bluuebunny/crossref_metadata_2025 huggingface dataset:
Room-temperature multiferroicity and diversified magnetoelectric couplings in 2D materials
Authors: Zhong Tingting , Li Xiaoyong , Wu Menghao , Liu Jun-Ming
Published: October 2019

Multiferroics are rare in nature due to the mutual exclusive origins of magnetism and ferroelectricity. The simultaneous coexistence of robust magnetism/ferroelectricity and strong magnetoelectric coupling in single multiferroics is hitherto unreported, which may also be attributed to their potential conflictions. In this paper, we show the first-principles evidence of such desired coexistence in ultrathin-layer CuCrS2 and CuCrSe2. The vertical ferroelectricity is neither induced by an empty d shell nor spin-driven, giving rise to an alternative possibility of resolving those intrinsic exclusions and contradictions. Compared with their bulk phases, the ferromagnetism in the thin-layer structures (two–six layers) can be greatly stabilized due to the enhanced carrier density and orbital shifting by vertical polarization, and the Curie temperatures of both ferromagnetism and ferroelectricity can be above room temperature. Moreover, a considerable net magnetization can be reversed upon ferroelectric switching, where the change in spin-resolved band structure also renders efficient ‘magnetic reading + electrical writing’. The thickness-different layers may even exhibit diversified types of magnetoelectric coupling, which both enriches the physics of multiferroics and facilitates their practical applications.
Five-Day Changes in Biomarkers of Exposure Among Adult Smokers After Completely Switching From Combustible Cigarettes to a Nicotine-Salt Pod System
Authors: Jay Joanna , Pfaunmiller Erika L , Huang Norman J , Cohen Gal , Graff Donald W
Published: October 2019

Introduction

This study examined changes in biomarkers of exposure (BoE) after 5 days of nicotine-salt pod system (NSPS) use, compared with continuation of usual-cigarette smoking and cigarette abstinence, among adult combustible cigarette smokers.

Aims and Methods

A randomized, open-label, parallel-cohort, confinement study of healthy adult smokers, naive to NSPS use, was conducted. Participants (N = 90) were randomized to six cohorts (n = 15 each): exclusive ad libitum use of NSPS (four flavors: Virginia Tobacco, Mint, Mango, Creme), continuation of usual-brand cigarette smoking, or cigarette abstinence. Total nicotine equivalents and BoE (NNN, NNAL, 3-HPMA, MHBMA, S-PMA, HMPMA, CEMA, 1-OHP, and COHb) were measured.

Results

Eight non-nicotine BoEs, measured in urine, were reduced by an aggregate of 85.0% in the pooled NSPS cohort; increased by 14.4% in the cigarette cohort (p < .001 for pooled NSPS vs. cigarette); and reduced by 85.3% in the abstinence cohort (p > .05; 99.6% relative reduction between pooled NSPS vs. abstinence). Similar changes in individual BoEs were also observed (p < .001 for each BoE between pooled NSPS vs. cigarettes; and abstinence vs. pooled NSPS; p > .05 for each BoE between pooled NSPS vs. abstinence). Blood COHb decreased by 71.8% in the pooled NSPS cohort and 69.1% in the abstinence cohort (p > .05) and increased by 13.3% in the cigarette cohort (p < .001). Mean total urine nicotine equivalents increased in the pooled NSPS and cigarette cohorts by 9% and 26%, respectively, and did not significantly differ (p > .05).

Conclusion

Complete switching from cigarettes to NSPS produced significant reductions in key non-nicotine BoEs associated with cigarette smoking.

Implications

The results of this study concorded with evidence that complete switching from combustible cigarettes to tobacco and nontobacco-flavored vapor products may reduce exposure to key carcinogens and other toxicants known to be associated with tobacco-related diseases. Future research is needed to assess the long-term health effects of NSPS use. These results should not be interpreted to mean that the use of NSPS is without any risk, particularly for nonusers of tobacco products.
Early Infectious Disease Consultation Is Associated With Lower Mortality in Patients With Severe Sepsis or Septic Shock Who Complete the 3-Hour Sepsis Treatment Bundle
Authors: Madaline Theresa , Wadskier Montagne Francis , Eisenberg Ruth , Mowrey Wenzhu , Kaur Jaskiran , Malik Maria , Gendlina Inessa , Guo Yi , White Deborah , Pirofski Liise-Anne , Sarwar Uzma
Published: October 2019

Objective

Severe sepsis and septic shock (SS/SS) treatment bundles reduce mortality, and early infectious diseases (ID) consultation also improves patient outcomes. We retrospectively examined whether early ID consultation further improves outcomes in Emergency Department (ED) patients with SS/SS who complete the sepsis bundle.

Method

We included 248 adult ED patients with SS/SS who completed the 3-hour bundle. Patients with ID consultation within 12 hours of ED triage (n = 111; early ID) were compared with patients who received standard care (n = 137) for in-hospital mortality, 30-day readmission, length of hospital stay (LOS), and antibiotic management. A competing risk survival analysis model compared risks of in-hospital mortality and discharge alive between groups.

Results

In-hospital mortality was lower in the early ID group unadjusted (24.3% vs 38.0%, P = .02) and adjusted for covariates (odds ratio, 0.47; 95% confidence interval (CI), 0.25–0.89; P = .02). There was no significant difference in 30-day readmission (22.6% vs 23.5%, P = .89) or median LOS (10.2 vs 12.1 days, P = .15) among patients who survived. A trend toward shorter time to antibiotic de-escalation in the early ID group (log-rank test P = .07) was observed. Early ID consultation was protective of in-hospital mortality (adjusted subdistribution hazard ratio (asHR), 0.60; 95% CI 0.36–1.00, P = .0497) and predictive of discharge alive (asHR 1.58, 95% CI, 1.11–2.23; P-value .01) after adjustment.

