bluuebunny/crossref_metadata_2025 huggingface dataset:
The impact of low-carbon emission reduction policies on economic growth
Authors: Sheng Yuqi
Published: June 2021

As the development of a green and low-carbon economy has received great attention from governments around the world, carbon peaking and carbon neutrality have become important issues raised by China. As a major energy consuming country, government has actively formulated and implemented various carbon emission reduction policies in order to curb carbon emissions. Whether these policies achieve economic growth in the process of energy conservation and emission reduction, and promote China’s green and low-carbon development transition is the focus of this paper. This paper selects data from 30 provinces in China from 2010 to 2019, establishes a model, and empirically analysis the impact of carbon emission reduction policy tools on economic growth. The results show that there is a significant negative correlation between mandatory carbon emission reduction policies and economic growth, while market-based carbon emission reduction policies enhance the economic strength of the region. In addition, this paper empirically tests that after the establishment of the carbon market in 2013, market-based carbon emission reduction policies have significantly promoted economic growth, and the impact of carbon emission reduction policies on economic growth have regional heterogeneity.
Application of Computer Technology in Legal Practice
Authors: Tan Yuanyuan , Li Ying
Published: June 2021

Based on the practice of law, the modern technology of electronic computer means and the practice that can be accepted by everyone who has been processed by electronic means have been obtained by the scientific and technological means that are now widely popular in the education field. Since its inception, in education A huge butterfly effect has been produced in the world, which has changed the thoughts, means and methods inherent in human practice in the past, making the practice of law more convenient, faster, visualized and foreseeable. The purpose of this article is to study the application of computer technology in legal practice. This article uses literature method, questionnaire survey method, expert interview method, field investigation method and other research methods, taking the application research of computer technology in the practice of law science as the research object, and conducts research on the application status and main problems of law practice courses in a university in this province. According to the survey and analysis, 28% of the students believe that their practical ability has been significantly improved after legal practice based on computer technology, master basic legal theory knowledge, and train themselves to use legal theory to analyze and solve individual legal cases. Ability, 42% of students believe that their transaction processing ability has improved to a certain extent compared to before.
Research on the cultivation of applied innovative talents in art design under the background of new liberal arts construction based on Cocos Digital Technology
Authors: Gao Jianjie , Lai Wenqing , Huang Xiurong
Published: June 2021

In today’s new era of digital technology-driven innovation, the continuous development of information technology has brought reforms and innovations to the education field, and has injected new vitality into the modernization of education in my country. The use of information technology to promote educational reforms is incorporated into education related policies. Innovation is the driving force of national development, and it is also the focus of international competition and talent training under the background of economic globalization. The construction of new liberal arts is an innovative development measure for China’s higher liberal arts education in the new era. It is the emphasis and requirement of liberal arts in the development of science and technology today. In the context of the new liberal arts, the training of art design professionals should be cross-integrated with computer science, information technology and other disciplines, combined with the development and needs of regional digital industries, breaking professional boundaries, and mastering cutting-edge technology on the premise of adhering to the core values of art and design education. At the same time, reconstruct the talent training model. This article elaborated on the development trend of digital and informatization of art design education in the talent training and discipline construction of the art design major, and the official team of Cocos Engine-Yaji Software to build the Cocos Digital Technology Industry College to create a new mode of efficient integration of production and education., To build a unique digital art talent training system, to effectively connect the talent chain and the industrial chain, to promote the industrialization of academic achievements, to cultivate application-oriented talents that meet the needs of the digital industry, and to promote the construction of a new liberal arts major in art design.
Portfolio Construction for Pharmaceutical Industry
Authors: Sun Xiqing , Li Baichuan , Pang Huatian
Published: June 2021

In finance area, portfolio construction is one of the most vital questions since the primary work of modern finance and attract numerous studies. In this paper, we focused on this issue in pharmaceutical industry since the industry is crucial for human beings. We adopted several methods for portfolio construction, like Equal Weighted Model, Monte Carlo simulation, and maximize Sharpe ratio etc. Specifically, five assets are selected. Then based on the Monte Carlo method, we constructed two optimized portfolios in the framework of the efficient frontier, i.e., portfolios with minimum variance and maximum Sharpe ratio. By analyzing the two portfolios, we found that the NVS accounts for the largest proportions in the optimized portfolio. The results in this paper may shed lights for certain investors who invest in pharmaceutical industry.
Prevalence of Atherosclerotic Cardiovascular Disease, Heart Failure, and Chronic Kidney Disease in Patients with Type 2 Diabetes Mellitus: A Primary Care Research Network-based Study
Authors: Goderis Geert , Vaes Bert , Mamouris Pavlos , van Craeyveld Eline , Mathieu Chantal
Published: June 2021

Aims This study aims to assess the prevalence of atherosclerotic cardiovascular disease (ASCVD), heart failure (HF), chronic kidney disease (CKD), and their combined presence in type 2 diabetes (T2D) patients in primary care for whom the 2019 ADA/EASD consensus update “Management of Hyperglycemia in Type 2 Diabetes” recommends GLP-1 receptor agonists (GLP-1RA) or sodium-glucose cotransporter-2 inhibitors (SGLT-I) as first-line medications after metformin.

