bluuebunny/crossref_metadata_2025 huggingface dataset:
Computational approaches for drug discovery against trypanosomatid-caused diseases
Authors: Pereira Claudio A. , Sayé Melisa , Reigada Chantal , Silber Ariel M. , Labadie Guillermo R. , Miranda Mariana R. , Valera-Vera Edward
Published: February 2020

During three decades, only about 20 new drugs have been developed for malaria, tuberculosis and all neglected tropical diseases (NTDs). This critical situation was reached because NTDs represent only 10% of health research investments; however, they comprise about 90% of the global disease burden. Computational simulations applied in virtual screening (VS) strategies are very efficient tools to identify pharmacologically active compounds or new indications for drugs already administered for other diseases. One of the advantages of this approach is the low time-consuming and low-budget first stage, which filters for testing experimentally a group of candidate compounds with high chances of binding to the target and present trypanocidal activity. In this work, we review the most common VS strategies that have been used for the identification of new drugs with special emphasis on those applied to trypanosomiasis and leishmaniasis. Computational simulations based on the selected protein targets or their ligands are explained, including the method selection criteria, examples of successful VS campaigns applied to NTDs, a list of validated molecular targets for drug development and repositioned drugs for trypanosomatid-caused diseases. Thereby, here we present the state-of-the-art of VS and drug repurposing to conclude pointing out the future perspectives in the field.
Authentic Versus Traditional Assessment: An Empirical Study Investigating the Difference in Seafarer Students' Academic Achievement
Authors: Ghosh Samrat , Brooks Benjamin , Ranmuthugala Dev , Bowles Marcus
Published: February 2020

Past research showed that traditional assessment methods that required seafarer students to construct responses based on memorisation and analysing information presented in absence of real-world contexts (e.g. oral examinations and multiple-choice questions) disengaged the students from learning. Memorising information is a lower-order cognitive ability, failure in which led to errors and low academic achievement for students. Authentic assessment methods require students to construct responses through the critical analysis of information presented in real-world contexts. Hence, this research investigated the difference in seafarer students' academic achievement (measured through scores obtained in assessment) in authentic assessment as compared with traditional assessment. Two separate and independent student groups (the ‘control’ group and ‘treatment’ group) were used for a selected unit of learning delivered at the Australian Maritime College within the Bachelor of Nautical Science degree program. Because some past researchers had defined and implemented traditional assessment methods as a single-occasion assessment, this project implemented the assessment in a summative format, as opposed to authentic assessments implemented during student preparation. Analysis of student scores revealed that the authentically assessed students were guided towards significantly higher academic achievement.
Distribution of zooplankton in the Indian sector of the Southern Ocean
Authors: Venkataramana V. , Anilkumar N. , Swadling K. , Mishra R.K. , Tripathy S.C. , Sarkar A. , Augusta Soares Melena , Sabu P. , Pillai Honey U.K.
Published: February 2020

The community composition of zooplankton with an emphasis on copepods was assessed in the frontal zones of the Indian sector of the Southern Ocean (SO) during summer 2013. Copepods were the dominant group in both the bongo net and multiple plankton sampler across the entire region. High zooplankton abundance was recorded along each transect in the Polar Front (PF). Community structure in this front was dominated by common taxa, includingCtenocalanus citer,Clausocalanusspp.,Calanoides acutus,Calanus propinquus,Calanus australisandRhincalanus gigas, which together accounted for > 62% of the total abundance.Calocalanusspp.,Neocalanus tonsusandC. propinquuswere indicator species in the Sub-Tropical Front (STF), Sub-Antarctic Front and PF, respectively. A strong contrast in population structure and biovolume was observed between then PF and the STF. The community structure of smaller copepods was associated with the high-temperature region, whereas communities of larger copepods were associated with the low-temperature region. Thus, it seems probable that physical and biological characteristics of the SO frontal regions are controlling the abundance and distribution of zooplankton community structure by restricting some species to the warmer stratified zones and some species to the well-mixed zone.
Retirement incentives and behavior of private and public sector workers
Authors: Coile Courtney , Stewart Susan
Published: February 2020

Over the past several decades, private sector workers in the USA with employed-sponsored pensions have experienced a dramatic shift from defined benefit (DB) to defined contribution plans, while this trend has been less pronounced for public sector workers. In this paper, we use data from the Health and Retirement Study to explore changes in the retirement incentives and retirement behavior of public and private sector workers over the past quarter-century. We find that both groups have become less likely to report having a DB pension or any pension. Compared to their private sector counterparts, public sector workers have a higher level of retirement wealth and a larger financial gain from continued work at older ages, and these differences by sector are growing across cohorts. Both groups respond to financial incentives in making retirement decisions. However, growing differences by sector in the gain to continued work do not appear to have translated into diverging retirement behavior, as we observe similar trends in the two groups.
IDENTIFYING THE UNKNOWN SOURCE OF A PRE-RAMEAU HARMONIC THEORIST: WHO WAS ALEXANDER MALCOLM'S MYSTERIOUS GHOSTWRITER?
Authors: TELESCO PAULA J.
Published: February 2020

Alexander Malcolm (1685–1763) published his monumentalTreatise of Musickin Edinburgh in 1721, one year before Rameau published hisTraité de l'harmonie. Malcolm's was the first important work on music theory published in Scotland, and it established his musical reputation, influencing theorists and historians for almost a hundred years, both in Europe and in the American colonies. Sir John Hawkins deemed it ‘one of the most valuable treatises on the subject of theoretical and practical music to be found in any of the modern languages’. Malcolm's chapter 13 is often cited by music theorists for anticipating the writings of Rameau. However, Malcolm's Introduction states that the thirteenth chapter was communicated to him by a ‘modest’ friend. Identifying this friend necessitated first determining the author(s) of two rare anonymous contemporaneous treatises, remarkably similar to each other, and one nearly identical to Malcolm's chapter 13. Several writers have speculated on possible authors – two in particular, Alexander Baillie and Alexander Bayne – but none has provided actual evidence. This study identifies the author of these two hitherto anonymous treatises: Malcolm's modest friend.
Island Rainfall Enhancement in the Maritime Continent
Authors: Ruppert James H. , Chen Xingchao
Published: February 2020

