bluuebunny/crossref_metadata_2025 huggingface dataset:
Study on Quantitative Analysis of Carbon and Nitrogen in Stoichiometric θ-Fe3C and γ′-Fe4N by Atom Probe Tomography
Authors: Takahashi Jun , Kawakami Kazuto , Kobayashi Yukiko
Published: March 2020

The quantitative analysis performance of carbon and nitrogen was investigated using stoichiometric θ-Fe3C (25 at% C) and γ′-Fe4N (~20 at% N) precipitates in pulsed voltage and pulsed laser atom probes. The dependencies of specimen temperature, pulse fraction, and laser pulse energy on the apparent concentrations of carbon and nitrogen were measured. Good coincidence with 25 at% carbon concentration in θ-Fe3C was obtained for the pulsed voltage atom probe by considering the mean number of carbon atoms per ion at 24 Da and the detection loss of iron, while better coincidence was obtained for the pulsed laser atom probe by considering only the mean number of carbon at 24 Da. On the other hand, a lack of nitrogen concentration in γ′-Fe4N was observed for the two atom probes. In particular, the pulsed laser atom probe showed a significant lack of nitrogen concentration. This implies that a large amount of 14N2+ was obscured by the main iron peak of 56Fe2+ at 28 Da in the mass-to-charge spectrum. Regarding preferential evaporation or retention, carbon in θ-Fe3C exhibited little of either, but nitrogen in γ′-Fe4N exhibited definite preferential retention. This result can be explained by the large difference in ionization energy between carbon and nitrogen.
Multi-modality management of extraosseous Ewing sarcoma: 10-year experience from a tertiary care centre
Authors: Sathyamurthy Arvind , Singh Ashish , Jose Tarun , Sebastian Patricia , Balakrishnan Rajesh , Prabhu Anne Jennifer , Backianathan Selvamani
Published: March 2020

Aim:

To analyse the presentation, diagnosis and patterns of care of extraosseous Ewing sarcoma treated at our institution between 2008 and 2018.

Methods:

Electronic medical records of extraosseous Ewing sarcoma patients treated at our institution between January 2008 and April 2018 were reviewed. Kaplan–Meier curves were plotted to assess the overall and disease-free survival with 95% confidence intervals. A univariate analysis was carried out to assess the impact of variables such as surgical excision, completeness of surgery, completeness of chemotherapy and addition of radiation therapy on the survivorship.

Results:

The records of 65 patients treated at our institution were available for review. The mean age was 26·4 years. The most frequent sites of extraosseous Ewing tumour were kidney—9/65 (13·8%) and brain—10/65 (15·4%). Sixteen (24·6%) patients presented with inoperable/metastatic disease at diagnosis. The other 49 (75·4%) had localised disease at presentation. The median overall survival of the 49 non-metastatic patients was 46 months, and the disease-free survival was 45 months.

Conclusion:

Extraosseous Ewing sarcoma is a rare and aggressive tumour diagnosed by molecular techniques. Multi-modality treatment including surgical resection with wide margins, adjuvant radiation when indicated and completion of systemic chemotherapy results in optimum outcomes.
Portuguese Patient Dignity Question: A cross-sectional study of palliative patients cared for in primary care
Authors: Lemos Caldas Mafalda , Julião Miguel , Santos Ana João , Chochinov Harvey Max
Published: March 2020

Introduction

The Patient Dignity Question (PDQ) is a clinical tool developed with the aim of reinforcing the sense of personhood and dignity, enabling health care providers (HCPs) to see patients as people and not solely based on their illness.

Objective

To study the acceptability and feasibility of the Portuguese version of the PDQ (PDQ-PT) in a sample of palliative care patients cared for in primary care (PC).

Method

A cross-sectional study using 20 palliative patients cared for in a PC unit. A post-PDQ satisfaction questionnaire was developed.

Results

Twenty participants were included, 75% were male; average age was 70 years old. Patients found the summary accurate, precise, and complete; all said that they would recommend the PDQ to others and want a copy of the summary placed on their family physician's medical chart. They felt the summary heightened their sense of dignity, considered it important that HCPs have access to the summary and indicated that this information could affect the way HCPs see and care for them. The PDQ-PT's took 7 min on average to answer, and 10 min to complete the summary.

Significance of results

The PDQ-PT is well accepted and feasible to use with palliative patients in the context of PC and seems to be a promising tool to be implemented. Future trials are now warranted.
Do the Two Seismic Gaps in the Southwestern Section of the Longmen Shan Fault Present the Same Seismic Hazard?
Authors: Liu Chang , Zhu Bojing , Shi Yaolin
Published: March 2020

There are two seismic gaps in the southwestern section of the Longmen Shan Fault (LMSF): (1) the gap amid the ruptures of the 2008 Wenchuan and 2013 Lushan earthquakes and (2) the gap in the southwestern‐most section of the LMSF. Conflicting explanations have previously been proposed to estimate the hazards associated with these seismic gaps. In this study, we used a complete earthquake (M ≥ 6.0) catalogue for the past 300 years to re‐evaluate the seismic hazards by calculating the change in the Coulomb stress caused by nearby large earthquakes. When combined with the inter‐seismic tectonic stress loading process, our results suggest that there is a high possibility of a future earthquake in seismic gap 1 because of the enhanced stress caused by the 2008 Wenchuan and 2013 Lushan earthquakes, although the 1970 Dayi earthquake (Ms 6.2) did rupture the center of the gap. However, the risk of an earthquake occurring in seismic gap 2 has decreased due to the unloading stress triggered by 14 large historical earthquakes on the Xianshui He Fault. This indicates that the seismic hazards of the two gaps differ even though they are less than 35 km apart. These findings differ from the results of previous studies, which were obtained using earthquake‐induced stress modeling, inter‐seismic stress modeling, estimates of earthquake moment accumulation and release, and paleoearthquake analysis. Our research sheds new insights on seismic hazard estimates for the southwestern LMSF and might be helpful in determining the disaster relief distribution in Sichuan province, China.
A Role for Gravity Currents in Cross‐Sill Estuarine Exchange and Subsurface Inflow to the Southern Strait of Georgia
Authors: Thomson Richard E. , Kulikov Evgueni A. , Spear David J. , Johannessen Sophia C. , Peter Wills W.
Published: March 2020