Methods Data were obtained in 2015 from Intego, a morbidity registration network of 111 general practitioners (GPs) working in 48 practices and including 123 261 registered patients.

Results Of 123 261 patients, 9616 had T2D. Of these patients, 4200 (43.7%) presented with ASCVD and/or CKD and/or HF. Specifically, 3348 (34.8%) patients had ASCVD, 388 (4.0%) had heart failure, and 1402 (14.6%) had CKD. Compared to patients without any of these comorbidities, patients with at least 1 of these conditions were older (69.7 ±12.6 vs. 63.1±12.5 years), had higher LDL-C values (104.2±35.8 mg/dl vs. 97.2±37.7) and less frequently achieved the systolic blood pressure target of 140 mm Hg (53 vs. 61%) (all p<0.001). Comorbid patients also had significantly more other comorbidities, such as dementia or cancer; received more recommended medications, such as statins; and received less metformin. Most patients with HF (325; 3.4%) had ASCVD (114; 1.2%), CKD (76; 0.8%), or both (135; 1.4%). In total, 478 patients with CKD (5.0%) also had ASCVD.

Conclusions At the primary care level, 44% of T2D patients suffer from ASCVD, CKD, and/or HF, and thus qualify for GLP-1RA or SGLT2-I therapy.
Additive Manufacturing: The Next Generation of Scapholunate Ligament Reconstruction
Authors: Rush Matthew N. , Salas Christina , Mottishaw Lorraine , Fountain Damian , Mercer Deana
Published: June 2021

Background Ligament reconstruction, as a surgical method used to stabilize joints, requires significant strength and tissue anchoring to restore function. Historically, reconstructive materials have been fraught with problems from an inability to withstand normal physiological loads to difficulties in fabricating the complex organization structure of native tissue at the ligament-to-bone interface. In combination, these factors have prevented the successful realization of nonautograft reconstruction.

Methods A review of recent improvements in additive manufacturing techniques and biomaterials highlight possible options for ligament replacement.

Description of Technique In combination, three dimensional-printing and electrospinning have begun to provide for nonautograft options that can meet the physiological load and architectures of native tissues; however, a combination of manufacturing methods is needed to allow for bone-ligament enthesis. Hybrid biofabrication of bone-ligament tissue scaffolds, through the simultaneous deposition of disparate materials, offer significant advantages over fused manufacturing methods which lack efficient integration between bone and ligament materials.

Results In this review, we discuss the important chemical and biological properties of ligament enthesis and describe recent advancements in additive manufacturing to meet mechanical and biological requirements for a successful bone–ligament–bone interface.

Conclusions With continued advancement of additive manufacturing technologies and improved biomaterial properties, tissue engineered bone-ligament scaffolds may soon enter the clinical realm.
Tokamak equilibria with incompressible flow parallel to the magnetic field and pressure anisotropy
Authors: Poulipoulis G. , Throumoulopoulos G. N.
Published: June 2021

It is believed that plasma rotation can affect transitions to the advanced confinement regimes in tokamaks. In addition, in order to achieve fusion temperatures, modern tokamaks rely on auxiliary heating methods. These methods generate pressure anisotropy in the plasma. For incompressible rotation with pressure anisotropy, the equilibrium is governed by a generalized Grad–Shafranov (GGS) equation and a decoupled Bernoulli-type equation for the effective pressure, p̄=(p∥+p⊥)/2, where p∥ (p⊥) is the pressure tensor element parallel (perpendicular) to the magnetic field. In the case of plasma rotation parallel to the magnetic field, the GGS equation can be transformed to one equation identical in form with the GS equation. In this study, by making use of the aforementioned property of the GGS equation for parallel plasma rotation, we have constructed ITER-like numerical equilibria by extending HELENA, an equilibrium fixed-boundary solver, and examined the impact of rotation and anisotropy on certain equilibrium quantities. The main conclusions are that the addition of pressure anisotropy to rotation allows the profile shaping of the equilibrium quantities to much more extent compared to the isotropic case, thus favoring the confinement, and allows extension of the parametric space of the Mach number corresponding to higher values. Furthermore, the impact of pressure anisotropy on the equilibrium quantities is stronger than that of the rotation for most of the quantities examined in view of respective experimental values. For the pressure components, the impact of the pressure anisotropy is the same, regardless of whether the power is deposited parallel or perpendicular to the magnetic surfaces, thus implying that there is no preferable heating direction, while for the current density, the heating parallel to the magnetic surfaces seems to be beneficial for the current gradient-driven instabilities.
Effect of hydrophobic association on the flow resistance of polymer solutions
Authors: Wang Jun , Shi Leiting , Zhu Shijie , Xiong Youming , Liu QingYou
Published: June 2021