The hypothesis that the islands of the Maritime Continent (MC) enhance total rainfall and time‐mean upward motion is tested using a convection‐permitting regional model. Sensitivity experiments with the islands removed greatly diminish both rainfall and upward motion, supporting the hypothesis. We examine the individual factors in this enhancement, isolating the impacts of the diurnal cycle from those of basic‐state (i.e., constant) forcing of orography and the land surface. We find that the basic‐state forcing by land is the only factor that substantially enhances total island rainfall, specifically through the enhancement of mean surface heat fluxes. The diurnal cycle and orographic forcing, however, substantially enhance rainfall in the seas surrounding the islands. Moreover, the diurnal cycle is found to be essential for promoting mesoscale circulations on the spatial scales of the islands, which are critical to both the upscale growth of deep convection and the most extreme rainfall rates.
Interannual Variabilities of Nutrients and Phytoplankton off the Changjiang Estuary in Response to Changing River Inputs
Authors: Ge Jianzhong , Shi Shenyang , Liu Jie , Xu Yi , Chen Changsheng , Bellerby Richard , Ding Pingxing
Published: February 2020

Coastal ecosystems are strongly influenced by terrestrial inputs of freshwater, sediments, and nutrients, particularly in a megariver estuary of the Changjiang River. A remarkable increase in nutrient loading from the Changjiang River to the shelf has been observed over the period from 1999 to 2016 and turned the region into a high eutrophication condition. The Finite‐Volume Community Ocean Model and the European Regional Seas Ecosystem Model were coupled to assess the impact of the nutrient loading on the interannual variability of nutrients and phytoplankton. The model was first validated via observational data, and then dynamical analysis were conducted. Singular vector decomposition analysis indicated that the rapid change of local ecosystem was highly correlated with the change in river nutrient contributions. The Changjiang estuarine ecosystem was phosphate limited. The phosphate exhibited local variation, while the abundant nitrate from the river was diluted by the low‐nitrate oceanic water. The suspended sediment was significantly correlated with phytoplankton but not with nutrients. The ratio of diatom biomass to dinoflagellate biomass respected a rapid response to strong oscillations in the river nutrient input. High diatom primary production occurred near the sediment front, whereas the dinoflagellate bloom extended significantly offshore. The spring diatom and dinoflagellate blooms had major peaks in the empirical orthogonal function Modes 1 and 2, and the autumn bloom is characterized by secondary peaks from Mode 2 in the autumn.
An ultra-compact particle size analyser using a CMOS image sensor and machine learning
Authors: Hussain Rubaiya , Alican Noyan Mehmet , Woyessa Getinet , Retamal Marín Rodrigo R. , Antonio Martinez Pedro , Mahdi Faiz M. , Finazzi Vittoria , Hazlehurst Thomas A. , Hunter Timothy N. , Coll Tomeu , Stintz Michael , Muller Frans , Chalkias Georgios , Pruneri Valerio
Published: February 2020

Light scattering is a fundamental property that can be exploited to create essential devices such as particle analysers. The most common particle size analyser relies on measuring the angle-dependent diffracted light from a sample illuminated by a laser beam. Compared to other non-light-based counterparts, such a laser diffraction scheme offers precision, but it does so at the expense of size, complexity and cost. In this paper, we introduce the concept of a new particle size analyser in a collimated beam configuration using a consumer electronic camera and machine learning. The key novelty is a small form factor angular spatial filter that allows for the collection of light scattered by the particles up to predefined discrete angles. The filter is combined with a light-emitting diode and a complementary metal-oxide-semiconductor image sensor array to acquire angularly resolved scattering images. From these images, a machine learning model predicts the volume median diameter of the particles. To validate the proposed device, glass beads with diameters ranging from 13 to 125 µm were measured in suspension at several concentrations. We were able to correct for multiple scattering effects and predict the particle size with mean absolute percentage errors of 5.09% and 2.5% for the cases without and with concentration as an input parameter, respectively. When only spherical particles were analysed, the former error was significantly reduced (0.72%). Given that it is compact (on the order of ten cm) and built with low-cost consumer electronics, the newly designed particle size analyser has significant potential for use outside a standard laboratory, for example, in online and in-line industrial process monitoring.
Selected discoveries from human research in space that are relevant to human health on Earth
Authors: Shelhamer Mark , Bloomberg Jacob , LeBlanc Adrian , Prisk G. Kim , Sibonga Jean , Smith Scott M. , Zwart Sara R. , Norsk Peter
Published: February 2020