Conclusions

Among patients receiving the SS/SS bundle, early ID consultation was associated with a 40% risk reduction for in-hospital mortality. The impact of team-based care and de-escalation on SS/SS outcomes warrants further study.
Basal cell adenoma of the lung identified with obstructive pneumonia
Authors: Shima Hideki , Yoshida Takayuki , Hamada Kunio , Ito Akihide , Ito Toshiki
Published: October 2019

The seromucinous glands of the bronchi can give rise to tumors resembling those of the salivary glands. Basal cell adenoma (BCA) has not been reported in salivary gland-type tumors of the lung. Here, we report a case of an 86-year-old Asian man who suffered from pneumonia in the left upper lung field that may be associated with an endobronchial tumor occluding B1 + 2a + b. The bronchoscopic biopsy of the tumor revealed that the basaloid cells, which constituted a major component of the tumor and were positive for p40/p63 immunohistochemistry, exhibited a cord-like structure. The Ki-67 (MKI67) staining was less than 1% positive. These findings suggest that the endobronchial tumor was BCA of the lung, which caused obstructive pneumonia in the patient.
Opioid Dose and Benzodiazepine Use Among Commercially Insured Individuals on Chronic Opioid Therapy
Authors: Kay Cynthia , Fergestrom Nicole , Spanbauer Charles , Jackson Jeffrey L
Published: October 2019

Objective

To examine morphine milligram equivalent (MME) trends, use of concurrent opioids and benzodiazepines, and opioid-related emergency department (ED) visits or hospitalizations in a national cohort of patients on chronic opioid therapy.

Design

Retrospective cohort analysis of prospectively collected data from the Truven Health MarketScan Commercial Claims and Encounters database from 2009 to 2015. This includes individuals in both the Commercial Claims and Medicare Supplemental databases of MarketScan.

Methods

MME comparisons of 1) patients on chronic opioids with and without opioid-related ED visits or hospitalizations, 2) patients on concurrent opioids and benzodiazepines with and without opioid-related ED visits or hospitalizations, and 3) patients on chronic opioids compared with those on concurrent opioid and benzodiazepine using the Student t test.

Results

MME decreased from 194 mg in 2009 to 119 mg in 2015 among patients on chronic opioids. Patients on opioids and benzodiazepines had higher doses than those on opioids alone for all years (P < 0.001). Those with an opioid-related ED visit or hospitalization had a higher average MME than those without, for all years except 2009 (P < 0.05). Patients on chronic opioids or on concurrent benzodiazepine with an MME >50 had a twofold increased risk of having an opioid-related ED visit or hospitalization compared with those with an MME <50, for all years.

Conclusions

Although the average MME decreased over time, patients on combination opioid and benzodiazepine and those with opioid-related ED visits and hospitalizations had significantly higher doses.
Quality of life trajectories during the first three years after diagnosis of breast cancer: the NEON-BC study
Authors: Lopes-Conceição Luisa , Brandão Mariana , Araújo Natália , Severo Milton , Dias Teresa , Peleteiro Bárbara , Fontes Filipa , Pereira Susana , Lunet Nuno
Published: October 2019

Background

We aimed to identify and characterize quality of life trajectories up to 3 years after breast cancer diagnosis.

Methods

A total of 460 patients were evaluated at baseline (before treatments), and after 1- and 3-years. Patient-reported outcomes, including quality of life (European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30, QLQ-C30), anxiety, depression and sleep quality, were assessed in all evaluations. Model-based clustering was used to identify quality of life trajectories.

Results

We identified four trajectories without intersection during 3 years. The two trajectories characterized by better quality of life depicted relatively stable scores; in the other trajectories, quality of life worsened until 1 year, though in one of them the score at 3 years improved. Sociodemographic and clinical characteristics at baseline did not differ between trajectories, except for mastectomy, which was higher in the worst trajectory. Anxiety, depression and poor sleep quality increased from the best to the worst trajectory.

Conclusions

The type of surgery and the variation of other patient-reported outcomes were associated with the course of quality of life over 3 years. More research to understand the heterogeneity of individual trajectories within these major patterns of variation is needed.
Cancer epidemiology literature from India: Does it reflect the reality?
Authors: Deepa K V , Venghateri Jubina Balan , Khajanchi Monty , Gadgil Anita , Roy Nobhojit
Published: October 2019

Background

The alarming escalation of cancers over infectious diseases in the lower and middle-income countries warrants a better understanding of this epidemiological transition. The epidemiology of cancers in India is sparsely addressed in the literature. Hence, in this manuscript, we present the review done, on research manuscripts, addressing cancer incidence, trends and risk factors from India over the last 12 years. Studies addressing screening, treatment and clinical trials were excluded.

Methods

We evaluated the studies for the theme addressed, study design, sample size, the region of origin and whether it was population or hospital-based study.

Results

The studies highlighted a significant shortage of multicenter population-based data in the incidence and risk factors associated with various malignancies in India. Further, we also observed that there was a relative lack of information from the northern and northeastern parts of India. The reviewed articles also indicated the need for a robust design for the studies, large sample size and uniformity in reporting incidence for appropriately drawing conclusions from a study. Reporting of country-specific risk factors with their geographical variations was also sparse.

