanding disease-disease interactions is therefore crucial for revealing shared molecular mechanisms among diseases and designing effective treatments. Here we introduce Flow Centrality (FC), a network-based approach to identify the genes mediating the interaction between two diseases in a protein-protein interaction network. We focus on asthma and COPD, two chronic respiratory diseases that have been long hypothesized to share common genetic determinants and mechanisms. We show that FC highlights potential mediator genes between the two diseases, and observe similar outcomes when applying FC to 66 additional pairs of related diseases. Further, we perform in vitro perturbation experiments on a widely replicated asthma gene, GSDMB, showing that FC identifies candidate mediators of the interactions between GSDMB and COPD-associated genes. Our results indicate that FC predicts promising gene candidates for further study of disease-disease interactions.
Cell and tissue manipulation with ultrashort infrared laser pulses in light-sheet microscopy
Authors: de Medeiros Gustavo , Kromm Dimitri , Balazs Balint , Norlin Nils , Günther Stefan , Izquierdo Emiliano , Ronchi Paolo , Komoto Shinya , Krzic Uros , Schwab Yannick , Peri Francesca , de Renzis Stefano , Leptin Maria , Rauzi Matteo , Hufnagel Lars
Published: February 2020

Three-dimensional live imaging has become an indispensable technique in the fields of cell, developmental and neural biology. Precise spatio-temporal manipulation of biological entities is often required for a deeper functional understanding of the underlying biological process. Here we present a home-built integrated framework and optical design that combines three-dimensional light-sheet imaging over time with precise spatio-temporal optical manipulations induced by short infrared laser pulses. We demonstrate their potential for sub-cellular ablation of neurons and nuclei, tissue cauterization and optogenetics by using the Drosophila melanogaster and zebrafish model systems.
Mental health-related conversations on social media and crisis episodes: a time-series regression analysis
Authors: Kolliakou Anna , Bakolis Ioannis , Chandran David , Derczynski Leon , Werbeloff Nomi , Osborn David P. J. , Bontcheva Kalina , Stewart Robert
Published: February 2020

We aimed to investigate whether daily fluctuations in mental health-relevant Twitter posts are associated with daily fluctuations in mental health crisis episodes. We conducted a primary and replicated time-series analysis of retrospectively collected data from Twitter and two London mental healthcare providers. Daily numbers of ‘crisis episodes’ were defined as incident inpatient, home treatment team and crisis house referrals between 2010 and 2014. Higher volumes of depression and schizophrenia tweets were associated with higher numbers of same-day crisis episodes for both sites. After adjusting for temporal trends, seven-day lagged analyses showed significant positive associations on day 1, changing to negative associations by day 4 and reverting to positive associations by day 7. There was a 15% increase in crisis episodes on days with above-median schizophrenia-related Twitter posts. A temporal association was thus found between Twitter-wide mental health-related social media content and crisis episodes in mental healthcare replicated across two services. Seven-day associations are consistent with both precipitating and longer-term risk associations. Sizes of effects were large enough to have potential local and national relevance and further research is needed to evaluate how services might better anticipate times of higher risk and identify the most vulnerable groups.
Prognosis of Vascular Access in Haemodialysis Patients with Autosomal Dominant Polycystic Kidney Disease
Authors: Lee Tsung-Lun , Chen Chun-Fan , Tan Ann Charis , Chan Chia-Hao , Ou Shuo-Ming , Chen Fan-Yu , Yu Ko-Wen , Chen Yung-Tai , Lin Chih-Ching
Published: February 2020

