bluuebunny/crossref_metadata_2025 huggingface dataset:
Global Analysis of Gene Expression Profiles Provides Novel Insights into the Development and Evolution of the Large Crustacean Eriocheir Sinensis
Authors: Wang Jun , Chen Xiaowen , He Funan , Song Xiao , Huang Shu , Yue Wucheng , Chen Yipei , Su Zhixi , Wang Chenghui
Published: December 2020

Chinese mitten crab (Eriocheir sinensis) is an important aquaculture species in Crustacea. Functional analysis, although essential, has been hindered due to the lack of sufficient genomic or transcriptomic resources. In this study, transcriptome sequencing was conducted on 59 samples representing diverse developmental stages (fertilized eggs, zoea, megalopa, three sub-stages of larvae, juvenile crabs, and adult crabs) and different tissues (eyestalk, hepatopancreas, and muscle from juvenile crabs, and eyestalk, hepatopancreas, muscle, heart, stomach, gill, thoracic ganglia, intestine, ovary, and testis from adult crabs) of E. sinensis. A comprehensive reference transcriptome was assembled, including 19,023 protein-coding genes. Hierarchical clustering based on 128 differentially expressed cuticle-related genes revealed two distinct expression patterns during the early larval developmental stages, demonstrating the distinct roles of these genes in “crab-like” cuticle formation during metamorphosis and cuticle calcification after molting. Phylogenetic analysis of 1406 one-to-one orthologous gene families identified from seven arthropod species and Caenorhabditis elegans strongly supported the hypothesis that Malacostraca and Branchiopoda do not form a monophyletic group. Furthermore, Branchiopoda is more phylogenetically closely related to Hexapoda, and the clade of Hexapoda and Branchiopoda and the clade of Malacostraca belong to the Pancrustacea. This study offers a high-quality transcriptome resource for E. sinensis and demonstrates the evolutionary relationships of major arthropod groups. The differentially expressed genes identified in this study facilitate further investigation of the cuticle-related gene expression networks which are likely associated with “crab-like” cuticle formation during metamorphosis and cuticle calcification after molting.
The effect of inhalation aromatherapy of geranium on pain and physiological indices after appendectomy: A double-blind randomized clinical trial
Authors: Gazerani Akram , Sarchahi Zohreh , Hosseini Sara Sadat , lakziyan Rasool , Abavisani Mahnaz
Published: December 2020

ABSTRACT

Introduction:

The aim of the present study was to evaluate the effect of inhalation aromatherapy with sweet-scented geranium essential oil on pain and physiological indices after appendectomy.

Methods:

This double-blind clinical trial was performed on 120 patients undergoing appendectomy. Aromatherapy was performed with 1% sweet-scented geranium and sweet almond oil in the experimental placebo groups, respectively. Physiological symptoms were recorded before induction of anesthesia, before surgery, 30 min and 4 h after surgery. The control group received no intervention and only pain intensity and physiological indices were recorded in the mentioned stages. The placebo group underwent sweet almond essential oil aromatherapy. Data collection tools included demographic information form, physiological index checklist, and visual pain scale.

Results:

Results of 7 measurements showed significant differences between the experimental and placebo groups as well as the experimental and control groups in terms of mean heart rate, systolic and diastolic blood pressure, blood oxygen percentage, and pain (P < 0.001).

Conclusion:

Results of the present study showed that the effect of inhalation aromatherapy with sweet-scented geranium essential oil after appendectomy reduces pain and physiological indices. Therefore, the above aromatherapy can be used as a complementary treatment along with other treatments.

Highlights
The Global Compact for Safe, Orderly and Regular Migration: a kaleidoscope of international law
Authors: Chetail Vincent
Published: December 2020

The Global Compact for Safe, Orderly and Regular Migration has prompted an intense political debate at both the international and domestic levels. Most controversies focus on its legal stance and highlight the hybrid character of the Compact as a soft-law instrument. While acknowledging the political nature of the Compact, this paper delves into its legal dimensions from the perspective of international law. This inquiry into its normative content discloses three main features: (1) the Compact is not a codification of international legal norms governing migration; it is an instrument of both (2) consolidation and (3) expansion of international law to foster inter-governmental co-operation and promote safe, orderly and regular migration.
Kompetente Eltern – Glückliche Kinder?
Authors: Supke Max , Hahlweg Kurt , Schulz Wolfgang
Published: December 2020

Zusammenfassung. Theoretischer Hintergrund. Im internationalen Vergleich befinden sich deutsche Kinder hinsichtlich ihrer gesundheitsbezogenen Lebensqualität (gLQ) im Mittelfeld, wobei psychische Auffälligkeiten die kindliche gLQ am stärksten einschränken. Fragestellung. Ziel war es zu untersuchen, ob Kindergartenkinder von Eltern, die am Positive Parenting Program (Triple P) teilgenommen haben, kurz- (1/‍2/‍3 Jahres-FU) und langfristige (10 Jahres-FU) positive Effekte in ihrer gLQ, gemessen mit dem KINDLR ( Ravens-Sieberer & Bullinger, 2000 ), zeigen. Methode. N = 219 Familien mit Kindergartenkindern aus dem Projekt Zukunft Familie wurden analysiert. Ergebnisse. Es konnten weder quer- noch längsschnittlich Effekte des Triple P aus Sicht der Kinder, Mütter und Väter auf die gLQ nachgewiesen werden. Sowohl Mütter als auch Väter überschätzen im Vergleich mit ihren Kindern die gLQ. Schlussfolgerungen. Das Triple P hat keinen signifikanten Einfluss auf den Verlauf der gLQ. In der zukünftigen Forschung sollten die Perspektiven von Kindern und Eltern berücksichtigt werden, da sie sich ergänzen könnten. Ein Modul in Elterntrainings, welches die gLQ fokussiert, könnte langfristige positive Effekte erzielen. Zukünftige Forschung zur positiven Beeinflussung der kindlichen gLQ ist notwendig.
Mesoscale Variability in the Boundaries of the Oxygen Minimum Zone in the Eastern South Pacific: Influence of Intrathermocline Eddies
Authors: Auger P. A. , Bento J. P. , Hormazabal S. , Morales C. E. , Bustamante A.
Published: December 2020