Multiyear current meter records from five sites are used to examine subsurface renewal processes in the southern Strait of Georgia. The lower layer inflow of dense oceanic‐derived water over the ~100‐m deep sill in Boundary Pass near the entrance to the strait reaches peak velocities during spring tides and rarely reverses direction. Corresponding changes in water density over the sill are inversely correlated with inflow velocity and, it is assumed, with temporal (t) variations in bottom layer thickness, h(t), arising from the fortnightly variations in tidal‐mixing. The dense bottom water crossing the sill transforms into a gravity current whose velocity is dependent on both h and sill depth, H. Gravity flow velocities, which peak at h(t)/H ~ 0.3 and weaken for h → 0 (neap tides) and h → H (spring tides), modulate the cross‐sill exchange with the strait. The density anomaly, Δρ, of the gravity flow determines its terminal depth and along‐strait extent. Lower‐density gravity flows generated during spring tides separate from the sloping bottom of the southern strait, but the higher‐density flows formed during neap tides can penetrate over 100 km northward to the deep central basin. The most extensive bottom intrusions occur monthly near neap tides in summer, when the underlying estuarine circulation delivers dense upwelled water from the coast to the sill. These deep inflows are accompanied by strong middepth outflow. There are typically three to five monthly replacement episodes each summer, but fewer during strong El Niño years due to reduced coastal upwelling.
Arctic Snow Depth and Sea Ice Thickness From ICESat‐2 and CryoSat‐2 Freeboards: A First Examination
Authors: Kwok R. , Kacimi S. , Webster M.A. , Kurtz N.T. , Petty A.A.
Published: March 2020

We present a first examination of Arctic sea ice snow depth estimates from differencing satellite lidar (ICESat‐2) and radar (CryoSat‐2) freeboards. These estimates cover the period between 14 October 2018 and the end of April 2019. Snow depth is related to freeboard differences by the refractive index/bulk density of the snow layer—the only free parameter in the approach. Area‐averaged snow depth ranges from 9 cm (on first‐year ice: 5 cm, multiyear ice: 14 cm) in late October to 19 cm (first‐year ice: 17 cm, multiyear ice: 27 cm) in April; on average, this snow is thinner over FYI. Spatial patterns and gradients of snow depth estimates compare well with reconstructions using snowfall from ERA‐Interim and ERA5, although snowfall from ERA5 is systematically higher. For all months, the results suggest that ~50% of the total freeboard is comprised of snow. Retrievals are within a few centimeters of snow depth data acquired by Operation IceBridge in April 2019. Sources of uncertainties associated with this freeboard‐differencing approach are discussed. Further, sea ice thicknesses calculated using the retrieved snow depth and a modified climatology are contrasted. Comparatively, the snow depth and calculated ice thickness using a modified climatology are higher by ~5 cm and 0.33 m, although these differences are not uniform throughout the season. Snow accumulation was slower between October and December but increased between December and January, unlike the modified climatology, which exhibited a monotonic accumulation for all months. Future opportunities for assessment and improvement of these estimates are discussed.
Topographic Influence on the African Easterly Jet and African Easterly Wave Energetics
Authors: Hamilton H. L. , Núñez Ocasio K. M. , Evans J. L. , Young G. S. , Fuentes J. D.
Published: March 2020

The topography of eastern Africa, namely, the Ethiopian Highlands and Marrah Mountains have been shown to play a key role in the genesis of African Easterly Waves (AEWs) through convective initiation in that region. Topographic influences on the African Easterly Jet, evolution and energetics of AEWs, and rainfall production across northern tropical Africa are examined here. The Weather Research and Forecasting model is employed to simulate the climate over a 60‐day period for three years (2004, 2005, and 2006) for three cases with varying topography: realistic, half‐height, and no topography. An energetics analysis for the resulting AEWs reveals that wave development by barotropic and baroclinic processes weakens when topography is flattened. These results show that topography in Africa plays a significant role in the wave development as they propagate westward, not only in their initiation over East Africa.
Orbit‐Spin Coupling and the Triggering of the Martian Planet‐Encircling Dust Storm of 2018
Authors: Shirley James H. , McKim Richard J. , Battalio J. Michael , Kass David M.
Published: March 2020