Vascular diseases are commonly observed in patients with autosomal dominant polycystic kidney disease (ADPKD). We aim to investigate the differences in the risk for arteriovenous fistula or graft (AVF/AVG) dysfunction in haemodialysis (HD) patients with and without ADPKD. 557 ADPKD and 1671 non-ADPKD patients were enrolled in the study after propensity score matching. The primary outcome measure is the incidence rate of AVF/AVG dysfunction. The incidence rates and risks of AVF/AVG dysfunction (per 100 person-years) for ADPKD and non-ADPKD patients were (1) 38.83 and 48.99 [SHR = 0.79, P = 0.137], respectively, for within 90 days, (2) 45.85 and 51.31 [SHR = 0.90, P = 0.300], respectively, for within 180 days, (3) 44.42 and 41.40 [SHR = 1.08, P = 0.361], respectively, for within the first year, (4) 27.38 and 24.69 [SHR = 1.09, P = 0.168], respectively, for within 5 years, (5) 17.35 and 13.80 [SHR = 1.19, P = 0.045], respectively, for between the 1st and 10th year, and (6) 25.40 and 21.22 [SHR = 1.14, P = 0.031], respectively, for all periods. ADPKD patients had lower incidence rates of AVF/AVG dysfunction within the first 180 days than non-ADPKD patients, but presented a higher incidence rate after 1 year of AVF/AVG creation and onwards.
Effect of Immune Activation during Early Gestation or Late Gestation on Inhibitory Markers in Adult Male Rats
Authors: Rahman Tasnim , Weickert Cynthia Shannon , Harms Lauren , Meehan Crystal , Schall Ulrich , Todd Juanita , Hodgson Deborah M. , Michie Patricia T. , Purves-Tyson Tertia
Published: February 2020

People with schizophrenia exhibit deficits in inhibitory neurons and cognition. The timing of maternal immune activation (MIA) may present distinct schizophrenia-like phenotypes in progeny. We investigated whether early gestation [gestational day (GD) 10] or late gestation (GD19) MIA, via viral mimetic polyI:C, produces deficits in inhibitory neuron indices (GAD1, PVALB, SST, SSTR2 mRNAs) within cortical, striatal, and hippocampal subregions of male adult rat offspring. In situ hybridisation revealed that polyI:C offspring had: (1) SST mRNA reductions in the cingulate cortex and nucleus accumbens shell, regardless of MIA timing; (2) SSTR2 mRNA reductions in the cortex and striatum of GD19, but not GD10, MIA; (3) no alterations in cortical or striatal GAD1 mRNA of polyI:C offspring, but an expected reduction of PVALB mRNA in the infralimbic cortex, and; (4) no alterations in inhibitory markers in hippocampus. Maternal IL-6 response negatively correlated with adult offspring SST mRNA in cortex and striatum, but not hippocampus. These results show lasting inhibitory-related deficits in cortex and striatum in adult offspring from MIA. SST downregulation in specific cortical and striatal subregions, with additional deficits in somatostatin-related signalling through SSTR2, may contribute to some of the adult behavioural changes resulting from MIA and its timing.
RETRACTED ARTICLE: Insomnia, sleepiness, anxiety and depression among different types of gamers in African countries
Authors: Sosso F. A. Etindele , Kuss D. J. , Vandelanotte C. , Jasso-Medrano J. L. , Husain M. E. , Curcio G. , Papadopoulos D. , Aseem A. , Bhati P. , Lopez-Rosales F. , Becerra J. Ramon , D’Aurizio G. , Mansouri H. , Khoury T. , Campbell M. , Toth A. J.
Published: February 2020