A substantial amount of life-sciences research has been performed in space since the beginning of human spaceflight. Investigations into bone loss, for example, are well known; other areas, such as neurovestibular function, were expected to be problematic even before humans ventured into space. Much of this research has been applied research, with a primary goal of maintaining the health and performance of astronauts in space, as opposed to research to obtain fundamental understanding or to translate to medical care on Earth. Some people—scientists and concerned citizens—have questioned the broader scientific value of this research, with the claim that the only reason to perform human research in space is to keep humans healthy in space. Here, we present examples that demonstrate that, although this research was focused on applied goals for spaceflight participants, the results of these studies are of fundamental scientific and biomedical importance. We will focus on results from bone physiology, cardiovascular and pulmonary systems, and neurovestibular studies. In these cases, findings from spaceflight research have provided a foundation for enhancing healthcare terrestrially and have increased our knowledge of basic physiological processes.
Publisher Correction: Butler enables rapid cloud-based analysis of thousands of human genomes
Authors: Yakneen Sergei , Waszak Sebastian M. ,   PCAWG Technical Working Group, Yakneen Sergei , Aminou Brice , Bartolome Javier , Boroevich Keith A. , Boyce Rich , Brooks Angela N. , Buchanan Alex , Buchhalter Ivo , Butler Adam P. , Byrne Niall J. , Cafferkey Andy , Campbell Peter J. , Chen Zhaohong , Cho Sunghoon , Choi Wan , Clapham Peter , Davis-Dusenbery Brandi N. , De La Vega Francisco M. , Demeulemeester Jonas , Dow Michelle T. , Dursi Lewis Jonathan , Eils Juergen , Eils Roland , Ellrott Kyle , Farcas Claudiu , Favero Francesco , Fayzullaev Nodirjon , Ferretti Vincent , Flicek Paul , Fonseca Nuno A. , Gelpi Josep Ll. , Getz Gad , Gibson Bob , Grossman Robert L. , Harismendy Olivier , Heath Allison P. , Heinold Michael C. , Hess Julian M. , Hofmann Oliver , Hong Jongwhi H. , Hudson Thomas J. , Hutter Barbara , Hutter Carolyn M. , Hübschmann Daniel , Imoto Seiya , Ivkovic Sinisa , Jeon Seung-Hyup , Jiao Wei , Jung Jongsun , Kabbe Rolf , Kahles Andre , Kerssemakers Jules N. A. , Kim Hyung-Lae , Kim Hyunghwan , Kim Jihoon , Kim Youngwook , Kleinheinz Kortine , Koscher Michael , Koures Antonios , Kovacevic Milena , Lawerenz Chris , Leshchiner Ignaty , Liu Jia , Livitz Dimitri , Mihaiescu George L. , Mijalkovic Sanja , Mijalkovic Lazic Ana , Miyano Satoru , Miyoshi Naoki , Nahal-Bose Hardeep K. , Nakagawa Hidewaki , Nastic Mia , Newhouse Steven J. , Nicholson Jonathan , O’Connor Brian D. , Ocana David , Ohi Kazuhiro , Ohno-Machado Lucila , Omberg Larsson , Ouellette B. F Francis , Paramasivam Nagarajan , Perry Marc D. , Pihl Todd D. , Prinz Manuel , Puiggròs Montserrat , Radovic Petar , Raine Keiran M. , Rheinbay Esther , Rosenberg Mara , Royo Romina , Rätsch Gunnar , Saksena Gordon , Schlesner Matthias , Shorser Solomon I. , Short Charles , Sofia Heidi J. , Spring Jonathan , Stein Lincoln D. , Struck Adam J. , Tiao Grace , Tijanic Nebojsa , Torrents David , Van Loo Peter , Vazquez Miguel , Vicente David , Wala Jeremiah A. , Wang Zhining , Waszak Sebastian M. , Weischenfeldt Joachim , Werner Johannes , Williams Ashley , Woo Youngchoon , Wright Adam J. , Xiang Qian , Yang Liming , Yuen Denis , Yung Christina K. , Zhang Junjun , Korbel Jan O. , Gertz Michael , Korbel Jan O. ,   PCAWG Consortium
Published: February 2020

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
Speleothem growth intervals reflect New Zealand montane vegetation response to temperature change over the last glacial cycle
Authors: Hellstrom John , Sniderman Kale , Drysdale Russell , Couchoud Isabelle , Hartland Adam , Pearson Andrew , Bajo Petra
Published: February 2020

Flowstone speleothem growth beneath Mount Arthur, New Zealand shows a clear relationship to vegetation density and soil development on the surface above. Flowstone does not currently form beneath sub-alpine Nothofagus forest above ca. 1000–1100 m altitude but U-Th dating shows it has formed there during past intervals of warmer-than-present conditions including an early–mid Holocene optimum and the last interglacial from ca. 131–119 ka. Some flowstones growing beneath ca. 600 m surface altitude, currently mantled with dense broadleaf-podocarp forest, grew during full glacial conditions, indicating that local tree line was never below this altitude. This implies that Last Glacial Maximum annual temperature was no more than ca. 4 °C cooler than today. Flowstone growth appears to be a robust indicator of dense surface vegetation and well-developed soil cover in this setting, and indicates that past interglacial climates of MIS 7e, 5e, the early–mid Holocene and possibly MIS 5a were more conducive to growth of trees than was the late Holocene, reflecting regional temperature changes similar in timing to Antarctic temperature changes. Here, flowstone speleothem growth is a sensitive indicator of vegetation density at high altitude, but may respond to other factors at lower altitudes.
Expression of RcHSP70, heat shock protein 70 gene from Chinese rose, enhances host resistance to abiotic stresses
Authors: Jiang Changhua , Bi Yuke , Zhang Ruyao , Feng Shucheng
Published: February 2020