The Martian global dust storm (GDS) of 2018 began soon after the southern spring equinox, which is quite early in the dust storm season. The origins of early‐season GDS, including those of 1977, 2001, and now 2018, have been mysterious, as atmospheric dynamical investigations and numerical modeling experiments have been unable to explain or reproduce the timing of these events. We employ a newly expanded catalog of historic Martian GDS for our investigation, which includes 2018 and the telescopically observed equinoctial dust storms of 1877 and 1909. All of the GDS of this catalog took place either (1) when orbit‐spin coupling torques on the Martian atmosphere were near peak values or (2) near times when the orbit‐spin coupling torques were changing most rapidly. The second category, here termed “Mode 2,” includes all six of the equinoctial GDS of the historic record, including 2018. Recognition of the existence of two triggering modes for GDS occurrence leads to a significant improvement in temporal resolution for both hindcasting and forecasting. Orbit‐spin coupling now provides explanations for the late‐season inception dates of the 1924 and 1973 storms, as well as for the equinoctial events. We provide conditional forecasts, with sub‐seasonal time resolution, for GDS occurrence and non‐occurrence in Mars years 35 through 40. We introduce a detailed working hypothesis for the genesis of equinoctial GDS that may be validated through numerical modeling. The characteristic timescale for frictional damping of an intensified Martian Hadley circulation is estimated to be O(10) sols.
Composition, Stratigraphy, and Geological History of the Noachian Basement Surrounding the Isidis Impact Basin
Authors: Scheller Eva L. , Ehlmann Bethany L.
Published: March 2020

The western part of the Isidis basin structure hosts a well‐characterized Early Noachian to Amazonian stratigraphy. The Noachian Basement comprises its oldest exposed rocks (Early to Mid‐Noachian) and was previously considered a single low‐Ca pyroxenes (LCP)‐ and Fe/Mg‐smectite‐bearing unit. Here, we divide the Noachian Basement Group into five distinct geological units (Stratified Basement Unit, Blue Fractured Unit, Mixed Lithology Plains Unit, LCP‐bearing Plateaus Unit, and Fe/Mg‐smectite‐bearing Mounds Unit), two geomorphological features (megabreccia and ridges), and a mineral deposit (kaolinite‐bearing bright materials), based on geomorphology, spectral characteristics, and stratigraphic relationships. Megabreccia contain four different pre‐Isidis lithologies, possibly including deeper crust or mantle materials, formed through mass wasting associated with transient crater collapse during Isidis basin formation. The Fe/Mg‐smectite‐bearing Stratified Basement Unit and LCP‐bearing Blue Fractured Unit likewise represent pre‐Isidis units within the Noachian Basement Group. Multiple Fe/Mg‐smectite‐bearing geological units with different stratigraphic positions and younger kaolinite‐bearing bright materials indicate several aqueous alteration episodes of different ages and styles. Units with slight changes in pyroxene spectral properties suggest a transition from low‐Ca pyroxene‐containing materials to those with higher proportions of pyroxenes higher in Ca and/or glass that could be related to different impact and/or igneous processes, or provenance. This long history of Noachian and potentially Pre‐Noachian geological processes, including impact basin formation, aqueous alteration, and multiple igneous and sedimentary petrogeneses, records changing ancient Mars environmental conditions. All units defined by this study are available 20 km outside of Jezero crater for in situ analysis and sampling during a potential extended mission scenario for the Mars 2020 rover.
An Environment‐Dependent Probabilistic Tropical Cyclone Model
Authors: Jing Renzhi , Lin Ning
Published: March 2020

The Princeton environment‐dependent probabilistic tropical cyclone (PepC) model is developed for generating synthetic tropical cyclones (TCs) to support TC risk assessment. PepC consists of three components: a hierarchical Poisson genesis model, an analog‐wind track model, and a Markov intensity model. The three model components are dependent on environmental variables that vary with the climate, including potential intensity, advection flow, vertical wind shear, relative humidity, and ocean‐cooling parameters. The present model is developed for the North Atlantic Basin. The three model components and the integrated model are verified against observations using out‐of‐sample testing. The model can generally capture the TC climatology and reproduce statistics of TC genesis, movement, rapid intensification, and lifetime maximum intensity, as well as local landfall frequency and intensity. It can be coupled with climate models and TC hazard models to quantify TC‐related wind, surge, and rainfall risks under various climate conditions. The modeling framework can be further improved when more relevant environmental variables are identified and become available in climate model outputs.
Tectonic Evolution of the Western High Atlas of Morocco: Oblique Convergence, Reactivation, and Transpression
Authors: Lanari R. , Faccenna C. , Fellin M. G. , Essaifi A. , Nahid A. , Medina F. , Youbi N.
Published: March 2020

The High Atlas of Morocco is a double‐vergent mountain belt developed by Cenozoic shortening and inversion of a Triassic‐Jurassic rift. The structural setting, the morphometric features, and the patterns of exhumation through time and space change remarkably both along and across the strike. Here we combine structural data with revised thermochronological data to unravel the kinematic and evolution of the western High Atlas. Our results show that the structural grain of the western High Atlas is defined by two main groups of faults, namely, thrust and oblique‐slip faults, which mainly strike subparallel from W‐E to NE‐SW. The slip direction of the thrust structures is NNW‐SSE to NW‐SE oriented, and the slip direction of the oblique‐slip faults is WSW‐ENE to NW‐SE oriented. Pieces of thermochronological and geological evidence indicate that in the last ~10 Ma the exhumation rate increased during the activity thrusts and oblique‐slip faults. The coexistence of these two fault systems also suggests partitioning of deformation under a transpressive regime. In the western High Atlas, we estimate a displacement of ~12 km on the frontal thrusts and of at least ~22 km on the axial oblique‐slip structures. Thrusts and oblique‐slip structures together result in a total cumulative displacement of ~25 km, which represents about half of the Africa‐Eurasia convergence.
TGF-β1 induces VEGF expression in human granulosa-lutein cells: a potential mechanism for the pathogenesis of ovarian hyperstimulation syndrome
Authors: Fang Lanlan , Li Yiran , Wang Sijia , Li Yuxi , Chang Hsun-Ming , Yi Yuyin , Yan Yang , Thakur Avinash , Leung Peter C. K. , Cheng Jung-Chien , Sun Ying-Pu
Published: March 2020