Comprehending the percolation law of polymer solutions in porous media is the basis of effective application of polymer flooding. The solution properties of partially hydrolyzed polyacrylamide (HPAM) and the hydrophobically associating polymer AP-P4 were compared, and the seepage characteristics in porous media were studied. The results showed that HPAM is a viscoelastic fluid dominated by a viscosity modulus. The smaller hydrodynamic size (≥3 µm) and low adsorption capacity (200 µg/g) caused an increase in the resistance factor of HPAM in porous media with the increase in injection velocity. Hydrophobic association greatly improved the solution properties of the polymer, with a stronger apparent viscosity, elastic modulus, hydrodynamic size (≥10 µm), and adsorption capacity (780 µg/g), showing that the viscoelastic fluid properties were dominated by the elastic modulus. The resistance factor of the polymer solution in porous media decreased with the increase in injection velocity.
Design and test of a piezoelectric micropump based on hydraulic amplification
Authors: Tian Xiao-chao , Wang Hai-gang , Wang Hu , Wang Zhi-cong , Sun Yu-ze , Zhu Jin-zhi , Zhao Jian , Zhang Si-da , Yang Zhi-gang
Published: June 2021

To solve the problem of the small deformation of piezoelectric vibrators and improve the overall performance of piezoelectric micro-pumps, a flexible-diaphragm piezoelectric micropump is designed based on hydraulic amplification. The micropump uses a piezoelectric vibrator to provide its driving force, and fluid is delivered by driving the liquid to amplify the displacement of the piezoelectric vibrator. First, the working principle of the piezoelectric micropump is analyzed, and then theoretical analysis and displacement output tests of the hydraulic amplifier unit are carried out. The test results are consistent with those of the theoretical analysis, and the amplification factor of the hydraulic amplifier unit is 3.29. Finally, prototypes are produced and an experimental platform is built for testing. The results indicate that the best-performing piezoelectric micropump has a self-priming height of 1200 mm, an output pressure of 22.16 kPa, and an output flow of 23.18 ml/min. Compared with an ordinary piezoelectric pump, the overall performance of the piezoelectric micropump is greatly improved.
Stability, Structure, and Permeability Studies of Copper Tripeptide Species in Aqueous Solution
Authors: Hammouda Ahmed N. , Elmagbari Fatin M. , Jackson Graham E. , Vicatos Giselle M. , Bonomo Raffaele P. , Valora Gabriele
Published: June 2021

The use of copper complexes to alleviate inflammation associated with rheumatoid arthritis (RA) is well known. This study focuses on designing a new drug that could be used to increase the bioavailability of copper and hence be more effective. The ligand chosen was sarcosyl-l-lysyl-l-lysine (Sar-Lys-Lys). The thermodynamic stability of H+, CuII, NiII, and ZnII complexes of Sar-Lys-Lys was measured in an aqueous solution at 298 ± 0.01°C and an ionic strength of 0.15 M (NaCl) using glass electrode potentiometry. UV-Vis, ESR, and 1H NMR spectroscopy was used to investigate the solution structures of the different species. At physiological pH, the ligand was found to coordinate via two amide nitrogens, the terminal amine, and the terminal carboxy group. The ε-amino group of lysine did not coordinate with the metal ion. Dermal absorption is the preferred method of administration and so this study used partition coefficients and tissue permeability studies to assess the bioavailability of the different complexes. Sar-Lys-Lys was found to increase the copper lipophilicity by a factor of 10 and increased tissue permeability by 30 %.
Salinity tolerance and avoidance mechanisms at germination among messina (
Authors: Jeffery Robert P. , Ryan Megan H. , Ayers Natasha L. , Nichols Phillip G. H.
Published: June 2021

Messina (Melilotus siculus) cv. Neptune, an annual pasture legume native to the Mediterranean Basin, has recently been released for saltland pastures in southern Australia following demonstration of biomass production and persistence superior to other commercial pasture legumes in saline environments prone to winter waterlogging. Self-regenerating annual pasture legumes also require seed adaptations for both tolerating and avoiding salinity at germination in these environments. This study examined diversity within Neptune and 20 other messina accessions for salt tolerance at germination, recovery of germinability from temporary salt stress, and timing and extent of hardseed softening, compared with balansa clover (Trifolium michelianum) cv. Frontier, burr medic (Medicago polymorpha) cv. Scimitar and white melilot (Melilotus albus) cv. Jota. Germination rates after 14 days at 300 mM NaCl relative to 0 mM NaCl were ≥99% for Neptune and 18 other messina accessions, 66% for Scimitar, 21% for Jota and 11% for Frontier. No genotype germinated at 600 mM NaCl; however, when transferred to 0 mM NaCl after 14 days at 600 mM, all genotypes except Scimitar and Jota recovered partial germination, ranging from 13% to 93% of controls (0 mM NaCl for 28 days). The softening rate of hard (impermeable) seeds in the field varied among genotypes, with deferral of hardseed softening until late autumn–early winter, when rainfall is more likely, indicating greater persistence. The months in which the hardseed level first became significantly lower than the initial level (in freshly harvested seeds) after placement on the soil surface in December were: March for Frontier; April for Scimitar, Jota and Neptune; and March–July for all messina accessions. This study confirmed that messina has high salt tolerance and several avoidance mechanisms at germination that contribute to its adaptation to saline soils in southern Australia. Several messina accessions were superior to Neptune for individual traits which could be exploited for plant breeding. These results also have implications for saltland pastures in other regions of the world with Mediterranean-type climates.
Recent trends in health assessments for older Australians
Authors: Mitchell Eleanor K. L. , D’Amore Angelo
Published: June 2021