There exist differences in the heat tolerance of Chinese rose varieties, and high temperature in summer can lead to failure of blooming in non-heat-tolerant Chinese rose varieties. We cloned a heat shock protein 70 gene (designated RcHSP70) from heat-tolerant varieties of Chinese rose (Rosa hybrida L.) to elucidate the molecular mechanism of heat tolerance and improve the quality of Chinese rose. Degenerate primers were designed for RcHSP70 according to the 5′- and 3′-end sequences of HSP70 genes in apple and tea. RcHSP70 was cloned from heat-tolerant Chinese rose varieties after heat shock. The heat shock-induced expression patterns of RcHSP70 in different Chinese rose varieties were analyzed by RT-PCR. Following heat shock (38 °C/3 h), RcHSP70 was highly expressed in the heat-tolerant varieties but not in the non-heat-tolerant varieties, indicating a close relationship between RcHSP70 and heat resistance in Chinese rose. To verify the function of RcHSP70, we constructed a prokaryotic expression recombinant vector for this gene and transformed it into Escherichia coli BL21. The tolerance of recombinant strains to abiotic stresses, including high temperature, low temperature, high salt, heavy metals, high pH, and oxidation, was evaluated. Additionally, RcHSP70 was transformed into tobacco plants. Because of the overexpression of this gene, transgenic tobacco plants improved their tolerance to high temperature and cold. In addition, transgenic tobacco showed better photosynthetic performance, relative electrical conductivity and proline content than wild tobacco after heat stress and cold stress. Our findings indicate that RcHSP70 is involved in the resistance of Chinese rose to abiotic stresses.
An interspecific variation in rhizosphere effects on soil anti-erodibility
Authors: Wang Zhenhong , Chiarucci Alessandro , Fang Hong , Chen Mouhui
Published: February 2020

Soil erosion due to underground leakage is a major factor causing land degradation in karst regions. Rhizosphere effects (REs) on soil anti-erodibility (SAE) can alleviate this type of soil erosion by improving soil physical processes such as aggregate stability. However, the magnitudes and causes of interspecific variation in REs on SAE remain unclear. We tested the rhizosphere SAE indices of 42 key woody species distributed worldwide. Biologically active matter (BAM) and analogs of antibiotics (AOAs) that affect the SAE in rhizosphere soils were tested by gas chromatography-mass spectrometry (GC-MS). We then used principal component analysis (PCA) and redundancy analysis (RA) to establish a spectrum of interspecific variability in the REs for the first time. The spectrum shows a gradient of change among species. Eleven species exerted negative REs on the SAE, while the remaining species showed positive effects along the spectrum. The species with large positive effects were mostly deciduous, which have high contents of both BAM and total organic matter and low contents of AOAs in their rhizosphere soil; compared with the other species tested, these species also have more leaves and roots and are better adapted to barren soils. The botanical characteristics of species with negative REs on the SAE differed from those with large positive effects. The contents of BAM in the rhizosphere accounted for 16–23% of the total variation in REs on the SAE. This study quantified interspecific variation in REs and identified root exudates with negative REs.
CNN3 acts as a potential oncogene in cervical cancer by affecting RPLP1 mRNA expression
Authors: Xia Lili , Yue Yongfang , Li Mingyue , Zhang Ya-Nan , Zhao Lu , Lu Weiguo , Wang Xinyu , Xie Xing
Published: February 2020

The prognosis of advanced stage cervical cancer is poorer due to cancer invasion and metastasis. Exploring new factors and signalling pathways associated with invasiveness and metastasis would help to identify new therapeutic targets for advanced cervical cancer. We searched the cancer microarray database, Oncomine, and found elevated calponin 3 (CNN3) mRNA expression in cervical cancer tissues. QRT-PCR verified the increased CNN3 expression in cervical cancer compared to para-cancer tissues. Proliferation, migration and invasion assays showed that overexpressed CNN3 promoted the viability and motility of cervical cancer cells, the opposite was observed in CNN3-knockdown cells. In addition, xenografted tumours, established from SiHa cells with CNN3 knockdown, displayed decreased growth and metastasis in vivo. Furthermore, RNA-sequencing showed that ribosomal protein lateral stalk subunit P1 (RPLP1) was a potential downstream gene. Gene function experiments revealed that RPLP1 had the same biological effects as CNN3 did. Rescue experiments demonstrated that the phenotypes inhibited by CNN3 silencing were partly or completely reversed by RPLP1 overexpression. In conclusion, we verified that CNN3 acts as an oncogene to promote the viability and motility of cervical cancer cells in vitro and accelerate the growth and metastasis of xenografted tumours in vivo, by affecting RPLP1 expression.
Assessment of recombinant protein production in E. coli with Time-Gated Surface Enhanced Raman Spectroscopy (TG-SERS)
Authors: Kögler Martin , Itkonen Jaakko , Viitala Tapani , Casteleijn Marco G.
Published: February 2020

Time-Gated Surface-Enhanced Raman spectroscopy (TG-SERS) was utilized to assess recombinant protein production in Escherichia coli. TG-SERS suppressed the fluorescence signal from the biomolecules in the bacteria and the culture media. Characteristic protein signatures at different time points of the cell cultivation were observed and compared to conventional continuous wave (CW)-Raman with SERS. TG-SERS can distinguish discrete features of proteins such as the secondary structures and is therefore indicative of folding or unfolding of the protein. A novel method utilizing nanofibrillar cellulose as a stabilizing agent for nanoparticles and bacterial cells was used for the first time in order to boost the Raman signal, while simultaneously suppressing background signals. We evaluated the expression of hCNTF, hHspA1, and hHsp27 in complex media using the batch fermentation mode. HCNTF was also cultivated using EnBase in a fed-batch like mode. HspA1 expressed poorly due to aggregation problems within the cell, while hCNTF expressed in batch mode was correctly folded and protein instabilities were identified in the EnBase cultivation. Time-gated Raman spectroscopy showed to be a powerful tool to evaluate protein production and correct folding within living E. coli cells during the cultivation.
Toxic tall fescue grazing increases susceptibility of the Angus steer fecal microbiota and plasma/urine metabolome to environmental effects
Authors: Mote Ryan S. , Hill Nicholas S. , Skarlupka Joseph H. , Tran ViLinh T. , Walker Douglas I. , Turner Zachary B. , Sanders Zachary P. , Jones Dean P. , Suen Garret , Filipov Nikolay M.
Published: February 2020