Ovarian hyperstimulation syndrome (OHSS) is one of the most serious and iatrogenic complications that can occur during in vitro fertilization treatment. Although the pathogenesis of OHSS is not fully understood, vascular endothelial growth factor (VEGF) has been recognized as an important mediator of the development of OHSS. Transforming growth factor-beta-1 (TGF-β1) is known to regulate various ovarian functions. However, whether VEGF can be regulated by TGF-β1 in human granulosa cells has not been determined. In addition, the role of TGF-β1 in the pathogenesis of OHSS remains unknown. In the present study, we demonstrate that TGF-β1 stimulates VEGF expression in and secretion from both immortalized human granulosa-lutein (hGL) cells and primary hGL cells. Our results demonstrate that the SMAD2/3, ERK1/2, and p38 MAPK signaling pathways are involved in TGF-β1-induced VEGF expression and secretion. Using a mouse OHSS model, we show that the expression levels of TGF-β1 and VEGF are increased in the ovaries of OHSS mice. Blocking TGF-β1 signaling inhibits the development of OHSS by attenuating VEGF expression. Moreover, clinical results reveal that the protein levels of TGF-β1 and VEGF are increased in the follicular fluid of patients with OHSS, and that the levels of these two proteins in the follicular fluid are positively correlated. The results of this study help to elucidate the mechanisms by which VEGF expression is regulated in hGL cells, which could lead to the development of alternative therapeutic approaches for treating OHSS.
Multilevel social factors and NICU quality of care in California
Authors: Padula Amy M. , Shariff-Marco Salma , Yang Juan , Jain Jennifer , Liu Jessica , Conroy Shannon M. , Carmichael Suzan L. , Gomez Scarlett L. , Phibbs Ciaran , Oehlert John , Gould Jeffrey B. , Profit Jochen
Published: March 2020

Objective

Our objective was to incorporate social and built environment factors into a compendium of multilevel factors among a cohort of very low birth weight infants to understand their contributions to inequities in NICU quality of care and support providers and NICUs in addressing these inequities via development of a health equity dashboard.

Study design

We examined bivariate associations between NICU patient pool and NICU catchment area characteristics and NICU quality of care with data from a cohort of 15,901 infants from 119 NICUs in California, born 2008–2011.

Result

NICUs with higher proportion of minority racial/ethnic patients and lower SES patients had lower quality scores. NICUs with catchment areas of lower SES, higher composition of minority residents, and more household crowding had lower quality scores.

Conclusion

Multilevel social factors impact quality of care in the NICU. Their incorporation into a health equity dashboard can inform providers of their patients’ potential resource needs.
ADAR1-mediated RNA editing is a novel oncogenic process in thyroid cancer and regulates miR-200 activity
Authors: Ramírez-Moya Julia , Baker Allison R. , Slack Frank J. , Santisteban Pilar
Published: March 2020

Adenosine deaminases acting on RNA (ADARs) convert adenosine to inosine in double-stranded RNA. A-to-I editing of RNA is a widespread posttranscriptional process that has recently emerged as an important mechanism in cancer biology. A-to-I editing levels are high in several human cancers, including thyroid cancer, but ADAR1 editase-dependent mechanisms governing thyroid cancer progression are unexplored. To address the importance of RNA A-to-I editing in thyroid cancer, we examined the role of ADAR1. Loss-of-function analysis showed that ADAR1 suppression profoundly repressed proliferation, invasion, and migration in thyroid tumor cell models. These observations were validated in an in vivo xenograft model, which showed that ADAR1-silenced cells had a diminished ability to form tumors. RNA editing of miRNAs has the potential to markedly alter target recognition. According to TCGA data, the tumor suppressor miR-200b is overedited in thyroid tumors, and its levels of editing correlate with a worse progression-free survival and disease stage. We confirmed miR-200b overediting in thyroid tumors and we showed that edited miR-200b has weakened activity against its target gene ZEB1 in thyroid cancer cells, likely explaining the reduced aggressiveness of ADAR1-silenced cells. We also found that RAS, but not BRAF, modulates ADAR1 levels, an effect mediated predominantly by PI3K and in part by MAPK. Lastly, pharmacological inhibition of ADAR1 activity with the editing inhibitor 8-azaadenosine reduced cancer cell aggressiveness. Overall, our data implicate ADAR1-mediated A-to-I editing as an important pathway in thyroid cancer progression, and highlight RNA editing as a potential therapeutic target in thyroid cancer.
Radiation resistance in head and neck squamous cell carcinoma: dire need for an appropriate sensitizer
Authors: Hutchinson Marsha-Kay N. D. , Mierzwa Michelle , D’Silva Nisha J.
Published: March 2020

Radiation is a significant treatment for patients with head and neck cancer. Despite advances to improve treatment, many tumors acquire radiation resistance resulting in poor survival. Radiation kills cancer cells by inducing DNA double-strand breaks. Therefore, radiation resistance is enhanced by efficient repair of damaged DNA. Head and neck cancers overexpress EGFR and have a high frequency of p53 mutations, both of which enhance DNA repair. This review discusses the clinical criteria for radiation resistance in patients with head and neck cancer and summarizes how cancer cells evade radiation-mediated apoptosis by p53- and epidermal growth factor receptor (EGFR)-mediated DNA repair. In addition, we explore the role of cancer stem cells in promoting radiation resistance, and how the abscopal effect provides rationale for combination strategies with immunotherapy.
A genome-wide approach for identification and characterisation of metabolite-inducible systems
Authors: Hanko Erik K. R. , Paiva Ana C. , Jonczyk Magdalena , Abbott Matthew , Minton Nigel P. , Malys Naglis
Published: March 2020

