bluuebunny/crossref_metadata_2025 huggingface dataset:
Aztec and Tlaxcalan Economic Interaction: Blockade or Interregional Exchange?
Authors: Gentil Bianca L. , Vicencio Castellanos A. Gabriel , Hirth Kenneth G.
Published: July 2021

This study investigates the impact of the Aztec Triple Alliance on trade and economic activity in the region of Puebla-Tlaxcala during the Late Postclassic period (AD 1200–1519). Ethnohistorical sources describe the Aztec Triple Alliance as constantly at war with settlements in the Tlaxcala region. To weaken their Tlaxcalteca rivals, the Aztecs imposed a trade blockade to reduce the flow of resources into Puebla-Tlaxcala. This article uses archaeological evidence to evaluate the effectiveness of this blockade. It compares the types of obsidian used to manufacture lithic tools from Aztec-controlled sources with those used within Puebla-Tlaxcala. Information from the large center of Tepeticpac and the small obsidian workshop site of Cinco Santos II, both in the Tlaxcala domain, are compared to other sites in Central Mexico prior to and during the height of Aztec influence. The results show little difference in regional trade patterns: obsidian from Sierra de las Navajas and Otumba was used in proportions in the Tlaxcala region in the Late Postclassic similar to those used during earlier periods. If an embargo was attempted, it was largely unsuccessful in isolating Tlaxcala from broader regional distribution networks.
The nutritional impact of replacing dietary meat with meat alternatives in the UK: a modelling analysis using nationally representative data
Authors: Farsi Dominic N. , Uthumange Dinithi , Munoz Munoz Jose , Commane Daniel M.
Published: July 2021

Dietary patterns high in meat compromise both planetary and human health. Meat alternatives may help to facilitate meat reduction; however, the nutritional implications of displacing meat with meat alternatives does not appear to have been evaluated. Here, the ninth cycle of the National Diet and Nutrition Survey was used as the basis of models to assess the effect of meat substitution on nutritional intake. We implemented three models; model 1 replaced 25 %, 50 %, 75 % or 100 % of the current meat intake with a weighted mean of meat alternatives within the UK market. Model 2 compared different ingredient categories of meat alternative; vegetable, mycoprotein, a combination of bean and pea, tofu, nut and soya. Model 3 compared fortified v. unfortified meat alternatives. The models elicited significant shifts in nutrients. Overall, carbohydrate, fibre, sugars and Na increased, whereas reductions were found for protein, total and saturated fat, Fe and B12. Greatest effects were seen for vegetable-based (+24·63g/d carbohydrates), mycoprotein-based (–6·12g/d total fat), nut-based (–19·79g/d protein, +10·23g/d fibre; −4·80g/d saturated fat, +7·44g/d sugars), soya-based (+495·98mg/d Na) and tofu-based (+7·63mg/d Fe, −2·02μg/d B12). Our results suggest that meat alternatives can be a healthful replacement for meat if chosen correctly. Consumers should choose meat alternatives low in Na and sugar, high in fibre, protein and with high micronutrient density, to avoid compromising nutritional intake if reducing meat intake. Manufacturers and policy makers should consider fortification of meat alternatives with nutrients such as Fe and B12 and focus on reducing Na and sugar content.
COMMUNITY INTERESTS AND THE PROTECTION OF THE MARINE ENVIRONMENT WITHIN NATIONAL JURISDICTION
Authors: McCreath Millicent
Published: July 2021

This article considers the under-studied question of the interests that the international community may have in the protection of the marine environment within national jurisdiction. This question is addressed on the basis of a comprehensive analysis of the major documents that reveal the convictions of the international community, including UN General Assembly resolutions, major international treaties and the outcomes of multilateral conferences. The core argument is that, despite the dominance of the zonal jurisdictional regime in the law of the sea, the international community has, in fact, clearly and consistently demonstrated an interest in the protection of the marine environment within national jurisdiction. Although a finding of community interest does not affect the character of the coastal State's primary environmental protection obligations, it may have implications for the rights of third States to challenge a coastal State's failure to protect its own marine environment. Whether third States choose to exercise this right in practice remains to be seen; however, this article's findings should indicate to States that their actions and policies concerning the protection of the marine environment of their own maritime zones are a matter of concern to all States.
Slab-geometry surface waves on steep gradients and the origin of related numerical issues in a variety of ICRF codes
Authors: Tierens Wouter , Colas Laurent ,   EUROfusion MST1 Team
Published: July 2021

In the ion cyclotron range of frequencies, electromagnetic surface waves are physically relevant for wave–filament interactions, parasitic edge losses and sheath–plasma waves. They are also important numerically, where non-physical surface waves may occur as side effects of slab-geometry approximations. We give new, completely general, mathematical techniques to construct dispersion relations for electromagnetic surface waves between any two media, isotropic or anisotropic, and first-order corrections for when the material interface is steep but continuous. We discuss numerical issues (localized non-convergence, undesired power generation) that arise in numerical calculations due to the presence of surface waves.
Altered effective connectivity of the extended face processing system in depression and its association with treatment response: findings from the YoDA-C randomized controlled trial
Authors: Jamieson Alec J. , Harrison Ben J. , Davey Christopher G.
Published: July 2021

Background

Depression is commonly associated with fronto-amygdala dysfunction during the processing of emotional face expressions. Interactions between these regions are hypothesized to contribute to negative emotional processing biases and as such have been highlighted as potential biomarkers of treatment response. This study aimed to investigate depression associated alterations to directional connectivity and assess the utility of these parameters as predictors of treatment response.