Impaired thermoregulation and lowered average daily gains (ADG) result when livestock graze toxic endophyte (Epichloë coenophialum)-infected tall fescue (E+) and are hallmark signs of fescue toxicosis (FT), a disease exacerbated by increased temperature and humidity (+temperature-humidity index; +THI). We previously reported FT is associated with metabolic and microbiota perturbations under thermoneutral conditions; here, we assessed the influence of E+ grazing and +THI on the microbiota:metabolome interactions. Using high-resolution metabolomics and 16S rRNA gene sequencing, plasma/urine metabolomes and the fecal microbiota of Angus steers grazing non-toxic or E+ tall fescue were evaluated in the context of +THI. E+ grazing affected the fecal microbiota profile; +THI conditions modulated the microbiota only in E+ steers. E+ also perturbed many metabolic pathways, namely amino acid and inflammation-related metabolism; +THI affected these pathways only in E+ steers. Integrative analyses revealed the E+ microbiota correlated and co-varied with the metabolomes in a THI-dependent manner. Operational taxonomic units in the families Peptococcaceae, Clostridiaceae, and Ruminococcaceae correlated with production parameters (e.g., ADG) and with multiple plasma/urine metabolic features, providing putative FT biomarkers and/or targets for the development of FT therapeutics. Overall, this study suggests that E+ grazing increases Angus steer susceptibility to +THI, and offers possible targets for FT interventions.
Relative roles of biological and physical processes influencing coral recruitment during the lag phase of reef community recovery
Authors: Gouezo Marine , Olsudong Dawnette , Fabricius Katharina , Harrison Peter , Golbuu Yimnang , Doropoulos Christopher
Published: February 2020

Following disturbances, corals recolonize space through the process of recruitment consisting of the three phases of propagule supply, settlement, and post-settlement survival. Yet, each phase is influenced by biophysical factors, leading to recruitment success variability through space. To resolve the relative contributions of biophysical factors on coral recruitment, the recovery of a 150 km long coral reefs in Palau was investigated after severe typhoon disturbances. Overall, we found that benthic organisms had a relatively weak interactive influence on larval settlement rates at the scale of individual tiles, with negative effects mainly exerted from high wave exposure for Acropora corals. In contrast, juvenile coral densities were well predicted by biophysical drivers, through both direct and indirect pathways. High densities of Acropora and Poritidae juveniles were directly explained by the availability of substrata free from space competitors. Juvenile Montipora were found in higher densities where coralline algae coverage was high, which occurred at reefs with high wave exposure, while high densities of juvenile Pocilloporidae occurred on structurally complex reefs with high biomass of bioeroder fish. Our findings demonstrate that strengths of biophysical interactions were taxon-specific and had cascading effects on coral recruitment, which need consideration for predicting reef recovery and conservation strategies.
Denosumab for dialysis patients with osteoporosis: A cohort study
Authors: Kunizawa Kyohei , Hiramatsu Rikako , Hoshino Junichi , Mizuno Hiroki , Ozawa Yuko , Sekine Akinari , Kawada Masahiro , Sumida Keiichi , Hasegawa Eiko , Yamanouchi Masayuki , Hayami Noriko , Suwabe Tatsuya , Sawa Naoki , Ubara Yoshifumi , Takaichi Kenmei
Published: February 2020

Evidence for the efficacy of denosumab in HD patients is limited. Accordingly, here we report a study on the safety and efficacy of denosumab in these patients. We prospectively followed 324 patients (121 HD and 203 non-HD patients) receiving denosumab between June 2013 and May 2018, assessing changes in bone mineral density (BMD) and bone metabolic markers, and noting side-effects. Annual changes in BMD at the lumbar spine in HD and non-HD patients from baseline were, respectively, 6.7 ± 11.1% and 7.5 ± 10.2% (p = 0.60), those at the femoral neck were 4.3 ± 7.9% and 3.1 ± 9.5% (p = 0.32), and those at the distal radius were −0.5 ± 6.4% and 0.2 ± 13.0% (p = 0.66). The prevalence of hypocalcemia (<8.5 mg/dL) was significantly higher in HD than in non-HD patients (35.6% vs 5.4%, p < 0.001). The median elapsed time between the first injection of denosumab and the occurrence of hypocalcemia was 7 days in HD patients. The decrease of serum calcium was greater in patients with higher TRACP5b, corticosteroid use, and those without CaCO3 supplementation. Our study suggests that denosumab was equally as effective in HD as non-HD patients. However, careful hypocalcemia monitoring, for at least 4 weeks, is recommended for HD patients.
Elevated HbA1c is not associated with recurrent venous thromboembolism in the elderly, but with all-cause mortality– the SWEETCO 65+ study
Authors: Mathis Alexandra , Villiger Lukas , Reiner Martin F. , Egloff Michael , Schmid Hans Ruedi , Stivala Simona , Limacher Andreas , Mean Marie , Aujesky Drahomir , Rodondi Nicolas , Angelillo-Scherrer Anna , Righini Marc , Staub Daniel , Aschwanden Markus , Frauchiger Beat , Osterwalder Joseph , Kucher Nils , Matter Christian M. , Banyai Martin , Hugli Oliver , Beer Juerg H.
Published: February 2020