Non-Indigenous older Australians (aged 75+ years) are encouraged to undertake an annual health assessment (75+HA) to identify overlooked medical conditions, holistically assess the management of current chronic conditions and highlight potential risk factors for poor health. Uptake in the 2000s has been previously reported to be slowly increasing, but still very low. This study aimed to identify the uptake of 75+HA between 2011 and 2019, comparing State and National trends over a 9-year period. The uptake of Medicare Items 701, 703, 705 and 707 between 2011 and 2019 was analysed. These results were incorporated with Australian Demographics data to present rate ratios by State and age groups. An increasing number of 75+HAs were performed between 2011 and 2019, and the 75+HAs performed were increasing in duration. Overall, the 75+HA uptake was still generally low, at approximately one-third of the eligible population; however, despite the low uptake, age-standardised figures showed upward trends. The 75+HA rate in the 85+ year group has now overtaken their younger (aged 75–84 years) counterparts. There were also clear variations between States. Given the low rates, strategies to improve uptake should be targeted so all eligible Australians receive an annual Medicare Benefits Schedule (MBS)-funded 75+HA.
Self-excitation of Leidenfrost drops and consequences on their stability
Authors: Bouillant Ambre , Cohen Caroline , Clanet Christophe , Quéré David
Published: June 2021

Significance

A volatile liquid placed on a hot plate is known to levitate on a cushion of vapor. Such drops have unusual behaviors, among which is the ability to transform in pulsating stars that sporadically appear for a few seconds. We report that the vapor cushion of Leidenfrost drops spontaneously vibrates, which can trigger the pulsating modes via a Faraday instability. The mediating waves and subsequent peripheric undulations resonate at well-defined drop sizes, which explains their transient nature and the mode hierarchy. These effects illustrate the unique nature of a situation combining hydrodynamics, aerodynamics, and phase change. Beyond the light shed on the origin of Leidenfrost stars, levitating drops also provide toy models for the Faraday instability in open, globular, small-size systems.
A globally fragmented and mobile lithosphere on Venus
Authors: Byrne Paul K. , Ghail Richard C. , Şengör A. M. Celâl , James Peter B. , Klimczak Christian , Solomon Sean C.
Published: June 2021

Significance

We have identified a pattern of tectonic deformation on Venus that suggests that many of the planet’s lowlands have fragmented into discrete crustal blocks, and that these blocks have moved relative to each other in the geologically recent past. These motions may be the result of mantle convection and, if so, constitute a style of interior–surface coupling not seen elsewhere in the inner Solar System except for continental interiors on Earth. Venus’ fragmented, mobile lithosphere may offer a framework for understanding how tectonics on Earth operated in the Archean.
Proton-and neutron-rich breakups near zero binding energy
Authors: Mukeru B
Published: June 2021

An analysis of the elastic scattering and breakup cross sections in the

17

F

/

17

O
+

208

Pb

reactions in the zero binding energy limit, is presented. The main motivation was to investigate whether finite reaction observables can be obtained for a neutron-rich system in this limit, where it can be regarded as an open quantum system. It is first found that as the binding energy tends to zero, the ground-state wave function of the

17

O

(

16

O

+n) system falls asymptotically as

∼
1

/

r

ℓ

b

(where

ℓ

b

=
2

, is the ground-state orbital angular momentum). For both projectiles, finite elastic scattering and breakup cross sections are obtained in the zero binding energy limit, where they also become insensitive to the variation of the binding energy. For the

17

F

projectile, this is due to the core-proton Coulomb barrier, whereas for the

17

O

projectile, it is due to the

∼
1

/

r

ℓ

b

asymptotic behavior of the ground-state wave function in this limit. In conclusion, finite reaction observables in the breakup of an open quantum system can be obtained for

ℓ

b

≥
2

.
Edge-of-field runoff prediction by a hybrid modeling approach using causal inference
Authors: Hu Yao , Fitzpatrick Lindsay , Fry Lauren M , Mason Lacey , Read Laura K , Goering Dustin C
Published: June 2021