Conclusion

Overall, the cancer epidemiology literature from India is sparse. More studies with robust designs representing all parts of the country are currently needed.
Predictive factors of severe infections in patients with systemic necrotizing vasculitides: data from 733 patients enrolled in five randomized controlled trials of the French Vasculitis Study Group
Authors: Lafarge Antoine , Joseph Adrien , Pagnoux Christian , Puéchal Xavier , Cohen Pascal , Samson Maxime , Hamidou Mohamed , Karras Alexandre , Quemeneur Thomas , Ribi Camillo , Groh Matthieu , Mouthon Luc , Guillevin Loïc , Terrier Benjamin ,   for the French Vasculitis Study Group (FVSG)
Published: October 2019

Objectives

Infections remain a major cause of morbidity and mortality in systemic necrotizing vasculitides (SNV). We aimed to identify factors predicting severe infections (SI) in SNV.

Methods

Data from five randomized controlled trials (RCTs) enrolling 733 patients were pooled. The primary end point was the occurrence of SI, defined by the need of a hospitalization and/or intravenous anti-infectious treatment and/or leading to death.

Results

After a median follow-up of 5.2 (interquartile range 3–9.7) years, 148 (20.2%) patients experienced 189 SI, and 98 (66.2%) presented their first SI within the first 2 years. Median interval from inclusion to SI was 14.9 (4.3–51.7) months. Age ≥65 years (hazard ratio (HR) 1.49 [1.07–2.07]; P=0.019), pulmonary involvement (HR 1.82 [1.26–2.62]; P=0.001) and Five Factor Score ≥1 (HR 1.21 [1.03–1.43]; P=0.019) were independent predictive factors of SI. Regarding induction therapy, the occurrence of SI was associated with the combination of GCs and CYC (HR 1.51 [1.03–2.22]; P = 0.036), while patients receiving only GCs were less likely to present SI (HR 0.69 [0.44–1.07]; P = 0.096). Finally, occurrence of SI had a significant negative impact on survival (P<0.001).

Conclusion

SI in SNV are frequent and impact mortality. Age, pulmonary involvement and Five Factor Score are baseline independent predictors of SI. No therapeutic regimen was significantly associated with SI but patients receiving glucocorticoids and CYC as induction tended to have more SI.
Inheritance, estate and gift tax treaties—Italy
Authors: Saccardo Nicola
Published: October 2019

Italy is party to seven inheritance/estate tax treaties, concluded with Denmark, France, Greece, Israel, Sweden, the USA and the UK. The treaty with France also covers gift tax. The article describes the ramifications of such treaties in terms of the elimination of double taxation, by either restricting Italian taxation as the State of situs of the assets or dealing with dual residence cases. The article also highlights both the interpretation issues raised by these (old) treaties and the limits of such treaties in eliminating double taxation.
Efficacy of oral meloxicam as primary pain mitigation following caustic paste disbudding of three day old Holstein calves
Authors: Karlen Kyle J , Baier Faith S , Odegard Sara L , Baumann Ruth M , Coetzee Johann F , Kehoe Sylvia I , Vogel Kurt D
Published: October 2019

The purpose of this study was to investigate the effects of perioperative administration of oral meloxicam prior to and following the application of caustic paste to disbud neonatal dairy calves. Sixty-one 3–4-d-old Holstein heifer calves were randomly assigned to one of four treatment groups of 15–16 calves. The treatment groups were: 1) M1, caustic paste disbudding and oral meloxicam (45 mg) with a placebo 24 h later; 2) M2, treatment M1 followed by a second 45-mg dose of meloxicam 24 h later instead of placebo; 3) CONTROL, treatment M1 with placebo in place of meloxicam; and 4) SHAM, sham disbudding with placebo in place of meloxicam. Infrared thermography was used to quantify eye and horn bud temperatures. Pressure algometry was used to measure Mechanical nociceptive threshold (MNT) surrounding the horn bud. Average daily gain and body weight (BW) were obtained by weighing each animal throughout the study and calculating the changes over time. Plasma was collected and analyzed for cortisol and substance P concentrations. Substance P and cortisol decreased in all animals over time, regardless of treatment. Mean plasma substance P concentration across all time points was greater (P < 0.05) in the SHAM group than M1 or M2 but not different (P > 0.05) than the CONTROL group. The MNT and ocular temperatures decreased over time across all treatments (P < 0.05). Mean BW increased over time across all treatments (P < 0.05). A significant interaction (P < 0.05) between treatment and sampling time was observed at 12 h following treatment application for both mean horn bud temperature and the ratio between horn bud and ocular temperature. Overall, the results of this study suggest that meloxicam administration at a dose of 45 mg per animal may have limited influence as the primary modulator of pain and inflammatory response in calves that have been disbudded with caustic paste at 3 d of age.
Brainstem serotonergic, catecholaminergic, and inflammatory adaptations during chronic hypercapnia in goats
Authors: Burgraff Nicholas J. , Neumueller Suzanne E. , Buchholz Kirstyn J. , LeClaire John , Hodges Matthew R. , Pan Lawrence , Forster Hubert V.
Published: October 2019