Methods

Ninety-two unmedicated adolescents and young adults (mean age 20.1; 56.5% female) with moderate-to-severe major depressive disorder and 88 healthy controls (mean age 19.8; 61.4% female) completed an implicit emotional face processing fMRI task. Patients were randomized to receive cognitive behavioral therapy for 12 weeks, plus either fluoxetine or placebo. Using dynamic causal modelling, we examined functional relationships between six brain regions implicated in emotional face processing, comparing both patients and controls and treatment responders and non-responders.

Results

Depressed patients demonstrated reduced inhibition from the dlPFC to vmPFC and reduced excitation from the dlPFC to amygdala during sad expression processing. During fearful expression processing patients showed reduced inhibition from the vmPFC to amygdala and reduced excitation from the amygdala to dlPFC. Response was associated with connectivity from the amygdala to dlPFC during sad expression processing and amygdala to vmPFC connectivity during fearful expression processing.

Conclusions

Our study clarifies the nature of face processing network alterations in adolescents and young adults with depression, highlighting key interactions between the amygdala and prefrontal cortex. Moreover, these findings highlight the potential utility of these interactions in predicting treatment response.
MEASUREMENT PROPERTIES OF A STANDARDIZED ELICITED IMITATION TEST: AN INTEGRATIVE DATA ANALYSIS
Authors: Isbell Daniel R. , Son Young-A
Published: July 2021

Elicited Imitation Tests (EITs) are commonly used in second language acquisition (SLA)/bilingualism research contexts to assess the general oral proficiency of study participants. While previous studies have provided valuable EIT construct-related validity evidence, some key gaps remain. This study uses an integrative data analysis to further probe the validity of the Korean EIT score interpretations by examining the performances of 318 Korean learners (198 second language, 79 foreign language, and 41 heritage) on the Korean EIT scored by five different raters. Expanding on previous EIT validation efforts, this study (a) examined both inter-rater reliability and differences in rater severity, (b) explored measurement bias across subpopulations of language learners, (c) identified relevant linguistic features which relate to item difficulty, and (d) provided a norm-referenced interpretation for Korean EIT scores. Overall, findings suggest that the Korean EIT can be used in diverse SLA/bilingualism research contexts, as it measures ability similarly across subgroups and raters.
The two extinctions of the Carolina ParakeetConuropsis carolinensis
Authors: BURGIO KEVIN R. , CARLSON COLIN J. , BOND ALEXANDER L. , RUBEGA MARGARET A. , TINGLEY MORGAN W.
Published: July 2021

Due to climate change and habitat conversion, estimates of the resulting levels of species extinction over the next century are alarming. Devising conservation solutions will require many different approaches, including examining the extinction processes of recently extinct species. Given that parrots are one of the most threatened groups of birds, information regarding parrot extinction is pressing. While most recent parrot extinctions have been island endemics, the Carolina ParakeetConuropsis carolinensishad an 18th-century range covering nearly half of the present-day United States, yet mostly disappeared by the end of the 19thcentury. Despite a great deal of speculation, the major cause of its extinction remains unknown. Establishing the date when a species went extinct is one of the first steps in determining what caused their extinction. While there have been estimates of their extinction date, these analyses used a limited dataset and did not include observational data. We used a recently published, extensive dataset of Carolina Parakeet specimens and observations combined with a Bayesian extinction estimating model to determine the most likely extinction dates. By considering each of the two subspecies independently, we found that they went extinct ˜30 years apart: the western subspeciesC. c. ludovicianusgoing extinct around 1914 and the eastern subspeciesC. c. carolinensiseither in the late 1930s or mid-1940s. Had we only considered all observations together, this pattern would have been obscured, possibly missing a major clue in solving the mystery of the parakeet’s extinction. Since the Carolina Parakeet was a wide-ranging species that went extinct during a period of rapid agricultural and industrial expansion, conditions that mirror those occurring in many parts of the world where parrot diversity is highest, any progress we make in unraveling the mystery of their disappearance may be vital to modern conservation efforts.
The Early Imperial fortress of Berkou, Eastern Desert, Egypt
Authors: Gates-Foster Jennifer , Goncalves Isabelle , Redon Bérangère , Cuvigny Hélène , Hepa Mariola , Faucher Thomas
Published: July 2021

In 2020, during excavations in the Wadi al-Ghozza in the Eastern Desert of Egypt, archaeologists from the French Archaeological Mission to the Eastern Desert of Egypt discovered a well-preserved Flavian praesidium. This small and unusually shaped fort, identified in ostraca found in the fortress as Berkou (Βɛρκου), lay along a track leading from ancient Kaine (Qena) to the imperial quarries at Porphyrites. The fort lay over the remains of a Ptolemaic village and incorporated elements from the water system of the older settlement. This article presents the results of those excavations, including an overview of the fort's architecture and associated finds, as well as a discussion of its role in the regional transportation and security network that supported Roman exploitation of the nearby porphyry quarries in the 1st c. CE.
A NOTE ON THE AXISYMMETRIC DIFFUSION EQUATION
Authors: PATKOWSKI ALEXANDER E.
Published: July 2021