Gaming has increasingly become a part of life in Africa. Currently, no data on gaming disorders or their association with mental disorders exist for African countries. This study for the first time investigated (1) the prevalence of insomnia, excessive daytime sleepiness, anxiety and depression among African gamers, (2) the association between these conditions and gamer types (i.e., non-problematic, engaged, problematic and addicted) and (3) the predictive power of socioeconomic markers (education, age, income, marital status, employment status) on these conditions. 10,566 people from 2 low- (Rwanda, Gabon), 6 lower-middle (Cameroon, Nigeria, Morocco, Tunisia, Senegal, Ivory Coast) and 1 upper-middle income countries (South Africa) completed online questionnaires containing validated measures on insomnia, sleepiness, anxiety, depression and gaming addiction. Results showed our sample of gamers (24 ± 2.8 yrs; 88.64% Male), 30% were addicted, 30% were problematic, 8% were engaged and 32% were non-problematic. Gaming significantly contributed to 86.9% of the variance in insomnia, 82.7% of the variance in daytime sleepiness and 82.3% of the variance in anxiety [p < 0.001]. This study establishes the prevalence of gaming, mood and sleep disorders, in a large African sample. Our results corroborate previous studies, reporting problematic and addicted gamers show poorer health outcomes compared with non-problematic gamers.
Publisher Correction: Cadmium and High-Fat Diet Disrupt Renal, Cardiac and Hepatic Essential Metals
Authors: Young Jamie L. , Yan Xiaofang , Xu Jianxiang , Yin Xinmin , Zhang Xiang , Arteel Gavin E. , Barnes Gregory N. , States J. Christopher , Watson Walter H. , Kong Maiying , Cai Lu , Freedman Jonathan H.
Published: February 2020

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
Genetic manipulation of the pigment pathway in a sea urchin reveals distinct lineage commitment prior to metamorphosis in the bilateral to radial body plan transition
Authors: Wessel Gary M. , Kiyomoto Masato , Shen Tun-Li , Yajima Mamiko
Published: February 2020

Echinoderms display a vast array of pigmentation and patterning in larval and adult life stages. This coloration is thought to be important for immune defense and camouflage. However, neither the cellular nor molecular mechanism that regulates this complex coloration in the adult is known. Here we knocked out three different genes thought to be involved in the pigmentation pathway(s) of larvae and grew the embryos to adulthood. The genes tested were polyketide synthase (PKS), Flavin-dependent monooxygenase family 3 (FMO3) and glial cells missing (GCM). We found that disabling of the PKS gene at fertilization resulted in albinism throughout all life stages and throughout all cells and tissues of this animal, including the immune cells of the coelomocytes. We also learned that FMO3 is an essential modifier of the polyketide. FMO3 activity is essential for larval pigmentation, but in juveniles and adults, loss of FMO3 activity resulted in the animal becoming pastel purple. Linking the LC-MS analysis of this modified pigment to a naturally purple animal suggested a conserved echinochrome profile yielding a pastel purple. We interpret this result as FMO3 modifies the parent polyketide to contribute to the normal brown/green color of the animal, and that in its absence, other biochemical modifications are revealed, perhaps by other members of the large FMO family in this animal. The FMO modularity revealed here may be important in the evolutionary changes between species and for different immune challenges. We also learned that glial cells missing (GCM), a key transcription factor of the endomesoderm gene regulatory network of embryos in the sea urchin, is required for pigmentation throughout the life stages of this sea urchin, but surprisingly, is not essential for larval development, metamorphosis, or maintenance of adulthood. Mosaic knockout of either PKS or GCM revealed spatial lineage commitment in the transition from bilaterality of the larva to a pentaradial body plan of the adult. The cellular lineages identified by pigment presence or absence (wild-type or knock-out lineages, respectively) followed a strict oral/aboral profile. No circumferential segments were seen and instead we observed 10-fold symmetry in the segments of pigment expression. This suggests that the adult lineage commitments in the five outgrowths of the hydropore in the larva are early, complete, fixed, and each bilaterally symmetric. Overall, these results suggest that pigmentation of this animal is genetically determined and dependent on a population of pigment stem cells that are set-aside in a sub-region of each outgrowth of the pentaradial adult rudiment prior to metamorphosis. This study reveals the complex chemistry of pigment applicable to many organisms, and further, provides an insight into the key transitions from bilateral to pentaradial body plans unique to echinoderms.
Quantum-inspired cascaded discrete-time quantum walks with induced chaotic dynamics and cryptographic applications
Authors: Abd El-Latif Ahmed A. , Abd-El-Atty Bassem , Amin Mohamed , Iliyasu Abdullah M.
Published: February 2020