Inducible gene expression systems are vital tools for the advancement of synthetic biology. Their application as genetically encoded biosensors has the potential to contribute to diagnostics and to revolutionise the field of microbial cell factory development. Currently, the number of compounds of biological interest by far exceeds the number of available biosensors. Here, we address this limitation by developing a generic genome-wide approach to identify transcription factor-based inducible gene expression systems. We construct and validate 15 functional biosensors, provide a characterisation workflow to facilitate forward engineering efforts, exemplify their broad-host-range applicability, and demonstrate their utility in enzyme screening. Previously uncharacterised interactions between sensors and compounds of biological relevance are identified by employing the largest reported library of metabolite-responsive biosensors in an automated high-throughput screen. With the rapidly growing genomic data these innovative capabilities offer a platform to vastly increase the number of biologically detectable molecules.
Photobactericidal activity activated by thiolated gold nanoclusters at low flux levels of white light
Authors: Hwang Gi Byoung , Huang He , Wu Gaowei , Shin Juhun , Kafizas Andreas , Karu Kersti , Toit Hendrik Du , Alotaibi Abdullah M. , Mohammad-Hadi Layla , Allan Elaine , MacRobert Alexander J. , Gavriilidis Asterios , Parkin Ivan P.
Published: March 2020

The emergence of antibiotic resistant bacteria is a major threat to the practice of modern medicine. Photobactericidal agents have obtained significant attention as promising candidates to kill bacteria, and they have been extensively studied. However, to obtain photobactericidal activity, an intense white light source or UV-activation is usually required. Here we report a photobactericidal polymer containing crystal violet (CV) and thiolated gold nanocluster ([Au25(Cys)18]) activated at a low flux levels of white light. It was shown that the polymer encapsulated with CV do not have photobactericidal activity under white light illumination of an average 312 lux. However, encapsulation of [Au25(Cys)18] and CV into the polymer activates potent photobactericidal activity. The study of the photobactericidal mechanism shows that additional encapsulation of [Au25(Cys)18] into the CV treated polymer promotes redox reactions through generation of alternative electron transfer pathways, while it reduces photochemical reaction type-ІІ pathways resulting in promotion of hydrogen peroxide (H2O2) production.
Polymicrobial periodontal disease triggers a wide radius of effect and unique virome
Authors: Gao Li , Kang Misun , Zhang Martin Jinye , Reza Sailani M. , Kuraji Ryutaro , Martinez April , Ye Changchang , Kamarajan Pachiyappan , Le Charles , Zhan Ling , Rangé Hélène , Ho Sunita P. , Kapila Yvonne L.
Published: March 2020

Periodontal disease is a microbially-mediated inflammatory disease of tooth-supporting tissues that leads to bone and tissue loss around teeth. Although bacterially-mediated mechanisms of alveolar bone destruction have been widely studied, the effects of a polymicrobial infection on the periodontal ligament and microbiome/virome have not been well explored. Therefore, the current investigation introduced a new mouse model of periodontal disease to examine the effects of a polymicrobial infection on periodontal ligament (PDL) properties, changes in bone loss, the host immune response, and the microbiome/virome using shotgun sequencing. Periodontal pathogens, namelyPorphyromonas gingivalis, Treponema denticola, Tannerella forsythia, andFusobacterium nucleatumwere used as the polymicrobial oral inoculum in BALB/cByJ mice. The polymicrobial infection triggered significant alveolar bone loss, a heightened antibody response, an elevated cytokine immune response, a significant shift in viral diversity and virome composition, and a widening of the PDL space; the latter two findings have not been previously reported in periodontal disease models. Changes in the PDL space were present at sites far away from the site of insult, indicating that the polymicrobial radius of effect extends beyond the bone loss areas and site of initial infection and wider than previously appreciated. Associations were found between bone loss, specific viral and bacterial species, immune genes, and PDL space changes. These findings may have significant implications for the pathogenesis of periodontal disease and biomechanical properties of the periodontium. This new polymicrobial mouse model of periodontal disease in a common mouse strain is useful for evaluating the features of periodontal disease.
Shared transcriptional responses to con- and heterospecific behavioral antagonists in a wild songbird
Authors: Louder Matthew I. M. , Lafayette Michael , Louder Amber A. , Uy Floria M. K. , Balakrishnan Christopher N. , Yasukawa Ken , Hauber Mark E.
Published: March 2020

The recognition of and differential responses to salient stimuli are among the main drivers of behavioral plasticity, yet, how animals evolve and modulate functional responses to novel classes of antagonistic stimuli remain poorly understood. We studied free-living male red-winged blackbirds (Agelaius phoeniceus) to test whether gene expression responses in blood are distinct or shared between patterns of aggressive behavioral responses directed at simulated conspecific versus heterospecific intruders. In this species, males defend territories against conspecific males and respond aggressively to female brown-headed cowbirds (Molothrus ater), a brood parasite that commonly lays eggs in blackbird nests. Both conspecific songs and parasitic calls elicited aggressive responses from focal subjects and caused a downregulation in genes associated with immune system response, relative to control calls of a second, harmless heterospecific species. In turn, only the conspecific song treatment elicited an increase in singing behavior and an upregulation of genes associated with metabolic processes relative to the two heterospecific calls. Our results suggest that aspects of antagonistic behaviors to both conspecifics and brood parasites can be mediated by similar physiological responses, suggestive of shared molecular and behavioral pathways involved in the recognition and reaction to both evolutionarily old and new enemies.
Glycemic control and use of glucose-lowering medications in hospital-admitted type 2 diabetes patients over 80 years
Authors: Gotfredsen Ditte Resendal , Vinther Siri , Petersen Tonny Studsgaard , Cortes Rikke , Jensen Thomas Bo , Jimenez-Solem Espen , Christensen Mikkel Bring
Published: March 2020