The vertical variability in the oxygen minimum zone (OMZ) in the eastern South Pacific (ESP; 0–40°S) is characterized by the influence of anticyclonic intrathermocline eddies (ITEs), which are subsurface‐intensified mesoscale features that are frequently generated in the coastal upwelling zone off Peru and Chile. The unique lens‐shaped signatures that ITEs leave on temperature, salinity, and dissolved oxygen vertical distributions are used as proxies to assess their influences on vertical OMZ boundaries and thickness. Data from in situ profiles in the region (World Ocean Database and Argo databases) are used in correlation analyses between anomalous depths (and vertical displacements) of oxyclines and isopycnals/isotherms, together with an objective eddy detection method based on satellite altimetry to identify the location of such profiles (i.e., outside or inside cyclonic and anticyclonic eddies). The results indicate that most of the vertical fluctuations in the climatological OMZ have a lens‐shaped signature and that those at the mesoscale are largely due to ITEs. ITEs are a main driver of the upper oxycline variability in the coastal band, the coastal transition zone (CTZ, 3–10° from the coast) and beyond at mid‐latitudes (12–26°S). The influence of ITEs on the upper and lower oxycline variability is mostly observed within the horizontal (offshore) climatological boundary of the OMZ, suggesting that ITEs play a role in the OMZ offshore extension in the ESP. ITEs may produce mesoscale variations in the thickness of the surface‐oxygenated layer, resulting in potential changes in prey‐predator interactions and in food web functioning.
Trends and Variability of Atmospheric Downward Longwave Radiation Over China From 1958 to 2015
Authors: Wei Yu , Zhang Xiaotong , Li Wenhong , Hou Ning , Zhang Weiyu , Xu Jiawen , Feng Chunjie , Jia Kun , Yao Yunjun , Cheng Jie , Jiang Bo , Wang Kaicun , Liang Shunlin
Published: December 2020

Surface downward longwave radiation (SDLR) is a major component of the energy budget. Although studies have reported the spatiotemporal variations of SDLR in China, the spatiotemporal coverage of the situ measurements used is always limited. In this study, the gradient boosting regression tree (GBRT) was developed to reconstruct SDLR based on air temperature (Ta), relative humidity (RH), and downward shortwave radiation (DSR). Ground measurements collected at the Baseline Surface Radiation Network (BSRN) and the Arid and Semi‐arid Region Collaborative Observation Project (ASRCOP) were used to build and evaluate the GBRT model. The evaluation results showed that the daily SDLR estimates are correlated well with the SDLR in situ, with an overall root mean square errors (RMSE) of 16.5 Wm−2 and a correlation coefficient (R) value of 0.91 for the validation data set. Comparison with existing SDLR products showed that accuracy and trends of the SDLR estimates based on the GBRT method are reasonable. To obtain long‐term SDLR data for spatiotemporal analysis over China, densely distributed reconstructed DSR and ground measured Ta and RH collected at 756 Chinese Meteorological Administration (CMA) stations were used as input to estimate the SDLR based on the GBRT method over China during 1958–2015. The long‐term estimated SDLRs at the selected 563 stations showed that SDLR increased at an average rate of 1.3 Wm−2 per decade over China from 1958 to 2015. The trend of SDLR is positively correlated with the trend in Ta and water vapor pressure, whereas negatively correlated with the trend in DSR.
Microseismic Events Cause Significant pH Drops in Groundwater
Authors: Stillings M. , Lunn R. J. , Pytharouli S. , Shipton Z. K. , Kinali M. , Lord R. , Thompson S.
Published: December 2020

Earthquakes cause rock fracturing, opening new flow pathways which can result in the mixing of previously isolated geofluids with differing geochemistries. Here, we present the first evidence that seismic events can significantly reduce groundwater pH without the requirement for fluid mixing, solely through the process of dynamic rock fracturing. At the Grimsel Test Site, Switzerland, we observe repeated, short‐lived groundwater pH drops of 1–3.5 units, while major and minor ion groundwater concentrations remain constant. Acidification coincides with reservoir drainage and induced microseismic events. In laboratory experiments, we demonstrate that fresh rock surfaces made by particle cracking interact with the in situ water molecules, likely through creation of surface silanols and silica radicals, increasing the H+ concentration and significantly lowering groundwater pH. Our findings are significant; pH exerts a fundamental control on the rate and outcome of most aqueous geochemical reactions and microseismic events are commonplace, even in seismically inactive regions.
A Stochastic View of the 2020 ElazığMw6.8 Earthquake (Turkey)
Authors: Ragon Théa , Simons Mark , Bletery Quentin , Cavalié Olivier , Fielding Eric
Published: December 2020