Designing efficient and secure cryptosystems has been a preoccupation for many scientists and engineers for a long time wherein they use chaotic systems to design new cryptosystems. While one dimensional (1-D) chaotic maps possess powerful properties compared to higher dimension ones, they are vulnerable to various attacks due to their small key space, chaotic discontinuous ranges, and degradation in chaotic dynamical behaviours. Moreover, when simulated on a computer, every such chaotic system produces a periodic cycle. Meanwhile, quantum random walks exhibit the potential for deployment in efficient cryptosystem design, which makes it an excellent solution for this problem. In this context, we present a new method for constructing substitution boxes (S-boxes) based on cascaded quantum-inspired quantum walks and chaos inducement. The performance of the proposed S-box scheme is investigated via established S-box evaluation criterion and outcomes suggest that the constructed S-box has significant qualities for viable applications information security. Further, we present an efficient scheme for pseudo-random numbers generation (PRNG) whose sustainability over long periods remedies the periodicity problem associated with traditional cryptographic applications. Furthermore, by combining the two mechanisms, an atypical image encryption scheme is introduced. Simulation results and analysis validate that the proposed image encryption algorithm will offer gains in many cryptographic applications.
Domestication leads to increased predation susceptibility
Authors: Solberg Monica F. , Robertsen Grethe , Sundt-Hansen Line E. , Hindar Kjetil , Glover Kevin A.
Published: February 2020

Domestication involves adapting animals to the human-controlled environment. Genetic changes occurring during the domestication process may manifest themselves in phenotypes that render domesticated animals maladaptive for life in the wild. Domesticated Atlantic salmon frequently interbreed with wild conspecifics, and their offspring display reduced survival in the wild. However, the mechanism(s) contributing to their lower survival in the wild remains a subject of conjecture. Here, we document higher susceptibility to predation by brown trout in fast-growing domesticated salmon, as compared to their slow-growing wild conspecifics, demonstrating that directional selection for increased growth comes at a cost of decreased survival when under the risk of predation, as predicted by the growth/predation risk trade-off. Despite earlier documentation of altered risk-taking behavior, this study demonstrates for the first time that domestication of Atlantic salmon has lead to increased predation susceptibility, and that this consitutes a mechanism underpinning the observed survial differences in the wild.
Seasonal to Inter-Annual Variability of Primary Production in Chesapeake Bay: Prospects to Reverse Eutrophication and Change Trophic Classification
Authors: Harding Lawrence W. , Mallonee Michael E. , Perry Elgin S. , David Miller W. , Adolf Jason E. , Gallegos Charles L. , Paerl Hans W.
Published: February 2020

Estuarine-coastal ecosystems are rich areas of the global ocean with elevated rates of organic matter production supporting major fisheries. Net and gross primary production (NPP, GPP) are essential properties of these ecosystems, characterized by high spatial, seasonal, and inter-annual variability associated with climatic effects on hydrology. Over 20 years ago, Nixon defined the trophic classification of marine ecosystems based on annual phytoplankton primary production (APPP), with categories ranging from “oligotrophic” to “hypertrophic”. Source data consisting of shipboard measurements of NPP and GPP from 1982 to 2004 for Chesapeake Bay in the mid-Atlantic region of the United States supported estimates of APPP from 300 to 500 g C m−2 yr−1, corresponding to “eutrophic” to “hypertrophic” categories. Here, we developed generalized additive models (GAM) to interpolate the limited spatio-temporal resolution of source data. Principal goals were: (1) to develop predictive models of NPP and GPP calibrated to source data (1982 to 2004); (2) to apply the models to historical (1960s, 1970s) and monitoring (1985 to 2015) data with adjustments for nutrient loadings and climatic effects; (3) to estimate APPP from model predictions of NPP; (4) to test effects of simulated reductions of phytoplankton biomass or nutrient loadings on trophic classification based on APPP. Simulated 40% decreases of euphotic-layer chl-a or TN and NO2 + NO3 loadings led to decreasing APPP sufficient to change trophic classification from “eutrophic’ to “mesotrophic” for oligohaline (OH) and polyhaline (PH) salinity zones, and from “hypertrophic” to “eutrophic” for the mesohaline (MH) salinity zone of the bay. These findings show that improved water quality is attainable with sustained reversal of nutrient over-enrichment sufficient to decrease phytoplankton biomass and APPP.
Active Cloaking of a Non-Uniform Scatterer
Authors: Ang Paris , Eleftheriades George V.
Published: February 2020