Despite the prevalence of CO2 retention in human disease, little is known about the adaptive neurobiological effects of chronic hypercapnia. We have recently shown 30‐d exposure to increased inspired CO2 (InCO2) leads to a steady‐state ventilation that exceeds the level predicted by the sustained acidosis and the acute CO2/H+ chemoreflex, suggesting plasticity within respiratory control centers. Based on data showing brainstem changes in aminergic and inflammatory signaling during carotid body denervation‐induced hypercapnia, we hypothesized chronic hypercapnia per se will lead to similar changes. We found that: 1) increased InCO2 increased IL‐1β in the medullary raphe (MR), ventral respiratory column, and cuneate nucleus after 24 h, but not after 30 d of hypercapnia; 2) the number of serotonergic and total neurons were reduced within the MR and ventrolateral medulla following 30 d of increased InCO2; 3) markers of tryptophan metabolism were altered following 24 h, but not 30 d of InCO2; and 4) there were few changes in brainstem amine levels following 24 h or 30 d of increased InCO2. We conclude that these changes may contribute to initiating or maintaining respiratory neuroplasticity during chronic hypercapnia but alone do not account for ventilatory acclimatization to chronic increased InCO2.—Burgraff, N. J., Neumueller, S. E., Buchholz, K. J., LeClaire, J., Hodges, M. R., Pan, L., Forster, H. V. Brainstem serotonergic, catecholaminergic, and inflammatory adaptations during chronic hypercapnia in goats. FASEB J. 33, 14491‐14505 (2019). www.fasebj.org
The tough process of unmasking the slow-growing mycobacterium: case report of Mycobacterium microti infection
Authors: van de Weg Cornelia A. M. , de Steenwinkel Jurriaan E. M. , Miedema Jelle R. , Bakker Marleen , van Ingen Jakko , Hoefsloot Wouter
Published: October 2019

Mycobacterium microti

belongs to the

Mycobacterium tuberculosis

complex (MTBC). It can cause pulmonary and extrapulmonary tuberculosis in humans. Compared to

M. tuberculosis

, which is the most prevalent subspecies of the MTBC,

M. microti

infection has a different etiology. Moreover, establishing the diagnosis with conventional bacteriology can be difficult. We will illustrate this with a case of an extrapulmonary tuberculosis of the hip caused by M .microti in an immunocompetent patient in The Netherlands.
Comparative transcriptome analysis of mule uncovered several heterosis-related genes for improving muscular endurance and cognition
Authors: Gao Shan
Published: October 2019

Heterosis has been widely exploited in animal and plant breeding to enhance the productive traits of hybrid progeny of two breeds or two species. Although, there were multiple models for explaining the hybrid vigor, such as dominance and over-dominance hypothesis, its underlying molecular genetic mechanisms remain equivocal. The aim of this study is through comparing the different expression genes (DEGs) and different alternative splicing (DAS) genes to explore the mechanism of heterosis. Here, we performed a genome-wide gene expression and alternative splicing analysis of two heterotic crosses between donkey and horse in three tissues. The results showed that the DAS genes influenced the heterosis-related phenotypes in a unique than DEGs and about 10% DEGs are DAS genes. In addition, over 69.7% DEGs and 87.2% DAS genes showed over-dominance or dominance, respectively. Furthermore, the “Muscle Contraction” and “Neuronal System” pathways were significantly enriched both for the DEGs and DAS genes in muscle. TNNC2 and RYR1 genes may contribute to mule’s great endurance while GRIA2 and GRIN1 genes may be related with mule’s cognition. Together, these DEGs and DAS genes provide the candidates for future studies of the genetic and molecular mechanism of heterosis in mule.
Loss of region-specific glial homeostatic signature in prion diseases
Authors: Makarava Natallia , Chang Jennifer Chen-Yu , Molesworth Kara , Baskakov Ilia V.
Published: October 2019

Background

Chronic neuroinflammation is recognized as a major neuropathological hallmark in a broad spectrum of neurodegenerative diseases including Alzheimer’s, Parkinson’s, Frontal Temporal Dementia, Amyotrophic Lateral Sclerosis, and prion diseases. Both microglia and astrocytes exhibit region-specific homeostatic transcriptional identities, which under chronic neurodegeneration, transform into reactive phenotypes in a region- and disease-specific manner. Little is known about region-specific identity of glia in prion diseases. The current study was designed to determine whether the region-specific homeostatic signature of glia changes with the progression of prion diseases, and whether these changes occur in a region-dependent or universal manner. Also of interest was whether different prion strains give rise to different reactive phenotypes.

Methods

To answer these questions, we analyzed gene expression in thalamus, cortex, hypothalamus and hippocampus of mice infected with 22L and ME7 prion strains using Nanostring Neuroinflammation panel at subclinical, early clinical and advanced stages of the disease.

Results

We found that at the preclinical stage of the disease, region-specific homeostatic identities were preserved. However, with the appearance of clinical signs, region-specific signatures were partially lost and replaced with a neuroinflammation signature. While the same sets of genes were activated by both prion strains, the timing of neuroinflammation and the degree of activation in different brain regions was strain-specific. Changes in astrocyte function scored at the top of activated pathways. Moreover, clustering analysis suggested that the astrocyte function pathway responded to prion infection prior to activated microglia or neuron and neurotransmission pathways.