Unforeseen runoff events cause nutrient losses that affect crop production, revenue, and contribute to deteriorated water quality, leading to harmful algal blooms and hypoxia in receiving water bodies in the Great Lakes region. To mitigate the negative impacts caused by runoff events, we developed a hybrid modeling approach by combining physics-based and statistical models to predict the occurrence and level of severity of daily runoff events, supporting agricultural producers to avoid nutrient application before significant runoff events. We chose to use the National Oceanic and Atmospheric Administration’s National Water Model (NWM) as the physical model given its flexible architecture design, technical robustness, model resolution, data availability, and wide application scale. For the statistical model, we developed a data-driven tool built from Directed Information and eXtreme Gradient Boosting (XGBoost) to estimate the occurrence and the level of severity of daily edge-of-eld (EOF) runoff events. This data-driven tool ingests a large variety of variables from NWM operational runs and translates them into the EOF runoff predictions on a daily scale in the Great Lakes region. Without calibrating the large-scale NWM for the local runoff prediction, the results show large improvements in the prediction of the occurrence and level of severity of daily EOF runoff using the hybrid physical-statistical modeling approach. Ultimately, the hybrid approach, when integrated into runoff risk decision support tools, is expected to provide dual benefits to agricultural producers and water quality, retaining more nutrients on their fields and lowering nutrient loads to water bodies during runoff events.
The evolutionary origin of near-death experiences: a systematic investigation
Authors: Peinkhofer Costanza , Martial Charlotte , Cassol Helena , Laureys Steven , Kondziella Daniel
Published: June 2021

Near-death experiences are known from all parts of the world, various times and numerous cultural backgrounds. This universality suggests that near-death experiences may have a biological origin and purpose. Adhering to a preregistered protocol, we investigate the hypothesis that thanatosis, aka death-feigning, a last-resort defense mechanism in animals, is the evolutionary origin of near-death experiences. We first show that thanatosis is a highly preserved survival strategy occurring at all major nodes in a cladogram ranging from insects to humans. We then show that humans under attack by animal, human and ‘modern’ predators can experience both thanatosis and near-death experiences, and we further show that the phenomenology and the effects of the two overlap. In summary, we build a line of evidence suggesting that thanatosis is the evolutionary foundation of near-death experiences and that their shared biological purpose is the benefit of survival. We propose that the acquisition of language enabled humans to transform these events from relatively stereotyped death-feigning under predatory attacks into the rich perceptions that form near-death experiences and extend to non-predatory situations.
Hilbert’s Tenth Problem for Complex Meromorphic Functions in Several Variables
Authors: Pheidas Thanases , Vidaux Xavier
Published: June 2021

We prove that Hilbert’s Tenth Problem for meromorphic functions and for entire functions in several variables is unsolvable over the language of rings, together with constant symbols for two of the variables and a predicate for a place. This is the first result in the literature, which proves unsolvability of a diophantine problem for the ring of complex analytic functions in a number of variables. The proof rests upon an interplay between analytic geometry, analysis, number theory, and logic.
KIC 9406652: A laboratory for tilted disks in cataclysmic variable stars. II. Modeling of the orbital light curves
Authors: Kimura Mariko , Osaki Yoji
Published: June 2021

KIC 9406652, one of the recently identified IW And-type dwarf novae, is the best target for studying the tilted disk in cataclysmic variable stars. In a previous paper by Kimura et al. (2020b, PASJ, 72, 94), we analyzed its Kepler light curves and found that its orbital light curves during the brightening stage were dominated by the reflection effect of the secondary star and varied with the orientation of the tilted disk; the amplitude was maximized at the minimum of the super-orbital signal and the phase of the light maximum shifted to an earlier one with the advance of the super-orbital phase. We argued in that work that this was direct evidence of the retrogradely precessing tilted disk as the secondary star acts like a reflecting object. In order to confirm this interpretation, we have performed numerical modeling of orbital light curves in this paper. We have succeeded in reproducing the main characteristics of the observed orbital light curves by a simple model in which the secondary star is irradiated by the tilted disk. We have also constrained the inclination angle, i, of the binary system and the tilt angle, θ, of the disk purely from photometric considerations. The best-fitting parameter set is found to be i ∼ 45° and $\theta \sim {2{_{.}^{\circ}}0}$, respectively. The orbital inclination thus estimated is consistent with that obtained from the spectroscopic considerations within the uncertainty limit. On the other hand, the tilt angle of the disk could be underestimated by using only the semi-amplitude of super-orbital signals.
Deciphering controversial results of cell proliferation on TiO2 nanotubes using machine learning
Authors: Shen Ziao , Wang Si , Shen Zhenyu , Tang Yufei , Xu Junbin , Lin Changjian , Chen Xun , Huang Qiaoling
Published: June 2021