Until theMw6.8 Elazığ earthquake ruptured the central portion of the East Anatolian Fault (EAF, Turkey) on January 24, 2020, the region had only experienced moderate magnitude (Mw < 6.2) earthquakes over the last century. We use geodetic data to constrain a model of subsurface fault slip. We adopt an unregularized Bayesian sampling approach relying solely on physically justifiable prior information and account for uncertainties in both the assumed elastic structure and fault geometry. The rupture of the Elazığ earthquake was mostly unilateral, with two primary disconnected regions of slip. This rupture pattern may be controlled by structural complexity. Both the Elazığ and 2010Mw6.1 Kovancılar events ruptured portions of the central EAF that are believed to be coupled during interseismic periods, and the Palu segment is the last portion of the EAF showing a large fault slip deficit which has not yet ruptured in the last 145 years.
Continuous Estimates of Glacier Mass Balance in High Mountain Asia Based on ICESat‐1,2 and GRACE/GRACE Follow‐On Data
Authors: Wang Qiuyu , Yi Shuang , Sun Wenke
Published: December 2020

Glacier melt in High Mountain Asia (HMA) is an indicator of climate change and has a major impact on the regional hydrology and freshwater supply. We determined the recent status of HMA glaciers based on the first analysis of Ice, Cloud, and Land Elevation Satellite‐2 (ICESat‐2) data. We used the Gravity Recovery and Climate Experiment (GRACE) and GRACE Follow‐On (FO) data to complement ICESat‐1,2 data and validate them independently. We find a good agreement between ICESat‐1,2 and GRACE/GRACE‐FO data, which demonstrates the high reliability of results. Based on our results, the continuous glacier mass change from 2003 to 2019 is −28 ± 6 Gt yr−1, which is more negative than stereo imagery‐based studies. The regional variability of the glaciers ranges from −1.07 ± 0.10 m yr−1 in southeastern Nyaingentanglha to +0.16 ± 0.10 m yr−1 in West Kunlun. ICESat‐2 data enable new insight into the continuous measurement of HMA glacier elevation change.
Genetic Relations Between the Aves Ridge and the Grenada Back‐Arc Basin, East Caribbean Sea
Authors: Garrocq Clément , Lallemand Serge , Marcaillou Boris , Lebrun Jean‐Frédéric , Padron Crelia , Klingelhoefer Frauke , Laigle Mireille , Münch Philippe , Gay Aurélien , Schenini Laure , Beslier Marie‐Odile , Cornée Jean‐Jacques , Mercier de Lépinay Bernard , Quillévéré Frédéric , BouDagher‐Fadel Marcelle ,   the GARANTI cruise team
Published: December 2020

The Grenada Basin separates the active Lesser Antilles Arc from the Aves Ridge, described as a Cretaceous‐Paleocene remnant of the “Great Arc of the Caribbean.” Although various tectonic models have been proposed for the opening of the Grenada Basin, the data on which they rely are insufficient to reach definitive conclusions. This study presents, a large set of deep‐penetrating multichannel seismic reflection data and dredge samples acquired during the GARANTI cruise in 2017. By combining them with published data including seismic reflection data, wide‐angle seismic data, well data and dredges, we refine the understanding of the basement structure, depositional history, tectonic deformation and vertical motions of the Grenada Basin and its margins as follows: (1) rifting occurred during the late Paleocene‐early Eocene in a NW‐SE direction and led to seafloor spreading during the middle Eocene; (2) this newly formed oceanic crust now extends across the eastern Grenada Basin between the latitude of Grenada and Martinique; (3) asymmetrical pre‐Miocene depocenters support the hypothesis that the southern Grenada Basin originally extended beneath the present‐day southern Lesser Antilles Arc and probably partly into the present‐day forearc before the late Oligocene‐Miocene rise of the Lesser Antilles Arc; and (4) the Aves Ridge has subsided along with the Grenada Basin since at least the middle Eocene, with a general subsidence slowdown or even an uplift during the late Oligocene, and a sharp acceleration on its southeastern flank during the late Miocene. Until this acceleration of subsidence, several bathymetric highs remained shallow enough to develop carbonate platforms.
Evidence for a Stratified Upper Mantle Preserved Within the South Pole‐Aitken Basin
Authors: Moriarty D. P. , Watkins R. N. , Valencia S. N. , Kendall J. D. , Evans A. J. , Dygert N. , Petro N. E.
Published: December 2020

The evolution and compositional structure of the lunar mantle has been extensively modeled but insufficiently constrained by observations. Here, we identify and characterize mantle materials exposed by the Moon's largest impact basin to better understand the composition, stratigraphy, and evolution of the upper mantle. The vast South Pole‐Aitken Basin (SPA) exhibits a broad, crescent‐shaped thorium and potassium distribution. These incompatible elements are predicted to be concentrated in the dregs of the lunar magma ocean during end‐stage crystallization. Through consideration of basin formation models convolved with subsequent geologic evolution, we demonstrate that the distribution and implied stratigraphy of Th‐ and K‐bearing materials across SPA are consistent with an upper mantle ejecta origin. The most pristine exposures of these materials are confined to northwest SPA and also exhibit elevated Ti and Fe (relative to the farside highlands) in association with a gabbronoritic mineralogy. This is consistent with late‐stage magma ocean assemblages predicted by petrologic models. In contrast, SPA impact melt derived from greater depths is associated with a low‐Ca pyroxene‐dominated assemblage. Together, these compositional patterns are evidence for a stratified ancient upper mantle. Importantly, the incompatible‐element‐enriched, ilmenite‐bearing ferroan gabbronoritic cumulates evidently had not participated in gravitational overturn at the time of SPA formation. Contrary to recent hypotheses invoking nearside sequestration of incompatible elements to explain hemispherical differences in crustal building and volcanic resurfacing, it follows that incompatible elements were globally distributed in the magma ocean at the time of SPA formation.
Self‐Limitation of Sand Storage in a Bedrock‐Canyon River Arising From the Interaction of Flow and Grain Size
Authors: Topping David J. , Grams Paul E. , Griffiths Ronald E. , Dean David J. , Wright Scott A. , Unema Joel A.
Published: December 2020