Conclusions

The current work established neuroinflammation gene expression signature associated with prion diseases. Our results illustrate that with the disease progression, the region-specific homeostatic transcriptome signatures are replaced by region-independent neuroinflammation signature, which was common for prion strains with different cell tropism. The prion-associated neuroinflammation signature identified in the current study overlapped only partially with the microglia degenerative phenotype and the disease-associated microglia phenotype reported for animal models of other neurodegenerative diseases.
Monosynaptic Inputs to Excitatory and Inhibitory Neurons of the Intermediate and Deep Layers of the Superior Colliculus
Authors: Doykos Ted K. , Gilmer Jesse I. , Person Abigail L. , Felsen Gidon
Published: October 2019

The intermediate and deep layers of the midbrain superior colliculus (SC) are a key locus for several critical functions, including spatial attention, multisensory integration and behavioral responses. While the SC is known to integrate input from a variety of brain regions, progress in understanding how these inputs contribute to SC-dependent functions has been hindered by the paucity of data on innervation patterns to specific types of SC neurons. Here, we use G-deleted rabies virus-mediated monosynaptic tracing to identify inputs to excitatory and inhibitory neurons of the intermediate and deep SC. We observed stronger and more numerous projections to excitatory than inhibitory SC neurons. However, a subpopulation of excitatory neurons thought to mediate behavioral output received weaker inputs, from far fewer brain regions, than the overall population of excitatory neurons. Additionally, extrinsic inputs tended to target rostral excitatory and inhibitory SC neurons more strongly than their caudal counterparts, and commissural SC neurons tended to project to similar rostrocaudal positions in the other SC. Our findings support the view that active intrinsic processes are critical to SC-dependent functions, and will enable the examination of how specific inputs contribute to these functions.
A Study of Representational Similarity: The Emergence of Object Concepts in Rapid Serial Visual Presentation Streams
Authors: Zhou Ivy , Grootswagers Tijl , Segula Blake , Robinson Amanda , Shatek Sophia , Whyte Christopher , Carlson Thomas
Published: October 2019

Disclaimer

This manuscript has been withdrawn by the authors as it was preliminary work that was submitted without the full consent of all the authors. Therefore, the authors do not wish this work to be cited as reference for the project. A new version is forthcoming. If you have any questions, please contact the corresponding author.
NFATC4 Promotes Quiescence and Chemotherapy Resistance in Ovarian Cancer
Authors: Cole Alexander J. , Iyengar Mangala , O’Hayer Patrick , Chan Daniel , Delgoffe Greg , Aird Katherine M. , Yoon Euisik , Bai Shoumei , Buckanovich Ronald J.
Published: October 2019

Development of chemotherapy resistance is a major problem in ovarian cancer. One understudied mechanism of chemoresistance is the induction of quiescence, a reversible non-proliferative state. Unfortunately, little is known about regulators of quiescence. Here we identify the master transcription factor NFATC4 as a regulator of quiescence in ovarian cancer. NFATC4 is enriched in ovarian cancer stem-like cells (CSC) and correlates with decreased proliferation and poor prognosis. Treatment of cancer cells with cisplatin results in NFATC4 nuclear translocation and activation of NFATC4 pathway, while inhibition of the pathway increased chemotherapy response. Induction of NFATC4 activity results in a marked decrease in proliferation, G0 cell cycle arrest and chemotherapy resistance, both in vitro and in vivo. Finally, NFATC4 drives a quiescent phenotype in part via downregulation of MYC. Together these data identify that NFATC4 as a driver of quiescence and a potential new target to combat chemoresistance in ovarian cancer.
Visualization of silver nanoparticle intracellular trafficking revealed nuclear translocation of silver ions leading to nuclear receptor impairment
Authors: Suárez Vanessa Tardillo , Karepina Elizaveta , Chevallet Mireille , Gallet Benoit , Cottet-Rousselle Cécile , Charbonnier Peggy , Moriscot Christine , Michaud-Soret Isabelle , Bal Wojciech , Fuchs Alexandra , Tucoulou Rémi , Jouneau Pierre-Henri , Veronesi Giulia , Deniaud Aurélien
Published: October 2019

The impact on human health of the increasing use of silver nanoparticles (AgNPs) in medical devices remains understudied, even though AgNP-containing dressings are known to release silver in the bloodstream leading to accumulation and slow clearance in the liver. Cellular studies have shown the intracellular dissolution of AgNPs within endo-lysosomes followed by Ag(I) binding to biomolecular thiolate-containing molecules. However, the precise subcellular distribution of Ag(I) and the nature of the disrupted physiological pathways remained unknown. Novel imaging approaches enabled us to visualize the trafficking of AgNP-containing lysosomes towards a perinuclear location and a direct nuclear transfer of Ag(I) species with accumulation in the nucleoli. These Ag(I) species impaired nuclear receptor activity, disrupting critical mechanisms of liver physiology in very low dose exposure scenarios, thus justifying further research into defining a framework for the safe use of AgNPs.
A selectable system to evaluate synthetic gene optimization features
Authors: Smider Brevin A. , Gil Jacob , Smider Vaughn V.
Published: October 2019

Heterologous gene expression – transferring genes from a natural cell or origin to another host cell, often across species – is a fundamental technique in biological research as well as biotechnological and pharmaceutical manufacturing. Optimization of gene sequences, therefore, is a critical factor when enhanced protein yield is needed. For any given protein, an enormous diversity of nucleotide sequences comprising the vast combinatorics of possible codon combinations could theoretically be used to encode the same amino acid sequence. The process of “codon optimization” typically replaces certain codons thought to be suboptimal with a more optimal codon encoding the same amino acid. However, such methods cannot address the enormity of possible nucleotide sequences possible to encode a given protein, or to decipher potential factors in addition to codon usage that may affect gene expression. Here we utilize the Sh ble gene encoding zeocin resistance in a system comprising bioinformatic synthetic gene production and an antibiotic selection platform. We find that supposedly codon optimized genes do not produce enhanced antibiotic resistance, suggesting that other factors are more important in synthetic gene optimization and heterologous gene expression.
DatView: a graphical user interface for visualizing and querying large data sets in serial femtosecond crystallography
Authors: Stander Natasha , Fromme Petra , Zatsepin Nadia
Published: October 2019