We consider the explicit solution to the axisymmetric diffusion equation. We recast the solution in the form of a Mellin inversion formula, and outline a method to compute a formula for
$u(r,t)$
as a series using the Cauchy residue theorem. As a consequence, we are able to represent the solution to the axisymmetric diffusion equation as a rapidly converging series.
NORMAL REFLECTION SUBGROUPS OF COMPLEX REFLECTION GROUPS
Authors: Arreche Carlos E. , Williams Nathan F.
Published: July 2021

We study normal reflection subgroups of complex reflection groups. Our approach leads to a refinement of a theorem of Orlik and Solomon to the effect that the generating function for fixed-space dimension over a reflection group is a product of linear factors involving generalised exponents. Our refinement gives a uniform proof and generalisation of a recent theorem of the second author.
On inequality, growth and trust: some evidence from the lab
Authors: D'Amato Marcello , O'Higgins Niall , Stimolo Marco
Published: July 2021

In a novel experimental design, we investigate the impact of exogenous variation in economic growth and inequality on trusting behaviour. In addition to a control with uniform endowment, three treatments were implemented where the initial endowment is exogenously changed to produce inequality and three growth scenarios where average endowments increase (boom), decrease (recession) or remain unaltered (steady state). We find that aggregate trust and trustworthiness both decrease due to the induced heterogeneity in endowments. Also, trust (but not trustworthiness) decreases (increases) due to recessions (booms). The impact of inequality on trust is greatest in a recession and absent in a boom. These aggregate effects are driven mainly by the reactions of those who, after treatment, end up at the bottom of the endowment distribution. These findings are close in sign and in the order of magnitude to those reported in observational studies on the relationship between growth, inequality and trust.
Re‐Analysis of the Cassini RPWS/LP Data in Titan's Ionosphere: 1. Detection of Several Electron Populations
Authors: Chatain A. , Wahlund J.‐E. , Shebanits O. , Hadid L. Z. , Morooka M. , Edberg N. J. T. , Guaitella O. , Carrasco N.
Published: July 2021

Current models of Titan's ionosphere have difficulties in explaining the observed electron density and/or temperature. In order to get new insights, we re‐analyzed the data taken in the ionosphere of Titan by the Cassini Langmuir probe (LP), part of the Radio and Plasma Wave Science (RPWS) instrument. This is the first of two papers that present the new analysis method (current paper) and statistics on the whole data set. We suggest that between two and four electron populations are necessary to fit the data. Each population is defined by a potential, an electron density and an electron temperature and is easily visualized by a distinct peak in the second derivative of the electron current, which is physically related to the electron energy distribution function (Druyvesteyn method). The detected populations vary with solar illumination and altitude. We suggest that the four electron populations are due to photo‐ionization, magnetospheric particles, dusty plasma and electron emission from the probe boom, respectively.
Diverse Responses of Global‐Mean Surface Temperature to External Forcings and Internal Climate Variability in Observations and CMIP6 Models
Authors: Rashid Harun A.
Published: July 2021

We investigate the impacts of external forcings and internal climate variability (ICV) on global‐mean surface air temperature (GMST) variations (1850–2014) in observation and an ensemble of sixth Coupled Model Intercomparison Project (CMIP6) historical simulations. Using multiple regression models, we estimate that 83% of the observed GMST variance is explained by global‐scale anthropogenic forcing. Most CMIP6 models underestimate this anthropogenic contribution (median explained variance is 67%), but compare better with observation when the North Atlantic regional contribution is included in the anthropogenic forcing (median 77%). The ICV contributions to the GMST variance are ∼8% for observation and ∼7% for the models (median). The models' GMST responses to the external forcings and ICV vary widely, with the two responses being oppositely related. The North Atlantic predominantly drives the free GMST variability in observations, whereas the Pacific drives this in most CMIP6 models due to stronger than observed simulated GMST‐Pacific ICV relationships.
The Solar Eclipse Effects on the Upper Thermosphere
Authors: Li Ruoxi , Lei Jiuhou , Dang Tong
Published: July 2021

Theoretical studies have shown that the solar eclipse can have significant impacts on the thermospheric mass density, which, however, has not been confirmed from the observational perspective. In this study, we present direct observations of the thermospheric density responses to three solar eclipses based on the measurements of Gravity Recovery and Climate Experiment (GRACE) and Gravity field and steady state Ocean Circulation Explorer (GOCE). It was observed that the eclipses induced about 20% and 25% density depletions at GRACE altitudes (360 and 480 km, respectively) and about 10% depletions at GOCE altitudes (∼270 km). Moreover, the eclipse could generate large‐scale traveling atmospheric disturbances (TADs), which propagate globally even from the duskside to the dawnside after the eclipse ended. Those thermospheric responses could be generally reproduced by Thermosphere Ionosphere Electrodynamics General Circulation Model (TIEGCM). However, the simulated densities recover more rapidly than the observations at the duskside. This study provides observational evidence to validate the results from theoretical models and further bring insights into the mechanism of eclipse effects on the ionosphere‐thermosphere system.
Illuminating the Pre‐, Co‐, and Post‐Seismic Phases of the 2016 M7.8 Kaikōura Earthquake With 10 Years of Seismicity
Authors: Chamberlain C. J. , Frank W. B. , Lanza F. , Townend J. , Warren‐Smith E.
Published: July 2021