Bedrock‐canyon rivers tend to be supply limited because they are efficient transporters of sediment and not because the upstream supply of sediment is small. A byproduct of this supply limitation is that the finer alluvium stored in these rivers has shorter residence times and smaller volumes than in alluvial rivers. To improve our understanding of disequilibrium sediment transport and its effect on sand storage in bedrock‐canyon rivers, we undertook a 20‐year study, synthesized herein, of the Colorado River in Grand Canyon. Despite the large loads for which it was renowned, this river exhibited evidence of natural sand‐supply limitation and became the perfect natural laboratory for studying sand transport in a bedrock canyon after upstream dam construction exacerbated this supply limitation. During our study, we made and analyzed an unprecedented ∼2.5 million measurements of the suspended and bed sediment. Results indicate that sand storage in this bedrock‐canyon river is self‐limiting owing to the physical controls of flow and grain size causing negative feedbacks that likely also operate in other bedrock‐canyon rivers. Following episodic tributary floods that supply finer sand, sand migrates quickly downstream in the form of a wave in which large systematic changes in bed‐sand grain size occur. These grain‐size changes cause discharge‐independent systematic changes in suspended‐sand concentration in excess of a factor of 20. Although the tributary supply of sand increases the amount of sand storage, it also greatly increases the downstream sand transport by causing bed‐sand fining, thus limiting the residence time and volume of sand storage.
Melatonin prevents doxorubicin-induced cardiotoxicity through suppression of AMPKα2-dependent mitochondrial damage
Authors: Yang Goowon , Song Minhyeok , Hoang Dang Hieu , Tran Quynh Hoa , Choe Wonchae , Kang Insug , Kim Sung Soo , Ha Joohun
Published: December 2020

The clinical application of doxorubicin, one of the most effective anticancer drugs, has been limited due to its adverse effects, including cardiotoxicity. One of the hallmarks of doxorubicin-induced cytotoxicity is mitochondrial dysfunction. Despite intensive research over recent decades, there are no effective approaches for alleviating doxorubicin-induced cytotoxicity. Melatonin, a natural hormone that is primarily secreted by the pineal gland, is emerging as a promising adjuvant that protects against doxorubicin-induced cytotoxicity owing to its pharmaceutical effect of preserving mitochondrial integrity. However, the underlying mechanisms are far from completely understood. Here, we provide novel evidence that treatment of H9c2 cardiomyoblasts with doxorubicin strongly induced AMP-activated protein kinase α2 (AMPKα2), which translocated to mitochondria and interfered with their function and integrity, ultimately leading to cellular apoptosis. These phenomena were significantly blocked by melatonin treatment. The levels of AMPKα2 in murine hearts were tightly associated with cardiotoxicity in the context of doxorubicin and melatonin treatment. Therefore, our study suggests that the maintenance of mitochondrial integrity is a key factor in reducing doxorubicin-induced cytotoxicity and indicates that AMPKα2 may serve as a novel target in the design of cytoprotective combination therapies that include doxorubicin.
Autophagy, apoptosis, and neurodevelopmental genes might underlie selective brain region vulnerability in attention-deficit/hyperactivity disorder
Authors: Hess Jonathan L. , Radonjić Nevena V. , Patak Jameson , Glatt Stephen J. , Faraone Stephen V.
Published: December 2020

Large-scale brain imaging studies by the ENIGMA Consortium identified structural changes associated with attention-deficit/hyperactivity disorder (ADHD). It is not clear why some brain regions are impaired and others spared by the etiological risks for ADHD. We hypothesized that spatial variation in brain cell organization and/or pathway expression levels contribute to selective brain region vulnerability (SBRV) in ADHD. In this study, we used the largest available collection of magnetic resonance imaging (MRI) results from the ADHD ENIGMA Consortium (subcortical MRI n = 3242; cortical MRI n = 4180) along with high-resolution postmortem brain microarray data from Allen Brain Atlas (donors n = 6) from 22 brain regions to investigate our SBRV hypothesis. We performed deconvolution of the bulk transcriptomic data to determine abundances of neuronal and nonneuronal cells in the brain. We assessed the relationships between gene-set expression levels, cell abundance, and standardized effect sizes representing regional changes in brain sizes in cases of ADHD. Our analysis yielded significant correlations between apoptosis, autophagy, and neurodevelopment genes with smaller brain sizes in ADHD, along with associations to regional abundances of astrocytes and oligodendrocytes. The lack of enrichment of common genetic risk variants for ADHD within implicated gene sets suggests an environmental etiology to these differences. This work provides novel mechanistic clues about SBRV in ADHD.
Physical activity and the risk of abdominal aortic aneurysm: a systematic review and meta-analysis of prospective studies
Authors: Aune Dagfinn , Sen Abhijit , Kobeissi Elsa , Hamer Mark , Norat Teresa , Riboli Elio
Published: December 2020