DatView is a new graphical user interface (GUI) for plotting parameters to explore correlations, identify outliers and export subsets of data. It was designed to simplify and expedite analysis of very large unmerged serial femtosecond crystallography (SFX) data sets composed of indexing results from hundreds of thousands of microcrystal diffraction patterns. However, DatView works with any tabulated data, offering its functionality to many applications outside serial crystallography. In DatView's user-friendly GUI, selections are drawn onto plots and synchronized across all other plots, so correlations between multiple parameters in large multi-parameter data sets can be rapidly identified. It also includes an item viewer for displaying images in the current selection alongside the associated metadata. For serial crystallography data processed by indexamajig from CrystFEL [White, Kirian, Martin, Aquila, Nass, Barty & Chapman (2012). J. Appl. Cryst.
45, 335–341], DatView generates a table of parameters and metadata from stream files and, optionally, the associated HDF5 files. By combining the functionality of several commonly needed tools for SFX in a single GUI that operates on tabulated data, the time needed to load and calculate statistics from large data sets is reduced. This paper describes how DatView facilitates (i) efficient feedback during data collection by examining trends in time, sample position or any parameter, (ii) determination of optimal indexing and integration parameters via the comparison mode, (iii) identification of systematic errors in unmerged SFX data sets, and (iv) sorting and highly flexible data filtering (plot selections, Boolean filters and more), including direct export of subset CrystFEL stream files for further processing.
Crystal structure and Hirshfeld surface analysis of 2-(4-nitrophenyl)-2-oxoethyl picolinate
Authors: Sanjeeva Murthy T. N. , Chidan Kumar C. S. , Naveen S. , Veeraiah M. K. , Raghava Reddy Kakarla , Warad Ismail
Published: October 2019

2-(4-Nitrophenyl)-2-oxoethyl picolinate, C14H10N2O5, was synthesized under mild conditions. The chemical and molecular structures were confirmed by single-crystal X-ray diffraction analysis. The molecules are linked by inversion into centrosymmetric dimers via weak intermolecular C—H...O interactions, forming R
2
2(10) ring motifs, and further strengthened by weak π–π interactions. Hirshfeld surface analyses, the d
norm surfaces, electrostatic potential and two-dimensional fingerprint (FP) plots were used to verify the contributions of the different intermolecular interactions within the supramolecular structure. The shape-index surface shows that two sides of the molecules are involved with the same contacts in neighbouring molecules and curvedness plots show flat surface patches that are characteristic of planar stacking.
Crystal structure and photoluminescence properties of catena-poly[[bis(1-benzyl-1H-imidazole-κN
3)cadmium(II)]-di-μ-azido-κ4
N
1:N
3]
Authors: Assavajamroon Ploy , Kielar Filip , Chainok Kittipong , Wannarit Nanthawat
Published: October 2019

The new title one-dimensional CdII coordination polymer, [Cd(C10H10N2)2(μ1,3-N3)2]
n
, has been synthesized and structurally characterized by single-crystal X-ray diffraction. The asymmetric unit consists of a CdII ion, one azide and one 1-benzylimidazole (bzi) ligand. The CdII ion is located on an inversion centre and is surrounded in a distorted octahedral coordination sphere by six N atoms from four symmetry-related azide ligands and two symmetry-related bzi ligands. The CdII ions are linked by double azide bridging ligands within a μ1,3-N3 end-to-end (EE) coordination mode, leading to a one-dimensional linear structure extending parallel to [100]. The supramolecular framework is stabilized by the presence of weak C—H...N interactions, π–π stacking [centroid-to-centroid distance of 3.832 (2) Å] and C—H...π interactions between neighbouring chains.
Crystal structure of catena-poly[[[(2-ethoxypyrazine-κN)copper(I)]-di-μ2-cyanido] [copper(I)-μ2-cyanido]]
Authors: Partsevska Sofiia V. , Sirenko Valerii Y. , Terebilenko Kateryna V. , Malinkin Sergey O. , Gural'skiy Il'ya A.
Published: October 2019

In the asymmetric unit of the title coordination compound, {[Cu(CN)(C4H3OC2H5N2)][Cu(CN)]}
n
, there are two Cu atoms with different coordination environments. One CuI ion is coordinated in a triangular coordination geometry by the N atom of the 2-ethoxypyrazine molecule and by two bridging cyanide ligands, equally disordered over two sites exchanging C and N atoms, thus forming polymeric chains parallel to the c axis. The other Cu atom is connected to two bridging cyanide groups disordered over two sites with an occupancy of 0.5 for each C and N atom, and forming an almost linear polymeric chain parallel to the b axis. In the crystal, the two types of chain, which are orthogonal to each other, are connected by cuprophilic Cu...Cu interactions [2.7958 (13) Å], forming two-dimensional metal–organic coordination layers parallel to the bc plane. The coordination framework is further stabilized by weak long-range (electrostatic type) C—H...π interactions between cyano groups and 2-ethoxypyrazine rings.
Visualization of protein crystals by high-energy phase-contrast X-ray imaging
Authors: Polikarpov Maxim , Bourenkov Gleb , Snigireva Irina , Snigirev Anatoly , Zimmermann Sophie , Csanko Krisztian , Brockhauser Sandor , Schneider Thomas R.
Published: October 2019