The 2016 M7.8 Kaikōura earthquake is one of the most complex earthquakes in recorded history, with significant rupture of at least 21 crustal faults. Using a matched‐filter detection routine, precise cross‐correlation pick corrections, and accurate location and relocation techniques, we construct a catalog of 33,328 earthquakes between 2009 and 2020 on and adjacent to the faults that ruptured in the Kaikōura earthquake. We also compute focal mechanisms for 1,755 of the earthquakes used as templates. Using this catalog we reassess the rupture pathway of the Kaikōura earthquake. In particular we show that: (a) the earthquake nucleated on the Humps Fault; (b) there is a likely linking offshore reverse fault between the southern fault system and the Papatea Fault, which could explain the anomalously high slip on the Papatea Fault; (c) the faults that ruptured in the 2013 Cook Strait sequence were reactivated by the Kaikōura earthquake and may have played a role in the termination of the earthquake; and (d) no seismicity on an underlying subduction interface is observed beneath almost all of the ruptured region suggesting that if deformation did occur on the plate interface then it occurred aseismically and did not play a significant role in generating co‐seismic ground motion.
Observations From NOAA's Newest Solar Proton Sensor
Authors: Kress B. T. , Rodriguez J. V. , Boudouridis A. , Onsager T. G. , Dichter B. K. , Galica G. E. , Tsui S.
Published: July 2021

Space weather instrumentation on board the National Oceanic and Atmospheric Administration's (NOAA's) newest Geostationary Operational Environmental Satellite (GOES)‐R series includes the Solar and Galactic Proton Sensor (SGPS), which has been collecting data since January 8, 2017. SGPS supports real‐time alerts of solar energetic particle events at the NOAA Space Weather Prediction Center (SWPC) and provides data to the space science community, advancing basic space science research and understanding of space weather effects on satellite systems. The first GOES‐R series spacecraft, GOES‐16, was launched on November 19, 2016. A series of solar particle events in September 2017 enabled cross‐calibration of GOES‐16 SGPS with the Energetic Particle Sensors on GOES‐13 and ‐15. This paper is intended as a resource for SGPS data users, including comparisons with legacy GOES energetic particle measurements, corrections applied to SGPS Level‐2 data, important caveats, background level fluxes, and measurements of trapped magnetospheric protons.
Exploring the genetic heterogeneity in major depression across diagnostic criteria
Authors: Jermy Bradley S. , Glanville Kylie P. , Coleman Jonathan R. I. , Lewis Cathryn M. , Vassos Evangelos
Published: July 2021

Major depressive disorder (MDD) is defined differently across genetic research studies and this may be a key source of heterogeneity. While previous literature highlights differences between minimal and strict phenotypes, the components contributing to this heterogeneity have not been identified. Using the cardinal symptoms (depressed mood/anhedonia) as a baseline, we build MDD phenotypes using five components—(1) five or more symptoms, (2) episode duration, (3) functional impairment, (4) episode persistence, and (5) episode recurrence—to determine the contributors to such heterogeneity. Thirty-two depression phenotypes which systematically incorporate different combinations of MDD components were created using the mental health questionnaire data within the UK Biobank. SNP-based heritabilities and genetic correlations with three previously defined major depression phenotypes were calculated (Psychiatric Genomics Consortium (PGC) defined depression, 23andMe self-reported depression and broad depression) and differences between estimates analysed. All phenotypes were heritable (h2SNP range: 0.102–0.162) and showed substantial genetic correlations with other major depression phenotypes (Rg range: 0.651–0.895 (PGC); 0.652–0.837 (23andMe); 0.699–0.900 (broad depression)). The strongest effect on SNP-based heritability was from the requirement for five or more symptoms (1.4% average increase) and for a long episode duration (2.7% average decrease). No significant differences were noted between genetic correlations. While there is some variation, the two cardinal symptoms largely reflect the genetic aetiology of phenotypes incorporating more MDD components. These components may index severity, however, their impact on heterogeneity in genetic results is likely to be limited.
A dimensional perspective on the genetics of obsessive-compulsive disorder
Authors: Strom Nora I. , Soda Takahiro , Mathews Carol A. , Davis Lea K.
Published: July 2021

This review covers recent findings in the genomics of obsessive-compulsive disorder (OCD), obsessive-compulsive symptoms, and related traits from a dimensional perspective. We focus on discoveries stemming from technical and methodological advances of the past five years and present a synthesis of human genomics research on OCD. On balance, reviewed studies demonstrate that OCD is a dimensional trait with a highly polygenic architecture and genetic correlations to multiple, often comorbid psychiatric phenotypes. We discuss the phenotypic and genetic findings of these studies in the context of the dimensional framework, relying on a continuous phenotype definition, and contrast these observations with discoveries based on a categorical diagnostic framework, relying on a dichotomous case/control definition. Finally, we highlight gaps in knowledge and new directions for OCD genetics research.
Contributing factors to advanced brain aging in depression and anxiety disorders
Authors: Han Laura K. M. , Schnack Hugo G. , Brouwer Rachel M. , Veltman Dick J. , van der Wee Nic J. A. , van Tol Marie-José , Aghajani Moji , Penninx Brenda W. J. H.
Published: July 2021