An object illuminated by an electromagnetic wave can be actively cloaked using a surface conformal array of radiating sources to cancel out scattering. This method is promising as elementary antennas can be used as sources while its active nature can surpass passivity-based performance limitations. While this technique has been conceptually extended to accommodate complex geometries, experimental validation past simple uniform scatterers is lacking. To address this scarcity, the design and experimental demonstration of a low-profile, active cloak capable of concealing a complex, metallic, polygonal target is presented. This cloak is constructed with commercially available monopoles and enclosed within a parallel-plate waveguide-based apparatus to approximate a quasi-2D environment. Performance is then assessed when the target is illuminated at either frontal or oblique incidence by a 1.2 GHz cylindrical wave. Overall, the cloak reduces the target’s scattering cross-section by an average of 7.2 dB at frontal incidence and 8.6 dB at oblique incidence. These results demonstrate the feasibility of this kind of active cloaking for more complex scatterers containing flat surfaces and edges. Further analysis shows that the cloak possesses a functional bandwidth of 14% and can be reconfigured for single frequency operation over 0.8–1.8 GHz.
Co-production of DHA and squalene by thraustochytrid from forest biomass
Authors: Patel Alok , Liefeldt Stephan , Rova Ulrika , Christakopoulos Paul , Matsakas Leonidas
Published: February 2020

Omega-3 fatty acids, and specifically docosahexaenoic acid (DHA), are important and essential nutrients for human health. Thraustochytrids are recognised as commercial strains for nutraceuticals production, they are group of marine oleaginous microorganisms capable of co-synthesis of DHA and other valuable carotenoids in their cellular compartment. The present study sought to optimize DHA and squalene production by the thraustochytrid Schizochytrium limacinum SR21. The highest biomass yield (0.46 g/gsubstrate) and lipid productivity (0.239 g/gsubstrate) were observed with 60 g/L of glucose, following cultivation in a bioreactor, with the DHA content to be 67.76% w/wtotal lipids. To reduce costs, cheaper feedstocks and simultaneous production of various value-added products for pharmaceutical or energy use should be attempted. To this end, we replaced pure glucose with organosolv-pretreated spruce hydrolysate and assessed the simultaneous production of DHA and squalene from S. limacinum SR21. After the 72 h of cultivation period in bioreactor, the maximum DHA content was observed to 66.72% w/wtotal lipids that was corresponded to 10.15 g/L of DHA concentration. While the highest DHA productivity was 3.38 ± 0.27 g/L/d and squalene reached a total of 933.72 ± 6.53 mg/L (16.34 ± 1.81 mg/gCDW). In summary, we show that the co-production of DHA and squalene makes S. limacinum SR21 appropriate strain for commercial-scale production of nutraceuticals.
Characterising the spatial distribution of opportunities and constraints for land sparing in Brazil
Authors: dos Santos Juliana Silveira , Feltran-Barbieri Rafael , Fonte Ellen S. , Balmford Andrew , Maioli Veronica , Latawiec Agnieszka , Strassburg Bernardo B. N. , Phalan Benjamin T.
Published: February 2020