The association between physical activity and risk of abdominal aortic aneurysm has been inconsistent with some studies reporting a reduced risk while others have found no association. We conducted a systematic review and meta-analysis of prospective studies to quantify the association. PubMed and Embase databases were searched up to 3 October 2020. Prospective studies were included if they reported adjusted relative risk (RR) estimates and 95% confidence intervals (CIs) of abdominal aortic aneurysm associated with physical activity. Summary RRs (95% CIs) were estimated using a random effects model. Nine prospective studies (2073 cases, 409,732 participants) were included. The summary RR for high vs. low physical activity was 0.70 (95% CI: 0.56–0.87, I2 = 58%) and per 20 metabolic equivalent task (MET)-hours/week increase of activity was 0.84 (95% CI: 0.74–0.95, I2 = 59%, n = 6). Although the test for nonlinearity was not significant (p = 0.09) the association appeared to be stronger when increasing the physical activity level from 0 to around 20–25 MET-hours/week than at higher levels. The current meta-analysis suggest that higher physical activity may reduce the risk of abdominal aortic aneurysm, however, further studies are needed to clarify the dose–response relationship between different subtypes and intensities of activity and abdominal aortic aneurysm risk.
Bumble bees in landscapes with abundant floral resources have lower pathogen loads
Authors: McNeil Darin J. , McCormick Elyse , Heimann Ashley C. , Kammerer Melanie , Douglas Margaret R. , Goslee Sarah C. , Grozinger Christina M. , Hines Heather M.
Published: December 2020

The pollination services provided by bees are essential for supporting natural and agricultural ecosystems. However, bee population declines have been documented across the world. Many of the factors known to undermine bee health (e.g., poor nutrition) can decrease immunocompetence and, thereby, increase bees’ susceptibility to diseases. Given the myriad of stressors that can exacerbate disease in wild bee populations, assessments of the relative impact of landscape habitat conditions on bee pathogen prevalence are needed to effectively conserve pollinator populations. Herein, we assess how landscape-level conditions, including various metrics of floral/nesting resources, insecticides, weather, and honey bee (Apis mellifera) abundance, drive variation in wild bumble bee (Bombus impatiens) pathogen loads. Specifically, we screened 890 bumble bee workers from varied habitats in Pennsylvania, USA for three pathogens (deformed wing virus, black queen cell virus, and Vairimorpha (= Nosema) bombi), Defensin expression, and body size. Bumble bees collected within low-quality landscapes exhibited the highest pathogen loads, with spring floral resources and nesting habitat availability serving as the main drivers. We also found higher loads of pathogens where honey bee apiaries are more abundant, a positive relationship between Vairimorpha loads and rainfall, and differences in pathogens by geographic region. Collectively, our results highlight the need to support high-quality landscapes (i.e., those with abundant floral/nesting resources) to maintain healthy wild bee populations.
Out of India, thrice: diversification of Asian forest scorpions reveals three colonizations of Southeast Asia
Authors: Loria Stephanie F. , Prendini Lorenzo
Published: December 2020

The ‘Out of India’ hypothesis is often invoked to explain patterns of distribution among Southeast Asian taxa. According to this hypothesis, Southeast Asian taxa originated in Gondwana, diverged from their Gondwanan relatives when the Indian subcontinent rifted from Gondwana in the Late Jurassic, and colonized Southeast Asia when it collided with Eurasia in the early Cenozoic. A growing body of evidence suggests these events were far more complex than previously understood, however. The first quantitative reconstruction of the biogeography of Asian forest scorpions (Scorpionidae Latreille, 1802: Heterometrinae Simon, 1879) is presented here. Divergence time estimation, ancestral range estimation, and diversification analyses are used to determine the origins, dispersal and diversification patterns of these scorpions, providing a timeline for their biogeographical history that can be summarized into four major events. (1) Heterometrinae diverged from other Scorpionidae on the African continent after the Indian subcontinent became separated in the Cretaceous. (2) Environmental stresses during the Cretaceous–Tertiary (KT) mass extinction caused range contraction, restricting one clade of Heterometrinae to refugia in southern India (the Western Ghats) and Sri Lanka (the Central Highlands). (3) Heterometrinae dispersed to Southeast Asia three times during India’s collision with Eurasia, the first dispersal event occurring as the Indian subcontinent brushed up against the western side of Sumatra, and the other two events occurring as India moved closer to Eurasia. (4) Indian Heterometrinae, confined to southern India and Sri Lanka during the KT mass extinction, recolonized the Deccan Plateau and northern India, diversifying into new, more arid habitats after environmental conditions stabilized. These hypotheses, which are congruent with the geological literature and biogeographical analyses of other taxa from South and Southeast Asia, contribute to an improved understanding of the dispersal and diversification patterns of taxa in this biodiverse and geologically complex region.
Evaluation of mutation rates, mosaicism and off target mutations when injecting Cas9 mRNA or protein for genome editing of bovine embryos
Authors: Hennig Sadie L. , Owen Joseph R. , Lin Jason C. , Young Amy E. , Ross Pablo J. , Van Eenennaam Alison L. , Murray James D.
Published: December 2020