For the extraction of the best possible X-ray diffraction data from macromolecular crystals, accurate positioning of the crystals with respect to the X-ray beam is crucial. In addition, information about the shape and internal defects of crystals allows the optimization of data-collection strategies. Here, it is demonstrated that the X-ray beam available on the macromolecular crystallography beamline P14 at the high-brilliance synchrotron-radiation source PETRA III at DESY, Hamburg, Germany can be used for high-energy phase-contrast microtomography of protein crystals mounted in an optically opaque lipidic cubic phase matrix. Three-dimensional tomograms have been obtained at X-ray doses that are substantially smaller and on time scales that are substantially shorter than those used for diffraction-scanning approaches that display protein crystals at micrometre resolution. Adding a compound refractive lens as an objective to the imaging setup, two-dimensional imaging at sub-micrometre resolution has been achieved. All experiments were performed on a standard macromolecular crystallography beamline and are compatible with standard diffraction data-collection workflows and apparatus. Phase-contrast X-ray imaging of macromolecular crystals could find wide application at existing and upcoming low-emittance synchrotron-radiation sources.
Solvent flows, conformation changes and lattice reordering in a cold protein crystal
Authors: Moreau David W. , Atakisi Hakan , Thorne Robert E.
Published: October 2019

When protein crystals are abruptly cooled, the unit-cell, protein and solvent-cavity volumes all contract, but the volume of bulk-like internal solvent may expand. Outflow of this solvent from the unit cell and its accumulation in defective interior crystal regions has been suggested as one cause of the large increase in crystal mosaicity on cooling. It is shown that when apoferritin crystals are abruptly cooled to temperatures between 220 and 260 K, the unit cell contracts, solvent is pushed out and the mosaicity grows. On temperature-dependent timescales of 10 to 200 s, the unit-cell and solvent-cavity volume then expand, solvent flows back in, and the mosaicity and B factor both drop. Expansion and reordering at fixed low temperature are associated with small-amplitude but large-scale changes in the conformation and packing of apoferritin. These results demonstrate that increases in mosaicity on cooling arise due to solvent flows out of or into the unit cell and to incomplete, arrested relaxation of protein conformation. They indicate a critical role for time in variable-temperature crystallographic studies, and the feasibility of probing interactions and cooperative conformational changes that underlie cold denaturation in the presence of liquid solvent at temperatures down to ∼200 K.
The evolving story of AtzT, a periplasmic binding protein
Authors: Dennis Matthew L. , Esquirol Lygie , Nebl Tom , Newman Janet , Scott Colin , Peat Thomas S.
Published: October 2019

Atrazine is an s-triazine-based herbicide that is used in many countries around the world in many millions of tons per year. A small number of organisms, such as Pseudomonas sp. strain ADP, have evolved to use this modified s-triazine as a food source, and the various genes required to metabolize atrazine can be found on a single plasmid. The atomic structures of seven of the eight proteins involved in the breakdown of atrazine by Pseudomonas sp. strain ADP have been determined by X-ray crystallography, but the structures of the proteins required by the cell to import atrazine for use as an energy source are still lacking. The structure of AtzT, a periplasmic binding protein that may be involved in the transport of a derivative of atrazine, 2-hydroxyatrazine, into the cell for mineralization, has now been determined. The structure was determined by SAD phasing using an ethylmercury phosphate derivative that diffracted X-rays to beyond 1.9 Å resolution. `Native' (guanine-bound) and 2-hydroxyatrazine-bound structures were also determined to high resolution (1.67 and 1.65 Å, respectively), showing that 2-hydroxyatrazine binds in a similar way to the purportedly native ligand. Structural similarities led to the belief that it may be possible to evolve AtzT from a purine-binding protein to a protein that can bind and detect atrazine in the environment.
2,4-Dichloro-6-[(2-hydroxy-5-methylanilino)methylidene]cyclohexa-2,4-dienone
Authors: Pal Tarun Kumar , Alam Md Ashraful , Hossain Md Dulal , Paul Subrata , Miyatake Ryuta , Sheikh Md Chanmiya
Published: October 2019

The title compound, C14H11Cl2NO2, has been prepared by the condensation of 3,5-dichlorosalicylaldehyde and 2-amino-4-methylphenol. The asymmetric unit consists of two independent molecules, both of which are almost planar; the dihedral angle between the two benzene rings is 10.61 (8)° for one molecule and 2.46 (8)° for the other. There is an intramolecular N—H...O hydrogen bond that generates S(6) ring motifs in each molecule. In the crystal, the two independent molecules are linked by O—H...O and C—H...Cl hydrogen bonds, forming a pseudo-inversion dimer. A π–π interaction, with a centroid–centroid distance of 3.6065 (12) Å, is also observed.
9α-Hydroxy-4,8-dimethyl-3′-phenyl-3,14-dioxatricyclo[9.3.0.02,4]tetradec-7-en-13-one-12-spiro-5′-isoxazole monohydrate
Authors: Outahar Fatima , Hannioui Abdellah , Rakib El Mostapha , Akssira Mohamed , Saadi Mohamed , El Ammari Lahcen
Published: October 2019

In the title compound, C22H25NO5·H2O, the ten-membered ring displays an approximate chair–chair conformation, whereas the five-membered furan ring has an envelope conformation, with the C atom of the methine group adjacent to the spiro C atom as the flap. The isoxazole ring is almost planar and its plane is slightly inclined to the plane of the attached phenyl ring. The mean plane of the furan ring is nearly perpendicular to that of the isoxazole ring, as indicated by the dihedral angle between them of 89.39 (12)°. In the crystal, the organic molecules are linked into [010] chains by O—H...O hydrogen bonds. The water molecule forms O—H...O and O—H...N hydrogen bonds and a weak C—H...O interaction is also observed. Together, these lead to a three-dimensional network.
The impact of party affiliation of governor and state political ideology on the labor market outcomes of transgender individuals
Authors: Cannonier Colin , Galloway Burke Monica
Published: October 2019

Purpose

The purpose of this paper is to investigate whether there is a causal impact of party affiliation of state governors operating within a liberal state legislature on labor market activity of transgender individuals. The common perception is that Republicans are more likely to believe a person’s gender is determined by their sex at birth than Democrats. Such beliefs can influence voting, policies and practices.