With the rapid development of biomedical sciences, contradictory results on the relationships between biological responses and material properties emerge continuously, adding to the challenge of interpreting the incomprehensible interfacial process. In the present paper, we use cell proliferation on titanium dioxide nanotubes (TNTs) as a case study and apply machine learning methodologies to decipher contradictory results in the literature. The gradient boosting decision tree model demonstrates that cell density has a higher impact on cell proliferation than other obtainable experimental features in most publications. Together with the variation of other essential features, the controversy of cell proliferation trends on various TNTs is understandable. By traversing all combinational experimental features and the corresponding forecast using an exhausted grid search strategy, we find that adjusting cell density and sterilization methods can simultaneously induce opposite cell proliferation trends on various TNTs diameter, which is further validated by experiments. This case study reveals that machine learning is a burgeoning tool in deciphering controversial results in biomedical researches, opening up an avenue to explore the structure–property relationships of biomaterials.
Effects of lipid and starch supplementation as water intake mitigation techniques on performance and efficiency of nursing Holstein calves
Authors: Macias Franco A , da Silva A E M , de Moura F H , Norris A B , Van Den Broek K , Valcheck M , de Mello A , Fonseca M
Published: June 2021

Exploring alternative supplementation sources capable of maximizing feed and water efficiency in nursing Holstein calves is often ignored. The goals herein involve investigating the effects of two isoenergetic supplements on a nonmedicated milk replacer diet on total water intake, milk water intake, fresh water intake, feed intake parameters, and performance of Holstein nursing bull calves. Twenty-three animals (body weight [BW] = 94.67 ± 12.07 kg, age = 67 days old) were randomly assigned to one of three treatments for 68 days: control (CON; ad libitum milk replacer, n = 7), carbohydrate supplement (CHO; corn starch on top of ad libitum milk replacer-based diet, n = 8), or lipid supplement (FAT; menhaden fish oil on top of ad libitum milk replacer-based diet, n = 8). The isoenergetic supplementation consisted of 3% menhaden fish oil addition on DM basis for FAT. This was matched energetically with corn starch for the CHO group resulting in a 7% composition in DM basis. All animals were provided free access to mineral mix and 120 g daily dried microbrewer’s spent grains (BG). Data were analyzed with the GLMMIX procedure of SAS in a completely randomized design with the diets as a fixed effect. Dry matter intake (DMI) adjusted by average daily gain (ADG; DMI/ADG) resulted in significantly lower values for supplemented groups with CON = 2.48, CHO = 2.38, and FAT = 2.27 kg/kg (ADG) (P = 0.033). Energy intake values were lower for CON when analyzing metabolizable energy intake (P < 0.0001), net energy intake for maintenance (P < 0.0001), and net energy intake for gain (P < 0.0001), followed by CHO, and then FAT. Total water intake (P < 0.0001), milk water intake (P < 0.0001), and fresh water intake (P < 0.0001) all resulted in CHO consuming 0.5 L or less water than the other two treatments. Energy requirements as digestible energy (P < 0.0001), metabolizable energy (P < 0.0001), net energy for maintenance (P < 0.0001), and net energy for gain (P < 0.0001) were lower for CHO, followed by CON, and then FAT having the highest requirements. Similar results were observed for residual feed (RFI; P = 0.006) and residual water intakes (RTWI; P = 0.902). Ultimately, no performance differences were detected with regards to BW (CON = 146.71, CHO = 146.25, and FAT = 150.48 kg; P > 0.1). These results indicate that lipid-based and starch-based supplementation can potentially increase feed efficiency and decrease voluntary water intake without adversely affecting performance.
Host microbe interactions in the primate gut: Implications for human origins
Authors: Gomez Andres , Torralba Manlito , Nelson Karen E. , Stumpf Rebecca , Blekhman Ran , Petrzelkova Klara
Published: June 2021

The breadth of microbiome research produced in the last decade has evidenced the vast diversity of human‐associated microbial systems, correlating specific microbial states to a myriad of host phenotypes. However, there is still a significant gap in our understanding of how humans and their residing microbes communicate, in light of environmental change and host evolution. By employing a meta‐OMIC approach (metatranscriptomics, metagenomics and metabolomics) in stool samples of wild western lowland gorillas (G.g.gorilla) and BaAka hunter‐gatherers (H.sapiens), and non‐invasive screening of host‐derived signals from fecal samples, we sought to characterize gene expression profiles in the tissue lining up the host distal gut, in the context of host‐specific bacterial composition, function and diets. The data show that despite the limited amount of host signals generated from fecal samples, unique gene regulation profiles distinguishing the colonic tissue of the 2 primate species correlate strongly with the abundance of particular metabolites and bacterial taxa; specifically, while increased expression of genes involved in metabolism and cell architecture characterizing the distal gut tissue of gorillas corresponded with higher abundance of phenolic metabolites; differential expression of immune‐associated genes in human colonic tissue showed associations with lipid‐derived metabolites and bacteria typically associated with the processing of simpler polysaccharides. As such, we discuss how diet‐derived metabolites and the gut microbiome converged to impact genes involved nutrition and immunity in the host along evolutionary timescales, and examine the pivotal role that diet could have had in human speciation and evolution, through a microbiome lens. Likewise, we show how studies of this nature could lay the foundations to understand mechanistic insights of gene regulation by the microbiome to impact diverse host phenotypes.