Treatment guidelines for type 2 diabetes (T2D) recommend avoidance of hypoglycemia and less stringent glycemic control in older patients. We examined the relation of glycemic control to glucose-lowering medications use in a cohort of patients aged>80 years with a diagnosis of T2D and a hospital admission in the Capital Region of Denmark in 2012–2016. We extracted data on medication use, diagnoses, and biochemistry from the hospitals’ records. We identified 5,172 T2D patients with high degree of co-morbidity and where 17% had an HbA1c in the range recommended for frail, comorbid, older patients with type 2 diabetes (58–75 mmol/mol (7.5–9%)). Half of the patients (n = 2,575) had an HbA1c <48 mmol/mol (<6.5%), and a majority of these (36% of all patients) did not meet the diagnostic criteria for T2D. Of patients treated with one or more glucose-lowering medications (n = 1,758), 20% had HbA1c-values <42 mmol/mol (<6%), and 1% had critically low Hba1c values <30 mmol/mol (<4.9%), In conclusion, among these hospitalized T2D patients, few had an HbA1c within the generally recommended glycemic targets. One third of patients did not meet the diagnostic criteria for T2D, and of the patients who were treated with glucose-lowering medications, one-fifth had HbA1c-values suggesting overtreatment.
Analysis of risk factors associated with acute pancreatitis after endoscopic papillectomy
Authors: Taglieri Eloy , Micelli-Neto Otávio , Bonin Eduardo Aimoré , Goldman Suzan Menasce , Kemp Rafael , dos Santos José Sebastião , Ardengh José Celso
Published: March 2020

Acute pancreatitis (AP) is a common adverse event (AE) of endoscopic papillectomy (EP). Prophylactic plastic pancreatic stent (PPS) placement appears to prevent AP. We evaluated factors associated with post-EP AP by a retrospective analysis of patients with tumors of the duodenal papilla who underwent EP from January 2008 to November 2016 at 2 tertiary care centers. Clinical, laboratory, endoscopic ultrasound parameters, and PPS placement were evaluated. Seventy-two patients underwent EP (37 men), with mean age of 60.3 (31–88) years. Mean main pancreatic duct (MPD) diameter was 0.44 (0.18–1.8) cm. Mean tumor size was 1.8 (0.5–9.6) cm. Tumors were staged as uT1N0, uT2N0, and uT1N1 in 87.5%, 11.1%, and 1.4%. Thirty-eight AEs occurred in 33 (45.8%) patients, with no mortality. Total bilirubin, tumor size, MPD diameter, and PPS placement had odds ratios (ORs) of 0.82, 0.14, 0.00, and 6.43 for AP. Multivariate analysis (PPS placement × MPD diameter) showed ORs of 4.62 (95%CI, 1.03–21.32; p = 0.049) and 0.000 (95%CI, 0.00–0.74; p = 0.042) for AP. In conclusion, patients with jaundice, large tumors, and dilated MPD seem less likely to have post-EP AP. PPS placement was associated with a higher risk of AP, which may question its use.
Kinetic study of the metal-dipeptide complex with ninhydrin facilitated by gemini (m-s-m) surfactant micelles
Authors: Azum Naved , Kumar Dileep
Published: March 2020

The three Gemini (m-s-m; m (head group) = 16 and s (spacer) = 4, 5, 6) surfactants have been synthesized and their impact on reaction of zinc(II)-glycylleucine complex ([Zn(II)-Gly-Leu]+) and ninhydrin were studied at temperature (343 K) and pH (5.0) using spectroscopic method. Influence of several factors, viz., [Zn(II)-Gly-Leu]+, [ninhydrin], temperature and pH were also carried out on title reaction in geminis. Rates of reaction are the first-order path in concentration of [Zn(II)-Gly-Leu]+complex and fractional order path in concentration of ninhydrin. The catalysis of gemini 16-s-16 surfactant micelles was investigated below and above their critical micelle concentration (cmc) value and detailed elaboration were provided in the text. In the present case, rate constants, kψ, increased on increasing geminis ([gemini] are below their cmc, region I) and stayed nearly constant (region II). The shape of (region I and II) surfactants ([gemini] = 0 to 400 × 10−5mol dm−3) are similar to a cetyltrimethylammonium bromide, CTAB (single hydrophilic head group and hydrophobic part). Later, a sharp increment in rate was observed with higher [gemini] (region III, (Fig. 5). The study was catalyzed and accelerated quite enough by geminis (at concentrations below their cmc) compared to aqueous. An appropriate mechanism has been proposed for accounting for the distribution of reactants between aqueous and micellar pseudo phases. Resulting kinetic data were used to determine the binding constants of micelle-substrate (KB) and micelle-ninhydrin (KNin).
De novo transcriptome of the diatom Cylindrotheca closterium identifies genes involved in the metabolism of anti-inflammatory compounds
Authors: Elagoz Ali M. , Ambrosino Luca , Lauritano Chiara
Published: March 2020