The CRISPR/Cas9 genome editing tool has the potential to improve the livestock breeding industry by allowing for the introduction of desirable traits. Although an efficient and targeted tool, the CRISPR/Cas9 system can have some drawbacks, including off-target mutations and mosaicism, particularly when used in developing embryos. Here, we introduced genome editing reagents into single-cell bovine embryos to compare the effect of Cas9 mRNA and protein on the mutation efficiency, level of mosaicism, and evaluate potential off-target mutations utilizing next generation sequencing. We designed guide-RNAs targeting three loci (POLLED, H11, and ZFX) in the bovine genome and saw a significantly higher rate of mutation in embryos injected with Cas9 protein (84.2%) vs. Cas9 mRNA (68.5%). In addition, the level of mosaicism was higher in embryos injected with Cas9 mRNA (100%) compared to those injected with Cas9 protein (94.2%), with little to no unintended off-target mutations detected. This study demonstrated that the use of gRNA/Cas9 ribonucleoprotein complex resulted in a high editing efficiency at three different loci in bovine embryos and decreased levels of mosaicism relative to Cas9 mRNA. Additional optimization will be required to further reduce mosaicism to levels that make single-step embryo editing in cattle commercially feasible.
Discovery and validation of an NMR-based metabolomic profile in urine as TB biomarker
Authors: Izquierdo-Garcia José Luis , Comella-del-Barrio Patricia , Campos-Olivas Ramón , Villar-Hernández Raquel , Prat-Aymerich Cristina , De Souza-Galvão Maria Luiza , Jiménez-Fuentes Maria Angeles , Ruiz-Manzano Juan , Stojanovic Zoran , González Adela , Serra-Vidal Mar , García-García Esther , Muriel-Moreno Beatriz , Millet Joan Pau , Molina-Pinargote Israel , Casas Xavier , Santiago Javier , Sabriá Fina , Martos Carmen , Herzmann Christian , Ruiz-Cabello Jesús , Domínguez José
Published: December 2020

Despite efforts to improve tuberculosis (TB) detection, limitations in access, quality and timeliness of diagnostic services in low- and middle-income countries are challenging for current TB diagnostics. This study aimed to identify and characterise a metabolic profile of TB in urine by high-field nuclear magnetic resonance (NMR) spectrometry and assess whether the TB metabolic profile is also detected by a low-field benchtop NMR spectrometer. We included 189 patients with tuberculosis, 42 patients with pneumococcal pneumonia, 61 individuals infected with latent tuberculosis and 40 uninfected individuals. We acquired the urine spectra from high and low-field NMR. We characterised a TB metabolic fingerprint from the Principal Component Analysis. We developed a classification model from the Partial Least Squares-Discriminant Analysis and evaluated its performance. We identified a metabolic fingerprint of 31 chemical shift regions assigned to eight metabolites (aminoadipic acid, citrate, creatine, creatinine, glucose, mannitol, phenylalanine, and hippurate). The model developed using low-field NMR urine spectra correctly classified 87.32%, 85.21% and 100% of the TB patients compared to pneumococcal pneumonia patients, LTBI and uninfected individuals, respectively. The model validation correctly classified 84.10% of the TB patients. We have identified and characterised a metabolic profile of TB in urine from a high-field NMR spectrometer and have also detected it using a low-field benchtop NMR spectrometer. The models developed from the metabolic profile of TB identified by both NMR technologies were able to discriminate TB patients from the rest of the study groups and the results were not influenced by anti-TB treatment or TB location. This provides a new approach in the search for possible biomarkers for the diagnosis of TB.
Cortical bone adaptation to a moderate level of mechanical loading in male Sost deficient mice
Authors: Yang Haisheng , Büttner Alexander , Albiol Laia , Julien Catherine , Thiele Tobias , Figge Christine , Kramer Ina , Kneissel Michaela , Duda Georg N. , Checa Sara , Willie Bettina M.
Published: December 2020

Loss-of-function mutations in the Sost gene lead to high bone mass phenotypes. Pharmacological inhibition of Sost/sclerostin provides a new drug strategy for treating osteoporosis. Questions remain as to how physical activity may affect bone mass under sclerostin inhibition and if that effect differs between males and females. We previously observed in female Sost knockout (KO) mice an enhanced cortical bone formation response to a moderate level of applied loading (900 με at the tibial midshaft). The purpose of the present study was to examine cortical bone adaptation to the same strain level applied to male Sost KO mice. Strain-matched in vivo compressive loading was applied to the tibiae of 10-, 26- and 52-week-old male Sost KO and littermate control (LC) mice. The effect of tibial loading on bone (re)modeling was measured by microCT, 3D time-lapse in vivo morphometry, 2D histomorphometry and gene expression analyses. As expected, Sost deficiency led to high cortical bone mass in 10- and 26-week-old male mice as a result of increased bone formation. However, the enhanced bone formation associated with Sost deficiency did not appear to diminish with skeletal maturation. An increase in bone resorption was observed with skeletal maturation in male LC and Sost KO mice. Two weeks of in vivo loading (900 με at the tibial midshaft) induced only a mild anabolic response in 10- and 26-week-old male mice, independent of Sost deficiency. A decrease in the Wnt inhibitor Dkk1 expression was observed 3 h after loading in 52-week-old Sost KO and LC mice, and an increase in Lef1 expression was observed 8 h after loading in 10-week-old Sost KO mice. The current results suggest that long-term inhibition of sclerostin in male mice does not influence the adaptive response of cortical bone to moderate levels of loading. In contrast with our previous strain-matched study in females showing enhanced bone responses with Sost ablation, these results in males indicate that the influence of Sost deficiency on the cortical bone formation response to a moderate level of loading differs between males and females. Clinical studies examining antibodies to inhibit sclerostin may need to consider that the efficacy of additional physical activity regimens may be sex dependent.
The relationship between resting-state functional connectivity, antidepressant discontinuation and depression relapse
Authors: Berwian Isabel M. , Wenzel Julia G. , Kuehn Leonie , Schnuerer Inga , Kasper Lars , Veer Ilya M. , Seifritz Erich , Stephan Klaas E. , Walter Henrik , Huys Quentin J. M.
Published: December 2020