Depression and anxiety are common and often comorbid mental health disorders that represent risk factors for aging-related conditions. Brain aging has shown to be more advanced in patients with major depressive disorder (MDD). Here, we extend prior work by investigating multivariate brain aging in patients with MDD, anxiety disorders, or both, and examine which factors contribute to older-appearing brains. Adults aged 18–57 years from the Netherlands Study of Depression and Anxiety underwent structural MRI. A pretrained brain-age prediction model based on >2000 samples from the ENIGMA consortium was applied to obtain brain-predicted age differences (brain PAD, predicted brain age minus chronological age) in 65 controls and 220 patients with current MDD and/or anxiety. Brain-PAD estimates were associated with clinical, somatic, lifestyle, and biological factors. After correcting for antidepressant use, brain PAD was significantly higher in MDD (+2.78 years, Cohen’sd = 0.25, 95% CI −0.10-0.60) and anxiety patients (+2.91 years, Cohen’sd = 0.27, 95% CI −0.08-0.61), compared with controls. There were no significant associations with lifestyle or biological stress systems. A multivariable model indicated unique contributions of higher severity of somatic depression symptoms (b = 4.21 years per unit increase on average sum score) and antidepressant use (−2.53 years) to brain PAD. Advanced brain aging in patients with MDD and anxiety was most strongly associated with somatic depressive symptomatology. We also present clinically relevant evidence for a potential neuroprotective antidepressant effect on the brain-PAD metric that requires follow-up in future research.
The combined detection of Amphiregulin, Cyclin A1 and DDX20/Gemin3 expression predicts aggressive forms of oral squamous cell carcinoma
Authors: Bourova-Flin Ekaterina , Derakhshan Samira , Goudarzi Afsaneh , Wang Tao , Vitte Anne-Laure , Chuffart Florent , Khochbin Saadi , Rousseaux Sophie , Aminishakib Pouyan
Published: July 2021

Background

Large-scale genetic and epigenetic deregulations enable cancer cells to ectopically activate tissue-specific expression programmes. A specifically designed strategy was applied to oral squamous cell carcinomas (OSCC) in order to detect ectopic gene activations and develop a prognostic stratification test.

Methods

A dedicated original prognosis biomarker discovery approach was implemented using genome-wide transcriptomic data of OSCC, including training and validation cohorts. Abnormal expressions of silent genes were systematically detected, correlated with survival probabilities and evaluated as predictive biomarkers. The resulting stratification test was confirmed in an independent cohort using immunohistochemistry.

Results

A specific gene expression signature, including a combination of three genes,AREG, CCNA1andDDX20, was found associated with high-risk OSCC in univariate and multivariate analyses. It was translated into an immunohistochemistry-based test, which successfully stratified patients of our own independent cohort.

Discussion

The exploration of the whole gene expression profile characterising aggressive OSCC tumours highlights their enhanced proliferative and poorly differentiated intrinsic nature. Experimental targeting ofCCNA1in OSCC cells is associated with a shift of transcriptomic signature towards the less aggressive form of OSCC, suggesting that CCNA1 could be a good target for therapeutic approaches.
PPM1G promotes the progression of hepatocellular carcinoma via phosphorylation regulation of alternative splicing protein SRSF3
Authors: Chen Dawei , Zhao Zhenguo , Chen Lu , Li Qinghua , Zou Jixue , Liu Shuanghai
Published: July 2021

Emerging evidence has demonstrated that alternative splicing has a vital role in regulating protein function, but how alternative splicing factors can be regulated remains unclear. We showed that the PPM1G, a protein phosphatase, regulated the phosphorylation of SRSF3 in hepatocellular carcinoma (HCC) and contributed to the proliferation, invasion, and metastasis of HCC. PPM1G was highly expressed in HCC tissues compared to adjacent normal tissues, and higher levels of PPM1G were observed in adverse staged HCCs. The higher levels of PPM1G were highly correlated with poor prognosis, which was further validated in the TCGA cohort. The knockdown of PPM1G inhibited the cell growth and invasion of HCC cell lines. Further studies showed that the knockdown of PPM1G inhibited tumor growth in vivo. The mechanistic analysis showed that the PPM1G interacted with proteins related to alternative splicing, including SRSF3. Overexpression of PPM1G promoted the dephosphorylation of SRSF3 and changed the alternative splicing patterns of genes related to the cell cycle, the transcriptional regulation in HCC cells. In addition, we also demonstrated that the promoter of PPM1G was activated by multiple transcription factors and co-activators, including MYC/MAX and EP300, MED1, and ELF1. Our study highlighted the essential role of PPM1G in HCC and shed new light on unveiling the regulation of alternative splicing in malignant transformation.
flDPnn: Accurate intrinsic disorder prediction with putative propensities of disorder functions
Authors: Hu Gang , Katuwawala Akila , Wang Kui , Wu Zhonghua , Ghadermarzi Sina , Gao Jianzhao , Kurgan Lukasz
Published: July 2021