Brazil is a megadiversity country with more tropical forest than any other, and is a leading agricultural producer. The technical potential to reconcile these roles by concentrating agriculture on existing farmland and sparing land for nature is well-established, but the spatial overlap of this potential with conservation priorities and institutional constraints remains poorly understood. We mapped conservation priorities, food production potential and socio-economic variables likely to influence the success of land sparing. Pasture occupies 70% of agricultural land but contributes ≤11% of the domestic food supply. Increasing yields on pasture would add little to Brazil’s food supply but – if combined with concerted conservation and restoration policies – provides the greatest opportunities for reducing land demand. Our study illustrates a method for identifying municipalities where land-sparing policies are most likely to succeed, and those where further effort is needed to overcome constraints such as land tenure insecurity, lack of access to technical advice, labour constraints, and non-compliance with environmental law.
Renoprotective effects of Gushen Jiedu capsule on diabetic nephropathy in rats
Authors: Zhang Lei , Yang Zhirui , Zhao Yidan , Yang Xinyu , Meng Xintong , Liu Juan , Liu Yi , Yan Can , Yan Dan
Published: February 2020

Gushen Jiedu capsule (GSJD) is a formula that has been widely used in traditional Chinese medicine for the prevention and treatment of diabetic nephropathy (DN). However, the mechanism underlying the protective effects of GSJD on DN is still unclear. This study was performed to clarify the therapeutic effects of GSJD on DN and its underlying mechanisms. High-fat diet- and streptozotocin-induced DN rats were treated with or without GSJD suspension by gavage for 8 weeks, and biochemical changes in blood and urine were analysed. Kidneys were isolated for histological, TUNEL and Western blot analysis. Compared to the DN group, the GSJD-treated groups exhibited decreased urinary albumin, ameliorated renal dysfunction, including serum creatinine and blood urea nitrogen, and attenuated total cholesterol, triglyceride and total protein levels. However, there were no significant effects of GSJD on body weight, fasting blood glucose or albuminuria. Histology showed that GSJD could retard the progression of DN and decrease the apoptosis rate from 52% to less than 20%. Western blot analysis showed that GSJD could regulate the mitochondrial apoptotic pathway by downregulating the expression of Bax and upregulating the expression of BCL-2 in the kidneys of DN rats. Moreover, the Akt pathway, an upstream signalling pathway of the BCL-2 family, was also ameliorated by GSJD. Further, the podocyte foot process markers podocin and nephrin were upregulated by GSJD in DN rats. This study demonstrated that GSJD might play a renoprotective role by inhibiting apoptosis and regulating the mitochondrial apoptotic and Akt pathways during pathological changes in DN.
Investigation of DNA variants specific to ROBO2 Isoform ‘a’ in Irish vesicoureteric reflux patients reveals marked CpG island variation
Authors: Darlow John M. , Dobson Mark G. , Green Andrew J. , Puri Prem , Barton David E.
Published: February 2020

ROBO2 gene disruption causes vesicoureteric reflux (VUR) amongst other congenital anomalies. Several VUR patient cohorts have been screened for variants in the ubiquitously expressed transcript, ROBO2b, but, apart from low levels in a few adult tissues, ROBO2a expression is confined to the embryo, and might be more relevant to VUR, a developmental disorder. ROBO2a has an alternative promoter and two alternative exons which replace the first exon of ROBO2b. We screened probands from 251 Irish VUR families for DNA variants in these. The CpG island of ROBO2a, which includes the non-coding first exon, was found to contain a run of six variants abolishing/creating CpG dinucleotides, including a novel variant, present in the VUR cases in one family, that was not present in 592 healthy Irish controls. In three of these positions, the CpG was created by the non-reference allele, and the reference allele was not the nucleotide that would result from spontaneous deamination of methylcytosine to thymine, suggesting that there might have been selection for variability in number of CpGs in this island. This is in marked contrast to the CpG island at the start of ROBO2b, which only contained a single variant that abolishes a CpG.
Holographic molecular binding assays
Authors: Zagzag Yvonne , Soddu M. Francesca , Hollingsworth Andrew D. , Grier David G.
Published: February 2020