The risk of relapsing into depression after stopping antidepressants is high, but no established predictors exist. Resting-state functional magnetic resonance imaging (rsfMRI) measures may help predict relapse and identify the mechanisms by which relapses occur. rsfMRI data were acquired from healthy controls and from patients with remitted major depressive disorder on antidepressants. Patients were assessed a second time either before or after discontinuation of the antidepressant, and followed up for six months to assess relapse. A seed-based functional connectivity analysis was conducted focusing on the left subgenual anterior cingulate cortex and left posterior cingulate cortex. Seeds in the amygdala and dorsolateral prefrontal cortex were explored. 44 healthy controls (age: 33.8 (10.5), 73% female) and 84 patients (age: 34.23 (10.8), 80% female) were included in the analysis. 29 patients went on to relapse and 38 remained well. The seed-based analysis showed that discontinuation resulted in an increased functional connectivity between the right dorsolateral prefrontal cortex and the parietal cortex in non-relapsers. In an exploratory analysis, this functional connectivity predicted relapse risk with a balanced accuracy of 0.86. Further seed-based analyses, however, failed to reveal differences in functional connectivity between patients and controls, between relapsers and non-relapsers before discontinuation and changes due to discontinuation independent of relapse. In conclusion, changes in the connectivity between the dorsolateral prefrontal cortex and the posterior default mode network were associated with and predictive of relapse after open-label antidepressant discontinuation. This finding requires replication in a larger dataset.
Application of feed forward and recurrent neural networks in simulation of left ventricular mechanics
Authors: Dabiri Yaghoub , Van der Velden Alex , Sack Kevin L. , Choy Jenny S. , Guccione Julius M. , Kassab Ghassan S.
Published: December 2020

An understanding of left ventricle (LV) mechanics is fundamental for designing better preventive, diagnostic, and treatment strategies for improved heart function. Because of the costs of clinical and experimental studies to treat and understand heart function, respectively, in-silico models play an important role. Finite element (FE) models, which have been used to create in-silico LV models for different cardiac health and disease conditions, as well as cardiac device design, are time-consuming and require powerful computational resources, which limits their use when real-time results are needed. As an alternative, we sought to use deep learning (DL) for LV in-silico modeling. We used 80 four-chamber heart FE models for feed forward, as well as recurrent neural network (RNN) with long short-term memory (LSTM) models for LV pressure and volume. We used 120 LV-only FE models for training LV stress predictions. The active material properties of the myocardium and time were features for the LV pressure and volume training, and passive material properties and element centroid coordinates were features of the LV stress prediction models. For six test FE models, the DL error for LV volume was 1.599 ± 1.227 ml, and the error for pressure was 1.257 ± 0.488 mmHg; for 20 LV FE test examples, the mean absolute errors were, respectively, 0.179 ± 0.050 for myofiber, 0.049 ± 0.017 for cross-fiber, and 0.039 ± 0.011 kPa for shear stress. After training, the DL runtime was in the order of seconds whereas equivalent FE runtime was in the order of several hours (pressure and volume) or 20 min (stress). We conclude that using DL, LV in-silico simulations can be provided for applications requiring real-time results.
Solid-phase extraction cartridges with multi-walled carbon nanotubes and effect of the oxygen functionalities on the recovery efficiency of organic micropollutants
Authors: Barbosa Marta O. , Ribeiro Rui S. , Ribeiro Ana R. L. , Pereira M. Fernando R. , Silva Adrián M. T.
Published: December 2020

Pristine and functionalized multi-walled carbon nanotubes (MWCNTs) were investigated as adsorbent materials inside solid-phase extraction (SPE) cartridges for extraction and preconcentration of 8 EU-relevant organic micropollutants (with different pKa and polarity) before chromatographic analysis of surface water. The recoveries obtained were > 60% for 5/8 target pollutants (acetamiprid, atrazine, carbamazepine, diclofenac, and isoproturon) using a low amount of this reusable adsorbent (50 mg) and an eco-friendly solvent (ethanol) for both conditioning and elution steps. The introduction of oxygenated surface groups in the carbon nanotubes by using a controlled HNO3 hydrothermal oxidation method, considerably improved the recoveries obtained for PFOS (perfluorooctanesulfonic acid) and methiocarb, which was ascribed to the hydrogen bond adsorption mechanism, but decreased those observed for the pesticide acetamiprid and for two pharmaceuticals (carbamazepine and diclofenac), suggesting π–π dispersive interactions. Moreover, a good correlation was found between the recovery obtained for methiocarb and the amount of oxygenated surface groups on functionalized MWCNTs, which was mainly attributed to the increase of phenols and carbonyl and quinone groups. Thus, the HNO3 hydrothermal oxidation method can be used to finely tune the surface chemistry (and texture) of MWCNTs according to the specific micropollutants to be extracted and quantified in real water samples.
Evaluation of product of two sigmoidal membership functions (psigmf) as an ANFIS membership function for prediction of nanofluid temperature
Authors: Babanezhad Meisam , Nakhjiri Ali Taghvaie , Marjani Azam , Rezakazemi Mashallah , Shirazian Saeed
Published: December 2020