Support or Funding Information

KONTAKT (American Science Information Agency, Czech‐American Scientific cooperation)

This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
The gut microbiome connection to Parkinson's disease
Authors: Mazmanian Sarkis K.
Published: June 2021

The intestinal microbiota influence neurodevelopment, modulate behavior, and contribute to neurological disorders. However, a functional link between gut bacteria and neurodegenerative diseases remains unexplored. Synucleinopathies are characterized by aggregation of the protein a–synuclein (aSyn), often resulting in motor dysfunction as exemplified by Parkinson's disease (PD). Using mice that overexpress aSyn, we report herein that gut microbiota are required for motor deficits, microglia activation, and aSyn pathology. Antibiotic treatment ameliorates, while microbial re‐colonization promotes, pathophysiology in adult animals, suggesting that postnatal signaling between the gut and the brain modulates disease. Indeed, oral administration of specific microbial metabolites to germ‐free mice promotes neuroinflammation and motor symptoms. Remarkably, colonization of aSyn‐overexpressing mice with microbiota from PD‐affected patients enhances physical impairments compared to microbiota transplants from healthy human donors. These findings reveal that gut bacteria regulate movement disorders in mice and suggest that alterations in the human microbiome represent a risk factor for PD.

Support or Funding Information

National Institutes of Health

This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Structural and Functional Studies of the Streptococcal Fibrillar Adhesin CshA
Authors: Back Catherine , Higman‐Davies Victoria , Sztukowska Maryta , Till Marisa , Crump Matthew , Lamont Richard , Jenkinson Howard , Nobbs Angela , Race Paul
Published: June 2021

Adherence of bacteria to biotic or abiotic surfaces is a prerequisite for host colonization and represents an important step in microbial pathogenicity. This attachment is facilitated by bacterial adhesins at the cell surface. Due to their size and often elaborate multi‐domain architectures, these polypeptides represent challenging targets for detailed structural and functional characterization. The multifunctional fibrillar adhesin CshA, which mediates binding to both host molecules and other microorganisms, is an important determinant of colonization by Streptococcus gordonii, an oral commensal and opportunistic human pathogen. CshA has a low sequence identity to other proteins, indicating potentially novel structural characteristics.

Our studies indicate that the N‐terminal region of CshA forms a functional head of the fibril, with a disordered portion at the tip. The C‐terminal region comprises 17 repeat blocks, each of ~99 aa residues (three incomplete), which form a long, flexible stalk, presenting the potential binding domain distal from the bacterial cell surface. In this study we present a structural analysis of CshA, derived from a combination of X‐ray crystallography, NMR, SAXS, and complementary biophysical methods. The data suggest that CshA has a novel structure not previously reported for bacterial cell surface adhesins.

CshA binds the high‐molecular‐weight glycoprotein fibronectin (Fn) via the N‐terminal non‐repetitive region, and this protein‐protein interaction has been proposed to promote S. gordonii colonization at multiple sites within the host. However, the molecular details of how these two proteins interact had not previously been investigated. In vitro binding studies support a hitherto unreported two‐state ‘catch‐clamp’ mechanism of Fn binding by CshA. The disordered N‐terminal domain of CshA acts to ‘catch’ Fn, via formation of a rapidly assembled but also readily dissociable pre‐complex, enabling its neighbouring ligand binding domain to tightly ‘clamp’ the two polypeptides together. This study presents a new paradigm for target binding by a bacterial adhesin, the identification of which will inform future efforts towards the development of anti‐adhesive agents that target S. gordonii and related streptococci.

Support or Funding Information

This work was supported in part by National Institutes of Health grants DE016690 (to H. F. J. and R. J. L.) and DE012505 (to R. J. L.), Biotechnology and Biological Sciences Research Council Grant BB/I006478/1 (to P. R. R.), and Royal Society University Research Fellowship Award UF080534 (to P. R. R.). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Chemical tools to investigate gene regulation by histone sumoylation
Authors: Chatterjee Champak
Published: June 2021

Histone modification by the small ubiquitin‐like modifier protein (SUMO) has been observed from yeast to humans. However, little is known regarding the precise biochemical roles of histone sumoylation, or its interplay with other key histone modifications such as methylation and acetylation. Efforts to investigate histone sumoylation are limited by the low abundance and transient nature of this modification in cells. Therefore, we developed and applied several facile chemical strategies to generate site‐specifically sumoylated histones in sufficient amounts for biochemical studies. Chemically sumoylated histones were reconstituted in nucleosomes and employed in a series of biochemical assays with the LSD1‐CoREST complex. Results from these experiments revealed an unprecedented relationship between histone sumoylation, methylation and acetylation and provided the first mechanistic clues toward gene regulation by SUMO.