Identification of intrinsic disorder in proteins relies in large part on computational predictors, which demands that their accuracy should be high. Since intrinsic disorder carries out a broad range of cellular functions, it is desirable to couple the disorder and disorder function predictions. We report a computational tool, flDPnn, that provides accurate, fast and comprehensive disorder and disorder function predictions from protein sequences. The recent Critical Assessment of protein Intrinsic Disorder prediction (CAID) experiment and results on other test datasets demonstrate that flDPnn offers accurate predictions of disorder, fully disordered proteins and four common disorder functions. These predictions are substantially better than the results of the existing disorder predictors and methods that predict functions of disorder. Ablation tests reveal that the high predictive performance stems from innovative ways used in flDPnn to derive sequence profiles and encode inputs. flDPnn’s webserver is available at http://biomine.cs.vcu.edu/servers/flDPnn/
A novel characteristic of a phytoplankton as a potential source of straight-chain alkanes
Authors: Harada Naomi , Hirose Yuu , Chihong Song , Kurita Hirofumi , Sato Miyako , Onodera Jonaotaro , Murata Kazuyoshi , Itoh Fumihiro
Published: July 2021

Biosynthesis of hydrocarbons is a promising approach for the production of alternative sources of energy because of the emerging need to reduce global consumption of fossil fuels. However, the suitability of biogenic hydrocarbons as fuels is limited because their range of the number of carbon atoms is small, and/or they contain unsaturated carbon bonds. Here, we report that a marine phytoplankton, Dicrateria rotunda, collected from the western Arctic Ocean, can synthesize a series of saturated hydrocarbons (n-alkanes) from C10H22 to C38H78, which are categorized as petrol (C10–C15), diesel oils (C16–C20), and fuel oils (C21–C38). The observation that these n-alkanes were also produced by ten other cultivated strains of Dicrateria collected from the Atlantic and Pacific oceans suggests that this capability is a common characteristic of Dicrateria. We also identified that the total contents of the n-alkanes in the Arctic D. rotunda strain increased under dark and nitrogen-deficient conditions. The unique characteristic of D. rotunda could contribute to the development of a new approach for the biosynthesis of n-alkanes.
A wireless spinal stimulation system for ventral activation of the rat cervical spinal cord
Authors: Hogan Matthew K. , Barber Sean M. , Rao Zhoulyu , Kondiles Bethany R. , Huang Meng , Steele William J. , Yu Cunjiang , Horner Philip J.
Published: July 2021

Electrical stimulation of the cervical spinal cord is gaining traction as a therapy following spinal cord injury; however, it is difficult to target the cervical motor region in a rodent using a non-penetrating stimulus compared with direct placement of intraspinal wire electrodes. Penetrating wire electrodes have been explored in rodent and pig models and, while they have proven beneficial in the injured spinal cord, the negative aspects of spinal parenchymal penetration (e.g., gliosis, neural tissue damage, and obdurate inflammation) are of concern when considering therapeutic potential. We therefore designed a novel approach for epidural stimulation of the rat spinal cord using a wireless stimulation system and ventral electrode array. Our approach allowed for preservation of mobility following surgery and was suitable for long term stimulation strategies in awake, freely functioning animals. Further, electrophysiology mapping of the ventral spinal cord revealed the ventral approach was suitable to target muscle groups of the rat forelimb and, at a single electrode lead position, different stimulation protocols could be applied to achieve unique activation patterns of the muscles of the forelimb.
Roux-en-Y gastric bypass potentially improved intestinal permeability by regulating gut innate immunity in diet-induced obese mice
Authors: Jin Zhangliu , Chen Kai , Zhou Zhe , Peng Weihui , Liu Wei
Published: July 2021

Roux-en-Y gastric bypass (RYGB) has been demonstrated to be the most effective treatment for morbid obesity, yet the impact of RYGB on intestinal permeability is not fully known. In this work, we subjected obese mice to RYGB and sham operation procedures. Serum lipopolysaccharide (LPS) level, inflammatory cytokines and intestinal permeability were measured at 8 weeks post surgery. In contrast to sham surgery, RYGB reduced body weight, improved glucose tolerance and insulin resistance, and decreased serum levels of LPS, IL6 and TNFα. Intestinal permeability of the common limb and colon was significantly improved in the RYGB group compared to the sham group. The mRNA levels of IL1β, IL6, and TLR4 in the intestine were significantly decreased in the RYGB group compared with the sham group. The expression levels of intestinal islet-derived 3β (REG3β), islet-derived 3γ (REG3γ) and intestinal alkaline phosphatase (IAP) were higher in the RYGB group than in the sham group. In conclusion, in a diet-induced obesity (DIO) mouse model, both decreased intestinal permeability and attenuated systemic inflammation after RYGB surgery were associated with improved innate immunity, which might result from enhanced production of IAP and antimicrobial peptides.
Dynamic differential evolution schemes of WRKY transcription factors in domesticated and wild rice
Authors: Villacastin Anne J. , Adams Keeley S. , Boonjue Rin , Rushton Paul J. , Han Mira , Shen Jeffery Q.
Published: July 2021