A nanofluid containing water and nanoparticles made of copper (Cu) inside a cavity with square shape is simulated utilizing the computational fluid dynamics (CFD) approach. The nanoparticles made up 15% of the nanofluid. By performing the simulation, the CFD output is characterized by the coordinates in the x, y, nanofluid temperature, and velocity in the y-direction that these outputs are obtained for different physical time iterations. Moreover, the CFD outputs are examined by one of the artificial techniques, i.e. adaptive network-based fuzzy inference system (ANFIS). For this purpose, the data was clustered via grid partition clustering, and the type of membership functions (MFs) was chosen product of two sigmoidal membership functions (psigmf). After reaching 99.9% of intelligence in ANFIS, the nanofluid temperature is predicted for the entire data, which are included in the learning processes. The results showed that the method of ANFIS can predict the thermal properties in different physical times at different computing points without having a training background at those times. Additionally, this study shows that with three membership functions at each input, the model’s accuracy is higher than four functions.
Insights into gene expression changes under conditions that facilitate horizontal gene transfer (mating) of a model archaeon
Authors: Makkay Andrea M. , Louyakis Artemis S. , Ram-Mohan Nikhil , Gophna Uri , Gogarten J. Peter , Papke R. Thane
Published: December 2020

Horizontal gene transfer is a means by which bacteria, archaea, and eukaryotes are able to trade DNA within and between species. While there are a variety of mechanisms through which this genetic exchange can take place, one means prevalent in the archaeonHaloferax volcaniiinvolves the transient formation of cytoplasmic bridges between cells and is referred to as mating. This process can result in the exchange of very large fragments of DNA between the participating cells. Genes governing the process of mating, including triggers to initiate mating, mechanisms of cell fusion, and DNA exchange, have yet to be characterized. We used a transcriptomic approach to gain a more detailed knowledge of how mating might transpire. By examining the differential expression of genes expressed in cells harvested from mating conditions on a filter over time and comparing them to those expressed in a shaking culture, we were able to identify genes and pathways potentially associated with mating. These analyses provide new insights into both the mechanisms and barriers of mating inHfx. volcanii.
Transcriptional profiles of human islet and exocrine endothelial cells in subjects with or without impaired glucose metabolism
Authors: Jonsson Alexander , Hedin Anders , Müller Malin , Skog Oskar , Korsgren Olle
Published: December 2020

In experimental studies, pancreatic islet microvasculature is essential for islet endocrine function and mass, and islet vascular morphology is altered in diabetic subjects. Even so, almost no information is available concerning human islet microvascular endothelial cell (MVEC) physiology and gene expression. In this study, islets and exocrine pancreatic tissue were acquired from organ donors with normoglycemia or impaired glucose metabolism (IGM) immediately after islet isolation. Following single-cell dissociation, primary islet- and exocrine MVECs were obtained through fluorescence-activated cell sorting (FACS) and transcriptional profiles were generated using AmpliSeq. Multiple gene sets involved in general vascular development and extracellular matrix remodeling were enriched in islet MVEC. In exocrine MVEC samples, multiple enriched gene sets that relate to biosynthesis and biomolecule catabolism were found. No statistically significant enrichment was found in gene sets related to autophagy or endoplasmic reticulum (ER) stress. Although ample differences were found between islet- and exocrine tissue endothelial cells, no differences could be observed between normoglycemic donors and donors with IGM at gene or gene set level. Our data is consistent with active angiogenesis and vascular remodeling in human islets and support the notion of ongoing endocrine pancreas tissue repair and regeneration even in the adult human.
Residual analysis of chitosan-based agronanofungicides as a sustainable alternative in oil palm disease management
Authors: Maluin Farhatun Najat , Hussein Mohd Zobir , Yusof Nor Azah , Fakurazi Sharida , Maznah Zainol , Idris Abu Seman , Hilmi Nur Hailini Zainol , Daim Leona Daniela Jeffery
Published: December 2020

The nanoformulations of pesticides have shown great interest from many parties due to their slow release capability and site-specific delivery. Hence, in this work, a new nanoformulation of a fungicide, namely chitosan-hexaconazole nanoparticles with a mean diameter size of 18 nm was subjected to the residual analysis on oil palm tissue, leaf and palm oil (crude palm oil and crude palm kernel oil) using a quick, easy, cheap, effective, rugged and safe (QuEChERS) method coupled with the gas chromatography–micro electron capture detector (GC–µECD). The chitosan-hexaconazole nanoparticles were applied using the trunk injection method at 4.5 g a.i./palm (standard single dose) and 9.0 g a.i./palm (double dose). The fungicide residue was analyzed at 0 (6 h after application), 1, 3, 7, 14, 30, 60, 90, and 120 days after treatment. The palm oil matrices; the crude palm oil (CPO) and crude palm kernel oil (CPKO) were found to be residue-free. However, it was observed that high accumulation of the fungicide in the stem tissue and leaf after the treatment using the chitosan-hexaconazole nanoparticles, which is good for better bioavailability for the treatment of the fungi, Ganoderma boninense. The dissipation kinetic at double dose treatment in the tissue and leaf was found to govern by the second-order kinetic with half-lives (t1/2) of 383 and 515 days, respectively.