Support or Funding Information

R01 GM110430

This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Semi‐Synthetic Glycosaminoglycan Ethers Decrease Receptors for Advanced Glycation End‐Products and Increase AXL Receptor in the Lung from Secondhand Smoke Treated Mice
Authors: Ostergar Adam , Egbert Kaleb , Clark Christian , Hall Parker , Davis Taylor , Hirschi Kelsey M. , Arroyo Juan A. , Reynolds Paul R.
Published: June 2021

Tobacco exposure is one of the top three global health risks leading to the development of chronic obstructive pulmonary disease (COPD). Although there is extensive research into the effects of cigarette smoke, the effect of secondhand smoke (SHS) in the lung remains limited. SHS induces Receptors for advanced glycation end‐products (RAGE) and an inflammatory response that leads to the development of COPD characteristics. Semi‐synthetic glycosaminoglycan ethers (SAGEs) are sulfated polysaccharides derived from hyaluronic acid (HA) that inhibit RAGE signaling. The growth arrest‐specific 6 (Gas6) protein is known to induce dynamic cellular responses and is correlated with cell function. Gas6 binds to the AXL tyrosine kinase receptor and AXL‐mediated signaling is implicated in proliferation and migratory mechanisms in several tissues. This project's purpose was to study the correlation between RAGE, AXL, and Gas6 during SHS exposure in the lung. C57/Bl6 mice were exposed to SHS alone or SHS + SAGEs for 4 weeks and compared to control animals exposed to room air (RA). At the time of necropsy lungs were extracted, frozen for mRNA studies or embedded for immunohistological analysis. Compared to controls we observed: 1) increased RAGE mRNA expression in SHS‐exposed lungs which was decreased by SAGEs; 2) no difference in Gas6 or AXL expression in SHS lungs and expression was significantly increased with SAGEs; 3) increased RAGE protein expression in SHS lungs that was decreased by SAGEs; and 4) decreased AXL protein in SHS animals and increased AXL protein in animals treated with SAGEs. Our results suggest that there is a direct correlation between RAGE and AXL during SHS exposure. These studies provide insight into tobacco‐mediated effects in the lung and clarify possible avenues for alleviating complications that could arise during SHS exposure such as those observed during COPD.

Support or Funding Information

This work was supported by a grant from the Flight Attendant's Medical Research Institute (FAMRI, PRR and JAA) and a BYU Mentoring Environment Grant (JAA and PRR).

This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Role of Farnesoid X Receptor Activation in Counteracting Tumor‐promoting Functions of Cancer‐Associated Fibroblasts in Breast Cancers
Authors: BARONE INES , Vircillo Valentina , Giordano Cinzia , Tarallo Roberta , Rinaldi Antonio , Bruno Giuseppina , Gyorffy Balazs , Bonofiglio Daniela , Andò Sebastiano , Catalano Stefania
Published: June 2021

Cancer‐associated fibroblasts (CAFs), the principal components of the tumor microenvironment, play multiple roles in breast cancer onset and progression. While their significance is widely accepted, treatment options to target CAFs in clinical practice have not yet been well established. The nuclear receptor superfamily encompasses a druggable class of molecules, expressed in various stroma and parenchymal cell types, with the interesting therapeutic potential to modulate also the reactive microenvironment. Previously, we have demonstrated that activation of the nuclear Farnesoid X Receptor (FXR) in mammary epithelial cancer cells was associated with a reduction of cell proliferation, migration, and invasion ‘in vitro’ and tumor growth ‘in vivo’. To extend these observations, here, we propose to assess the function of FXR in CAFs and evaluate whether this receptor may affect their tumor‐promoting features.

Our results evidenced, for the first time, FXR mRNA and protein expression in CAFs isolated from biopsies of primary human breast tumors. Treatment with the FXR agonist GW4064 treatment was able to significantly decrease CAF motility, stress fiber formation and their contractility. RNA sequencing highlighted cell movement and migration of cells among the most down‐regulated functions and identified signalings known to govern cell cytoskeleton organization and migration (i.e. ILK‐actin cytoskeletal‐Rho signalings) among the most down‐regulated ingenuity canonical pathways in response to GW4064 treatment. Accordingly, decreased expression and activation of proteins and/or downstream effectors of these pathways were observed in GW4064‐treated CAFs. Moreover, FXR activation reduced expression of different secreted factors, that act as mediators of tumor‐stroma interaction. Indeed, coculture experiments revealed a significant inhibition in growth and motility of breast cancer cells treated with conditioned‐media derived from GW4064‐treated CAFs compared to vehicle‐treated CAFs. All this sounds to fit with the clinical relevance that increased FXR levels in bulk tumors are associated with a statistically significant longer survival of patients.

In conclusion, FXR ligands, by targeting both breast cancer epithelial cells and tumor associated stroma, may represent emerging pharmacological tools to be exploited for the future management of breast cancer.

Support or Funding Information

My First AIRC Grant #16899 to IB

This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.