WRKY transcription factors play key roles in stress responses, growth, and development. We previously reported on the evolution of WRKYs from unicellular green algae to land plants. To address recent evolution events, we studied three domesticated and eight wild species in the genus Oryza, an ideal model due to its long history of domestication, economic importance, and central role as a model system. We have identified prevalence of Group III WRKYs despite differences in breeding of cultivated and wild species. Same groups of WRKY genes tend to cluster together, suggesting recent, multiple duplication events. Duplications followed by divergence may result in neofunctionalizations of co-expressed WRKY genes that finely tune the regulation of target genes in a same metabolic or response pathway. WRKY genes have undergone recent rearrangements to form novel genes. Group Ib WRKYs, unique to AA genome type Oryza species, are derived from Group III genes dated back to 6.76 million years ago. Gene tree reconciliation analysis with the species tree revealed details of duplication and loss events in the 11 genomes. Selection analysis on single copy orthologs reveals the highly conserved nature of the WRKY domain and clusters of fast evolving sites under strong positive selection pressure. Also, the numbers of single copy orthologs under positive or negative selection almost evenly split. Our results provide valuable insights into the preservation and diversification of an important gene family under strong selective pressure for biotechnological improvements of the world’s most valued food crop.
Rasch analysis for development and reduction of Symptom Questionnaire for Visual Dysfunctions (SQVD)
Authors: Cantó-Cerdán Mario , Cacho-Martínez Pilar , Lara-Lacárcel Francisco , García-Muñoz Ángel
Published: July 2021

To develop the Symptom Questionnaire for Visual Dysfunctions (SQVD) and to perform a psychometric analysis using Rasch method to obtain an instrument which allows to detect the presence and frequency of visual symptoms related to any visual dysfunction. A pilot version of 33 items was carried out on a sample of 125 patients from an optometric clinic. Rasch model (using Andrich Rating Scale Model) was applied to investigate the category probability curves and Andrich thresholds, infit and outfit mean square, local dependency using Yen’s Q3 statistic, Differential item functioning (DIF) for gender and presbyopia, person and item reliability, unidimensionality, targeting and ordinal to interval conversion table. Category probability curves suggested to collapse a response category. Rasch analysis reduced the questionnaire from 33 to 14 items. The final SQVD showed that 14 items fit to the model without local dependency and no significant DIF for gender and presbyopia. Person reliability was satisfactory (0.81). The first contrast of the residual was 1.908 eigenvalue, showing unidimensionality and targeting was − 1.59 logits. In general, the SQVD is a well-structured tool which shows that data adequately fit the Rasch model, with adequate psychometric properties, making it a reliable and valid instrument to measure visual symptoms.
On the robustness of inference of association with the gut microbiota in stool, rectal swab and mucosal tissue samples
Authors: Sun Shan , Zhu Xiangzhu , Huang Xiang , Murff Harvey J. , Ness Reid M. , Seidner Douglas L. , Sorgen Alicia A. , Blakley Ivory C. , Yu Chang , Dai Qi , Azcarate-Peril M. Andrea , Shrubsole Martha J. , Fodor Anthony A.
Published: July 2021

The gut microbiota plays an important role in human health and disease. Stool, rectal swab and rectal mucosal tissue samples have been used in individual studies to survey the microbial community but the consequences of using these different sample types are not completely understood. In this study, we report differences in stool, rectal swab and rectal mucosal tissue microbial communities with shotgun metagenome sequencing of 1397 stool, swab and mucosal tissue samples from 240 participants. The taxonomic composition of stool and swab samples was distinct, but less different to each other than mucosal tissue samples. Functional profile differences between stool and swab samples are smaller, but mucosal tissue samples remained distinct from the other two types. When the taxonomic and functional profiles were used for inference in association with host phenotypes of age, sex, body mass index (BMI), antibiotics or non-steroidal anti-inflammatory drugs (NSAIDs) use, hypothesis testing using either stool or rectal swab gave broadly significantly correlated results, but inference performed on mucosal tissue samples gave results that were generally less consistent with either stool or swab. Our study represents an important resource for determination of how inference can change for taxa and pathways depending on the choice of where to sample within the human gut.
Drug-associated cues and drug dosage contribute to increased opioid seeking after abstinence
Authors: Zanda Mary Tresa , Floris Gabriele , Daws Stephanie E.
Published: July 2021

Patients with opioid use disorder experience high rates of relapse during recovery, despite successful completion of rehabilitation programs. A key factor contributing to this problem is the long-lasting nature of drug-seeking behavior associated with opioid use. We modeled this behavior in a rat drug self-administration paradigm in which drug-seeking is higher after extended abstinence than during the acute abstinence phase. The goal of this study was to determine the contribution of discrete or discriminative drug cues and drug dosage to time-dependent increases in drug-seeking. We examined heroin-seeking after 2 or 21 days of abstinence from two different self-administration cue-context environments using high or low doses of heroin and matched animals for their drug intake history. When lower dosages of heroin are used in discriminative or discrete cue protocols, drug intake history contributed to drug-seeking after abstinence, regardless of abstinence length. Incubation of opioid craving at higher dosages paired with discrete drug cues was not dependent on drug intake. Thus, interactions between drug cues and drug dosage uniquely determined conditions permissible for incubation of heroin craving. Understanding factors that contribute to long-lasting opioid-seeking can provide essential insight into environmental stimuli and drug-taking patterns that promote relapse after periods of successful abstinence.
A new immunochemical strategy for triple-negative breast cancer therapy
Authors: Lin Chih-Wei , Zheng Tianqing , Grande Geramie , Nanna Alex R. , Rader Christoph , Lerner Richard A.
Published: July 2021