Diatoms are the most diverse and abundant group of phytoplankton species and represent a huge reservoir of marine natural products with possible application for human health. Several diatoms are known to have anticancer, anti-inflammatory, antioxidant and anti-microbial properties, but the compounds responsible of these activities are often still unknown. The diatom Cylindrotheca closterium showed anti-inflammatory properties inhibiting TNFα release in human monocytic leukemia cells. In this study, we present the full transcriptome of C. closterium, and used an -omic approach to identify transcripts coding enzymes that can be involved in the synthesis/degradation of anti-inflammatory compounds. This approach allowed to identify phosphatidylinositol-3-phosphatase, phosphatidylinositol 3-kinase catalytic subunit type 3, phosphatidylinositol N-acetylglucosaminyltransferase subunit A, monogalactosyldiacylglycerol synthase and violaxanthin de-epoxidase, which are known to be involved in anti-inflammatory compound metabolism. When C. closterium was cultured in silica-starvation conditions, selected as stress condition to potentially trigger the synthesis of bioactive metabolites, anti-inflammatory activity was lost and expression levels of the analyzed transcripts were reduced. These data suggested that the control culturing condition was the most active. This study used for the first time a transcriptomic-guided approach to identify enzymes involved in anti-inflammatory compound metabolism, directing future discoveries of marine natural products in microalgae.
Identification of Novel Human Monocyte Subsets and Evidence for Phenotypic Groups Defined by Interindividual Variations of Expression of Adhesion Molecules
Authors: Merah-Mourah F. , Cohen S. O. , Charron D. , Mooney N. , Haziot A.
Published: March 2020

Monocytes contribute to immune responses as a source for subsets of dendritic cells and macrophages. Human blood monocytes are classified as classical, non-classical and intermediate cells. However, the particular functions of these subsets have been hard to define, with conflicting results and significant overlaps. One likely reason for these ambiguities is in the heterogeneity of these monocyte subsets regrouping cells with divergent functions. To better define monocyte populations, we have analysed expression of 17 markers by multicolour flow cytometry in samples obtained from 28 control donors. Data acquisition was tailored to detect populations present at low frequencies. Our results reveal the existence of novel monocyte subsets detected as larger CD14+ cells that were CD16+ or CD16neg. These large monocytes differed from regular, smaller monocytes with respect to expression of various cell surface molecules, such as FcR, chemokine receptors, and adhesion molecules. Unsupervised multidimensional analysis confirmed the existence of large monocytes and revealed interindividual variations that were grouped according to unique patterns of expression of adhesion molecules CD62L, CD49d, and CD43. Distinct inflammatory responses to TLR agonists were found in small and large monocytes. Overall, refining the definition of monocyte subsets should lead to the identification of populations with specific functions.
A highly conserved complete accessory Escherichia coli type III secretion system 2 is widespread in bloodstream isolates of the ST69 lineage
Authors: Fox Stephen , Goswami Cosmika , Holden Matthew , Connolly James P. R. , Mordue James , O’Boyle Nicky , Roe Andrew , Connor Martin , Leanord Alistair , Evans Tom J.
Published: March 2020

Bacterial type III secretion systems (T3SSs) play an important role in pathogenesis of Gram-negative infections. Enteropathogenic and enterohemorrhagic Escherichia coli contain a well-defined T3SS but in addition a second T3SS termed E. coli T3SS 2 (ETT2) has been described in a number of strains of E. coli. The majority of pathogenic E. coli contain elements of a genetic locus encoding ETT2, but which has undergone significant mutational attrition rendering it without predicted function. Only a very few strains have been reported to contain an intact ETT2 locus. To investigate the occurrence of the ETT2 locus in strains of human pathogenic E. coli, we carried out genomic sequencing of 162 isolates obtained from patient blood cultures in Scotland. We found that 22 of 26 sequence type (ST) 69 isolates from this collection contained an intact ETT2 together with an associated eip locus which encodes putative secreted ETT2 effectors as well as eilA, a gene encoding a putative transcriptional regulator of ETT2 associated genes. Using a reporter gene for eilA activation, we defined conditions under which this gene was differentially activated. Analysis of published E. coli genomes with worldwide representation showed that ST69 contained an intact ETT2 in these strains as well. The conservation of the genes encoding ETT2 in human pathogenic ST69 strains strongly suggests it has importance in infection, although its exact functional role remains obscure.
Both higher fitness level and higher current physical activity level may be required for intramyocellular lipid accumulation in non-athlete men
Authors: Yamasaki Nozomu , Tamura Yoshifumi , Takeno Kageumi , Kakehi Saori , Someya Yuki , Funayama Takashi , Furukawa Yasuhiko , Kaga Hideyoshi , Suzuki Ruriko , Sugimoto Daisuke , Kadowaki Satoshi , Sato Motonori , Nakagata Takashi , Nishitani-Yokoyama Miho , Shimada Kazunori , Daida Hiroyuki , Aoki Shigeki , Satoh Hiroaki , Kawamori Ryuzo , Watada Hirotaka
Published: March 2020