The association of glycated hemoglobin (HbA1c) with venous thromboembolism (VTE) and death in the elderly is unknown. In the SWEETCO 65+ study we analyzed prospectively a Swiss Cohort of Elderly Patients with Venous Thromboembolism (SWITCO 65+). 888 patients were enrolled for the SWEETCO 65+ analysis. HbA1c was determined at baseline and divided into three categories (HbA1c < 5.7%, normal range; 5.7–6.49%, pre-diabetic range; and >6.5%, diabetic range). Median follow-up was 2.5 years. The primary endpoint was recurrent VTE. Secondary endpoints included all-cause mortality and major bleeds. The total prevalence of diabetes was 22.1%. The risk of recurrent VTE was similar in patients with HbA1c with pre-diabetes (adjusted subhazard ratio (aSHR) 1.07 [0.70 to 1.63]) and diabetes (aSHR 0.73 [0.39 to 1.37]) as compared to those with a HbA1c in the normal range. However, a HbA1c ≥ 6.5% (median IQ range 7.0 [6.70;7.60]) was significantly associated with a higher risk of all-cause mortality (adjusted hazard ratio [aHR] 1.83 [1.21 to 2.75]). In summary we found no association between HbA1c and major bleeding. Elevated HbA1c levels are not associated with recurrent VTE but with increased all-cause mortality in an elderly population with acute VTE.
Challenging the concept that eumelanin is the polymorphic brown banded pigment in Cepaea nemoralis
Authors: Affenzeller Susanne , Wolkenstein Klaus , Frauendorf Holm , Jackson Daniel J.
Published: February 2020

The common grove snail Cepaea nemoralis displays a stable pigmentation polymorphism in its shell that has held the attention of scientists for decades. While the details of the molecular mechanisms that generate and maintain this diversity remain elusive, it has long been employed as a model system to address questions related to ecology, population genetics and evolution. In order to contribute to the ongoing efforts to identify the genes that generate this polymorphism we have tested the long-standing assumption that melanin is the pigment that comprises the dark-brown bands. Surprisingly, using a newly established analytical chemical method, we find no evidence that eumelanin is differentially distributed within the shells of C. nemoralis. Furthermore, genes known to be responsible for melanin deposition in other metazoans are not differentially expressed within the shell-forming mantle tissue of C. nemoralis. These results have implications for the continuing search for the supergene that generates the various pigmentation morphotypes.
Restricted immunological and cellular pathways are shared by murine models of chronic alcohol consumption
Authors: Vogle Alyx , Qian Tongqi , Zhu Shijia , Burnett Elizabeth , Fey Holger , Zhu Zhibin , Keshavarzian Ali , Shaikh Maliha , Hoshida Yujin , Kim Miran , Aloman Costica
Published: February 2020

Murine models of chronic alcohol consumption are frequently used to investigate alcoholic liver injury and define new therapeutic targets. Lieber-DeCarli diet (LD) and Meadows-Cook diet (MC) are the most accepted models of chronic alcohol consumption. It is unclear how similar these models are at the cellular, immunologic, and transcriptome levels. We investigated the common and specific pathways of LD and MC models. Livers from LD and MC mice were subjected to histologic changes, hepatic leukocyte population, hepatic transcripts level related to leukocyte recruitment, and hepatic RNA-seq analysis. Cross-species comparison was performed using the alcoholic liver disease (ALD) transcriptomic public dataset. Despite LD mice have increased liver injury and steatosis by alcohol exposure, the number of CD45+cells were reduced. Opposite, MC mice have an increased number of monocytes/liver by alcohol. The pattern of chemokine gradient, adhesion molecules, and cytokine transcripts is highly specific for each model, not shared with advanced human alcoholic liver disease. Moreover, hepatic RNA-seq revealed a limited and restricted number of shared genes differentially changed by alcohol exposure in these 2 models. Thus, mechanisms involved in alcohol tissue injury are model-dependent at multiple levels and raise the consideration of significant pathophysiological diversity of human alcoholic liver injury.
Two-dimensional Wrinkle Resonators for Random Lasing in Organic Glasses
Authors: Hoinka Nicolai M. , Ostwald Christoph , Fuhrmann-Lieker Thomas
Published: February 2020

Random lasers consisting of slab waveguides with two-dimensional disordered wrinkling patterns that act as scattering resonators are reported. As active material 2,2′,7,7′-tetraphenyl-9,9′-spirobifluorene is used which is sandwiched between an oxidized silicon wafer and a cladding with higher glass transition temperature. Wrinkles with tailorable periodicity have been induced by thermal annealing. Photopumping experiments show the transition from amplified spontaneous emission to a multiple peak laser spectrum with linewidths as low as 0.1 nm, demonstrating the applicability of this approach for random laser design.
Novel Mutation Hotspots within Non-Coding Regulatory Regions of the Chronic Lymphocytic Leukemia Genome
Authors: Mosquera Orgueira Adrián , Rodríguez Antelo Beatriz , Díaz Arias José Ángel , Díaz Varela Nicolás , Alonso Vence Natalia , González Pérez Marta Sonia , Bello López José Luis
Published: February 2020

Mutations in non-coding DNA regions are increasingly recognized as cancer drivers. These mutations can modify gene expression in cis or by inducing high-order chormatin structure modifications with long-range effects. Previous analysis reported the detection of recurrent and functional non-coding DNA mutations in the chronic lymphocytic leukemia (CLL) genome, such as those in the 3′ untranslated region of NOTCH1 and in the PAX5 super-enhancer. In this report, we used whole genome sequencing data produced by the International Cancer Genome Consortium in order to analyze regions with previously reported regulatory activity. This approach enabled the identification of numerous recurrently mutated regions that were frequently positioned in the proximity of genes involved in immune and oncogenic pathways. By correlating these mutations with expression of their nearest genes, we detected significant transcriptional changes in genes such as PHF2 and S1PR2. More research is needed to clarify the function of these mutations in CLL, particularly those found in intergenic regions.
Effects of PM10 on mortality in pure COPD and asthma-COPD overlap: difference in exposure duration, gender, and smoking status
Authors: Lee Yu Min , Lee Jin Hwa , Kim Hawn-Cheol , Ha Eunhee
Published: February 2020