Triple-negative breast cancer (TNBC) is a highly diverse group of malignant neoplasms which tend to have poor outcomes, and the development of new targets and strategies to treat these cancers is sorely needed. Antibody–drug conjugate (ADC) therapy has been shown to be a promising targeted therapy for treating many cancers, but has only rarely been tried in patients with TNBC. A major reason the efficacy of ADC therapy in the setting of TNBC has not been more fully investigated is the lack of appropriate target molecules. In this work we were able to identify an effective TNBC target for use in immunotherapy. We were guided by our previous observation that in some breast cancer patients the protein tropomyosin receptor kinase B cell surface protein (TrkB) had become immunogenic, suggesting that it was somehow sufficiently chemically different enough (presumably by mutation) to escaped immune tolerance. We postulated that this difference might well offer a means for selective targeting by antibodies. We engineered site-specific ADCs using a dual variable domain (DVD) format which combines anti-TrkB antibody with the h38C2 catalytic antibody. This format enables rapid, one-step, and homogeneous conjugation of β-lactam-derivatized drugs. Following conjugation to β-lactam-derivatized monomethyl auristatin F, the TrkB-targeting DVD-ADCs showed potency against multiple breast cancer cell lines, including TNBC cell lines. In addition, our isolation of antibody that specifically recognized the breast cancer-associated mutant form of TrkB, but not the wild type TrkB, indicates the possibility of further refining the selectivity of anti-TrkB DVD-ADCs, which should enhance their therapeutic index. These results confirmed our supposition that TrkB is a potential target for immunotherapy for TNBC, as well as for other cancers with mutated cell surface proteins.
Automated scoring for a Tablet-based Rey Figure copy task differentiates constructional, organisational, and motor abilities
Authors: Petilli Marco A. , Daini Roberta , Saibene Francesca Lea , Rabuffetti Marco
Published: July 2021

Accuracy in copying a figure is one of the most sensitive measures of visuo-constructional ability. However, drawing tasks also involve other cognitive and motor abilities, which may influence the final graphic produced. Nevertheless, these aspects are not taken into account in conventional scoring methodologies. In this study, we have implemented a novel Tablet-based assessment, acquiring data and information for the entire execution of the Rey Complex Figure copy task (T-RCF). This system extracts 12 indices capturing various dimensions of drawing abilities. We have also analysed the structure of relationships between these indices and provided insights into the constructs that they capture. 102 healthy adults completed the T-RCF. A subgroup of 35 participants also completed a paper-and-pencil drawing battery from which constructional, procedural, and motor measures were obtained. Principal component analysis of the T-RCF indices was performed, identifying spatial, procedural and kinematic components as distinct dimensions of drawing execution. Accordingly, a composite score for each dimension was determined. Correlational analyses provided indications of their validity by showing that spatial, procedural, and kinematic scores were associated with constructional, organisational and motor measures of drawing, respectively. Importantly, final copy accuracy was found to be associated with all of these aspects of drawing. In conclusion, copying complex figures entails an interplay of multiple functions. T-RCF provides a unique opportunity to analyse the entire drawing process and to extract scores for three critical dimensions of drawing execution.
Enhancing and quantifying spatial homogeneity in monolayer WS2
Authors: Cao Yameng , Wood Sebastian , Richheimer Filipe , Blakesley J. , Young Robert J. , Castro Fernando A.
Published: July 2021

Controlling the radiative properties of monolayer transition metal dichalcogenides is key to the development of atomically thin optoelectronic devices applicable to a wide range of industries. A common problem for exfoliated materials is the inherent disorder causing spatially varying nonradiative losses and therefore inhomogeneity. Here we demonstrate a five-fold reduction in the spatial inhomogeneity in monolayer WS2, resulting in enhanced overall photoluminescence emission and quality of WS2 flakes, by using an ambient-compatible laser illumination process. We propose a method to quantify spatial uniformity using statistics of spectral photoluminescence mapping. Analysis of the dynamic spectral changes shows that the enhancement is due to a spatially sensitive reduction of the charged exciton spectral weighting. The methods presented here are based on widely adopted instrumentation. They can be easily automated, making them ideal candidates for quality assessment of transition metal dichalcogenide materials, both in the laboratory and industrial environments.
AST to Platelet Ratio Index (APRI) is an easy-to-use predictor score for cardiovascular risk in metabolic subjects
Authors: De Matteis Carlo , Cariello Marica , Graziano Giusi , Battaglia Stefano , Suppressa Patrizia , Piazzolla Giuseppina , Sabbà Carlo , Moschetta Antonio
Published: July 2021

Visceral obesity is characterized by a low-grade inflammatory systemic state that contributes to the genesis of non-alcoholic fatty liver disease (NAFLD), frequently associated with liver fibrosis. Non-invasive serum markers have recently emerged as reliable, easy-to-use scores to predict liver fibrosis. NAFLD is often linked to metabolic and cardiovascular risk. Thus, in this cross-sectional study, we investigated in a population of 1225 subjects if AST to Platelet Ratio Index (APRI), one of the non-invasive liver fibrosis serum markers, can predict cardiovascular risk (CVR). APRI has been previously validated as an efficient score to predict liver fibrosis in viral hepatitis patients with a cut-off of 0.5 for fibrosis and 1.5 for cirrhosis. Our study showed that APRI significantly correlates with CVR and determines, when elevated, a significant increase in CVR for both genders, especially females. This spike in CVR, observed when APRI is elevated, is relatively high in patients in the age of 51–65 years, but it is significantly higher in younger and premenopausal women, approaching risk values usually typical of men at the same age. Taken together, our data highlighted the role of APRI as a reliable predictor easy-to-use score for CVR in metabolic patients.