Accumulation of intramyocellular lipid (IMCL) is observed in individuals with insulin resistance as well as insulin-sensitive endurance athletes with high peak oxygen consumption (VO2peak), which is called the athlete’s paradox. It remains unclear whether non-athletes with higher fitness levels have IMCL accumulation and higher insulin sensitivity in general. In this study, we investigated the association between IMCL accumulation and muscle insulin sensitivity (M-IS) in subjects with high or low VO2peak. We studied 61 nonobese (BMI, 23 to 25 kg/m2), non-athlete Japanese men. We divided the subjects into four groups based on the median value of VO2peak and IMCL in the soleus muscle. We evaluated M-IS using a two-step hyperinsulinemic-euglycemic clamp. Among subjects with higher VO2peak (n = 32), half of those (n = 16) had lower IMCL levels. Both High-VO2peak groups had higher M-IS than the Low-VO2peak groups. On the other hand, M-IS was comparable between the High-VO2peak/High-IMCL and High-VO2peak/Low-IMCL groups, whereas the High-VO2peak/High-IMCL group had IMCL levels that were twice as high as those in the High-VO2peak/Low-IMCL group. On the other hand, the High-VO2peak/High-IMCL group had significantly higher physical activity levels (approximately 1.8-fold) than the other three groups. In conclusion, in nonobese, non-athlete Japanese men, subjects with higher VO2peak and higher IMCL had higher physical activity levels. IMCL accumulation is not associated with insulin resistance in individuals with higher or lower fitness levels.
Cryptochromes modulate E2F family transcription factors
Authors: Chan Alanna B. , Huber Anne-Laure , Lamia Katja A.
Published: March 2020

Early 2 factor (E2F) family transcription factors participate in myriad cell biological processes including: the cell cycle, DNA repair, apoptosis, development, differentiation, and metabolism. Circadian rhythms influence many of these phenomena. Here we find that a mammalian circadian rhythm component, Cryptochrome 2 (CRY2), regulates E2F family members. Furthermore, CRY1 and CRY2 cooperate with the E3 ligase complex SKP-CULLIN-FBXL3 (SCFFBXL3) to reduce E2F steady state protein levels. These findings reveal an unrecognized molecular connection between circadian clocks and cell cycle regulation and highlight another mechanism to maintain appropriate E2F protein levels for proper cell growth.
Ecological Risks Arising from the Impact of Large-scale Afforestation on the Regional Water Supply Balance in Southwest China
Authors: Xiao Yang , Xiao Qiang , Sun Xuefeng
Published: March 2020

Ecological degradation impedes sustainable development in Southwest China, and artificial afforestation has been a key strategy of the Government of China to effectively curb it. However, the water consumed by large-scale afforestation has a huge impact on water supply in Southwest China, which also arise a new challenge causing severe drought here recently. In order to determine the impact of artificial afforestation on the region, this study conducts spatiotemporal, abrupt change, and correlation and regression analyses. Results show that although water resources fluctuate, they exhibit a general declining trend. Especially after 2000, water resources showed a significant downward trend. In terms of spatial tendency, there has been an obvious decrease in water resources in the Sichuan Basin, the mountainous region of eastern Chongqing, and the Yunnan–Guizhou Plateau. Due to extensive afforestation and vegetation cover growth, there has been an increase in most trends of forest-shrub ecosystems, resulting in substantially enhanced evapotranspiration effects. The uptake of water by afforestation in Southwest China could reach 40.42 billion m3, which is equivalent to 10.69% of its annul available water supply (1980–2015). Generally, afforestation disrupts the water balance of the region. This study recommends substituting afforestation for natural restoration or, at the very least, selecting vegetation that requires less water for the restoration of the ecological environment of Southwest China, which provide scientific method for regional sustainable development.
Investigating the Muscular and Kinematic Responses to Sudden Wrist Perturbations During a Dynamic Tracking Task
Authors: Forman Garrick N. , Forman Davis A. , Avila-Mireles Edwin J. , Zenzeri Jacopo , Holmes Michael W. R.
Published: March 2020

Sudden disturbances (perturbations) to the hand and wrist are commonplace in daily activities and workplaces when interacting with tools and the environment. It is important to understand how perturbations influence forearm musculature and task performance when identifying injury mechanisms. The purpose of this work was to evaluate changes in forearm muscle activity and co-contraction caused by wrist perturbations during a dynamic wrist tracking task. Surface electromyography was recorded from eight muscles of the upper-limb. Participants performed trials consisting of 17 repetitions of ±40° of wrist flexion/extension using a robotic device. During trials, participants received radial or ulnar perturbations that were delivered during flexion or extension, and with known or unknown timing. Co-contraction ratios for all muscle pairs showed significantly greater extensor activity across all experimental conditions. Of all antagonistic muscle pairs, the flexor carpi radialis (FCR)-extensor carpi radialis (ECR) muscle pair had the greatest change in co-contraction, producing 1602% greater co-contraction during flexion trials than during extensions trials. Expected perturbations produced greater anticipatory (immediately prior to the perturbation) muscle activity than unexpected, resulting in a 30% decrease in wrist displacement. While improving performance, this increase in anticipatory muscle activity may leave muscles susceptible to early-onset fatigue, which could lead to chronic overuse injuries in the workplace.
Long-term metal exposure changes gut microbiota of residents surrounding a mining and smelting area
Authors: Shao Mengmeng , Zhu Yi
Published: March 2020

In this epidemiologic study, 16 S rRNA sequencing was used to investigate the changes of diversity and composition profile of gut microbiota resulting from long-term exposure to multiple metals, including arsenic (As), cadmium (Cd), cuprum (Cu), lead (Pb), and zinc (Zn). Due to long-term exposure to various metals, the relative abundances of Lachnospiraceae, Eubacterium eligens, Ruminococcaceae UGG-014, Erysipelotrichaceae UCG-003, Tyzzerella 3, Bacteroides, Slackia, italics, and Roseburia were found to become much higher, whereas the abundance of Prevotella 9 presented an opposite trend. Additionally, differences between males and female groups were found, such as the greater richness and evenness of bacteria for men subjected to long-term metal exposure in polluted areas. The changes of men’s microbiomes were more significant as a result of higher daily intake, mining and smelting activity, and living habits. This research presents a new theoretical basis for the correlation between long-term metal exposure and gut health for people living in contaminated areas.