We demonstrate that holographic particle characterization can directly detect binding of proteins to functionalized colloidal probe particles by monitoring the associated change in the particles’ size. This label-free molecular binding assay uses in-line holographic video microscopy to measure the diameter and refractive index of individual probe spheres as they flow down a microfluidic channel. Pooling measurements on 104 particles yields the population-average diameter with an uncertainty smaller than 0.5 nm, which is sufficient to detect sub-monolayer coverage by bound proteins. We demonstrate this method by monitoring binding of NeutrAvidin to biotinylated spheres and binding of immunoglobulin G to spheres functionalized with protein A.
Selective interaction between phytomediated anionic silver nanoparticles and mercury leading to amalgam formation enables highly sensitive, colorimetric and memristor-based detection of mercury
Authors: Sangaonkar Geetanjali M. , Desai Megha P. , Dongale Tukaram D. , Pawar Kiran D.
Published: February 2020

Presently, nanotechnology is being foreseen to play an important role in developing analytical assays for the detection of pollutants like mercury (Hg2+). In this study, Kokum fruit mediated silver nanoparticles (AgNPs) were differentially centrifuged to prepare anionic, monodispersed AgNPs to develop a highly sensitive, colorimetric and memristor-based assay for detection of Hg2+ in water samples. The investigation of the highly selective reaction between AgNPs and Hg2+ using HAADF-STEM images and EDS spectrum indicated the amalgam formation through etching and under potential deposition which resulted in a visible color change from brown to colorless, change in SPR intensity and also change in memristive switching like property of AgNPs. The developed colorimetric assay detected Hg2+ with a limit of detection (LOD) of 6.2 ppb and limit of quantification (LOQ) of 18.9 ppb and, quantitatively recovered Hg2+ with good accuracy and precision (RSD < 2%). Further, the test of memristive switching like property of AgNPs demonstrated frequency-dependent shrinkage of I–V hysteresis loop indicating memristive switching like property. The test of the sensitivity of Hg2+ detection was estimated to be 8.7 ppb as the LOD and 26.4 ppb as LOQ. Like the colorimetric assay, the memristor-based assay also recovered Hg2+ with good accuracy and precision.
High-density neutrophils in MGUS and multiple myeloma are dysfunctional and immune-suppressive due to increased STAT3 downstream signaling
Authors: Romano A. , Parrinello N. L. , Simeon V. , Puglisi F. , La Cava P. , Bellofiore C. , Giallongo C. , Camiolo G. , D’Auria F. , Grieco V. , Larocca F. , Barbato A. , Cambria D. , La Spina E. , Tibullo D. , Palumbo G. A. , Conticello C. , Musto P. , Di Raimondo F.
Published: February 2020

To understand neutrophil impairment in the progression from MGUS through active MM, we investigated the function of mature, high-density neutrophils (HDNs), isolated from peripheral blood. In 7 MM, 3 MGUS and 3 healthy subjects by gene expression profile, we identified a total of 551 upregulated and 343 downregulated genes in MM-HDN, involved in chemokine signaling pathway and FC-gamma receptor mediated phagocytosis conveying in the activation of STAT proteins. In a series of 60 newly diagnosed MM and 30 MGUS patients, by flow-cytometry we found that HDN from MM, and to a lesser extend MGUS, had an up-regulation of the inducible FcγRI (also known as CD64) and a down-regulation of the constitutive FcγRIIIa (also known as CD16) together with a reduced phagocytic activity and oxidative burst, associated to increased immune-suppression that could be reverted by arginase inhibitors in co-culture with lymphocytes. In 43 consecutive newly-diagnosed MM patients, who received first-line treatment based on bortezomib, thalidomide and dexamethasone, high CD64 could identify at diagnosis patients with inferior median overall survival (39.5 versus 86.7 months, p = 0.04). Thus, HDNs are significantly different among healthy, MGUS and MM subjects. In both MGUS and MM neutrophils may play a role in supporting both the increased susceptibility to infection and the immunological dysfunction that leads to tumor progression.