Design/methodology/approach

Survey data on employment outcomes and other individual level characteristics are used from two surveys focusing on transgender individuals for the periods 2008 and 2015. These surveys represent the largest collection of data that examines the experiences of transgender people in the USA. To establish a casual effect, this analysis employs fixed effects Ordinary Least Squares methods and Propensity Score Matching algorithms.

Findings

Exploiting variations in the party affiliation of governors and liberal state governments, the study finds mixed employment effects of living in a Democratic-governed liberal state. Specifically, this paper shows that transgender people living in such states have an 18 percentage point (or 26 percent) higher likelihood of being employed in the 2008 survey, but a 16.4 percentage point (or 25 percent) lower likelihood of being employed in the 2015 survey. Despite the lower propensity to be out of the labor market in the 2008 sample, results from both surveys indicate a higher likelihood of being unemployed. These findings are robust to the inclusion of additional covariates (including confounders), alternative specifications and different estimation techniques. Heterogeneous effects are also explored.

Originality/value

To the authors’ current knowledge, this is the first study to systematically investigate the relationship between living in democratically governed liberal states and labor market circumstances of transgender people in the USA. This is the first paper to establish a causal relationship using matching techniques. The paper also provides suggestive evidence of the role of government ideology in influencing the working lives of transgender people.
Predation shapes invertebrate diversity in tropical but not temperate seagrass communities
Authors: Freestone Amy L. , Carroll Elizabeth W. , Papacostas Katherine J. , Ruiz Gregory M. , Torchin Mark E. , Sewall Brent J.
Published: October 2019

The hypothesis that biotic interactions are stronger at lower relative to higher latitudes has a rich history, drawing from ecological and evolutionary theory. While this hypothesis suggests that stronger interactions at lower latitudes may contribute to the maintenance of contemporary patterns of diversity, there remain few standardized biogeographic comparisons of community effects of species interactions.

Using marine seagrasses as a focal ecosystem of conservation importance and sessile marine invertebrates as model prey, we tested the hypothesis that predation is stronger at lower latitudes and can shape contemporary patterns of prey diversity. To further advance understanding beyond prior studies, we also explored mechanisms that likely underlie a change in interaction outcomes with latitude.

Multiple observational and experimental approaches were employed to test for effects of predators, and the mechanisms that may underlie these effects, in seagrass ecosystems of the western Atlantic Ocean spanning 30° of latitude from the temperate zone to the tropics.

In predator exclusion experiments conducted in a temperate and a tropical region, predation decreased sessile invertebrate abundance, richness and diversity on both natural and standardized artificial seagrass at tropical but not temperate sites. Further, predation reduced invertebrate richness at both local and regional scales in the tropics. Additional experiments demonstrated that predation reduced invertebrate recruitment in the tropics but not the temperate zone. Finally, direct observations of predators showed higher but variable consumption rates on invertebrates at tropical relative to temperate latitudes.

Together, these results demonstrate that strong predation in the tropics can have consequential impacts on prey communities through discrete effects on early life stages as well as longer‐term cumulative effects on community structure and diversity. Our detailed experiments also provide some of the first data linking large‐scale biogeographic patterns, community‐scale interaction outcomes and direct observation of predators in the temperate zone and tropics. Therefore, our results support the hypothesis that predation is stronger in the tropics, but also elucidate some of the causes and consequences of this variation in shaping contemporary patterns of diversity.
The Verticillium dahliae Sho1‐MAPK pathway regulates melanin biosynthesis and is required for cotton infection
Authors: Li Jun‐Jiao , Zhou Lei , Yin Chun‐Mei , Zhang Dan‐Dan , Klosterman Steven J. , Wang Bao‐Li , Song Jian , Wang Dan , Hu Xiao‐Ping , Subbarao Krishna V. , Chen Jie‐Yin , Dai Xiao‐Feng
Published: October 2019

Verticillium dahliae is a soil‐borne fungus that causes vascular wilt on numerous plants worldwide. The fungus survives in the soil for up to 14 years by producing melanized microsclerotia. The protective function of melanin in abiotic stresses is well documented. Here, we found that the V. dahliae tetraspan transmembrane protein VdSho1, a homolog of the Saccharomyces cerevisiae Sho1, acts as an osmosensor, and is required for plant penetration and melanin biosynthesis. The deletion mutant ΔSho1 was incubated on a cellophane membrane substrate that mimics the plant epidermis, revealing that the penetration of ΔSho1 strain was reduced compared to the wild‐type strain. Furthermore, VdSho1 regulates melanin biosynthesis by a signalling mechanism requiring a kinase‐kinase signalling module of Vst50‐Vst11‐Vst7. Strains, ΔVst50, ΔVst7 and ΔVst11 also displayed defective penetration and melanin production like the ΔSho1 strain. Defects in penetration and melanin production in ΔSho1 were restored by overexpression of Vst50, suggesting that Vst50 lies downstream of VdSho1 in the regulatory pathway governing penetration and melanin biosynthesis. Data analyses revealed that the transmembrane portion of VdSho1 was essential for both membrane penetration and melanin production. This study demonstrates that Vst50‐Vst11‐Vst7 module regulates VdSho1‐mediated plant penetration and melanin production in V. dahliae, contributing to virulence.