We investigated the effects of particulate matter (PM) on mortality in patients diagnosed with asthma-COPD overlap (ACO) or ‘pure COPD’. Subjects from the National Health Insurance Service–National Sample Cohort of Korea, who were aged 40 years or above and had newly diagnosed COPD since 2009 were selected. Finally, 6,313 patients were enrolled and divided into ‘pure COPD’ and ACO groups. Average PM10 exposure data were obtained using Kriging interpolation from 2001 to 2013. Hazard ratios(HR) were estimated using a time-varying Cox regression model. Exposure to PM10 for 1, 3, and 6 months was associated with an increase in non-accidental mortality in the entire COPD group, especially the ACO group. When a stratified analysis of 3-month exposure was performed by sex, the highest HR was found in women with ACO (HR = 1.153; 95% confidence intervals [CI]: 1.121, 1.185). A stratified analysis according to smoking status showed that ACO patients had the highest HR among never smokers (HR = 1.151; 95% CI; 1.124, 1.178). Average exposure to PM10 was associated with non-accidental mortality in patients with COPD, especially those diagnosed with ACO. In addition, the adverse effects of PM10 exposure are more severe in women and never-smokers.
In vitro modeling of dendritic atrophy in Rett syndrome: determinants for phenotypic drug screening in neurodevelopmental disorders
Authors: Nerli Elisa , Roggero Ottavia Maria , Baj Gabriele , Tongiorgi Enrico
Published: February 2020

Dendritic atrophy, defined as the reduction in complexity of the neuronal arborization, is a hallmark of several neurodevelopmental disorders, including Rett Syndrome (RTT). RTT, affecting 1:10,000 girls worldwide, is mainly caused by mutations in the MECP2 gene and has no cure. We describe here an in vitro model of dendritic atrophy in Mecp2−/y mouse hippocampal primary cultures, suitable for phenotypic drug-screening. Using High-Content Imaging techniques, we systematically investigated the impact of culturing determinants on several parameters such as neuronal survival, total dendritic length, dendritic endpoints, soma size, cell clusterization, spontaneous activity. Determinants included cell-seeding density, glass or polystyrene substrates, coating with poly-Ornithine with/without Matrigel and miniaturization from 24 to 96-half surface multiwell plates. We show that in all plate-sizes at densities below 320 cells/mm2, morphological parameters remained constant while spontaneous network activity decreased according to the cell-density. Mecp2−/y neurons cultured at 160 cells/mm2 density in 96 multiwell plates, displayed significant dendritic atrophy and showed a marked increase in dendritic length following treatment with Brain-derived neurotrophic factor (BDNF) or Mirtazapine. In conclusion, we have established a phenotypic assay suitable for fast screening of hundreds of compounds, which may be extended to other neurodevelopmental diseases with dendritic atrophy.
The association between predicted inflammatory status and colorectal adenoma
Authors: Kim Sejin , Song Sihan , Kim Young Sun , Yang Sun Young , Lee Jung Eun
Published: February 2020

We developed a diet and lifestyle score based on high sensitivity C-reactive protein (hsCRP), and investigated its association with odds of adenoma. We performed stepwise linear regression to develop the predicted hsCRP score among 23,330 participants in the Health Examinee Study and examined its association with colorectal adenoma among 1,711 participants in a cross-sectional study of colorectal adenoma. We estimated odds ratios (ORs) and 95% confidence intervals (CIs) of colorectal adenoma using logistic regression models. Variances in hsCRP explained by body mass index were 61.1% in men and 64.5% in women in the prediction model. The increasing predicted hsCRP score was positively associated with colorectal adenoma (ORquartile 4 VS quartile 1 1.71, 95% CI: 1.12–2.62; Ptrend = 0.011 in men; ORquartile 4 VS quartile 1 2.86, 95% CI: 1.26–6.49; Ptrend = 0.019 in women). In subgroups, the associations differed by age and menopausal status among women, with stronger associations among women aged less than 50 years (OR≥median VS <median 3.74, 95% CI: 1.77–7.90, p for interaction 0.014) or premenopausal women (OR≥median vs <median 4.21, 95% CI: 2.12–8.36, p for interaction <0.001). The associations were more pronounced in the advanced or distal colon/rectum in men and in the advanced or proximal colon in women. The associations were attenuated after further adjustment for body mass index. In conclusion, we found that the predicted hsCRP score was positively associated with colorectal adenoma, suggesting that diet and lifestyle lowering inflammation may be a strategy to prevent colorectal neoplasia.
(−)-Epigallocatechin gallate inhibits stemness and tumourigenicity stimulated by AXL receptor tyrosine kinase in human lung cancer cells
Authors: Namiki Kozue , Wongsirisin Pattama , Yokoyama Shota , Sato Motoi , Rawangkan Anchalee , Sakai Ryo , Iida Keisuke , Suganuma Masami
Published: February 2020

Cancer stem cells (H1299-sdCSCs) were obtained from tumour spheres of H1299 human lung cancer cells. We studied low stiffness, a unique biophysical property of cancer cells, in H1299-sdCSCs and parental H1299. Atomic force microscopy revealed an average Young’s modulus value of 1.52 kPa for H1299-sdCSCs, which showed low stiffness compared with that of H1299 cells, with a Young’s modulus value of 2.24 kPa. (−)-Epigallocatechin gallate (EGCG) reversed the average Young’s modulus value of H1299-sdCSCs to that of H1299 cells. EGCG treatment inhibited tumour sphere formation and ALDH1A1 and SNAI2 (Slug) expression. AXL receptor tyrosine kinase is highly expressed in H1299-sdCSCs and AXL knockdown with siAXLs significantly reduced tumour sphere formation and ALDH1A1 and SNAI2 (Slug) expression. An AXL-high population of H1299-sdCSCs was similarly reduced by treatment with EGCG and siAXLs. Transplantation of an AXL-high clone isolated from H1299 cells into SCID/Beige mice induced faster development of bigger tumour than bulk H1299 cells, whereas transplantation of the AXL-low clone yielded no tumours. Oral administration of EGCG and green tea extract (GTE) inhibited tumour growth in mice and reduced p-AXL, ALDH1A1, and SLUG in tumours. Thus, EGCG inhibits the stemness and tumourigenicity of human lung cancer cells by inhibiting AXL.
Author Correction: Visualizing flow in an intact CSF network using optical coherence tomography: implications for human congenital hydrocephalus
Authors: Date Priya , Ackermann Pascal , Furey Charuta , Fink Ina Berenice , Jonas Stephan , Khokha Mustafa K. , Kahle Kristopher T. , Deniz Engin
Published: February 2020

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
A Highly-sensitized Response of B-type Natriuretic Peptide to Cardiac Ischaemia Quantified by Intracoronary Pressure Measurements
Authors: Itakura Ryosuke , Inoue Yasunori , Ogawa Kazuo , Nagoshi Tomohisa , Minai Kosuke , Ogawa Takayuki , Kawai Makoto , Yoshimura Michihiro
Published: February 2020

B-type natriuretic peptide (BNP) secretion is stimulated by cardiac dysfunction. However, it is unclear how finely myocardial ischaemia contributes to BNP secretion and whether increases in BNP secretion contribute to coronary vasodilation. This study investigated the direct interaction between plasma BNP levels and cardiac ischaemia using the baseline distal-to-aortic pressure ratio (Pd/Pa). We examined the baseline Pd/Pa and fractional flow reserve (FFR) in 167 patients with intermediate coronary stenosis. The plasma BNP level appeared to be associated with the baseline Pd/Pa in the study population, and this association appeared to become clear only in patients with an FFR ≤ 0.80. To examine the effect of the baseline Pd/Pa on the BNP level in these patients, structural equation modeling (SEM) was performed. The baseline Pd/Pa significantly affected the BNP level (β: −0.37, p = 0.003) and the left ventricular ejection fraction (β: 0.43, p = 0.001). To examine the role of BNP in coronary vasodilation, we proposed another path model using a novel value obtained by dividing the FFR by the baseline Pd/Pa (FFR/baseline Pd/Pa) as an index of the hyperaemic response. The BNP level significantly affected the FFR/baseline Pd/Pa (β: 0.48, p = 0.037). This study demonstrated that BNP finely responded to an exacerbation of cardiac ischaemia and that increases in BNP secretion effectively ameliorated coronary vasoconstriction.
Valorization of Eggshell Biowaste for Sustainable Environmental Remediation
Authors: Mignardi Silvano , Archilletti Luana , Medeghini Laura , De Vito Caterina
Published: February 2020

The management of large amounts of eggshell waste annually produced in the world is problematic as generally this material is only disposed at landfills with odor production and microbial growth. On the contrary, significant environmental and economic advantages could be obtained transforming this biowaste into new value-added products. Eggshell biowaste was the starting material for the synthesis of hydroxyapatite by a simple and sustainable procedure and applied for the removal of Co2+ from aqueous solutions. The effects of contact time and initial metal concentration were investigated in batch experiments. Eggshell-based hydroxyapatite (ESHAP) before and after Co2+ removal was characterized by X-ray diffraction and scanning electron microscopy. The process was rapid and reached equilibrium within 80 min. The removal efficiency was in the range 70–80% which is generally higher than other waste-derived adsorbents. Adsorption of Co2+ on the surface of ESHAP particles and ion exchange with Ca2+ resulting in the formation of a Co-phosphate are the main mechanisms of the metal removal. The conversion of eggshell waste to a low-cost adsorbent for the treatment of metal contaminated waters could contribute to a more sustainable and effective management of this biowaste.
Ultrasound localization microscopy of renal tumor xenografts in chicken embryo is correlated to hypoxia
Authors: Lowerison Matthew R. , Huang Chengwu , Lucien Fabrice , Chen Shigao , Song Pengfei
Published: February 2020

Ultrasound localization microscopy (ULM) permits the reconstruction of super-resolved microvascular images at clinically relevant penetration depths, which can be potentially leveraged to provide non-invasive quantitative measures of tissue hemodynamics and hypoxic status. We demonstrate that ULM microbubble data processing methods, applied to images acquired with a Verasonics Vantage 256 system, can provide a non-invasive imaging surrogate biomarker of tissue oxygenation status. This technique was applied to evaluate the microvascular structure, vascular perfusion, and hypoxia of a renal cell carcinoma xenograft model grown in the chorioallantoic membrane of chicken embryos. Histological microvascular density was significantly correlated to ULM measures of intervessel distance (R = −0.92, CI95 = [−0.99,−0.42], p = 0.01). The Distance Metric, a measure of vascular tortuosity, was found to be significantly correlated to hypoxyprobe quantifications (R = 0.86, CI95 = [0.17, 0.99], p = 0.03). ULM, by providing non-invasive in vivo microvascular structural information, has the potential to be a crucial clinical imaging modality for the diagnosis and therapy monitoring of solid tumors.